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Self-Reflectiveness and cortical thickness. A) Random field theory thresholded map showing Self-Reflectiveness at baseline regressed against cortical thickness in participants with a FEP, controlling for age, sex, proxy brain volume, handedness and SAPS global delusions. Higher Self-Reflectiveness was significantly associated with thinner cortex in right occipital cortex (r = −0.27, p = 0.002, 123 df, 1097 vertices). L = left, D = dorsal, R = right, M = medial, P = posterior, A = anterior. B) Mean cortical thickness plots for association between SelfReflectiveness and right occipital cortical thinness.
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Among individuals with psychosis, those with poor cognitive insight (lower Self-Reflectiveness, higher Self-Certainty) show volumetric reductions in cortical structure. We evaluated whether changes in cognitive insight are associated with progressive changes in cortical structure in first-episode psychosis (FEP) and control subjects. Beck Cognitive...
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Context 1
... FEP, higher Self-Reflectiveness was significantly associated with thinner cortex in right occipital lobe at baseline (r = − 0.27, p = Table 1 Demographic and clinical characteristics of the first-episode of psychosis and control participants at the baseline scan. 0.0026, 123 df, 1097 vertices), and this result is shown in Fig. 1. Self- Certainty was not significantly associated with thickness in any cortical ...
Context 2
... analyses with a lowered threshold revealed that in FEP participants, higher Self-Certainty was associated with thinner cortex in left posterior cingulate and precuneus across all time-points. Cortical thinning in the precuneus has been linked to poorer clinical insight in people with a FEP (Buchy et al., 2011) and is known to be important Table 2 Cognitive insight scores and clinical information of the FEP sample at baseline, and 1-year and 2-year follow-ups. Baseline (n = 130) 1-year (n = 59) 2-years (n = 53) ...
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Citations
... Excessive synaptic elimination with loss of dendritic spines is suspected to underwrite the MRI-readout of reduced thickness [24]. This account is consistent with progressive cortical thinning noted in the early phase of psychosis [25,26]. ...
Background
Recent genetic evidence implicates glutamatergic-receptor variations in schizophrenia. Glutamatergic excess during early life in people with schizophrenia may cause excitotoxicity and produce structural deficits in the brain. Cortical thickness and gyrification are reduced in schizophrenia, but only a subgroup of patients exhibits such structural deficits. We delineate the structural variations among unaffected siblings and patients with schizophrenia and study the role of key glutamate-receptor polymorphisms on these variations.
Methods
Gaussian Mixture Model clustering was applied to the cortical thickness and gyrification data of 114 patients, 112 healthy controls, and 42 unaffected siblings to identify subgroups. The distribution of glutamate-receptor (GRM3, GRIN2A, and GRIA1) and voltage-gated calcium channel (CACNA1C) variations across the MRI-based subgroups was studied. The comparisons in clinical symptoms and cognition between patient subgroups were conducted.
Results
We observed a “hypogyric,” “impoverished-thickness,” and “supra-normal” subgroups of patients, with higher negative symptom burden and poorer verbal fluency in the hypogyric subgroup and notable functional deterioration in the impoverished-thickness subgroup. Compared to healthy subjects, the hypogyric subgroup had significant GRIN2A and GRM3 variations, the impoverished-thickness subgroup had CACNA1C variations while the supra-normal group had no differences.
Conclusions
Disrupted gyrification and thickness can be traced to the glutamatergic receptor and voltage-gated calcium channel dysfunction respectively in schizophrenia. This raises the question of whether MRI-based multimetric subtyping may be relevant for clinical trials of agents affecting the glutamatergic system.
... A few studies have investigated the neural correlates of cognitive insight in healthy individuals and SCZ. They have reported SR to be correlated to bilateral ventrolateral prefrontal cortex (VLPFC) volumes (Orfei et al., 2013) and to have a positive relationship with the thickness of the frontal, temporal, parietal, and occipital cortices (Buchy et al., 2016) SC on the other hand has been correlated with hippocampal volumes (Buchy et al., 2010) and negatively correlated with cortical thickness in the frontal, temporal, parietal, and posterior cingulate cortices (PCC) (Buchy et al., 2018). In another study, SR was related to cortical thickness in the right PCC and left ventrolateral prefrontal cortex (VLPFC) in SCZ (Jacob et al., 2019). ...
