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Neurobiology of emotion and high risk for schizophrenia: Role of the amygdala and the X-chromosome
Abstract
Abnormalities in emotion processing and in structure of the amygdala have consistently been documented in schizophrenia. A major question is whether amygdala abnormalities reflect a genetic vulnerability for the disease. In the present paper, we reviewed Magnetic Resonance Imaging (MRI) studies that reported amygdala measures in several high-risk populations: subjects from the general population with subclinical schizophrenia symptoms and relatives of schizophrenia patients. In addition, we reviewed the evidence regarding Klinefelter syndrome (characterised by an additional X-chromosome), which has also been related to an increased risk for schizophrenia. Overall, the evidence points to structural abnormalities of the amygdala in individuals at increased risk for schizophrenia. Although the genetic basis of amygdala deficits remains unclear, abnormalities (of genes) on the X-chromosome might play a role as suggested by the evidence from individuals with sex chromosome aneuploidies. We propose that amygdala abnormalities are an endophenotype in schizophrenia and may account for subtle emotional processing deficits that have been described in these high-risk groups.
... Arbib and Mundhenk (2005) link such impairments to the mirror neuron system, in suggesting that functional dissociations between action or speech imagination, and enactment of movement or speech, lead to misattribution of agency and consequent confabulation and rationalizing, which manifests as auditory hallucination, delusions, and paranoia. Similar considerations may apply to the mirror-neuron system underlying face perception and emotional resonance, which is also dysregulated in schizophrenia in the context of emotion inappropriate to social context and flat affect (e.g., van Rijn et al. 2005). A recent review of functionalimaging studies of social brain dysfunction in schizophrenia also suggests that two mirror-neuron regions -the inferior frontal cortex and the inferior parietal lobe (see Arbib & Mundhenk 2005) -are selectively responsible for some core cognitive manifestations of this disorder, as well as strongly implicating the medial prefrontal cortex, anterior cingulate cortex, and amygdala (Brunet-Gouet & Decety 2006). ...
... The most severe neurological and cognitive impairments are found, in both disorders, where the direction of genomic-imprinting dysregulation opposes the sex difference: in females with autism, and in males with schizophrenia. This hypothesis may also help to explain some of the many striking neuroanatomical and other differences between females and males with schizophrenia (e.g., DeLisi et al. 2002;Highley et al. 2003;Troisi et al. 2001; see also Cahill et al. 2004), as well as the more female-like hormonal profiles of male schizophrenics with predominantly negative symptoms (Akhondzadeh et al. 2006;Simpson et al. 2003), a high prevalence of homosexual ideation in male schizophrenics (Planansky & Johnston 1962), the female-biased sex ratio in major depression (e.g., Piccinelli & Wilkinson 2000), and the relatively high incidences of psychosis in Klinefelter syndrome (Boks et al. 2007a;DeLisi et al. 2005;van Rijn et al. 2005) and autism in Turner syndrome . ...
... This symptom overlap can be observed in particular between high functioning autistic disorder or Asperger's syndrome and early-onset schizophrenia, which tends to be characterized by negative symptoms with social interaction impairments (Bailer et al. 1996) and a chronic course (Krauss et al. 2000). Furthermore, retrospective studies conducted on patients with schizophrenia or longitudinal studies of children with autistic disorder reported frequent associations between these two disorders (antecedents of autistic disorder in the childhood of the schizophrenic group and appearance of schizophrenia in the autistic group) (Alaghband-Rad et al. 1995;Bender & Faetra 1972;Jansen et al. 2000;Petty et al. 1984;Van Engeland & Van Der Gaag 1994). ...
... Psychiatric conditions associated with Klinefelter syndome include anxiety, depression, bipolar disorder, schizoaffective disorder and schizophrenia (DeLisi et al. 1994(DeLisi et al. , 2005Mizukami et al. 1989;Everman and Stoudemire 1994;van Rijn et al. 2005van Rijn et al. , 2006Boks et al. 2007). Several studies have demonstrated that schizophrenia in particular shows a high prevalence in Klinefelter syndrome, with a four-fold to ten-fold increase (DeLisi et al. 1994van Rijn et al. 2006). ...
... DeLisi et al. (2005) also noted that the neurocognitive profiles are similar in Klinefelter syndrome and idiopathic (cause-unknown) schizophrenia, and Van Rijn et al. (2006) showed that Klinefelter individuals scored significantly high than controls on scales of schizotypy. Klinefelter syndrome also involves an uneven profile of hyperfunctional emotional experience and reactivity, but impaired ability to identify and verbalize emotions, which resembles the pattern seen in schizophrenics (van Rijn 2005(van Rijn , 2006. ...
... For the set of neurogenetic sister-disorders analyzed here, the clearest overall pattern is that one of the pairs has been commonly associated with autism spectrum conditions (Table 2), a finding that concurs with the results of recent studies showing that a notable proportion of cases of autism can be ascribed to effects of copy-number variants (Sebat et al. 2007;Christian et al. 2008;Marshall et al. 2008;Mefford et al. 2008;. By contrast, the sister-disorders of the autismassociated conditions noted in Table 2 appear to involve a suite of phenotypic traits that are characteristic of what has been termed the schizophrenia spectrum or psychotic spectrum, which is exemplified by the set of psychological and psychiatric conditions described for Velocardiofacial syndrome by Gothelf (2007, Table 2), as well as for Klinefelter syndrome Mizukami et al. 1989;Everman and Stoudemire 1994;van Rijn et al. 2005van Rijn et al. , 2006Boks et al. 2007); these conditions include schizophrenia, schizoaffective disorder, bipolar disorder, unipolar depression, schizotypy, phobias, generalized anxiety disorder, panic disorders, and psychotic symptoms. The former five conditions have been demonstrated to exhibit strong patterns of overlap with regard to their genetic underpinnings (Craddock and Forty 2006;Potash 2006;Blackwood et al. 2007;Fanous et al. 2007), and rates of comorbidity of anxiety and phobias with schizophrenia, schizoaffective disorder, and bipolar disorder are on the order of 40-60% (Cosoff and Hafner 1998;Huppert and Smith 2005;Zutshi et al. 2006). ...
Genomic sister-disorders are defined here as diseases mediated by duplications versus deletions of the same region. Such disorders can provide unique information concerning the genomic underpinnings of human neurodevelopment because effects of diametric variation in gene copy number on cognitive and behavioral phenotypes can be inferred. We describe evidence from the literature on deletions versus duplications for the regions underlying the best-known human neurogenetic sister-disorders, including Williams syndrome, Velocardiofacial syndrome, and Smith–Magenis syndrome, as well as the X-chromosomal conditions Klinefelter and Turner syndromes. These data suggest that diametric copy-number alterations can, like diametric alterations to imprinted genes, generate contrasting phenotypes associated with autistic-spectrum and psychotic-spectrum conditions. Genomically based perturbations to the development of the human social brain are thus apparently mediated to a notable degree by effects of variation in gene copy number. We also conducted the first analyses of positive selection for genes in the regions affected by these disorders. We found evidence consistent with adaptive evolution of protein-coding genes, or selective sweeps, for three of the four sets of sister-syndromes analyzed. These studies of selection facilitate identification of candidate genes for the phenotypes observed and lend a novel evolutionary dimension to the analysis of human cognitive architecture and neurogenetic disorders.
... Mors, Mortensen & Ewald (2001) reported a significantly lower incidence of schizophrenia and bipolar disorder (considered together) in Turner females, compared to normal 46,XX females. An increased incidence of schizophrenia has been described in some studies of Turner syndrome females, but these reported increases are apparently due almost exclusively to cases that involve mosaic karyotypes, such that females exhibit some mixture of 45,X, 46,XX, and 47,XXX chromosome complements (Beumont & Mayou, 1971;Fishbain & Vilasuso, 1981;Kunugi, Lee & Nanko, 1999;Donnelly et al., 2000;Prior, Chue & Tibbo, 2000;van Rijn et al., 2005). These findings, and reports of increased rates of schizophrenia in 47,XXX females (DeLisi et al., 1994;Kumra et al., 1998), suggest that psychosis in sex-chromosome anomalous females is due entirely or predominantly to X trisomy (DeLisi et al., 1994;Patwardhan et al., 2002). ...
... Klinefelter syndrome (usually 47,XXY) is associated with impairment of verbal abilities, especially in language processing and working verbal memory (Graham et al., 1988;Fales et al., 2003;Itti et al., 2003Itti et al., , 2006Simpson et al., 2003;DeLisi et al., 2005). This syndrome also involves a four to tenfold increase in liability to psychosis (Mizukami et al., 1989;DeLisi et al., 1994DeLisi et al., , 2005Everman & Stoudemire, 1994;Kebers et al., 2002;van Rijn et al., 2005van Rijn et al., , 2006aBoks et al., 2007a). Psychosis in Klinefelter syndrome normally involves a relatively high incidence of positive features, such as auditory hallucinations and paranoia, rather than the negative features more common in affected 46,XY males, and it also exhibits a later, femaletypical age of onset (Pinabel, Gorwood & Ades, 1997;DeLisi et al., 2005;van Rijn et al., 2005). ...
... This syndrome also involves a four to tenfold increase in liability to psychosis (Mizukami et al., 1989;DeLisi et al., 1994DeLisi et al., , 2005Everman & Stoudemire, 1994;Kebers et al., 2002;van Rijn et al., 2005van Rijn et al., , 2006aBoks et al., 2007a). Psychosis in Klinefelter syndrome normally involves a relatively high incidence of positive features, such as auditory hallucinations and paranoia, rather than the negative features more common in affected 46,XY males, and it also exhibits a later, femaletypical age of onset (Pinabel, Gorwood & Ades, 1997;DeLisi et al., 2005;van Rijn et al., 2005). ...
I review and evaluate genetic and genomic evidence salient to the hypothesis that the development and evolution of psychotic spectrum conditions have been mediated in part by alterations of imprinted genes expressed in the brain. Evidence from the genetics and genomics of schizophrenia, bipolar disorder, major depression, Prader-Willi syndrome, Klinefelter syndrome, and other neurogenetic conditions support the hypothesis that the etiologies of psychotic spectrum conditions commonly involve genetic and epigenetic imbalances in the effects of imprinted genes, with a bias towards increased relative effects from imprinted genes with maternal expression or other genes favouring maternal interests. By contrast, autistic spectrum conditions, including Kanner autism, Asperger syndrome, Rett syndrome, Turner syndrome, Angelman syndrome, and Beckwith-Wiedemann syndrome, commonly engender increased relative effects from paternally expressed imprinted genes, or reduced effects from genes favouring maternal interests. Imprinted-gene effects on the etiologies of autistic and psychotic spectrum conditions parallel the diametric effects of imprinted genes in placental and foetal development, in that psychotic spectrum conditions tend to be associated with undergrowth and relatively-slow brain development, whereas some autistic spectrum conditions involve brain and body overgrowth, especially in foetal development and early childhood. An important role for imprinted genes in the etiologies of psychotic and autistic spectrum conditions is consistent with neurodevelopmental models of these disorders, and with predictions from the conflict theory of genomic imprinting.
... van Rijn et al., in press), studying social cognitive processing in Klinefelter syndrome may prove to be an important contribution to the development of more general models describing pathways to neuropsychiatric disorders characterized by social cognitive disturbances (Van Rijn et al., 2005). ...
... This neuroanatomical model describes amygdala dysfunctions that arise from structural abnormalities of the amygdala in combination with an imbalance in dopamine systems, with specific effects on intra-amygdaloid processing. Indeed, Klinefelter syndrome, as well as other populations at increased risk for schizophrenia, has been associated with structural abnormalities of the amygdala (Van Rijn et al., 2005). Interestingly, such a dissociation between cognitive appraisal of emotions on the one hand and autonomic, emotional arousal on the other hand has also been reported for females with Turner syndrome, characterised by X monosomy (45,X) and a 200-fold increased risk for autism. ...
... E. DeLisi et al., 2005;Gillberg, 1995;Swaab et al., in prep.;van Rijn et al., in press;Van Rijn et al., 2005). Although speculative, X-related disturbances in social cognitive processing may be one of many pathways to psychiatric disorders such as schizophrenia and autism. ...
Studying Klinefelter syndrome (47,XXY), a genetically defined disorder characterized by the presence of an additional X chromosome, can reveal insights into genotype-phenotype associations. Increased vulnerability to psychiatric disorders characterized by difficulties in social interactions, such as schizophrenia and autism, has been reported for this population. The reported social difficulties in 47,XXY men may arise as a consequence of impairments in the processing of social and emotional information. The present study is the first investigation of social-emotional information processing in this X chromosomal disorder. 32 Klinefelter men and 26 men from the general population, with the groups matched for age, educational level and I.Q., participated in the study. Several tasks were included, reflecting aspects of social-emotional information processing on levels of perception, experience and expression: labeling of facial expressions of emotion, emotion-cognition interactions in decision making and emotion regulation, that refers to subjective experience and identification of emotional arousal as well as verbal expression of emotions. A discrepancy between cognitive appraisal of emotions and emotional arousal was observed in Klinefelter syndrome. Taken together, Klinefelter men seem less accurate in perception of socio-emotional cues such as angry facial expressions, they are less able to identify and verbalize their emotions, but experience increased levels of emotional arousal, in comparison to the general population. Besides describing the social-emotional phenotype of this X chromosomal disorder, the present data may prove to be an important contribution to the development of more general models describing pathways to neuropsychiatric disorders characterized by social cognitive disturbances.
... SC had widespread cognitive impairments, which were consistent with previous research findings [19,20] Additionally, we discovered a significant increase in local neural activity in the left amygdala. Previous research has suggested a close relationship between the amygdala and the observed mood dysregulation in SC, with abnormal structure and function of the amygdala being associated with psychotic symptoms [13,[21][22][23][24]. Some researchers had indicated that SC patients have reduced volume changes in the amygdala [21,25,26], while others had concluded that early and comprehensive treatment could repair brain atrophy in SC patients [27]. ...
... Previous research has suggested a close relationship between the amygdala and the observed mood dysregulation in SC, with abnormal structure and function of the amygdala being associated with psychotic symptoms [13,[21][22][23][24]. Some researchers had indicated that SC patients have reduced volume changes in the amygdala [21,25,26], while others had concluded that early and comprehensive treatment could repair brain atrophy in SC patients [27]. However, our study did not find any significant volume differences between SC patients and HC, which may be attributed to our selection of treatment-naïve SC individuals. ...
