Martina Amanzio

Università degli Studi di Torino | UNITO · Dipartimento di Psicologia

Alongside rapid population ageing, we are experiencing increasing numbers of people with cognitive impairment and dementia. There is great scientific effort being committed to understanding cognitive and brain functioning, with the aim of helping to promote healthy ageing and independence, and improve quality of life. This Cognitive Ageing Collecti...

The response of older people to the COVID-19 pandemic has attracted much attention as they are at increased risk of adverse outcomes. A longitudinal study has shown that improvement in global cognitive, executive and language functioning in healthy older adults enrolled at the University of the Third Age appears to play a protective role against em...

The role of placebo analgesia and nocebo hyperalgesia in patients with Alzheimer disease (AD) is largely unknown, with only few studies in the area. Therefore, this study aims to investigate to which extent placebo analgesia and nocebo hyperalgesia effects are present in patients experiencing mild-to-moderate AD. Twenty-one patients with AD (test p...

Mental flexibility (MF) has long been defined as cognitive flexibility. Specifically, it has been mainly studied within the executive functions domain. However, there has recently been increased attention towards its affective and physiological aspects. As a result, MF has been described as an ecological and cross-subject skill consisting of respon...

Older adults have been reported to have increased susceptibility to the adverse effects of SARS-CoV-2 infection, such as fatal outcomes, cognitive decline, and changes in physical and/or mental health. However, few studies have examined neuropsychological changes by comparing measurements before and during the pandemic in healthy older people. In a...

The aging process is a multifaceted phenomenon that affects cognitive-affective and physical functioning as well as interactions with the environment. Although subjective cognitive decline may be part of normal aging, negative changes objectified as cognitive impairment are present in neurocognitive disorders and functional abilities are most impai...

Introduction: The COVID-19 pandemic had remarkable effects on psychological distress. The main stressors were prolonged quarantine and social isolation, fear of infection and death, stigmatization, infodemic, financial difficulties, and job loss. These negative stressors, which affect mental and physical health, make people more vulnerable to noce...

Objective: Placebo-induced adverse events, or nocebo effects, occur when doctor-patient communication anticipates the onset of negative symptoms. They have been found to correlate with the anxiety-related activity of the hypothalamic-pituitary-adrenal system. Here we try to determine if prenatal hyperactivity of this system, as assessed through pl...

Among healthcare workers (HCWs), SARS-CoV-2 vaccine hesitancy may be linked to a higher susceptibility to nocebo effects, i.e., adverse events (AEs) experienced after medical treatments due to negative expectations. To investigate this hypothesis a cross-sectional survey was performed with a self-completed questionnaire that included a tool (Q-No)...

The SARS-CoV-2 pandemic, characterized by home confinement and other restrictive measures to reduce the spread of the infection, led to significant changes in people’s habits and lifestyle. One of the most common problems is the worsening of sleep quality or quantity, which could have negative effects on psychological wellbeing, particularly in old...

Background For safety assessment in clinical trials, adverse events (AEs) are reported for the drug under evaluation and compared with AEs in the placebo group. Little is known about the nature of the AEs associated with clinical trials of SARS-CoV-2 vaccines and the extent to which these can be traced to nocebo effects, where negative treatment-re...

Participants of clinical trials who receive a placebo treatment often report a variety of adverse events, sometimes called nocebo effects. The reason why these adverse events occur is not clear, and understanding the underlying mechanisms represents a challenge that is likely to improve the interpretation of clinical trials as well as medical pract...

The COVID-19 pandemic is known to increase older adults’ vulnerability to adverse outcomes. Alongside increased physical frailty, anxiety symptoms associated with the risk of SARS-CoV-2 contagion appear to represent its most prominent ‘sequelae’. The attentional and linguistic resources required for decoding virus-related information may also influ...

The COVID-19 pandemic is a health issue leading older adults to an increased vulnerability to unfavorable outcomes. Indeed, the presence of physical frailty has recently led to higher mortality due to SARS-CoV-2 infection. However, no longitudinal studies have investigated the role of neuropsychogeriatric factors associated with lockdown fatigue in...