Objective
Cognitive insight comprising self-reflection and self-certainty is an important determinant of functional outcomes in Schizophrenia. The neural correlates of cognitive insight in Schizophrenia are underexamined. The frontal pole (FP) is implicated in metacognitive function in healthy individuals, but its role is not well examined in Schizophrenia. We had earlier reported the relationship between Frontal pole volumes and cognitive insight in a small sample of only male patients. Hence, we studied this relationship in an independent sample of schizophrenia patients and healthy controls.
Methods
We examined 41 healthy volunteers (HV) and 57 patients with Schizophrenia (SCZ). We used a previously validated manual morphometric method to perform FP parcellation on images obtained from a 3 T scanner and calculated the volumes. Cognitive insight was measured using Beck’s Cognitive insight scale (BCIS). To assess the relationship between FP volumes and BCIS scores, multiple linear regression analyses were performed.
Results
In the overall sample, age, years of education, and intracranial volume were significant predictors of BCIS scores. Within the SCZ group, age and left FP volume were significant predictors of BCIS composite scores and age, ICV for BCIS-self certainty. There was no significant relationship between age and FP volumes in either SCZ or HV group.
Discussion
The current study in an independent sample further supports the critical role of the frontal pole in cognitive insight, earlier reported by us. As cognitive insight has a vital role in functional outcome, our findings have potential clinical implications.
... Залогом хорошей когнитивной критики к состоянию являются высокая саморефлексивность и низкая самоуверенность [59]. Данная реципрокность находит отражение и в нейровизуализационной картине толщины коры в соответствующих областях головного мозга [61]. Высокая саморефлексивность имеет положительную предсказательную силу в отношении ремиссии первого психотического эпизода в горизонте 4 лет [62]. ...
... Это было выявлено в ходе сравнения пациентов с продромальными состояниями, первым психотическим эпизодом и множественными психотическими эпизодами [49] и у пациентов с купированными симптомами болезни [67]. Исследования когнитивного компонента критики к состоянию с использованием нейровизулизацион-ных маркеров у пациентов с первым психотическим эпизодом и здоровых добровольцев выявили неизменность этих характеристик в течение 2 лет наблюдения -у всех групп отмечалась стабильная разница в толщине коры в соответствующих зонах головного мозга, что в очередной раз навело на мысль, что когнитивный компонент критики (саморефлексивность и самоуверенность) является чертой, а не приобретенным состоянием [61]. ...
The goal of the up-to-date treatment of patients with schizophrenia spectrum disorders is recovery, including personal recovery. This goal is a part of the patient-centered approach. This review examines factors that may influence recovery achievement. Compliance plays a key role in relapse prevention. Its formation, in turn, depends on patients' participation in the treatment process, level of insight and patients' ability and willingness to play an active role in the treatment and apply self-management. All of the mentioned above should be taken into account while implementing patient-centered approach. This dictates the need to develop clear evaluation criteria of recovery factors in medical care of patients with schizophrenia spectrum disorders.
... Although this reduction appears to be related to the severity of the disease, as demonstrated in patients with schizophrenia with impaired cognition (Van Rheenen et al., 2018), it has also been reported in subjects with high self-reflexivity (Buchy et al., 2018). Conversely, other results have shown increased occipital thickness, especially in patients with long-standing illness (Guo et al., 2016). ...
Cortical thickness (CT) and local gyrification index (LGI) in psychotic disorders may show modifications that relate to clinical course. This observational study aimed to analyse such variables in patients with schizophrenia, compared to healthy controls (HCs). We compared CT and LGI of 18 patients with first-episode psychosis with that of 21 with multi-episode schizophrenia and 16 HCs. CT corrected for false-positive cases (Family-Wise Error Rate) showed a reduction in the multi-episode group compared to HCs in left temporal and parietal, and right temporal, parietal, occipital, and hippocampal cortices. Family-wise corrected LGI was increased in the left inferior and middle frontal cortices, and in the right fusiform gyrus, cingulate, lingual, and parahippocampal gyri in first onset patients compared to HCs. Increased LGI was absent from later stages of psychosis, suggesting that specific CT and LGI alterations may underlie different stages of illness.
... A few studies have examined the neural correlates of cognitive insight in schizophrenia. SC has been found to negatively correlate with cortical thickness in the frontal, temporal, parietal, and posterior cingulate cortices (PCC) (Buchy et al., 2018a(Buchy et al., , 2016a, while SR positively correlated with thickness of the frontal, temporal, parietal, and occipital cortices (Buchy et al., 2016b). We found SR to be related to cortical thickness in the right PCC and left ventrolateral prefrontal cortex (VLPFC) in SCZ (Jacob et al., 2019). ...