Background
Amygdala plays an important role in schizophrenia (SC), but its mechanisms are still unclear. Therefore, we investigated the relationship between the resting-state magnetic resonance imaging (rsMRI) signals of the amygdala and cognitive functions, providing references for future research in this area.
Methods
We collected 40 drug-naïve SC patients and 33 healthy controls (HC) from the Third People’s Hospital of Foshan. We used rsMRI and the automatic segmentation tool to extract the structural volume and local neural activity values of the amygdala and conducted Pearson correlation analysis with the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores. Finally, we compared the clinical data, as well as the volume and functional changes of the amygdala in SC patients before and after treatment.
Results
Compared with HC, SC had widespread cognitive impairments, significant abnormalities in left amygdala function, while the reduction in volume of SC was not significant. Further Pearson correlation analysis with Bonferroni correction showed that only Immediate memory (learning) was significantly negatively correlated with fractional amplitude of low-frequency fluctuation (FALFF, r = -0.343, p = 0.001, p’ = 0.014 (Bonferroni correction)). When compared and analyzed the data difference of SC before and after treatment, we found that immediate memory and delayed memory of SC showed varying degrees of recovery after treatment (tlearning = -2.641, plearning = 0.011; tstory memory = -3.349, pstory memory = 0.001; tlist recall = -2.071, plist recall = 0.043; tstory recall = -2.424, pstory recall = 0.018). But the brain structure and function did not recover.
Conclusion
There was significant dysfunction in the amygdala in SC, and after conventional treatment, the function of the amygdala did not improve with the improvement of clinical symptoms and cognitive function.
... Supporting the hypothesis that KS can be a risk factor for BD, several studies have highlighted the association between 47,XXY aneuploidy and psychiatric disorders, such as depression, anxiety, and schizophrenia (Bender et al., 1999;van Rijn et al., 2005;Bruining et al., 2009Bruining et al., , 2010. ...
... Genetic studies have investigated individuals with KS because of their increased risk for schizophrenia (van Rijn et al., 2005;Bruining et al., 2010). DeLisi et al. (2005) investigated KS as a genetic model for psychotic disorders. ...
Klinefelter syndrome (KS) is the most common sex chromosomal disorder with an estimated prevalence of 1 in 500-1000. Increased incidences of anxiety, depression, substance abuse, psychotic and behavioral disorders, and sexual disorders have been reported in patients with KS. The aim of this case study was to report a case of a man with untreated KS who was also diagnosed with type II bipolar disorder. This case report raises awareness regarding psychiatric diagnoses that may be associated with such a highly prevalent condition. A 46-year-old man who had previously been diagnosed with an untreated KS was examined in our Psychiatric Department with an acute hypomanic episode. Clinical improvement was observed within 4 days and psychiatric symptoms were resolved in 7 days without use of medication. A psychiatric history of a depressive episode and at least two hypomanic episodes, as well as a family history of two relatives diagnosed with bipolar disorder, strongly suggest that our patient has type II bipolar disorder. Bipolar disorder may be a comorbid disorder in patients with KS. Routine screening for mood disorders and appropriate referral and evaluation should be performed. Future genetic research is warranted to explore why some chromosomal abnormalities (e.g., duplications), especially those located on the X chromosome, such as Klinefelter syndrome, may be associated with a bipolar or psychotic disorder in some individuals but not in others.
... However, it has not been determined whether CB2R KO mice also display other phenotypes resembling schizophrenia-related behaviors. Patients with schizophrenia have working memory deficits (for review, see [36]) and impaired functions of the hippocampus (for reviews, see [37,38]) and amygdala (for reviews, see [39,40]). These features are often recapitulated in animal models of schizophrenia (for reviews, see [41,42]). ...
... As introduced earlier, the abnormality of CNR2 in humans is related to schizophrenia [31,32] and CB2R KO mice display schizophrenia-like phenotypes, for example, impairment in sensory-motor gating and an increase in depressive behavior [34]. Individuals with schizophrenia have deficits in working memory (for review, see [36]), hippocampal functions (for reviews, see [37,38]), amygdala functions (for reviews, see [39,40]), and anxiety (for review, see [58]). However, our study indicates that CB2R KO mice display improved working memory, normal cued fear memory (which requires amygdala function), and normal anxiety levels. ...
Neurocognitive effects of cannabinoids have been extensively studied with a focus on CB1 cannabinoid receptors because CB1 receptors have been considered the major cannabinoid receptor in the nervous system. However, recent discoveries of CB2 cannabinoid receptors in the brain demand accurate determination of whether and how CB2 receptors are involved in the cognitive effects of cannabinoids. CB2 cannabinoid receptors are primarily involved in immune functions, but also implicated in psychiatric disorders such as schizophrenia and depression. Here, we examined the effects of CB2 receptor knockout in mice on memory to determine the roles of CB2 receptors in modulating cognitive function. Behavioral assays revealed that hippocampus-dependent, long-term contextual fear memory was impaired whereas hippocampus-independent, cued fear memory was normal in CB2 receptor knockout mice. These mice also displayed enhanced spatial working memory when tested in a Y-maze. Motor activity and anxiety of CB2 receptor knockout mice were intact when assessed in an open field arena and an elevated zero maze. In contrast to the knockout of CB2 receptors, acute blockade of CB2 receptors by AM603 in C57BL/6J mice had no effect on memory, motor activity, or anxiety. Our results suggest that CB2 cannabinoid receptors play diverse roles in regulating memory depending on memory types and/or brain areas.
... However, it has not been determined whether CB2R KO mice also display other phenotypes resembling schizophrenia-related behaviors. Patients with schizophrenia have working memory deficits (for review, see [36]) and impaired functions of the hippocampus (for reviews, see [37, 38]) and amygdala (for reviews, see [39, 40]). These features are often recapitulated in animal models of schizophrenia (for reviews, see [41, 42]). ...
... As introduced earlier, the abnormality of CNR2 in humans is related to schizophrenia [31, 32] and CB2R KO mice display schizophrenia-like phenotypes, for example, impairment in sensory-motor gating and an increase in depressive behavior [34]. Individuals with schizophrenia have deficits in working memory (for review, see [36]), hippocampal functions (for reviews, see [37, 38]), amygdala functions (for reviews, see [39, 40]), and anxiety (for review, see [58]). However, our study indicates that CB2R KO mice display improved working memory, normal cued fear memory (which requires amygdala function), and normal anxiety levels. ...
... However, it has not been determined whether CB2R KO mice also display other phenotypes resembling schizophrenia-related behaviors. Patients with schizophrenia have working memory deficits (for review, see [36]) and impaired functions of the hippocampus (for reviews, see [37, 38]) and amygdala (for reviews, see [39, 40]). These features are often recapitulated in animal models of schizophrenia (for reviews, see [41, 42]). ...
... As introduced earlier, the abnormality of CNR2 in humans is related to schizophrenia [31, 32] and CB2R KO mice display schizophrenia-like phenotypes, for example, impairment in sensory-motor gating and an increase in depressive behavior [34]. Individuals with schizophrenia have deficits in working memory (for review, see [36]), hippocampal functions (for reviews, see [37, 38]), amygdala functions (for reviews, see [39, 40]), and anxiety (for review, see [58]). However, our study indicates that CB2R KO mice display improved working memory, normal cued fear memory (which requires amygdala function), and normal anxiety levels. ...
... 7T MRI is known to have higher sensitivity to tissue changes and anatomical details, which thus produces higher spatial resolution and clearer tissue boundaries [29]. Interestingly, we did not show differences between groups in amygdala volume, which is also a key element of the limbic brain network that plays a central role in emotional and social information processing, is involved in complex social judgements and is part of a neural network underlying social cognition [30]. Since social impairments have frequently been reported in 47,XXX, we expected to find alterations in amygdala volume in our study. ...
Background
Triple X syndrome (47,XXX) is a relatively common sex chromosomal aneuploidy characterized by the presence of a supernumerary X chromosome in females and has been associated with a variable cognitive, behavioural and psychiatric phenotype. 47,XXX may serve as a suitable model for studying the effect of genetic architecture on brain morphology. Previous studies have shown alterations in brain structure in 47,XXX particularly in childhood and adolescence. In this study, we examined subcortical and cortical brain morphology in adult women with 47,XXX using ultra-high field 7T MRI. Given previous evidence of impaired social functioning and emotion recognition in adults with 47,XXX, we also investigated the relationship of these functions with brain morphology.
Methods
Twenty-one adult women with 47,XXX and 22 age- and sex-matched healthy controls were included. Structural T1-weighted images were acquired using a 7-Tesla magnetic resonance scanner. Measures of subcortical brain volumes, cortical surface area and thickness, and cortical folding were obtained and compared between the groups using general linear models. Additionally, we examined potential relationships between brain outcome measures and social functioning and social cognition in 47,XXX using correlation analyses.
Results
Adults with 47,XXX showed lower volumes of the thalamus, caudate, putamen, hippocampus, nucleus accumbens and pallidum, and larger lateral ventricle volumes. Lower surface area was found in the superior frontal gyrus and superior temporal gyrus in 47,XXX participants compared to healthy controls. Altered cortical thickness and cortical folding were not present in 47,XXX. Cortical thickness was associated with social cognition in 47,XXX.
Conclusions
Results suggest that a supernumerary X chromosome in females affects subcortical and lateral ventricle volumes, and cortical surface area in adulthood. 47,XXX may serve as a suitable model for studying genetic influences on structural brain morphology across developmental stages in order to understand neurobiological mechanisms underlying cognitive and behavioural impairments.
... More specifically, abnormal functional activation in risk groups has been reported in the prefrontal cortex, anterior cingulate cortex, amygdala, and temporal cortex (141,142). Notably, also reduced amygdala volumes have been found in individuals at risk of psychosis (137,142,143), emphasizing the role of amygdala alteration as a potential liability to developing primary psychosis in those risk groups. ...
Autism spectrum disorder (ASD) and primary psychosis are classified as distinct neurodevelopmental disorders, yet they display overlapping epidemiological, environmental, and genetic components as well as endophenotypic similarities. For instance, both disorders are characterized by impairments in facial expression processing, a crucial skill for effective social communication, and both disorders display an increased prevalence of adverse childhood events (ACE). This narrative review provides a brief summary of findings from neuroimaging studies investigating facial expression processing in ASD and primary psychosis with a focus on the commonalities and differences between these disorders. Individuals with ASD and primary psychosis activate the same brain regions as healthy controls during facial expression processing, albeit to a different extent. Overall, both groups display altered activation in the fusiform gyrus and amygdala as well as altered connectivity among the broader face processing network, probably indicating reduced facial expression processing abilities. Furthermore, delayed or reduced N170 responses have been reported in ASD and primary psychosis, but the significance of these findings is questioned, and alternative frequency-tagging electroencephalography (EEG) measures are currently explored to capture facial expression processing impairments more selectively. Face perception is an innate process, but it is also guided by visual learning and social experiences. Extreme environmental factors, such as adverse childhood events, can disrupt normative development and alter facial expression processing. ACE are hypothesized to induce altered neural facial expression processing, in particular a hyperactive amygdala response toward negative expressions. Future studies should account for the comorbidity among ASD, primary psychosis, and ACE when assessing facial expression processing in these clinical groups, as it may explain some of the inconsistencies and confound reported in the field.
... La prosodia es un conjunto de rasgos suprasegmentales en los que se incluyen el acento, la entonación, el tono, el ritmo, la melodía, las pausas, la velocidad de elocución y la cualidad de la voz (Llisterri, 2016), y es un rasgo de la lengua oral que ayuda a llevar estados emocionales o afectivos en las oraciones (Saá, 2001). Numerosos autores distinguen entre prosodia semántica o lingüística y afectiva o emocional (Couper-Kuhlen,1986;Murphy y Cutting, 1990;Edwards et al., 2001;Van Rijn et al., 2005;Hoekert et al., 2007;Difaldis et al., 2013); Martínez et al. (2015) definen ambos conceptos de la siguiente manera: Estos dos tipos de prosodia son definidos como: prosodia semántica, que es la que se refiere al significado, y prosodia afectiva, que es la que se refiere a la expresión de las emociones. Son estos tres parámetros, junto con la gestualidad y el contenido del discurso, los que nos dan la sensación de emoción cuando escuchamos a alguien, y de acuerdo con estudios anteriores, podemos asociar ciertos parámetros acústicos con el reconocimiento y la expresión de emociones. ...
El objetivo de este trabajo es determinar si la elección lingüística coincide con la visual al escuchar una emoción. Para ello se grabó el cuento de Caperucita Roja en el que aparecían tres emociones básicas simuladas por una joven bilingüe procedente del País Vasco y se diseñó un test específico para la investigación, en el que los 178 participantes bilingües con edades comprendidas entre los 8 y 15 años, (99 son de género masculino y el 79 son del femenino), estudiantes de tercer y cuarto curso de Educación Primaria y de primero y segundo de Educación Secundaria Obligatoria, de un colegio concertado tenían que elegir la emoción básica a la que correspondía lo escuchado. Según los resultados, vincular el estímulo auditivo con el tipo de emoción verbalizada no es complicado, genera contradicciones y parece que entraña una mayor dificultad para los sujetos relacionar éstos con los estímulos visuales.
... Differently, few studies focused on the volume changes of amygdala subregions in patients with schizophrenia, although much research has reported the abnormal volume changes of the whole amygdala (20,21). The previous study has demonstrated that schizophrenia patients have smaller volume in bilateral amygdala and hippocampus compared with healthy control (13). ...
Background:
Many studies have found volume changes in the hippocampus and amygdala in patients with schizophrenia, but these findings have not reached an agreement. Particularly, few results showed the volumes of the sub-regions of the amygdala. In this research, we aim to clarify volume changes of hippocampus and amygdala sub-regions in patients with schizophrenia.
Methods:
The sample consisted of 69 patients with schizophrenia and 72 control subjects aged from 18 to 65 years. FreeSurfer 6.0 software was used on T1-weighted images to assess the volumes of hippocampus and amygdala and their sub-regions. The general linear model (GLM) was used to analyze the volume changes between the two groups. False discovery rate (FDR) correction was performed, and the significance level was set at 0.05.