Frailty is a dynamic clinical condition characterized by the reduction of interconnections among different psychobiological domains, which leads to a homeostatic vulnerability. The association between physical frailty and cognitive dysfunctions is a possible predictor of poor prognosis in patients with neurodegenerative disorders. However, this con...

Introduction Randomized clinical trials (RCTs) are useful to study the role of individual and contextual factors in which therapies vs placebos are administered, and to provide an important perspective for understanding the phenomenon of nocebo-related risks. Areas covered The results of nocebo effects in RCTs placebo groups, measured in terms of...

Frailty is an age-related dynamic status, characterized by a reduced resistance to stressors due to the cumulative decline of multiple physiological systems. Several researches have highlighted a relationship between physical frailty and cognitive decline; however, the role of specific cognitive domains has not been deeply clarified yet. Current st...

The COVID-19 pandemic is a major health issue, which leads to psychological and behavioural changes. In particular, among various negative feelings, fear seems to be one of the main emotional reactions that can be as contagious as the virus itself. The actual pandemic is likely to function as an important stressor, especially in terms of chronic an...

Reduced self-awareness is a well-known phenomenon investigated in patients with vascular disease; however, its impact on neuropsychological functions remains to be clarified. Importantly, selective vascular lesions provide an opportunity to investigate the key neuropsychological features of reduced self-awareness in neurocognitive disorders. Becaus...

Awareness of deficits in patients with neurological disorders may be described as a theoretical unitary phenomenon, which has been analysed reaching interesting results in the last decades. Awareness of deficits manifests itself in a continuum ranging from full awareness to total absence. In line with a neurocognitive approach, a reduction in self-...

The exacerbation of a clinical condition or the occurrence of negative symptoms after an inert substance dispensation or a sham treatment is known as “nocebo effect.” Nocebo is the psychobiological effect due to the negative psychosocial context that accompanies a therapy, and it is a direct consequence of negative expectations by the patients and...

Background: Antipsychotic clinical trials use to present adverse events (AEs) for the drug under evaluation to treat schizophrenia. Interestingly, patients who receive the placebo during antipsychotic trials often report several AEs, but little is known about the essence of these negative effects in patients with schizophrenia spectrum disorders (S...

Neural correlates of placebo analgesia (PA) in patients with neurocognitive disorders have not yet been elucidated. The present study aimed to evaluate how and to what extent executive (dys)functions of the medial prefrontal cortex (MPFC) may be related to PA. To this end, twenty-three subjects complaining of different cognitive deficits (from mild...

Objectives: The detection of dyskinesias-reduced-self-awareness (DRSA), in Parkinson’s disease (PD), was previously associated to executive and metacognitive deficits mainly due to dopaminergic overstimulation of mesocorticolimbic circuits. Response-inhibition dysfunction is often observed in PD. Apart from being engaged in response-inhibition task...

Since baseline executive dysfunction predicts worsening Instrumental Activities of Daily Living (i-ADL) over time and progression to Alzheimer's Disease (AD), we aimed to analyze the role of neuropsychological variables to outline which factors can contribute to functional impairment. Specific attention to executive functions (EFs) has been given....

Background Recent studies have suggested that cognitive functions in patients with neurocognitive disorders have a significant role in the pathogenic mechanisms of frailty. Although pre-frailty is considered an intermediate, preclinical state, epidemiological research has begun to dislodge cognition and frailty into their specific subcomponents to...

CSF assessment synopsis. The results of all subjects are reported.

Background: Although dyskinesias-reduced-self-awareness (DRSA) in Parkinson's disease (PD) is related to deficit in metacognition, other factors, such as "Theory of Mind" (ToM), could operate. Methods: Forty-one PD patients were assessed using the Global Awareness of Movement Disorders (GAM) and the Dyskinesias Subtracted-Index (DS-I). To study...

Nocebo is the evil twin of placebo, in which expectation of a negative outcome may lead to the worsening of a symptom. Although the study of nocebo is limited, owing to the ethical constraints of its stressful and anxiogenic procedure, some of the underlying psychological and neurobiological mechanisms have been unraveled over the past few years. P...