Absence of insight owing to impaired self-reflection and lack of touch with reality is a hallmark of schizophrenia. Functional imaging studies in healthy individuals have implicated the frontal pole (FP), sub-division of the prefrontal cortex in self-reflective processes. Despite the significance of self-referential processing in the pathogenesis of schizophrenia, the relationship between FP volume and cognitive insight in this disorder is underexplored. We examined the relationship between cognitive insight and volume of FP using precise manual morphometry of high resolution magnetic resonance images in 19 schizophrenia patients (SCZ) and 21 healthy-volunteers (HV). The manual morphometry technique was replicated from a previous study based on a cytoarchitectonically and functionally valid definition of FP and cognitive insight was measured using Beck's cognitive insight scale. Left frontal pole volume was a significant predictor of self-reflection sub-score of Beck's cognitive insight scale (β=0.68; t = 2.86; p = 0.01). A significant inverse relationship between age and bilateral FP volumes was noted in HV (left FP - r=-0.45; p = 0.04; right FP - r=-0.57; p = 0.008) but not in SCZ (p>0.05). Our findings provide anatomical substrates to devise intervention strategies targeting cognitive insight, thereby improving treatment adherence and functional outcomes.
... Although neuroimaging abnormalities in patients with first episode psychosis (FEP) have been demonstrated, their quantitative distribution is still are under debate. Different patterns of atrophy in the frontal cortex, cingulate cortex, parahippocampal gyri, the basal ganglia, and the thalamus has been reported from multiple groups in the past (Buchy, Makowski, Malla, Joober, & Lepage, 2018;Calvo, Delvecchio, Altamura, Soares, & Brambilla, 2019;Castro-de-Araujo & Kanaan, 2017;Kuang et al., 2017;Makowski et al., 2019;Nakamura et al., 2007;Schubert, Clark, & Baune, 2015;Tordesillas-Gutierrez et al., 2018). The inverse trend (gray matter increase) has also been reported (Dukart et al., 2017). ...
... The inconsistency of imaging study findings in FEP can be attributed to several factors. These include the inconsistency among studies regarding the actual definition of FEP (Breitborde, Srihari, & Woods, 2009), the limited power to detect subtle abnormalities in small samples (Buchy et al., 2018;Emsley et al., 2017;Guma et al., 2017;Kong et al., 2011;Kuang et al., 2017;Lee et al., 2012;Lian et al., 2018;McNabb et al., 2018;Peters et al., 2008;Serpa et al., 2017), as well as the bias in the selection of MRI modalities and regions of interest (ROIs) (Baglivo et al., 2018;Forns-Nadal et al., 2017;Huttlova et al., 2014;Lang et al., 2006;McHugo et al., 2018;Parellada et al., 2017;Sauras et al., 2017;Ublinskii et al., 2015;Vargas et al., 2018). Analyzing features through multiple MRI modalities over the whole brain became possible with the evolution of the scanners. ...
Multi‐institutional brain imaging studies have emerged to resolve conflicting results among individual studies. However, adjusting multiple variables at the technical and cohort levels is challenging. Therefore, it is important to explore approaches that provide meaningful results from relatively small samples at institutional levels. We studied 87 first episode psychosis (FEP) patients and 62 healthy subjects by combining supervised integrated factor analysis (SIFA) with a novel pipeline for automated structure‐based analysis, an efficient and comprehensive method for dimensional data reduction that our group recently established. We integrated multiple MRI features (volume, DTI indices, resting state fMRI—rsfMRI) in the whole brain of each participant in an unbiased manner. The automated structure‐based analysis showed widespread DTI abnormalities in FEP and rs‐fMRI differences between FEP and healthy subjects mostly centered in thalamus. The combination of multiple modalities with SIFA was more efficient than the use of single modalities to stratify a subgroup of FEP (individuals with schizophrenia or schizoaffective disorder) that had more robust deficits from the overall FEP group. The information from multiple MRI modalities and analytical methods highlighted the thalamus as significantly abnormal in FEP. This study serves as a proof‐of‐concept for the potential of this methodology to reveal disease underpins and to stratify populations into more homogeneous sub‐groups.