Results:
The hippocampus volume in schizophrenia showed reduction compared to healthy control (P<0.05). Several hippocampal subfields showed smaller volume in schizophrenia patients, including bilateral presubiculum and molecular layer, left hippocampal tail, subiculum and cornus ammonis (CA)1, and right parasubiculum (P<0.05). Left amygdala volume showed a decrease as well, sub-regions including the bilateral basal nucleus, anterior-amygdaloid-area (AAA), paralaminar nucleus and left lateral nucleus (P<0.05).
Conclusions:
Several sub-regions of hippocampus and amygdala showed a volumetric decline in patients group, which suggest the key roles of these regions in the pathophysiology of schizophrenia. Based on these results, we speculate that these regions could be used to assess the early finding of schizophrenia.
... Studies have demonstrated that genes in the sex chromosome may influence psychiatric disease by altering the basic differentiation process of the neurons [3], encoding proteins [4], synaptic transmission [5] and so on. For example, X-linked genes have specific impacts on the development of the amygdala and its connections with cortical centers involved in social-cognition processing as shown in Figure 1 [6], while structural abnormalities of the amygdala in individuals have been proven to increase risk for schizophrenia [7]. Therefore, the study of sex chromosomes in psychiatric diseases may provide a new angle to understand the sex differences in the pathogeneses of psychiatric diseases. ...
Excesses of sex chromosome abnormalities in patients with psychiatric diseases have recently been observed. It remains unclear whether sex chromosome abnormalities are related to sex differences in some psychiatric diseases. While studies showed evidence of susceptibility loci over many sex chromosomal regions related to various mental diseases, others demonstrated that the sex chromosome aneuploidies may be the key to exploring the pathogenesis of psychiatric disease. In this review, we will outline the current evidence on the interaction of sex chromosome abnormalities with schizophrenia, autism, ADHD and mood disorders.
... These synapses could be the site of primary abnormalities that disrupt downstream neural circuits; however, this remains to be demonstrated. In addition, patients with Klinefelter's syndrome, which is characterized by an additional X chromosome, are likely to have structural abnormalities of the amygdala and are at an increased risk of schizophrenia (van Rijn et al. 2005). Other neural structures altered in patients with schizophrenia include the hippocampus, prefrontal cortex, and dorsal thalamus (Owen et al. 2005). ...
... Schizophrenia is typically regarded as a neurocognitive disorder with a genetic component, which suggests that emotional disturbances reflect abnormalities in brain areas important for emotion processing (Phillips, et al., 2003). Indeed, emotion abnormalities observed in schizophrenia even extend to persons at risk for schizophrenia, including relatives of patients with schizophrenia (van Rijn, et al., 2005) and other psychotic disorders. Interestingly, there appears to be some specificity in these emotion deficits. ...
Introduction & Objective: The previous studies investigating alexithymia in psychotic patients indicated that such patients have difficulty in identifying and expressing their feelings. The purpose of this study is to investigate the extent of alexithymia in patients with psychotic disorders, non psychotic disorders, and normal people.Materials & Methods: In this causal-comparative study 60 psychotic, 60 non-psychotic patients and 140 students were selected via available sampling method (the results of Leven's test indicated the homogeneity of variance among the three groups). Using Torento Alexithymia Scale( TAS-20),we compared them with each others.Results: Results showed that the extent of alexithymia in psychotic and non-psychotic patients was higher than that of normal people(P
... Medial temporal lobe abnormalities (amygdala, hippocampus, parahippocampal gyrus), although robustly identified in schizophrenia samples (Honea, Crow, Passingham, & MacKay, 2005), are inconsistently identified in schizotypal personality disorder (Siever & Davis, 2004). It has been suggested that reduced medial temporal lobe volume may be more prevalent among familial or genetic high-risk individuals van Rijn, Aleman, Swaab, & Kahn, 2005) than in nonfamilial high-risk phenotypes like schizotypal personality disorder (Velakoulis et al., 2006). Altogether, these findings led Siever & Davis (2004) to hypothesize that normal or compensatory frontal lobe function and/or subcortical stability may protect psychosis-prone individuals from primary temporal lobe abnormalities that could otherwise develop into full-blown psychosis. ...
... Schizophrenia is typically regarded as a neurocognitive disorder with a genetic component, which suggests that emotional disturbances reflect abnormalities in brain areas important for emotion processing (Phillips, et al., 2003). Indeed, emotion abnormalities observed in schizophrenia even extend to persons at risk for schizophrenia, including relatives of patients with schizophrenia (van Rijn, et al., 2005) and other psychotic disorders. Interestingly, there appears to be some specificity in these emotion deficits. ...
In the present study attempt has been made to investigate the extent of alexithymia in patients with schizophrenia spectrum disorders, non-psychotic disorders and normal people. The research sample consisted of 60 patients with schizophrenia spectrum disorders and 60 non-psychotic disorders from inpatients and outpatients of Mostafa Khomeini and Hazrat Rasoul hospitals, and 140 students from Tehran university (results of Leven test indicated the homogeneity of variance among three groups). Using Torento Alexithymia Scale (TAS-20) they were compared. Results showed that alexithymia had significant difference in patients with schizophrenia spectrum disorders and normal people; and non-psychotic disorders and normal people, but differences weren't significant between patients with schizophrenia spectrum disorders and non-psychotic disorders. The difficulty in describing feelings, difficulty in identifying feelings and externally-oriented thinking were higher in patients with schizophrenia spectrum disorders than other groups. In all groups, males had more problems in describing feelings and externally-oriented thinking. These results suggest that high level of alexithymia could contribute to a greater vulnerability for schizophrenia spectrum disorders and it could set males at high risk for these disorders. thus, it is essential to contrive a special treatment to decrease alexithymia in these patients.
... Such research should also take into account the role of the amygdala, which has been implied in social information processing (Adolphs et al., 1998). Abnormalities of the amygdala have been documented in patients with schizophrenia as well as their relatives and Klinefelter patients (Van Rijn et al., 2005). ...
Schizophrenia is characterized by disturbances in social functioning. In the search for determinants of social dysfunction in schizophrenia patients, social cognitive capacities appear to be of crucial importance. The ability to process basic social cues, such as gaze direction and biological motion direction, quickly and automatically is thought to be a prerequisite for establishing successful social interactions and especially for construing a sense of 'social intuition'. However, studies that address the ability to automatically process such basic social cues in schizophrenia are lacking. We used a new visual illusion measuring the extent in which social cues are processed effortlessly and implicitly in three different groups characterized by the presence of traits or symptoms from the schizophrenia spectrum, i.e. 33 patients with schizophrenia, 32 siblings of patients with schizophrenia and 32 individuals with Klinefelter syndrome (47,XXY). These groups were compared to 50 age-, sex-and education-matched healthy control subjects. Results indicated that, in contrast to control subjects, patients with schizophrenia showed insensitivity to social cues. This was particularly pronounced in patients with negative symptoms. The reduced influence of social cues was also observed in first-degree relatives of patients with schizophrenia as well as in Klinefelter subjects. We suggest that the insensitivity for social cues is a cognitive aspect of schizophrenia that may be seen as an endophenotype as it appears to be present both in relatives who are at increased genetic risk and a genetic disorder associated with schizophrenia spectrum psychopathology. These social cue-processing deficits could contribute, in part, to the difficulties in higher order social cognitive tasks and hence decreased social competence that have been observed in these groups.
... Dysfunction of this system, specifically amygdalohippocampal (e.g., Gur et al., 2007;Pinkham et al., 2011) and fronto-temporal structures (e.g., Lawrie et al., 2002;Li et al., 2012) and their connectivity, has been implicated in impaired facial emotion identification in schizophrenia. Similar findings on a structural (e.g., van Rijn et al., 2005;Borgwardt et al., 2012;Li et al., 2012) and functional level (e.g., Modinos et al., 2012) have been documented in high-risk persons. These functional and structural brain findings, along with emotion perception impairment extensively documented in schizophrenia (Kohler et al., 2010), support the investigation of emotion perception in persons at risk for schizophrenia. ...
... The positive association between the E-N170 and SCP scores was significant also in ADHD patients, SFDRs and controls, opening new branches for additional research. From neural signatures of emotional modulation to social cognition SCAN (2014) Common genetic backgrounds and shared symptomatology with respect to the neurocognitive profiles have been proposed for SCZ families (van Rijn et al., 2005), BD and SCZ (Hill et al., 2008), ADHD and SCZ (Marsh and Williams, 2006) and ADHD and BD (Passarotti and Pavuluri, 2011). These disorders share some symptoms, are often co-morbid, and present emotional processing impairments. ...
t is commonly assumed thatearly emotional signals provide relevant informationfor social cognition tasks. The goal of this study was to test the association between (a) cortical markers of face emotional processing and (b) social-cognitive measures,and also to build a model which can predictthis association (a & b) in healthy volunteers as well as in different groups of psychiatric patients. Thus, we investigated the early cortical processing of emotional stimuli (N170, using a face and word valence task) and their relationship with the social-cognitive profiles (SCPs, indexed by measures of theory of mind, fluid intelligence, speed processing, and executive functions). Group comparisons and individual differences were assessed among schizophrenia (SCZ) patients and their relatives, individuals with attention deficit hyperactivity disorder (ADHD), individuals with euthymic bipolar disorder (BD) and healthy participants (educational level, handedness, age and gendermatched). Our results provide evidence of emotional N170 impairments in the affected groups (SCZ and relatives, ADHD and BD) as well as subtle group differences. Importantly, cortical processing of emotional stimuli predicted the social cognition profile (SCP), as evidenced by a structural equation model (SEM) analysis. This is the first study to report anassociation model of brain markers of emotional processing and SCP.
... We know from previous clinical studies that many KS boys suffer from learning impairment, especially in the verbal area (8,14); lower IQ, especially verbal IQ (9); psychosocial problems (11); autistic features (15); and psychiatric diseases (13,16) that may lead to poor adaptation and success in the educational system and perhaps to a reduced success in regard to forming viable amorous relations. These problems are most likely reflected in the consistently lower income in KS persons throughout their life span, which can be an effect of their low level of education, but it was also present when excluding all persons (KS and controls alike) with an education. ...
Context: Klinefelter syndrome (KS) is associated with male infertility, hypogonadism, and learning disability. Morbidity and mortality are increased and the causes behind remain unknown. Is it the chromosome aberration or is it caused by postulated poorer socioeconomic status? Aim: The aim of the study was to study the socioeconomic profile in KS and the impact of these factors on mortality. Materials and Methods: This was a register study using Danish nationwide registries. One thousand forty-nine KS men and 100,824 controls were included. Information concerning cohabitation, fatherhoods, level of education, income, retirement, and death were obtained. Two hundred four KS and 14,725 controls died during the study period. For the socioeconomic parameters, median age at first relevant episode was calculated. Cohabitation, fatherhood, educational level, and retirement were analyzed using Cox regression, and income was analyzed using conditional logistic regression. Both analyses using each case and his m
... These synapses could be the site of primary abnormalities that disrupt downstream neural circuits; however, this remains to be demonstrated. In addition, patients with Klinefelter's syndrome, which is characterized by an additional X chromosome, are likely to have structural abnormalities of the amygdala and are at an increased risk of schizophrenia (van Rijn et al. 2005). Other neural structures altered in patients with schizophrenia include the hippocampus, prefrontal cortex, and dorsal thalamus (Owen et al. 2005). ...
Introduction:
An ideal antipsychotic would rapidly stabilize acute psychotic symptoms and maintain the patient, without relapse, for prolonged periods in the absence of extrapyramidal, endocrine, diabetic, or cardiovascular side effects, and without weight gain. The dopamine partial agonist aripiprazole is compared with this ideal and with conventional antipsychotics, such as haloperidol, and with atypical antipsychotics.
Aims:
To review the evidence for the clinical impact of aripiprazole in the treatment of patients with schizophrenia.
Evidence review:
There is clear evidence that aripiprazole is as effective as haloperidol in reducing the positive and negative symptoms of schizophrenia and schizoaffective disorder. In patients with schizophrenia, aripiprazole has been shown to stabilize acute psychotic symptoms, prevent relapse in stabilized patients, and maintain patients with schizophrenia following acute relapse. Furthermore, in common with other atypical antipsychotics, aripiprazole appears to be associated with a lower incidence of side effects than typical antipsychotics and may reduce discontinuation of drug therapy. Evidence also suggests that aripiprazole may be associated with a lower incidence of extrapyramidal symptoms than conventional antipsychotics, but further long-term studies concerning tardive dyskinesia are required. Studies on the cost effectiveness of aripiprazole, as well as the quality of life and general functioning of patients taking the drug are still required, although there is some evidence of improved quality of life. Further evidence comparing aripiprazole with other atypical antipsychotics would be welcome.
Clinical value:
In conclusion, aripiprazole is an atypical antipsychotic suitable for first-line use in patients with schizophrenia. Its clinical value in relation to other atypical antipsychotics remains to be elucidated.
... Among the most famous examples are the relationships between (a) fear and the amygdala (e.g., Adolphs et al., 1994; Krolak-Salmon et al., 2004) and the (b) putamen/insula and disgust (e.g., Calder et al., 2000; Krolak-Salmon et al., 2003). The amygdala and the insula/basal ganglia are affected in various neurological and psychiatric conditions, including schizophrenia and obsessive–compulsive disorder, where these brain anomalies may contribute to impaired face–emotion processing (for a more thorough discussion, see Sprengelmeyer et al., 1997; Aleman and Kahn, 2005; Shayegan and Stahl, 2005; Van Rijn et al., 2005). Importantly, however, differential or emotion-specific impairments may not necessarily reflect specific neural anomalies and may arise from differences in low-level properties of the stimuli (e.g., Calder et al., 2001; Deruelle and Fagot, 2005) or from attentional or cognitive deficits (Adolphs et al., 2005). ...