XLVII Congresso Società Italiana di Neurologia

It has been demonstrated that patients in the placebo arm of a clinical trial may experience adverse events (AEs), which may lead to nonadherence and dropout. However, so far, it is unknown to which extent this phenomenon is observed consistently across different diseases such as pain and neurodegenerative disorders. The current review shows for th...

A decline in instrumental activities of daily living has been described as the earliest functional deficit in patients with neurodegenerative disease. It embraces specific competencies such as: “recalling the date and telephone calls, orienting to new places, remembering the location of objects at home, understanding conversation and the plot of a...

Studies on placebo analgesic effects have shown that they can mimic the neurophysiological effects of active medication and can result in subjective pain relief. Classical conditioning and expectancy have been implicated as mechanisms mediating the placebo response. Given that the effects of placebo, psychological treatments, and active medications...

The psychosocial context surrounding the patient and the psychobiological model do offer interesting perspectives from which to study the placebo response. The term ‘response’ should only be reserved for an active neurobiological process that occurs as a result of a dummy treatment. The context surrounding the administration of a placebo can also l...

Introduction to Pain and its relation to Nervous System Disorders provides an accessible overview of the latest developments in the science underpinning pain research, including, but not limited to, the physiological, pathological and psychological aspects. This unique book fills a gap in current literature by focussing on the intricate relationshi...

A placebo effect is the effect that follows the administration of a placebo, that is, of an inert pharmacological or physical treatment. It is important to point out that the inert treatment is given along with contextual stimuli, for example, verbal suggestions of clinical improvement that make the patient believe that the treatment is real and ef...

The psychosocial context surrounding the patient and the psychobiological model offer interesting perspectives from which to study the placebo response. Some authors use the term placebo response to mean any type of improvement in a placebo group under clinical trial, even if that improvement is related to statistical artefacts such as sampling bia...

Cognitive impairment (CI) can develop during the course of ageing and is a feature of many neurological and neurodegenerative diseases. Many individuals with CI have substantial, sustained and complex healthcare needs which frequently include pain. However, individuals with CI can have difficulty communicating the features of their pain to others,...

The role of psychosocial context around patient and therapy can be studied through randomized clinical trials. The analysis of the results of clinical trials, and considering the adverse events (AEs) in the placebo groups, provides an important perspective of study for this phenomenon. In double-blind, randomized clinical trials, the side effects r...

Pain is one of the most important non motor symptoms in Parkinson’s Disease that should be taken into consideration carefully in these types of patients. Indeed, it is the most bothersome symptom ranked after slowness, tremor and stiffness that is extremely distressful for patients. Pain often remains undetected and it is a major cause of heath red...

Reduced awareness of illness is a well-known phenomenon that has been understudied in remitted patients with bipolar disorder. In particular, the relationship between reduced awareness and executive dysfunction is an intriguing question that has yet to be resolved. The aim of the current study is to analyze the link between reduced awareness, brain...

The anticipation of pain has been investigated in a variety of brain imaging studies. Importantly, today there is no clear overall picture of the areas that are involved in different studies and the exact role of these regions in pain expectation remains especially unexploited. To address this issue, we used activation likelihood estimation meta-an...

AnstractThe placebo effect in randomized clinical trials (RCTs) appears to have increased thereby contributing to problems of demonstrating statistically reliable effects of treatments that directly target biological mechanisms. The shortcomings of RCTs are currently discussed along with potential improvements of trial designs. In this review we ex...

The investigation of nocebo effects is evolving and a few literature reviews have emerged, however, so far without quantifying such effects. This quantitative systematic review investigated nocebo effects in pain. We searched the databases PubMed, EMBASE, Scopus, and the Cochrane Controlled Trial Register with the term "nocebo". Only studies that i...

The monitoring attentional system represented by the Anterior Cingulate Cortex serves to ensure that the elaboration processes in other brain regions are of the highest efficiency, in relation to the demands of the tasks that are taking place. The interactions with the prefrontal cortex can select the buffer of the working memory. The interactions...