... Of these studies, Buchy et al. (2016) found significant associations between both self-reflectiveness and self-certainty and cortical thickness in the ventrolateral prefrontal cortex, and other frontal, parietal and temporal areas (Orfei et al. (2013) found that lower self-reflectiveness was related to lower volume of the right ventrolateral prefrontal cortex, while no significant relations were found for self-certainty nor BCIS composite index scores (Orfei et al., 2013). Buchy et al. (2018) reported a significant correlation between higher self-reflectiveness and cortical thickness in the right occipital cortex in first-episode patients but their sample overlapped with a previous study of their group (Buchy et al., 2018(Buchy et al., , 2016. ...
... Of these studies, Buchy et al. (2016) found significant associations between both self-reflectiveness and self-certainty and cortical thickness in the ventrolateral prefrontal cortex, and other frontal, parietal and temporal areas (Orfei et al. (2013) found that lower self-reflectiveness was related to lower volume of the right ventrolateral prefrontal cortex, while no significant relations were found for self-certainty nor BCIS composite index scores (Orfei et al., 2013). Buchy et al. (2018) reported a significant correlation between higher self-reflectiveness and cortical thickness in the right occipital cortex in first-episode patients but their sample overlapped with a previous study of their group (Buchy et al., 2018(Buchy et al., , 2016. ...
... Finally, Buchy et al. (2010) also found that total cognitive insight was positively related to left hippocampal volume (Buchy et al., 2010). A last study of which the sample partially overlapped with a previous publication of this group (Buchy et al., 2016) found a negative relationship between self-reflectiveness and cortical thickness of the right occipital lobe (Buchy et al., 2018). ...
In the past years, ample interest in brain abnormalities related to clinical and cognitive insight in psychosis has contributed several neuroimaging studies to the literature. Published findings on the neural substrates of clinical and cognitive insight in psychosis are integrated by performing a systematic review and meta-analysis.
Coordinate-based meta-analyses were performed with the parametric coordinate-based meta-analysis approach, non-coordinate based meta-analyses were conducted with the metafor package in R. Papers that could not be included in the meta-analyses were systematically reviewed.
Thirty-seven studies were retrieved, of which 21 studies were included in meta-analyses. Poorer clinical insight was related to smaller whole brain gray and white matter volume and gray matter volume of the frontal gyri. Cognitive insight was predominantly positively associated with structure and function of the hippocampus and ventrolateral prefrontal cortex.
Impaired clinical insight is not associated with abnormalities of isolated brain regions, but with spatially diffuse global and frontal abnormalities and might rely on a range of cognitive and self-evaluative processes. Cognitive insight is associated with specific areas and appears to rely more on retrieving and integrating self-related information.
... Cognitive insight is self-awareness of cognitive distortions and misinterpretations 13 and willingness to modify these with corrective information. 14,15 This contrasts with clinical insight (self-awareness of one's own mental disorder and effects of medication 16 ). In schizophrenia, cognitive and clinical insight appear to form independent constructs. ...
... 15 Although we found that FEP had significantly thinner cortex within vlPFC (which accords with previous findings 47,48 ), this did not correlate with BCIS scores. Another recent study also failed to find any association even when assessed longitudinally, 14 suggesting that the relationship might not be robust. It is noteworthy that inconsistencies also exist in findings linking BCIS to frontal (executive) functioning. ...
... Likewise, follow-up studies by those same groups did not replicate their findings. 14,15,23 This lack of consistency across studies suggests that the BCIS might not be an optimal method for determining the neural structures underlying metacognition in schizophrenia. ...
Metacognition is impaired in schizophrenia and is an important predictor of functional outcome, but the underlying neuropathology is not clear. Studies have implicated frontal regions and there is also some evidence that the hippocampus might play a pivotal role, but findings are inconsistent. We set out to more comprehensively investigate the neural underpinnings of insight in first-episode psychosis (FEP) using 2 metacognitive measures (the Beck Cognitive Insight Scale [BCIS]) and a perceptual metacognitive accuracy task alongside structural magnetic resonance imaging (MRI). We measured cortical thickness in insula and frontal regions, hippocampal (including subfield) volumes, hippocampal microstructure (using neurite orientation dispersion and density imaging [NODDI]), and fractional anisotropy in fornix. Relative to controls, FEP showed poorer metacognitive accuracy, thinner cortex in frontal regions and lower fornix integrity. In healthy controls (but not FEP), metacognitive accuracy correlated with cortical thickness in frontal cortex and insula. Conversely, in FEP (but not controls), metacognitive accuracy correlated with hippocampal volume and microstructural indices. Subicular hippocampal subregions were particularly implicated. No structural correlates of BCIS were found. These findings suggest that the neural bases of metacognition might differ in FEP: hippocampal (rather than frontal) integrity seems to be critical. Further, the use of objectively measured metacognitive indices seems to be a more powerful method for understanding the neurocircuitry of metacognition in FEP, which has the potential to inform therapeutic strategies and improve outcome in these patients.