Patients suffering from various neurological and psychiatric disorders show different levels of facial emotion recognition (FER) impairment, sometimes from the early phases of the disease. Investigating the relative severity of deficits in FER across different clinical and high-risk populations has potential implications for the diagnosis and treatment of these diseases, and could also allow us to understand the neurobiological mechanisms of emotion perception itself. To investigate the role of the dopaminergic system and of the frontotemporal network in FER, we reanalyzed and compared data from four of our previous studies investigating FER performance in patients with frontotemporal dysfunctions and/or dopaminergic system abnormalities at different stages. The performance of patients was compared to the performance obtained by a specific group of matched healthy controls using Cohen’s d effect size. We thus compared emotion and gender recognition in patients with frontotemporal dementia (FTD), amnestic mild cognitive impairment (aMCI), Alzheimer’s disease (AD) at the mild dementia stage, major depressive disorder, Parkinson’s disease treated by l-DOPA (PD-ON) or not (PD-OFF), remitted schizophrenia (SCZ-rem), first-episode schizophrenia treated by antipsychotic medication (SCZ-ON), and drug-naïve first-episode schizophrenia (SCZ-OFF), as well as in unaffected siblings of patients with schizophrenia (SIB). The analyses revealed a pattern of differential impairment of emotion (but not gender) recognition across pathological conditions. On the one hand, dopaminergic medication seems not to modify the moderate deficits observed in SCZ and PD groups (ON vs. OFF), suggesting that the deficit is independent from the dopaminergic system. On the other hand, the observed increase in effect size of the deficit among the aMCI, AD, and FTD groups (and also among the SIB and SCZ-rem groups) suggests that the deficit is dependent on neurodegeneration of the frontotemporal neural networks. Our transnosographic approach combining clinical and high-risk populations with the impact of medication provides new information on the trajectory of impaired emotion perception in neuropsychiatric conditions, and on the role of the dopaminergic system and the frontotemporal network in emotion perception.
... Although its exact role is still unclear, the amygdala is a key component in the emotional processing of patients with schizophrenia (Brunet-Gouet and Decety, 2006). Van Rijn et al. (2005) concluded in their review that amygdalar reduction is a risk factor for schizophrenia and they even proposed amygdala abnormalities as an endophenotype in schizophrenia. Aleman and Kahn (2005) have proposed a model supporting a role for amygdalar hyperactivation in the genesis of positive symptoms. ...
... Using a high resolution 3T MRI, we obtained fresh evidence of structural changes in the amygdala in both schizophrenic patients and their unaffected relatives. This finding reemphasized previous discoveries of structural disturbances of the amygdala in schizophrenia and their potential as markers for genetic liability for this disease [51]. Unlike the schizophrenic patients in our study, their parents showed no significant gray matter loss in several previously reported regions, such as the hippocampus and cingulate cortexTable 1. Brain regions with functional connectivity changes with the left amygdala in common between schizophrenic patients and their parents. ...
Shared neuropathological features between schizophrenic patients and their first-degree relatives have potential as indicators of genetic vulnerability to schizophrenia. We sought to explore genetic influences on brain morphology and function in schizophrenic patients and their relatives.
Using a multimodal imaging strategy, we studied 33 schizophrenic patients, 55 of their unaffected parents, 30 healthy controls for patients, and 29 healthy controls for parents with voxel-based morphometry of structural MRI scans and functional connectivity analysis of resting-state functional MRI data.
Schizophrenic patients showed widespread gray matter reductions in the bilateral frontal cortices, bilateral insulae, bilateral occipital cortices, left amygdala and right thalamus, whereas their parents showed more localized reductions in the left amygdala, left thalamus and right orbitofrontal cortex. Patients and their parents shared gray matter loss in the left amygdala. Further investigation of the resting-state functional connectivity of the amygdala in the patients showed abnormal functional connectivity with the bilateral orbitofrontal cortices, bilateral precunei, bilateral dorsolateral frontal cortices and right insula. Their parents showed slightly less, but similar changes in the pattern in the amygdala connectivity. Co-occurrences of abnormal connectivity of the left amygdala with the left orbitofrontal cortex, right dorsolateral frontal cortex and right precuneus were observed in schizophrenic patients and their parents.
Our findings suggest a potential genetic influence on structural and functional abnormalities of the amygdala in schizophrenia. Such information could help future efforts to identify the endophenotypes that characterize the complex disorder of schizophrenia.
... Animal data and functional neuroimaging studies in humans indicate that emotion perception may be dependent upon the functioning of a ventral system, including the amygdala, insula, ventral striatum, and ventral regions of the anterior cingulate gyrus and prefrontal cortex (Phillips et al., 2003). Abnormalities in emotion processing and in the structure of the amygdala have consistently been documented in schizophrenia (e.g.,Rauch et al., 2003;Shayegan and Stahl, 2005;van Rijn et al., 2005). It has been hypothesized that hedonic deficit anhedonia is associated with dysfunction of the dopaminergic reward system (Wise, 2008) and the activity of the ventral striatum and orbitofrontal cortex (Gorwood, 2008;Harvey et al., 2010). ...
The aim of the current study was to investigate an association of physical and social hedonic deficits with health-related quality of life (HRQL), controlling for related distressing and protective factors. Eighty-seven stable patients with schizophrenia (SZ) and schizoaffective disorder (SA) were assessed using the revised Physical Anhedonia Scale (PAS) and the Social Anhedonia Scale (SAS), the Quality of Life Enjoyment and Life Satisfaction Questionnaire (Q-LES-Q), and related factors. Hedonic and HRQL deficit scores did not reach significant differences between SZ and SA patients. General and domain-specific Q-LES-Q scores were significantly correlated with PAS and SAS scores independent of the adverse effects and psychopathological symptoms. Dissatisfaction with HRQL increased from "normal hedonics" (4.8%) to "hypohedonics" (28.6%) and "double anhedonics" (66.7%). Permanently dissatisfied patients who revealed deterioration in general quality of life across 10 years had significantly higher PAS and SAS scores than did patients who were permanently satisfied and improved. An exploratory factor analysis yielded a three-factor solution; PAS and SAS scores were joined to the second factor together with Q-LES-Q, self-efficacy, coping styles, and social support scores. PAS scores accounted for 7% to 13% of the total variance in three domains and in the general quality-of-life alterations. SAS scores did not predict variability in the Q-LES-Q domains. Therefore, physical and social hedonic deficits significantly associated with poor HRQL independent of the adverse effects and psychopathological symptoms of SZ/SA. Physical anhedonia may be a predictor for quality-of-life deficit.
... Research aimed at understanding the causes of social cognitive processing and emotion regulation problems found in individuals with XXY have attributed these problems to structural brain differences 2,34 and overexpression of genes on the X chromosome that may be involved in social cognition and susceptibility to psychiatric disorders. 4,35,36 Moreover, an association between hypogonadism and depression has been suggested, although study results are inconsistent. One population-based study reported a hazard ratio of 4.2 for depression among hypogonadal men. ...
To determine the prevalence and psychosocial correlates of depressive symptoms among adolescents and adults with Klinefelter syndrome.
Individuals (n = 310) aged 14-75 years with self-reported Klinefelter syndrome were recruited from regional and national support networks to complete a web-based survey. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Perceived consequences (Illness Perceptions Questionnaire), perceived stigma (Perceived Social Stigmatization Scale), and coping (Ways of Coping Checklist-Revised) were also measured and evaluated as correlates of depressive symptoms.
Overall, 68.8% of the study participants reported clinically significant levels of depressive symptoms as indicated by a Center for Epidemiologic Studies Depression Scale score ≥16. The use of emotion-focused coping strategies (P < 0.01), perceptions of stigmatization (P < 0.01), perceived negative consequences of Klinefelter syndrome (P < 0.01), and the importance of having children in the future (P < 0.05) were all significantly associated with depressive symptoms.
Individuals with Klinefelter syndrome may be at increased risk for depression. Routine screening for depressive symptoms and appropriate referral and evaluation may be warranted.
... Structural and functional brain dysfunctions associated with emotion processing that are found to be altered in those at familial risk include the prefrontal cortex, 70 amygdala, the amygdala-hippocampal complex (AHC), 71,72 and the hippocampus. 73 Thus far, a metaanalysis of structural magnetic resonance imaging studies demonstrates that the strongest familial link is with the hippocampus, especially on the left side. ...
Evidence suggests that individuals with schizophrenia demonstrate emotion-processing deficits. However, the nature and extent
of emotion abnormalities in individuals considered at risk for schizophrenia have not been previously summarized. This article
provides a review of the recent literature pertaining to emotion processing in 3 at-risk populations: those at familial high
risk, those with schizotypal characteristics, and those in the putative prodrome to psychosis. Studies are reviewed across
the components of emotion perception, experience, and expression. Further, we discuss investigations into psychophysiology,
brain structure, and brain function that employ emotion probes. Review of the literature suggests that individuals at high
risk demonstrate similar abnormalities to those with schizophrenia but at an attenuated level. The most robust findings in
at-risk groups are in the areas of reduced emotion perception, self-reported anhedonia, and increased negative affect. We
conclude with an agenda for future research.
... [23] Consistent with these studies, both neuroanatomical as well as neurofunctional imaging studies have demonstrated abnormalities in many of these brain regions in schizophrenia patients during emotion processing tasks. [24,25] However, the neural basis of facial emotion processing in unaffected subjects at high risk for schizophrenia (HR subjects) has not been examined adequately. To the best of our knowledge, only one functional Magnetic Resonance Imaging (fMRI) study has examined in non-affected brothers of schizophrenia patients (N=13) in which the HR subjects demonstrated hypoactivity of amygdale. ...
Emotion processing abnormalities are considered among the core deficits in schizophrenia. Subjects at high risk (HR) for schizophrenia also show these deficits. Structural neuroimaging studies examining unaffected relatives at high risk for schizophrenia have demonstrated neuroanatomical abnormalities involving neo-cortical and sub-cortical brain regions related to emotion processing. The brain functional correlates of emotion processing in these HR subjects in the context of ecologically valid, real-life dynamic images using functional Magnetic Resonance Imaging (fMRI) has not been examined previously.
To examine the neurohemodynamic abnormalities during emotion processing in unaffected subjects at high risk for schizophrenia in comparison with age-, sex-, handedness- and education-matched healthy controls, using fMRI.
HR subjects for schizophrenia (n=17) and matched healthy controls (n=16) were examined. The emotion processing of fearful facial expression was examined using a culturally appropriate and valid tool for Indian subjects. The fMRI was performed in a 1.5-T scanner during an implicit emotion processing paradigm. The fMRI analyses were performed using the Statistical Parametric Mapping 2 (SPM2) software.
HR subjects had significantly reduced brain activations in left insula, left medial frontal gyrus, left inferior frontal gyrus, right cingulate gyrus, right precentral gyrus and right inferior parietal lobule. Hypothesis-driven region-of-interest analysis revealed hypoactivation of right amygdala in HR subjects.
Study findings suggest that neurohemodynamic abnormalities involving limbic and frontal cortices could be potential indicators for increased vulnerability toward schizophrenia. The clinical utility of these novel findings in predicting the development of psychosis needs to be evaluated.
... The amygdala has been shown to improve facial processing by orienting attention toward eye and mouth (82). In addition, abnormalities in this brain region have been associated with impaired fear and anger recognition (13,83), whereas smaller amygdala volume in patients with schizophrenia has been associated with impairments in sadness recognition (84,85). There is less evidence for dopaminergic modulation of facial affect recognition, with the exception of anger recognition (3). ...
Emotional impairments are important determinants of functional outcome in psychosis, and current treatments are not particularly effective. Modafinil is a wake-promoting drug that has been shown to improve emotion discrimination in healthy individuals and attention and executive function in schizophrenia. We aimed to establish whether modafinil might have a role in the adjuvant treatment of emotional impairments in the first episode of psychosis, when therapeutic endeavor is arguably most vital.
Forty patients with a first episode of psychosis participated in a randomized, double-blind, placebo-controlled crossover design study testing the effects of a single dose of 200 mg modafinil on neuropsychological performance. Emotional functions were evaluated with the emotional face recognition test, the affective go-no go task, and the reward and punishment learning test. Visual analogue scales were used throughout the study to assess subjective mood changes.
Modafinil significantly improved the recognition of sad facial expressions (z = 2.98, p = .003). In contrast, there was no effect of modafinil on subjective mood ratings, on tasks measuring emotional sensitivity to reward or punishment, or on interference of emotional valence on cognitive function, as measured by the affective go-no go task.
Modafinil improves the analysis of emotional face expressions. This might enhance social function in people with a first episode of psychosis.
... De neuroanatomische bevindingen werden vergeleken met wat er bekend is over neuroanatomische afwijkingen van de amygdala in populaties met een verhoogde kwetsbaarheid voor schizofrenie, namelijk: mensen uit de algemene populatie die milde symptomen of kenmerken van de stoornis laten zien en genetische verwanten van patiënten met schizofrenie die een genetische predispositie bij zich kunnen dragen. Een kleiner volume van de amygdala bleek zowel voor te komen bij het Klinefelter syndroom als bij populaties met een verhoogd risico op schizofrenie, dus over een breed spectrum van kwetsbaarheid voor schizofrenie (Van Rijn et al, 2005a). De bevinding dat abnormale ontwikkeling van de amygdala niet alleen een kenmerk is van patiënten met schizofrenie, maar ook gevonden wordt mensen met een verhoogde gevoeligheid voor schizofrenie suggereert dat dit een uiting kan zijn in het brein van kwetsbaarheid voor deze stoornis. ...
Spontaan ontstane genetische variaties bieden de mogelijkheid om de effecten van specifieke genen op de ontwikkeling van de
hersenen, cognitieve vaardigheden en gedrag te bestuderen. Een syndroom waarbij zich een genetische variatie in een van de
geslachtschromosomen voordoet, is het Klinefelter-syndroom. Door de aanwezigheid van een extra x-chromosoom hebben mannen met dit syndroom het xxy-chromosomale patroon.
... It is well known that the amygdala is crucially involved in the evaluation, recognition, storage and reaction to emotionally-charged events van Rijn et al., 2005). Indeed, the amygdala receives sensory information that allows the individual to determine and respond to the presence of danger; therefore, this structure is also involved in fear reactions (Adolphs et al., 1998;LeDoux, 2000). ...