Reduced awareness of illness is a well-known phenomenon that has been studied in patients with vascular disease, but the precise nature of their executive dysfunction is an intriguing question that still has to be resolved. It would be particularly interesting to study patients with reduced awareness of disease possibly related to vascular lesions...

The psychosocial context surrounding the patient and the psychobiological model offer interesting perspectives from which to study the nocebo response. The term “response” should only be reserved for an active neurobiological process that occurs as a result of a dummy treatment administered in a negative psychosocial context. In particular, data fr...

Acute and chronic pain conditions are often present in elderly individuals, but only a small minority of patients with dementia are prescribed analgesics and thus, these patients may be severely undertreated for their pain. To further exacerbate the situation, even when patients with dementia receive analgesic treatment, they have shown a reduced p...

Placebo analgesia (PA) is one of the most studied placebo effects. Brain imaging studies published over the last decade, using either positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), suggest that multiple brain regions may play a pivotal role in this process. However, there continues to be much debate as to which...

The present study analyzed the awareness of deficits in 117 mild Alzheimer's disease participants. Since few studies have examined the cognitive and behavioral domains of reduced awareness in detail, we performed a domain-specific assessment using the Awareness of deficit Questionnaire - Dementia scale with the novel aim of describing the relations...

The idea of a 'pain matrix' specifically devoted to the processing of nociceptive inputs has been challenged. Alternative views now propose that the activity of the primary and secondary somatosensory cortices (SI, SII), the insula and cingulate cortex may be related to a basic defensive system through which significant potentially dangerous events...

Additional tables showing the papers involved in the study and the results of each topic-related metaanalysis. (PDF)

Additional figures and infographics. (PDF)

Subjects suffering from Parkinson’s Disease (PD) are sometimes partially or completely unaware of the deficits caused by the disease. Specifically, PD patients may complain of drug-induced dyskinesias less than their caregivers. An improved understanding of unawareness of involuntary movements in PD is important in order to appreciate the impact of...

Subjects suffering from Parkinson's Disease (PD) are sometimes partially or completely unaware of the deficits caused by the disease. Specifically, PD patients may complain of drug-induced dyskinesias less than their caregivers. An improved understanding of unawareness of involuntary movements in PD is important in order to appreciate the impact of...

In randomized clinical trials, adverse events (AEs) are reported for the drug under evaluation and compared with the placebo group. Patients who receive placebo treatment report a high frequency of AEs, but little is understood about the nature of these. No study has yet analyzed the level of cognitive impairment as a crucial aspect for the AEs rep...

Placebo analgesia (PA) is one of the most studied placebo effects. Brain imaging studies published over the last decade, using either positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), suggest that multiple brain regions may play a pivotal role in this process. However, there continues to be much debate as to which...

Placebo analgesia is mediated by both opioid and nonopioid mechanisms, but so far nothing is known about the nonopioid component. Here we show that the specific CB1 cannabinoid receptor antagonist 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (rimonabant or SR141716) blocks nonopioid placebo analge...

During this workshop we will review recent evidence regarding the neurobiology underlying placebo and nocebo hyperalgesia and discuss the potentially far reaching implications for medical practice and clinical trial design. First, we will present the data from neuroimaging studies and from experimental and clinical pain experiments revealing the n...

The concept of awareness of illness refers to the ability that people have in recognizing their disturbances. The presence of a possible unawareness of illness is well described in different clinical pathologies. The awareness of deficits may be sometimes altered in patients suffering from Parkinson's disease (PD). In order to have a greater clinic...

Unawareness of deficits is a symptom of Alzheimer's disease that can be observed even in the early stages of the disease. The frontal hypoperfusion associated with reduced awareness of deficits has led to suggestions of the existence of a hypofunctioning prefrontal pathway involving the right dorsolateral prefrontal cortex, inferior parietal lobe,...

The concept of awareness of illness refers to the ability that people have in recognizing their disturbances. The presence of a possible unawareness of illness is well described in different clinical pathologies. The awareness of deficits may be sometimes altered in patients suffering from Parkinson’s disease (PD). In order to have a greater clinic...