... On similar lines, several studies have examined the neural correlates of cognitive insight using structural imaging methods such as voxel based morphometry, cortical thickness measurements and structural covariance technique. (Buchy et al., 2010(Buchy et al., , 2016(Buchy et al., , 2018Ćurčić-Blake et al., 2015;Gerretsen et al., 2014;Kuang et al., 2017;Orfei et al., 2013Orfei et al., , 2017. These studies have reported significant associations between BCIS subscales and regional brain structure. ...
... These studies have reported significant associations between BCIS subscales and regional brain structure. One of the studies reported negative correlations between self-certainty and cortical thickness in the frontal, temporal, and parietal regions and posterior cingulate cortex (PCC) (Buchy et al., 2016(Buchy et al., , 2018. On the other hand, positive correlations between SR and thickness in the frontal, temporal, parietal, and occipital cortices have also been reported (Buchy et al., 2016). ...
... We then used this projected surface map (SMP) to perform group level investigations on predefined regions of interest (ROIs). We obtained the ROIs for the current study after reviewing previous studies on this topic and those regions which were found to be associated with cognitive insight in at least two studies were selected (Buchy et al., 2010(Buchy et al., , 2015(Buchy et al., , 2016(Buchy et al., , 2018Caletti et al., 2017;Ćurčić-Blake et al., 2015;Gerretsen et al., 2014;Kuang et al., 2017;Orfei et al., 2013Orfei et al., , 2017Pu et al., 2013;Van Der Meer et al., 2013) (details in Supplementary Table S4). Based on this literature, we selected the following ROIs in both hemispheres; posterior cingulate cortex (PCC) [Brodmann area (BA) 31], precuneus (BA 7), superior frontal cortex (BA 9), orbitofrontal cortex (OFC) (BA 10,11, 47) ventrolateral prefrontal cortex (VLPFC) (BA 44), inferior frontal gyrus (IFG) (BA 47) inferior temporal cortex (BA20), and temporal pole (BA 38). ...
... Yüksel et al. 2018), and furthermore, an effect of polygenic risk scores for psychiatric disorders on brain activation (Yüksel et al. 2017;Krug et al. 2018) future investigations should pay attention on functional differences and the influence of genetic risk factors/-variants on GMV. In addition, as several studies investigated longitudinal changes of cortical thickness or surface during childhood and adolescence (Shaw et al. 2008;Raznahan et al. 2011;Herting et al. 2015) or in psychiatric subjects such as psychotic patients (Buchy et al. 2018), future studies should investigate these longitudinal changes in MDD. Yet, the investigation of these parameters in combination with clinical variables is of great interest for future research. ...
Patients with major depressive disorder (MDD) exhibit gray matter volume (GMV) reductions in limbic regions. Clinical variables-such as the number of depressive episodes-seem to affect volume alterations. It is unclear whether the observed cross-sectional GMV abnormalities in MDD change over time, and whether there is a longitudinal relationship between GMV changes and the course of disorder. We investigated T1 structural MRI images of 54 healthy control (HC) and 37 MDD patients in a 3-Tesla-MRI with a follow-up interval of 3 years. The Cat12 toolbox was used to analyze longitudinal data (p < 0.05, FWE-corrected, whole-brain analysis; flexible factorial design). Interaction effects indicated increasing GMV in MDD in the bilateral amygdala, and decreasing GMV in the right thalamus between T1 and T2. Further analyses comparing patients with a mild course of disorder (MCD; 0-1 depressive episode during the follow-up) to patients with a severe course of disorder (SCD; > 1 depressive episode during the follow-up) revealed increasing amygdalar volume in MCD. Our study confirms structural alterations in limbic regions in MDD patients and an association between these impairments and the course of disorder. Thus, we assume that the reported volumetric alterations in the left amygdala (i.e. volumetric normalization) are reversible and apparently driven by the clinical phenotype. Hence, these results support the assumption that the severity and progression of disease influences amygdalar GMV changes in MDD or vice versa.