Suicide is a major cause of death in schizophrenia. Neurobiological studies suggest that suicidality is associated with abnormal brain structure and connectivity in fronto-temporo-limbic regions. However, it is still unclear whether suicidality in schizophrenia is related to volumetric abnormalities in subcortical structures that play a key role in emotion regulation, aggression and impulse control. Therefore, we aimed to examine whether the volume of selected subcortical regions is associated with previous suicidal attempts and self-aggression in schizophrenia. For this cross-sectional study, we recruited 50 outpatients with schizophrenia and 50 healthy controls (HC) matched for age and gender. Fourteen patients had a history of one or more suicide attempts. Different forms of aggression were assessed using the Modified Overt Aggression Scale. All participants underwent structural MR imaging at 3 Tesla. Physical volumetric measures were calculated for the lateral ventricles, thalamus, hippocampus, amygdala, caudate, putamen, pallidum and accumbens using an automatic segmentation method on T1-weighted high-resolution (voxel size 1×1×1mm(3)) images. Multivariate and follow-up univariate ANOVAs revealed a selective increase in volume in the right amygdala of patients with a history of suicidality compared both to patients without such a history and HC. Moreover, in the entire patient group increased right amygdala volume was related to increased self-aggression. Our findings suggest that right amygdala hypertrophy may be a risk factor for suicide attempts in patients with schizophrenia and this could be relevant for suicide prevention.
... Structural and functional magnetic resonance imaging (MRI) studies have focused mainly on the limbic and paralimbic areas (amygdala and prefrontal cortex), and have suggested that abnormalities in the amygdala may account for deficits in emotional processing. Supportive evidence for structural abnormalities comes from the bilateral reduction of amygdala volume in schizophrenia patients (Wright et al., 2000;Lawrie et al., 2003;Garcia-Marti et al., 2008) and populations at risk of developing schizophrenia (Van Rijn et al., 2005). Functional MRI (fMRI) studies have also demonstrated abnormal amygdala activity. ...
Hallucinations in patients with schizophrenia have strong emotional connotations. Functional neuroimaging techniques have been widely used to study brain activity in patients with schizophrenia with hallucinations or emotional impairments. However, few of these studies have investigated the association between hallucinations and emotional dysfunctions using an emotional auditory paradigm. Independent component analysis (ICA) is an analysis method that is especially useful for decomposing activation during complex cognitive tasks in which multiple operations occur simultaneously. Our aim in this study is to analyze brain activation after the presentation of emotional auditory stimuli in patients with schizophrenia with and without chronic auditory hallucinations using ICA methodology. It was hypothesized that functional connectivity differences in limbic regions responsible for emotional processing would be demonstrated.
The present functional magnetic resonance imaging (fMRI) study compared neural activity in 41 patients with schizophrenia (27 with auditory hallucinations, 14 without auditory hallucinations) with 31 controls. Neural activity data was generated while participants were presented with an auditory paradigm containing emotional words. The comparison was performed using a multivariate approach, ICA. Differences in temporo-spatial aspects of limbic network were examined in three study groups.
Limbic networks responded differently in patients with auditory hallucinations compared to healthy controls and patients without auditory hallucinations. Unlike control subjects and non-hallucinators, the group of hallucinatory patients showed an increase of activity in the parahippocampal gyrus and the amygdala during the emotional session.
These findings may reflect an increase in parahippocampal gyrus and amygdala activity during passive listening of emotional words in patients with schizophrenia and auditory hallucinations.
... The possible vulnerability to schizophrenia-spectrum disorders in 47,XXY may suggest a link between X chromosomal abnormality and schizophrenia. In addition, decreased size of the amygdala is a potential anatomic basis for the emotional differences and schizophrenia-spectrum pathology with 47,XXY (Patwardhan et al. 2002;van Rijn et al. 2005). ...
Klinefelter syndrome (47,XXY) was initially described in the context of its endocrinologic and physical features; however, subsequent studies have revealed specific impairments in verbal skills and social functioning. Males with sex chromosomal aneuploidies are known to have variability in their developmental profile with the majority presenting with expressive language deficits. As a consequence of language delays, they have an increased likelihood of language-based learning disabilities and social-emotional problems that may persist through adulthood. Studies on males with 47,XXY have revealed unique behavioral and social profiles with possible vulnerability to autistic traits. The prevalence of males with more than one extra sex chromosome (e.g., 48,XXYY and 48,XXXY) and an additional Y (e.g., 47,XYY) is less common, but it is important to understand their social functioning as it provides insight into treatment implications.
... They conclude that reductions of amygdala and hippocampus might represent the vulnerability for the schizophrenia spectrum. Consistent with this, a recent review of amygdala studies in samples at high risk of developing schizophrenia concluded that amygdala reduction is a risk factor for schizophrenia (Van Rijn et al., 2005). Notably, impairment of emotion perception has also been reported in nonpsychotic relatives of schizophrenia patients (Toomey et al., 1999). ...
Schizophrenia is widely regarded to be a neurocognitive disorder, i.e. a dysfunction of the neural and cognitive systems subserving thinking and reasoning, memory, language, attention and perception. However, although cognitive dysfunction is certainly a cardinal feature of schizophrenia, we argue that dysfunction of emotional brain systems may be even more important in understanding the disorder. Indeed, in recent years research on the emotional aspects of schizophrenia is accumulating at a high rate. Here, we review the available evidence regarding behavioral and neural manifestations of abnormal emotional systems in schizophrenia. This evidence comes from patient studies using tasks of emotion recognition, emotional expression and emotional experience. Furthermore, studies of schizophrenia patients using structural MRI have demonstrated volume reductions of the amygdala, a key structure of the emotional brain. Finally, functional fMRI studies have revealed an attenuated response of the amygdala to emotional stimuli as compared to neutral stimuli. Beyond demonstrating that dysfunction of the emotional brain is a hallmark of schizophrenia, we propose a model that integrates previous neural accounts of emotional abnormalities in schizophrenia, and specifies a neural basis for differential emotional correlates of positive and negative symptoms. Specifically, a lesion to the amygdala in combination with reduced interconnectivity with the prefrontal cortex is hypothesized to give rise to reduced emotional expression (affective flattening) and emotion recognition deficits. In contrast, an imbalance in dopamine systems may underlie increased anxiety and autonomic arousal, and the assignment of emotional salience to insignificant stimuli, associated with psychosis. We also hypothesize that the central and basolateral nuclei of the amygdala may contribute differentially to these abnormalities.
... With regard to structural and functional neuroanatomy, ample evidence also shows impairment of emotion circuits in schizophrenia. For example, volume reductions of the amygdala, a key structure of the emotional brain, have consistently been reported (Pinkham et al., 2003) and have also been observed in groups at high risk for developing schizophrenia (Van Rijn, Aleman, Swaab, & Kahn, 2005). Moreover, several fMRI studies have shown that schizophrenia patients in general are characterized by reduced activation of the amygdala in response to emotional stimuli (Pinkham et al., 2003). ...
The authors comment on the article "The primacy of cognition in schizophrenia," by R. W. Heinrichs (see record 2005-03019-003). They state that Heinrichs persuasively argued as to the primacy of cognition in schizophrenia by citing an impressive body of evidence in favor of the view that schizophrenia is a complex biobehavioral disorder that manifests itself primarily in cognition. His conclusion is something of an anticlimax. At the same time, however, he acknowledged that "the glass of evidence is half empty as well as half full" (Heinrichs, 2005, p. 238). That is to say, the symptoms that mark out schizophrenia--the hallucinations, delusions, and so forth--do not appear to map onto cognitive deficits, or at least they do not map onto those that are measured with traditional neuropsychological tests. To fill the other half of the glass, the authors propose that a focus on emotion (largely neglected in the target article) will be of crucial importance. Furthermore, they commend the methods of cognitive neuropsychiatry as being eminently suitable to guide this research. The authors briefly illustrate the value of this approach with reference to affective characteristics of hallucinations and cognitive-emotional interactions in source monitoring.
... The present work extended the basic research work on single neuron activity to focus on the psychopharmacodynamics of gating in the amygdala, a limbic system brain structure thought to be critically involved in emotion and psychiatric illness (Adolphs et al. 2003;Aleman and Kahn 2005;LeDoux 1993;van Rijn et al. 2005). ...
Inhibitory gating is thought to be a basic process for filtering incoming stimuli to the brain. Little information is currently available concerning local neural networks of inhibitory gating or the intrinsic neurochemical substrates involved in the process.
The goal of the present study was to examine the pharmacological aspects of inhibitory gating from single units in the amygdala. We tested the effects of ketamine (80 mg/kg) and haloperidol (1 mg/kg) on inhibitory gating. Additionally, we examined the effect of nicotine (1.2 mg/kg) on single unit gating in this same brain structure.
We found that in one subset of neurons, ketamine administration significantly reduced tone responsiveness with a subsequent loss of inhibitory gating, whereas the other subset persisted in both auditory responding and gating albeit at a weaker level. Haloperidol and nicotine had very similar effects, exemplified by a dramatic increase in the response to the initial "conditioning" tone with a subsequent improvement in inhibitory gating.
Tone responsiveness and inhibitory gating persists in a subset of neurons after glutamate N-methyl-D-aspartate receptor blockade. Dopamine and nicotine modulate gating in these normal animals and have similar effects of enhancing responsiveness to auditory stimulation at the single unit and evoked potential level.
Klinefelter syndrome (KS), characterized by an additional X-chromosome in males, manifests in a wide range of neuroendocrine and psychiatric symptoms. Individuals with KS often face increased risks of hormonal dysfunction, leading to depression and anxiety, although extended research during pediatric and adolescent age is still limited. This critical phase, decisive for KS children, is influenced by a combination of genetic, environmental and familial factors, which impact brain plasticity. In this report, we reviewed, in a narrative form, the crucial KS psychopathological hallmarks in children. To better describe neuroendocrine and neuropsychiatric outcomes in children with KS, we presented the case of an 11-year-old prepubertal child with mosaic KS who was referred to our Center of Developmental Psychopathology due to a decline in his academic performance, excessive daytime fatigue and increased distractibility over the past few months. Family history revealed psychiatric conditions among first- and second-degree relatives, including recently divorced parents and a 15-year-old sister. Early-onset persistent depressive disorder and anxious traits were diagnosed. Timely identification of susceptible children, with thorough examination of familial psychiatric history, environmental influences and neurocognitive profile, alongside targeted interventions, could potentially mitigate lifelong psychopathology-related disabilities in pediatric and adolescent KS cases, including those with mosaic KS.
Background
The syndrome Klinefelter (KS) is a genetic disorder due to an extra X chromosome in males. Many cases remain undiagnosed until the onset of major manifestations, which include hypergonadotropic hypogonadism and infertility. This condition is associated with many comorbidities that interest the cardiovascular, the endocrine, and the immune systems. Last but not least, individuals with KS show a high risk of developing psychiatric and mood disorders in adult age.
Objective
While many studies are accessible for KS adults’ individuals the neuroinflammatory condition in adolescent and prepubertal KS individuals is not fully known.
Methods
Our study aims to evaluate in prepubertal and adolescent KS individuals for the first time the levels in the serum of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), cytokines having subtle roles in oxidative processes, and neuroinflammation as TNF-α, TGF-β, MCP-1, IL-1α, IL-2, IL-6, IL-10, and IL-12 and oxidative stress as free oxygen radicals defense and free oxygen radicals’ test.
Results
We found no changes in NGF and oxidative stress parameters, but BDNF decreased compared to healthy children. Quite interestingly, our data showed reduced levels of IL-2, IL-1α. IL-12, IL-10, and IL-6 in prepubertal KS children.
Conclusion
The present study discloses disrupted immune system and neurotrophins pathways in KS children.
Although first identified over 70 years ago, Klinefelter syndrome (KS) continue to pose significant diagnostic challenges, as many patients are still misdiagnosed, or remain undiagnosed. In fact, as few as 25% of KS patients are accurately diagnosed, and most of these diagnoses are not made until adulthood. Classic characteristics of KS include small testes, infertility, hypergonadothropic hypogonadism, and cognitive impairment. However, the pathophysiology behind KS is not well understood, although genetic effects are also thought to play a role. For example, recent developments in genetics and genomics point to a fundamental change in our understanding of KS, with global epigenetic and RNA expression changes playing a central role for the phenotype.
KS is also associated with more general health markers, including higher morbidity and mortality rates, and lower socio-economic status (which likely affects both morbidity and mortality). In addition, hypogonadism is associated with greater risk of of metabolic syndrome, type 2 diabetes, cardiovascular disease, breast cancer, and extragonadal germ cell tumors. Medical treatment typically focuses on testosterone replacement therapy (TRT), although the effects of this therapy has not been studied rigorously, and future studies need to evaluate the effects of TRT on metabolic risk and neurocognitive outcomes.
This review presents a comprehensive, interdisciplinary examination of recent developments in genetic, endocrine and neurocognitive science, including the study of animal models regarding KS. It also provides a number of recommendations for improving the effectiveness of research and clinical practice, including neonatal KS screening programs, and a multidisciplinary approach to KS treatment from childhood until senescence.
In this chapter the author describes the conceptual basis of the health related quality of life (HRQL) impairment syndrome
in severe mental disorders (SMD) such as schizophrenia, schizoaffective, mood and anxiety disorders. He presents the evidence
for its validity, and identifies some likely directions for future research and development. Based on the author’s and his
team research contributions and complementary theoretical considerations, the author explores four issues in this chapter:
the quality of life concept, interpreting HRQL findings, conceptualizing HRQL impairment in the framework of the Distress/Protection
Vulnerability Model (DPV), and implications for future research. Evidence for the concept’s validity is assessed, followed
by a discussion of the possible evolvement of the concept, to encompass biologic domains. Finally, there is a review of the
research implications of the HRQL impairment concept and the DPV model followed by a discussion of some major areas of unresolved
questions for future research
Patients with schizophrenia exhibit an exceedingly wide range of symptoms, and a broad spectrum of cognitive impairments.
In addition, it has become increasingly apparent that the disorder is, to variable degrees, accompanied by quality of life
impairments. This chapter addresses the question of whether the health-related quality of life (HRQL) impairment or deficit
is a syndrome in schizophrenia. Therefore, first, we discuss what the general and domain-specific HRQL impairments are. Then,
we address distressing and protective factors, and a factor structure of HRQL impairment. The literature, as well as new and
previously published findings from the Shaar Menashe Longitudinal Study of Quality of Life will be presented in detail.