The large number of randomized controlled clinical trials on migraine have drawn the attention of some authors to the need to improve the design of such trials. In particular, adequate methodology is a critical issue in their planning and execution, as different methodological approaches can translate into different results. The side-effects observ...

Placebos are known to induce analgesia through the activation of μ-opioid receptors in some circumstances, such as after morphine pre-conditioning, an effect that is blocked by opioid antagonists. On the basis of the anti-opioid action of cholecystokinin, here we tested whether the activation of the cholecystokinin type-2 receptors abolishes opioid...

This study analyzed the presence of awareness of movement disorders (dyskinesias and hypokinesias) in 25 patients with Parkinson's disease (PD) and motor fluctuations (dyskinesias, wearing off, on-off fluctuations). Of the few studies that have dealt with this topic, none have analyzed the differences in the awareness of motor deficits by comparing...

In analgesic clinical trials, adverse events are reported for the painkiller under evaluation and compared with adverse events in the placebo group. Interestingly, patients who receive the placebo often report a high frequency of adverse events, but little is understood about the nature of these negative effects. In the present study, we compared t...

Some authors have hypothesized that the impaired awareness of deficits in Alzheimer's disease (AD) patients is caused by poor "online" memory self-monitoring that is related to frontal lobe dysfunctions. In the present chapter, the unawareness of the deficit in AD populations is analyzed in light of a biopsychosocial model, which takes into account...

The comprehension of non-literal language was investigated in 20 probable Alzheimer's disease (pAD) patients by comparing their performance to that of 20 matched control subjects. pAD patients were unimpaired in the comprehension of conventional metaphors and idioms. However, their performance was significantly lower in the case of non-conventional...

Despite the increasing research on placebos in recent times, little is known about the nocebo effect, a phenomenon that is opposite to the placebo effect and whereby expectations of symptom worsening play a crucial role. By studying experimental ischemic arm pain in healthy volunteers and by using a neuropharmacological approach, we found that verb...

Response expectancies have been proposed as the major determinant of placebo effects. Here we report that different expectations produce different analgesic effects which in turn can be harnessed in clinical practice. Thoracotomized patients were treated with buprenorphine on request for 3 consecutive days, together with a basal intravenous infusio...

Several studies suggest that patients with migraine respond physiologically to stress differently from controls, yet experimental data are scarce. In order to evaluate the reactivity to stress in migraine, we recorded the quantitative electroencephalogram (qEEG) during non-noxious and noxious ischaemic arm stress in two groups of healthy controls a...

Individual differences in pharmacokinetics and pharmacodynamics, the type of pain and the method of drug administration can account for the response variability to analgesics. By integrating a clinical and an experimental approach, we report here that another important source of variability is represented by individual differences in non-specific (...

We induced specific expectations of analgesia on four different parts of the body to understand how endogenous opioid systems are activated by expectancies. The left hand, right hand, left foot, and right foot were simultaneously stimulated by means of a subcutaneous injection of capsaicin, which produces a painful burning sensation. Specific expec...

Several lines of evidence indicate that placebos produce analgesia through the activation of endogenous opioid systems. Recently, we showed that placebos may also produce respiratory depressant responses, a typical side-effect of narcotics, when a subject had a prior experience of respiratory depression in the course of narcotic treatment. In the p...

We investigated the mechanisms underlying the activation of endogenous opioids in placebo analgesia by using the model of human experimental ischemic arm pain. Different types of placebo analgesic responses were evoked by means of cognitive expectation cues, drug conditioning, or a combination of both. Drug conditioning was performed by means of ei...

Cholecystokinin (CCK) is a peptide widely distributed in the central nervous system. Since its characterization in the porcine intestine, evidence has accumulated that it plays an essential role in several brain functions such as nociception, anxiety, memory, sleep and dopamine modulation. In mammalian brain, CCK is mainly found as an octapeptide (...

Although in most of the cases the placebo response appears to be unpredictable, several factors have been considered in order to explain the placebo analgesic effect. For example, it is widely recognized, albeit with little empirical evidence, that placebo analgesia is more likely to occur after a successful analgesic therapy. On the basis of this...