We argue that HRQL deficit is highly prevalent and fairly marked in schizophrenia patients: 49% of the patients are clinically
severely impaired regarding general life quality, 42% - in general activities, 39% - in subjective feelings, 30% - in both
leisure time activities and social relationships. The HRQL impairment has been observed before individuals exhibit the signs
and psychotic symptoms of schizophrenia; it is relatively stable throughout the course of the illness. HRQL impairment syndrome
appears to be relatively independent of symptomatology and neurocognitive deficit. Finally, the authors suggest that impairment
in general and the domain-specific quality of life in particular is sufficiently reliable, stable, and specific enough syndromes
to warrant inclusion in the diagnostic criteria for schizophrenia. Limitations in the current knowledge in this area are identified,
and suggestions for future research are provided
In the present chapter, we compared the psychometric properties of the Quality of Life Enjoyment and Satisfaction Questionnaire
(Q-LES-Q) with the Quality of Life Scale (QLS) and the Lancashire Quality of Life Profile (LQOLP) in the same patients with
schizophrenia, schizoaffective, and mood disorders. These instruments were chosen since they are mental illness-related, and
Q-LES-Q is a self-report evaluation scale, whereas QLS is observer-rated, and LQOLP has domains similar to Q-LES-Q, which
enables a comparison of the instruments. The compared instruments proved to be mental health-related, but none were mental-disorder-specific.
Despite the acceptable psychometric properties and the correlation of the general indices, similar domains proved to be instrument-specific
and were not sufficiently compatible. These discrepancies should be considered when comparing evaluations from similar domains
in these scales
Klinefelter syndrome (KS) is associated with male infertility, hypogonadism, and learning disability. Morbidity and mortality are increased and the causes behind remain unknown. Is it the chromosome aberration or is it caused by postulated poorer socioeconomic status?
The aim of the study was to study the socioeconomic profile in KS and the impact of these factors on mortality.
This was a register study using Danish nationwide registries. One thousand forty-nine KS men and 100,824 controls were included. Information concerning cohabitation, fatherhoods, level of education, income, retirement, and death were obtained. Two hundred four KS and 14,725 controls died during the study period. For the socioeconomic parameters, median age at first relevant episode was calculated. Cohabitation, fatherhood, educational level, and retirement were analyzed using Cox regression, and income was analyzed using conditional logistic regression. Both analyses using each case and his matched controls as one stratum.
KS men had significantly fewer partnerships [hazard ratio (HR) 0.66] and entered them later (median age 27.1 vs. 24.6 yr), fewer fatherhoods (HR 0.24),and they occurred later (median age 32.0 vs. 27.0 yr), lower educational level (HR 0.27), and lower income and were retired at an earlier age (43.5 vs. 60.3 yr). Mortality among KS men was significantly increased (HR 1.9), and after adjustment for cohabitation and educational status, mortality was still significantly increased (HR 1.5).
A severely inferior outcome in all investigated socioeconomic parameters compared with the background population was present and mortality was increased and may partially be caused by the poorer socioeconomic status.
De novo occurring genetic variations provide an opportunity the study the effects of genes on brain development and behavior. In this regard, Klinefelter syndrome, characterized by a XXY chromosomal pattern, is of significant interest. Although intelligence in XXY men is within the normal range, specific effects on brain structure, cognition and behavior have been observed. The most prominent behavioral problems are found in the domain of social adaptation. In a series of experiments we have investigated social cognitive capacities dealing with language, emotion an social insight in XXY men. We used neuropsychological tasks as well as functional Magentic Resonance Imaging (MRI) to explore social cognitive impairments and underlying brain abnormalities, that may explain the difficulties in social interaction in these men. As disabilites in social cognition and -behavior are characteristic of autism spectrum- as well as schizophrenia spectrum disorders, we also examined whether XXY men display increased levels of autism- or schizophrenia spectrum pathology. We observed deficits in various domains of social cognition in XXY men, which may contribute to the difficulties in social interactions that have been described for these men. Domains of social cognition that were affected in Klinefelter syndrome were processing affective facial expressions, decoding affective tone of voice, emotion regulation and automatic processing of basic social cues (such as gaze direction and implied biological motion). With regard to the underlying neurobiology, abnormal functioning of the amygdala in XXY men was found using functional MRI. This brain region plays a central role in socio-emotional processing. Reduced lateralization of brain activation during language processing was also observed, which was related to disorganization of thought and language. Measures of psychopathology indicated increased levels of both autistic traits as well as schizotypal traits and schizophrenia symptoms in XXY men. Our findings indicate profound social cognitive deficits, underlying functional brain abnormalities, and increased autism- and schizophrenia-related psychopathology in XXY men. The extra X chromosome in Klinefelter syndrome may play a role in abnormal development of some of the brain mechanisms involved in language, emotion and social behavior, which are considered core domains of disabilities in autism and schizophrenia. Although speculative, studying X-linked genetic mechanisms in Klinefelter syndrome might help us understand pathways from genes to psychopathology in the autism- and schizophrenia spectrum.
Difficulties in social communication in individuals with Klinefelter syndrome (XXY chromosomal pattern) have largely been attributed to deficits in left hemisphere-mediated, language functions. This study examined the ability of XXY men to decode emotions from tone of voice, a pragmatic aspect of social communication that may be associated with right hemisphere functioning. A total of 26 XXY men and 20 men from the general population completed tasks involving emotion discrimination in speech, based on verbal content or tone of voice. The XXY group displayed relative difficulties in discriminating emotions in tone of voice, and, to a lesser extend, in verbal content. This finding suggests that the XXY chromosomal pattern may not only be associated with difficulties in semantic aspects of language, but with prosodic aspects, as well. Our findings may contribute to the development of more comprehensive models addressing the role of the X chromosome in normal and abnormal development of social communication.
Klinefelter syndrome is the most common chromosome abnormality in humans. The estimated prevalence is one in 500 to one in 1000 males but due to the widely variable and often aspecific features, only one in four cases are recognized. The most specific clinical features which can be observed at adult age are small testes, gynecomastia, female distribution of fat and body hair, slightly increased body length due to an increased leg length and azoospermia. Cognition is characterized by verbal deficits and psychosocial features include autistiform behavior. Structural brain abnormalities have been observed by MRI, such as decreased brain volumes and a decrease of asymmetry in areas corresponding to language performance. In the vast majority of cases a non-mosaic 47,XXY karyotype is observed. Parental imprinting of the extra X chromosome, variable inactivation of some X-chromosomal genes and CAG repeat length polymorphism of the androgen receptor may all be related to the variability of the phenotype. Surgical procedures of obtaining sperm in combination with repeated intracytoplasmic sperm injection/in vitro fertilization treatment may allow up to one in four men with Klinefelter syndrome to father children.
the present thesis I have described how we investigated some of the neural phenomena that generate these deficits. By focusing on the neural basis of social perception, and paying particular attention to the amygdala, we were able to demonstrate that abnormalities in amygdala function are likely to contribute to the social cognitive deficits that are often observed in patients with schizophrenia. Furthermore, the inclusion of unaffected siblings of patients enabled us to demonstrate that siblings, like their affected family members, display abnormalities in social perception, although the severity of these symptoms is reduced compared to those observed in patients. Finally, the combined use of genetic and functional neuroimaging techniques revealed that variation in the serotonin transporter linked polymorphic region (5-HTTLPR) influences amygdala activation, as well as the level of paranoia experienced by the subjects.
Confirming the early conceptualization of Bleuler (1911) and Kraepelin (1919), magnetic resonance imaging (MRI) studies have demonstrated structural and functional brain abnormalities, predominantly involving the frontal and temporal lobes, in schizophrenia. Most of the abnormalities are already present at illness onset. However, there is, growing evidence for treatment-related neural changes in schizophrenia, such as enlargement of the caudate nucleus (neurotoxic effect) with the use of typical antipsychotics and increases in cortical volumes and improved functional responses (neurotrophic effect) with the use of atypical antipsychotics. More recently, brain changes during the prodrome and transition-to-illness stages of schizophrenia have begun to be characterized. Another area of importance is the use of MRI, as a biological marker, to monitor and define partial or full resistance to medication. Understanding the trait- and state-related influences of brain abnormalities during the course of the illness is critical for developing effective treatment and possibly prevention strategies in schizophrenia.
Face recognition is thought to rely on configural visual processing. Where face recognition impairments have been identified, qualitatively delayed or anomalous configural processing has also been found. A group of women with Turner syndrome (TS) with monosomy for a single maternal X chromosome (45, Xm) showed an impairment in face recognition skills compared with normally developing women. However, normal configural face-processing abilities were apparent. The ability to recognize facial expressions of emotion, particularly fear, was also impaired in this TS subgroup. Face recognition and fear recognition accuracy were significantly correlated in the female control group but not in women with TS. The authors therefore suggest that anomalies in amygdala function may be a neurological feature of TS of this karyotype.
The authors present an overview of the neural bases of emotion. They underscore the role of the prefrontal cortex (PFC) and amygdala in 2 broad approach- and withdrawal-related emotion systems. Components and measures of affective style are identified. Emphasis is given to affective chronometry and a role for the PFC in this process is proposed. Plasticity in the central circuitry of emotion is considered, and implications of data showing experience-induced changes in the hippocampus for understanding psychopathology and stress-related symptoms are discussed. Two key forms of affective plasticity are described—context and regulation. A role for the hippocampus in context-dependent normal and dysfunctional emotional responding is proposed. Finally, implications of these data for understanding the impact on neural circuitry of interventions to promote positive affect and on mechanisms that govern health and disease are considered.
The heterogeneity of schizotypal traits, suggested in previous research, was further investigated in a sample of subjects (N = 1095) administered a composite questionnaire consisting of a large number of published scales the majority of which were designed to measure psychotic characteristics. Factor analysis confirmed the four components previously indicated in our work with the same instrument; namely, 'aberrant perceptions and beliefs', 'cognitive disorganization', 'introvertive anhedonia ' and ' asocial behaviour '. This structure was maintained regardless of whether or not the analysis included scales from the Eysenck Personality Questionnaire, which might otherwise have been held to explain the variance. ' Aberrant perceptions and beliefs '-reminiscent of the positive symptoms of schizophrenia-was the strongest component; but given the multidimensional nature of the data, together with the pattern of factor loadings and intercorrelations
for the sees involved, it was concluded that the broader term 'psychosis proneness' or 'psychoticism' (in a non-Eysenckian sense) might be a better descriptor of the clinical and personality domain sampled.
OBJECTIVE
Although affective prosody seems to be a dominant and lateralised communication function of the right hemisphere, focal lesions of either hemisphere may cause problems with its modulation. When impairment occurs after brain damage, the profiles of affective-prosodic disturbances differ depending on the hemisphere injured. Patients with left brain damage (LBD) improve their performance whereas patients with right brain damage (RBD) do not when the verbal-articulatory demands of the test stimuli are reduced systematically. One of the major arguments for a right hemispheric contribution to schizophrenia has been the documentation of affective prosodic deficits under the assumption that these abnormalities reflect right hemispheric dysfunction. Thus, an essential question to resolve is whether the profile of affective prosodic disturbances in schizophrenia is similar to LBD or RBD, or represents a unique variation.METHODS
Data were collected from four subject groups: 45 chronic, medication-stabilised, schizophrenic patients, 10 patients with focal LBD, nine patients with focal RBD, and 19 controls. All groups were tested on the aprosodia battery, which uses stimuli having incrementally reduced verbal-articulatory demands. Schizophrenic and aphasic symptoms were evaluated using standard assessment tools.RESULTSFor patients with impaired performance on the aprosodia battery, schizophrenic patients were statistically identical to patients with RBD and robustly different from those with LBD. Thirty eight schizophrenic patients (84.4%) were found to have some type of affective prosodic deficit with the predominant pattern indicating, at minimum, right posterior sylvian dysfunction (57.8%). When schizophrenic symptoms and aprosodic deficits were examined using a principal component analysis, affective comprehension and repetition loaded uniquely as separate factors.CONCLUSIONS
The profile of affective-prosodic deficits found in impaired schizophrenic patients is characteristic of RBD, supporting the concept that schizophrenia is a bihemispheric disease process. These deficits may also represent cardinal symptoms of schizophrenia as they are highly prevalent and, except for spontaneous affective prosody, are not associated statistically with traditional clusters of schizophrenic symptoms.
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This study evaluated (a) whether chronic, medicated schizophrenia patients show deficits in emotion recognition compared to nonpatients, and (b) whether deficits in emotion recognition are related to poorer social competence. Two emotion recognition tests developed by S. L. Kerr and J. M. Neale (1993) and Benton's Test of Facial Recognition (A. Benton, M. VanAllen, K. Hamsher, & H. Levin, 1978) were given to patients with chronic schizophrenia and nonpatient controls. Patients' social skills, social adjustment, and symptomatology were assessed. Like Kerr and Neale's unmedicated patients, these patients performed worse than controls on both emotion recognition tests and the control test. For patients, facial perception was related to the chronicity of illness and social competence. Chronicity of illness may contribute to face perception deficits in schizophrenia, which may affect social competence. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Klinefelter Syndrome (KS) is a relatively common (1/500 to 1/1,000) genetic syndrome caused by an extra X chromosome in males, leading to an XXY karyotype. In most cases, the physical and neurobehavioral characteristics of KS are relatively mild, and KS is not usually associated with moderate or severe mental retardation. However, KS is often associated with significant language-based learning disabilities and executive dysfunction, making it a plausible genetic model for understanding the neurobiology of these areas of cognition that are so fundamental to learning in a classroom. Additionally, the psychosocial aspects of KS, which can have a significant impact on school performance and learning, have been explored only on an anecdotal level. We have conducted pilot studies in a small group of KS adolescents and adults to begin to identify the social, emotional, and adaptive behavior issues facing KS subjects and have identified several areas for further research. This includes characterization of mild maladaptive behaviors, as well as significant strengths in other areas. Further work is needed to determine how the social-emotional and cognitive features of the disorder interact or change over the lifetime of subjects and how the learning disabilities respond to hormonal or cognitive-based therapy.
Brain activity was monitored while 36 participants produced facial configurations denoting anger, disgust, fear, joy, and sadness. EEG alpha power was analyzed during each facial pose, with facial conditions grouped according to the approach/withdrawal motivational model of emotion. This model suggests that “approach” emotions are associated with relatively greater left frontal brain activity whereas “withdrawal” emotions are associated with relatively greater right frontal brain activity. In the context of a bilateral decrease in activation, facial poses of emotions in the withdrawal condition resulted in relatively less left frontal activation in the lateral-frontal, midfrontal and frontal-temporal-central region, but not in the parietal region, as predicted. Findings in the approach condition were less consistently supportive of predictions of the approach/withdrawal model. Implications for the approach/withdrawal model and for the emotion eliciting potential of voluntary facial movement are discussed.
The Convention on Biological Diversity aims to encourage and enable countries to conserve biological diversity, to use its components sustainably and to share benefits equitably. Species richness and endemism are two key attributes of biodiversity that reflect the complexity and uniqueness of natural ecosystems. National data on vertebrates and higher plants indicate global concentrations of biodiversity and can assist in defining priorities for action. Projections indicate that species and ecosystems will be at maximum risk from human activities during the next few decades. Prompt action by the world community can minimise the eventual loss of species. Highest priorities should be to: (i) strengthen the management of ecosystems containing a large proportion of global biodiversity; (ii) help developing countries complete their biodiversity strategies and action plans, monitor their own biodiversity, and establish and maintain adequate national systems of conservation areas; (iii) support actions at the global level, providing benefit to all countries in managing their own biodiversity. Generally, resources will best be spent in safeguarding ecosystems and habitats that are viable and important for global biodiversity, and which are threatened by factors that can be controlled cost-effectively. Other important criteria are representativeness, complementarity and insurance.
The objective of this study was to describe the prevalence of Klinefelter syndrome (KS) prenatally and postnatally in Denmark and determine the influence of maternal age. All chromosomal examinations in Denmark are registered in the Danish Cytogenetic Central Registry. Individuals with KS diagnosed prenatally or postnatally were extracted from the registry with information about age at the time of diagnosis and mother's age. In the period 1970-2000, 76,526 prenatal examinations on male fetuses resulted in the diagnosis of 163 fetuses with KS karyotype, corresponding to a prevalence of 213 per 100,000 male fetuses. Standardization according to maternal age resulted in a prevalence of 153 per 100,000 males. Postnatally, 696 males of 2,480,858 live born were diagnosed with KS, corresponding to a prevalence among adult men of approximately 40 per 100,000. Less than 10% of the expected number was diagnosed before puberty. Advanced maternal age had a significant impact on the prevalence. KS is severely under
The authors' goal was to determine whether patients with schizophrenia differ from comparison subjects in regional brain volumes and whether these differences are similar in male and female subjects.
They conducted a systematic search for structural magnetic resonance imaging (MRI) studies of patients with schizophrenia that reported volume measurements of selected cortical, subcortical, and ventricular regions in relation to comparison groups. They carried out a meta-analysis of the volumes of these regions in the patients with schizophrenia and the comparison subjects using a random effects model; they also used random effects regression analysis to examine the influence of gender on effect sizes.
Fifty-eight studies were identified as suitable for analysis; these studies included 1,588 independent patients with schizophrenia. Assuming a volume of 100% in the comparison group, they found that the mean cerebral volume of the subjects with schizophrenia was smaller (98%), but the mean total ventricular volume of the subjects with schizophrenia was greater (126%). Relative to the cerebral volume differences, the regional volumes of the subjects with schizophrenia were 94% in the left and right amygdala, 94% in the left and 95% in the right hippocampus/amygdala, and 93% in the left and 95% in the right parahippocampus. Relative to the global ventricular system differences, the largest differences in ventricular subdivisions were in the right and left body of the lateral ventricle, where the volumes of schizophrenic subjects were 116% and 116%, respectively. For most regions, effect size was not significantly related to gender.
Regional structural differences in patients with schizophrenia include bilaterally reduced volume of medial temporal lobe structures. There is a need for greater integration of results from structural MRI studies to avoid redundant research activity.
Localized amygdalar lesions in humans produce deficits in the recognition of fearful facial expressions. We used functional neuroimaging to test two hypotheses: (i) that the amygdala and some of its functionally connected structures mediate specific neural responses to fearful expressions; (ii) that the early visual processing of emotional faces can be influenced by amygdalar activity. Normal subjects were scanned using PET while they performed a gender discrimination task involving static grey-scale images of faces expressing varying degrees of fear or happiness. In support of the first hypothesis, enhanced activity in the left amygdala, left pulvinar, left anterior insula and bilateral anterior cingulate gyri was observed during the processing of fearful faces. Evidence consistent with the second hypothesis was obtained by a demonstration that amygdalar responses predict expression-specific neural activity in extrastriate cortex.
When animals, including humans, communicate, they convey information and express their perceptions of the world. Because different organisms are able to produce and perceive different signals, the animal world contains a diversity of communication systems. Based on the approach laid out in the 1950s by Nobel laureate Nikolaas Tinbergen, this book looks at animal communication from the four perspectives of mechanisms, ontogeny, function, and phylogeny.
The book's great strength is its broad comparative perspective, which enables the reader to appreciate the diversity of solutions to particular problems of signal design and perception. For example, although the neural circuitry underlying the production of acoustic signals is different in frogs, songbirds, bats, and humans, each involves a set of dedicated pathways designed to solve particular problems of communicative efficiency. Such comparative findings form the basis of a conceptual framework for understanding the mechanisms underlying communication systems and their evolution.
Bradford Books imprint
Several decades of research on behaviorally defined syndromes such as autism, ADHD and learning disabilities suggest that rapid progress toward understanding underlying genetic factors may be impeded by the etiological heterogeneity of individuals meeting the standardized diagnostic criteria that define these disorders. Accordingly, we are in need of biological markers and new methodology to improve our understanding of etiologically meaningful subgroups and the pathophysiology of childhood onset neuropsychiatric and cognitive disorders. Behavioral neurogenetics research is an innovative method of scientific inquiry that focuses on investigation of neuropsychiatric dysfunction associated with specific genetic conditions. As an important complement to "traditional" scientific inquiry into the etiologies of behaviorally defined syndromes, behavioral neurogenetics research provides a powerful method for investigation into human gene-brain-behavior linkages. In addition to providing critical information about individuals affected with specific genetic conditions, behavioral neurogenetics research has potentially wider applicability as these conditions are looked upon as models of conditions occurring in the general population; for example, fragile X syndrome as a model for autism, social anxiety disorder and math disability, VCFS as a model for psychosis, Turner syndrome as a model of ADHD, and Klinefelter syndrome as a model for specific language disability and dyslexia.
OBJECTIVE: The authors sought to investigate the contribution of genotype on structural brain abnormalities in schizophrenia. METHOD: Intracranial volumes and volumes of the cerebrum, white and gray matter, lateral and third ventricles, frontal lobes, caudate nucleus, amygdala, hippocampus, parahippocampal gyrus, and the cerebellum were measured in 32 same-sex siblings discordant for schizophrenia and 32 matched comparison subjects by means of magnetic resonance imaging. RESULTS: Third ventricle volumes did not differ between the schizophrenic patients and their healthy siblings. However, both had higher third ventricle volumes than did the comparison subjects. The schizophrenic patients had lower cerebrum volumes than did the comparison subjects, whereas the cerebrum volume of the healthy siblings did not significantly differ from the patients or comparison subjects. Additionally, patients with schizophrenia displayed a volume reduction of the frontal lobe gray matter and a volume increase of the caudate nuclei and lateral ventricles compared to both their healthy siblings and comparison subjects. Intracranial volume, CSF volume, or volumes of the cerebellum, amygdala, hippocampus, or the parahippocampal gyrus did not significantly differ among the patients, siblings, and comparison subjects. CONCLUSIONS: Healthy siblings share third ventricle enlargement with their affected relatives and may partially display a reduction in cerebral volume. These findings suggest that third ventricular enlargement, and to some extent cerebral volume decrease, may be related to genetic defects that produce a susceptibility to schizophrenia.
Localized amygdalar lesions in humans produce deficits in the recognition of fearful facial expressions. We used functional neuroimaging to test two hypotheses: (i) that the amygdala and some of its functionally connected structures mediate specific neural responses to fearful expressions; (ii) that the early visual processing of emotional faces can be influenced by amygdalar activity. Normal subjects were scanned using PET while they performed a gender discrimination task involving static grey-scale images of faces expressing varying degrees of fear or happiness. In support of the first hypothesis, enhanced activity in the left amygdala, left pulvinar, left anterior insula and bilateral anterior cingulate gyri was observed during the processing of fearful faces. Evidence consistent with the second hypothesis was obtained by a demonstration that amygdalar responses predict expression-specific neural activity in extrastriate cortex.
Genetic factors play a substantial part in the aetiology of autism, although no satisfactory model has been proposed that could account for the excess of male phenotypes. We present five cases of autism from an unselected sample of 150 subjects with Turner syndrome, a genetic disorder associated with either the absence, or a structural abnormality, of the second X-chromosome in females. The population prevalence of autism is no more than 1:lO 000 normal females. All of the cases considered possessed an intact maternal X-chromosome and a structurally abnormal or absent paternal X-chromosome. We have previously presented evidence that cases of Turner syndrome in which the single X-chromosome is maternal have impaired social cognitive skills, compared with those in whom it is paternal. Based on these earlier findings, we suggested that an imprinted X-linked genetic locus could exist, which is expressed from the paternal X-chromosome of normal females, but which is silent in normal males whose single X is always maternal. This mechanism could serve to protect normal females (who always possess a paternal X-chromosome) from neurodevelopmental disorders affecting social cognition, such as autism. These case reports are the first account of autism in association with Turner syndrome.
Background:
Our previous investigation of the prevalence of mental illness among the biological and adoptive relatives of schizophrenic adoptees in Copenhagen, Denmark, showed a significant concentration of chronic schizophrenia (5.6%) and what Bleuler called "latent schizophrenia" (14.8%) in the biological relatives of chronic schizophrenic adoptees, indicating the operation of heritable factors in the liability for schizophrenic illness.
Methods:
We now report the results of a replication of that study in the rest of Denmark (the "Provincial Sample").
Results:
In this sample, the corresponding prevalences were 4.7% and 8.2%. In the combined "National Sample" of adoptees with chronic schizophrenia, that disorder was found exclusively in their biological relatives and its prevalence overall was 10 times greater than that in the biological relatives of controls.
Conclusions:
This study and its confirmation of previous results in the Copenhagen Study speak for a syndrome that can be reliably recognized in which genetic factors play a significant etiologic role. These findings provide important and necessary support for the assumption often made in family studies: observed familial clustering in schizophrenia is an expression of shared genetic factors.
10.1176/appi.ajp.160.4.636
At the X chromosome workshop of the Sixth World Congress on Psychiatric Genetics, new data regarding psychiatric phenotypes and the X chromosome were presented. In the last year a number of groups have published linkage results for the X chromosome in schizophrenia, which provide no significant evidence for linkage. Presentations by groups from Cardiff, Oxford, State University of New York (SUNY), and Finland provide weak nonsignificant evidence for linkage of markers on the Xp11.4-p11.3, Xq21, and Xq26 with schizophrenia. However, the presence of a male-specific transmission ratio distorter (DMS1) that maps to Xp11.4-21.2 [Naumova et al., 1998: Am. J. Hum. Genet. 62:1493–1499] makes the interpretation of linkage findings in brother-brother pairs difficult in this region. Regarding bipolar affective disorder, little new data were reported, but previous reports provide evidence for linkage to Xq25-q26. Summary tables of linkage results for schizophrenia and bipolar disorder can be obtained from http://www.camh.net/research/x-chromosome/. No linkage or transmission disequilibrium of polymorphisms of MAOA and MAOB in attention deficit hyperactivity disorder was seen. Negative results for transmission disequilibrium of polymorphisms of HTR2C and MAOA with autism were provided from German and Austrian families. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:279–286, 1999. © 1999 Wiley-Liss, Inc.
In this article, we extend earlier findings of age‐related changes in brain morphology on magnetic resonance images to include measurements of the mesial temporal lobe as well as asymmetry measures in regional cortical and subcortical structures. The earlier sample was increased to include 57 children and young adults aged 8 to 35 years. The participants were studied using quantitative image analytic techniques. Estimated volumes of limbic and anterior diencephalic structures increased significantly with age; although inferior lateral cortex, superior cortex, caudate nuclei, thalamus, and lenticular nuclei all decreased significantly with age. Of the 7 regions measured, only the lenticular nucleus and anterior diencephalon showed significant changes in asymmetry with increasing age. It is hypothesized that some of these changes may be related to the changing levels of gonadal steroid hormones known to occur during this age range. They may also have important implications for the study of late developing higher cognitive functions and the loss of behavioral plasticity.
Aggleton, J.P. and Young, A.W. (1999). The enigma of the amygdala: on its contribution to human emotion. In L. Nadel and R.D. Lane (Eds.), Emotion and cognitive neuroscience. New York: Oxford University Press, 106-128.
Chance et al ([2002][1]) described volumetric measurement of the amygdala and found few differences between normal and schizophrenia post-mortem samples. This fails to confirm published magnetic resonance imaging (MRI) data on hundreds of individuals which have been systematically reviewed and
Resting anterior brain electrical activity, self-report measures of Behavioral Approach and Inhibition System (BAS and BIS) strength, and general levels of positive and negative affect (PA and NA) were collected from 46 unselected undergraduates on two separate occasions Electroencephalogram (EEG) measures of prefrontal asymmetry and the self-report measures showed excellent internal consistency reliability and adequate test-retest stability Aggregate measures across the two assessments were computed for all indices Subjects with greater relative left prefrontal activation reported higher levels of BAS strength, whereas those with greater relative right prefrontal activation reported higher levels of BIS strength Prefrontal EEG asymmetry accounted for more than 25% of the variance in the self-report measure of relative BAS-BIS strength Prefrontal EEG, however, was not significantly correlated with PA or NA, or the relative strength of PA versus NA Posterior asymmetry was unrelated to the self-report measures
Purpose of review: Within the past 20 years a growing body of literature has examined emotion recognition deficits in schizophrenia and the association with cognition and social functioning. Comparisons of studies on emotion recognition have been limited by the use of different facial stimuli, different test designs and patient groups. This article reviews studies on emotion recognition in schizophrenia published between September 2002 and October 2003, which reflect the increasing interest and importance of emotional processing in schizophrenia. Recent findings: Recent investigations have focused on emotion processing and neurocognitive and social functioning using neuroimaging and behavioral techniques. Findings suggest that schizophrenia patients may be particularly impaired in the recognition of fear, show abnormal visual fixation upon scanning of facial features, and exhibit impaired right hemispheric and amygdala processing of emotional faces. Some studies have revealed potentially interesting findings of schizophrenia-like brain processing in healthy adults. Summary: Studies continue to use stimuli limited in color format, age and ethnicity of poser, and are limited to posed and unfelt emotions. Future research will benefit from more exact guidelines on what defines emotion recognition and discrimination tests, the number of stimuli and presentation, similar to guidelines that exist for cognitive tests. There remains a need to study and compare emotion recognition groups with similar phenomenology, such as schizophrenia versus bipolar disorder or major depression with psychotic features, different types of epilepsies and dementias. Such comparisons linked with anatomical findings of limbic system structures will inform us about the specificity of emotion processing deficits in different brain disorders and associated neural circuitry.
We used the Schizotypal Personality Questionnaire to evaluate schizotypal traits in 44 normal volunteers and 40 non-psychotic, biological relatives of schizophrenic probands. Relatives endorsed more cognitive–perceptual traits than did controls; a group-by-sex interaction indicated that male relatives accounted for this difference. Although not statistically significant, a similar pattern was observed for interpersonal traits. Thus, elevated rates of some schizotypal traits appear to be more prominent in male than in female relatives of schizophrenic probands, at least when assessed by self-report. Subscale analysis indicated that differences were accounted for primarily by suspiciousness and ideas of reference, suggesting that paranoid-like phenomena from both the cognitive–perceptual and interpersonal factors may constitute an important dimension of schizotypy in relatives. Unlike previous studies, we did not find any differences in constricted affect or disorganization signs. Interviews and other non-self-report techniques are probably best suited for an assessment of these features, although the question remains as to whether the combination of both approaches might provide some incremental discriminatory power.
Although the amygdala is widely believed to have a role in the recognition of emotion, a central issue concerns whether it is involved in the recognition of all emotions or whether it is more important to some emotions than to others. We describe studies of two people, DR and SE, with impaired recognition of facial expressions in the context of bilateral amygdala damage. When tested with photographs showing facial expressions of emotion from the Ekman and Friesen (1976) series, both DR and SE showed deficits in the recognition of fear. Problems in recognising fear were also found using photographic quality images interpolated ("morphed") between prototypes of the six emotions in the Ekman and Friesen (1976) series to create a hexagonal continuum (running from happiness to surprise to fear to sadness to disgust to anger to happiness). Control subjects identified these morphed images as belonging to distinct regions of the continuum, corresponding to the nearest prototype expression. However, DR and SE were impaired on this task, with problems again being most clearly apparent in the region of the fear prototype, An equivalent test of recognition of morphed identities of six famous faces was performed normally by DR, confirming the dissociability of impairments affecting the recognition of identity and expression from the face. Further two-way forced-choice tests showed that DR was unable to tell fear from anger, but could tell happiness from sadness without difficulty. The finding that the recognition of fear can be differentially severely affected by brain injury is consistent with reports of the effects of bilateral amygdala damage in another case (Adolphs, Tranel, Damasio, & Damasio, 1994, 1995). The recognition of facial expressions of basic emotions may therefore be linked, to some extent, to specific neural substrates.
Purpose of review: Cerebral asymmetry (the torque from right frontal to left occipital) is the defining feature of the human brain, and as Broca proposed, the putative neural correlate of language. If as has been suggested schizophrenia is the price that Homo sapiens pays for language, the torque together with its functional correlates is of central significance. Recent evidence from anatomical, functional and genetic studies is reviewed.
Recent findings: Both post-mortem and anatomical imaging studies show evidence of a reduction or reversal of aspects of asymmetry particularly in the occipito-temporo-parietal association cortex. In some studies there is an interaction with sex. There is evidence that change in the left temporal lobe is sometimes progressive. Functional studies add substance to the concept that the lateralization of language is reduced and in some aspects reversed.
Summary: The dimension of asymmetry stands out as the variable that can make sense of observations across fields of investigation, and provides a key to the genetic basis of psychosis. Discordant monozygotic twin studies indicate strongly that the relevant variation is epigenetic; this is consistent with the possibility that the variation is related to recent structural changes (the Xq21.3/Yp duplicative transposition) on the sex chromosomes.
The volume of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus was quantified from magnetic images of the brains of 99 healthy children and adolescents aged 4–18 years. Variability in volume was high for all structures examined. When adjusted for a 9% larger total cerebral volume in males, there were no significant volume differences between sexes. However, sex-specific maturational changes were noted in the volumes of medial temporal structures, with the left amygdala increasing significantly only in males and with the right hippocampus increasing significantly only in females. Right-greater-than-left laterality effects were found for temporal lobe, superior temporal gyrus, amygdala, and hippocampal volumes. These results are consistent with previous preclinical and human studies that have indicated hormonal responsivity of these structures and extend quantitative morphologic findings from the adult literature. In addition to highlighting the need for large samples and sex-matched controls in pediatric neuroimaging studies, the information from this understudied age group may be of use in evaluating developmental hypotheses of neuropsychiatric disorders. © 1996 Wiley-Liss, Inc.†
Both Turner syndrome and schizophrenia are relatively infrequent conditions. Consequently, individuals having both illnesses are rare. Previous reviews of sex chromosome abnormalities in schizophrenia have focused primarily on the presence of supernumerary X-chromosomes. After identifying two female patients with schizophrenia and Turner syndrome, we reevaluated the available literature that survey female schizophrenics for the presence of chromosomal abnormalities. Eleven patients with Turner syndrome were identified among 6,483 females with schizophrenia in non-case-report studies. These survey results indicate that Turner syndrome occurs approximately three-fold more frequently in schizophrenic females than in the general female population (P < 0.02). Including 6 other case reports and our 2 cases, a total of 19 females with both schizophrenia and Turner syndrome were reported. Interestingly, whereas most Turner syndrome patients have the 45,X karyotype, the majority (18/19) of women with both illnesses have a mosaic karyotype (P < 0.0002). Given the potential role of genes on the X-chromosome in the pathogenesis of schizophrenia, the study of unique populations with abnormalities in this chromosome, such as women with Turner syndrome, may offer clues into this illness. Am J Med Genet (Neuropsychiatr Genet) 96:373–378, 2000. © 2000 Wiley-Liss, Inc.
Substantial evidence suggests that nonpsychotic relatives of schizophrenia patients manifest subtle abnormalities in communication, eye movements, event-related potentials, and neuropsychological processes of attention, reasoning, and memory. We sought to determine whether adult relatives without psychosis or schizophrenia spectrum diagnoses might also have structural brain abnormalities, particularly in subcortical regions found to be impaired in patients with schizophrenia itself. Subjects were six sisters of schizophrenic patients and eleven normal female controls. Sixty contiguous 3 mm coronal, T1-weighted 3D magnetic resonance images (MRI) of the entire brain were acquired on a 1.5 Tesla magnet. Cortical and subcortical gray and white matter was segmented using a semiautomated intensity contour mapping algorithm. Volumes were adjusted for total brain volumes. Adjusted gray matter subcortical volumes were significantly smaller in relatives than in controls in total hippocampus, right amygdala, right putamen, left thalamus, and brainstem. Relatives had significantly enlarged left and total inferior lateral ventricles. These results, though preliminary, suggest that some never-psychotic relatives of schizophrenic patients have abnormal brain structure. If replicated in a larger sample including both sexes, these results would suggest that the genetic liability to schizophrenia is also expressed as structural brain abnormalities. Am. J. Med. Genet. 74:507–514, 1997. © 1997 Wiley-Liss, Inc.
Very little is known about the adult adaptation of individuals with sex chromosome abnormalities (SCA) except for a few reports based upon biased samples of clinically identified patients. This first report from the Denver SCA study on the adult psychosocial adaptation of 36 unselected propositi, identified at birth, shows a continuation of mild psychological and social problems. Psychiatric interviews and self-reported information revealed that adaptation is quite variable, with many of the nonmosaic propositi not faring as well as their siblings, but in a few instances exceeding the success of brothers and sisters. Within this group of SCA subjects a subset demonstrated more marked pathology and a tendency to overrate their social adaptation relative to the psychiatric interviewer, suggesting that the exclusive use of self-report questionnaires may not provide accurate assessment of psychological characteristics in this and other special populations. The full adult SCA behavioral phenotype has not yet been established but is emerging through additional reports from this and other studies of unselected SCA adults. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:200–206, 1999. © 1999 Wiley-Liss, Inc.
Although infantile autism was first described as a disorder of “affective contact,” in the past 20 years it has been largely regarded as a cognitive disorder, with socially deviant behavior seen as a secondary manifestation. After a discussion of diagnostic issues, the nature of the socially deviant behavior is described, and a brief history of theories to account for this behavior is presented. It is then suggested that the social symptoms may more fruitfully be viewed as primary because of (1) the dissociability of social and cognitive impairments both within and across developmentally disabled populations, (2) the special difficulty autistic children may have with social or affective stimuli, and (3) the rarity of social isolation even in severely damaged babies, and its resistance to modification in autistic children. In addition, the specific cognitive deficits suggested to be central to autism (4) can be found in at least as severe a form in sociable retarded children, (5) are theoretically inadequate to explain autistic aloofness, (6) cannot be found in all autistic children, and (7) may be the very cognitive abilities which rest most heavily on social functioning. Some implications are drawn for neuropsychological models of autism.
A substantial percentage of normal people has been documented to report hallucinatory experiences. We investigated the multi-dimensionality of such experiences in 243 subjects from the normal population who completed the Launay–Slade Hallucination Scale. Principal components analysis with oblique rotation was performed on the data. Three factors were obtained loading on items reflecting (1) tendency towards hallucinatory experiences, (2) subjective externality of thought, and (3) vivid daydreams. An additional exploratory factor analysis revealed highly similar factors. The results support the concept of hallucinatory disposition as a multi-dimensional construct.
Recent magnetic resonance imaging (MRI) studies found abnormalities of medial temporal lobe and basal ganglia structures. We used an inversion recovery (IR) protocol with the assistance of the Talairach atlas to identify neuroanatomical regions of interest in 19 male schizophrenic patients and 14 matched control subjects. The patient group showed smaller amygdala- hippocampus volume as compared with normal control subjects. This finding was more pronounced for the left side, although no diagnosis × side interaction was present. Third ventricle volume was also enlarged in schizophrenic patients. Trends toward an overall reduction of basal ganglia (striatum and lenticular nucleus) and limbic structures and toward an increase in ventricle-brain ratio were also seen. The study confirms previous evidence of mesial temporal lobe shrinkage, more evident on the left side in a group of relapsing noninstitutionalized male schizophrenic patients.
Research on the behavioral characteristics of girls and women with Turner syndrome has identified an increased risk for learning disabilities as well as social and behavioral problems (poor concentration, immaturity, anxiety) that typically present during childhood and adolescence. Most adult women with Turner syndrome, however, are emotionally stable, living self-sufficient lives. This chapter will summarize findings on the social and behavioral development of girls and women with Turner syndrome consider the mechanisms underlying these patterns, and present strategies for assuring optimal psychosocial development and adjustment.
Recent surveys of psychometric studies with respect to the construct and/or factorial validity of self-report assertion measures (e.g. Beck and Heimberg, 1983) point to the paucity of systematic research addressing such issues. To date no attempts have been made to examine the cross-sample generalisability of dimensions of assertion by means of objective techniques of factorial invariance (i.e. hypothesis-testing variations of principal factor or principal components analysis). Employing such a technique in the present study, distress and performance factors identified previously in a phobic population (N = 703) with a Dutch measure of assertion (Scale for Interpersonal Behaviour) — the factors being: (I) DISPLAY OF NEGATIVE FEELINGS, (II) EXPRESSION of and DEALING with PERSONAL LIMITATIONS, (III) INITIATING ASSERTIVENESS and (IV) POSITIVE ASSERTION — were shown to be replicable in a new phobic sample (N = 119) and invariant across three distinct samples, namely psychiatric outpatients (N = 253), (non-patient) students (N = 412) and (non-student) normals (N = 250). Additional reliability and validity data supported the utility of a fifth overall measure within the Scale, which was termed GENERAL ASSERTIVENESS. These data also underline the contention of Futch et al. (1982) that it would be unwise to take any demonstrated multidimensionality of an assertion construct as evidence in the context of the trait-state issue (e.g. Eisler et al., 1975). However, the exclusive use of an overall assertion scale of a purportedly multidimensional measure is likely to invalidate research findings (including clinical research) since it masks relevant component information. To counteract this problem it is proposed that either the subscales should be used on their own or that the subscales and the overall scale should be used together. It is further concluded that (1) in developing and using an assertion measure a multidimensional approach should be taken, there being at least four distress and four performance factors to be taken account of; (2) of these four factors, that of Positive Assertion in particular should be considered more thoroughly in adequately defining and operationalising the assertion construct.
To investigate the adolescent and early adult adaptation of a group of 47,XXX women as compared with their siblings, addressing developmental differences in adaptation and psychiatric status.
Subjects included eleven 47,XXX women and nine female sibling controls. Interviews during adolescence and during early adulthood were semistructured and included a psychiatric evaluation. Four areas of inquiry were (1) relationships with other family members, (2) sense of self-esteem, (3) sexual identity and preference, and (4) responses to life stressors. A DSM-IV psychiatric diagnosis was assigned where appropriate. The Schedule for Affective Disorders and Schizophrenia-Lifetime version was also administered, and assessments of overall functioning and adaptation were completed.
The 47,XXX women during adolescence and young adulthood were less well adapted; had more stress; had more work, leisure, and relationship problems; had a lower IQ; and showed more psychopathology when contrasted with the comparison group. However, most of the 47,XXX women were self-sufficient and functioning reasonably well, albeit less well than their siblings.
This longitudinal study has clarified that previously reported outcomes of severe psychopathology and antisocial behavior in individuals with sex chromosome anomalies are rare and variability in the behavioral phenotype is much larger than originally appreciated.