Clozapine modulates retinoid homeostasis in human brain and normalizes serum retinoic acid deficit in patients with schizophrenia.

The atypical antipsychotic clozapine is one of the most potent drugs of its class, yet its precise mechanisms of action remain insufficiently understood. Recent evidence points toward the involvement of endogenous retinoic acid (RA) signaling in the pathophysiology of schizophrenia. Here we investigated whether clozapine may modulate RA-signaling. Effects of clozapine on the catabolism of all-trans RA (at-RA), the biologically most active metabolite of Vitamin A, were assessed in murine and human brain tissue and peripheral blood-derived mononuclear cells (PBMC). In patients with schizophrenia with and without clozapine treatment and matched healthy controls, at-RA serum levels and blood mRNA expression of retinoid-related genes in PBMCs were quantified. Clozapine and its metabolites potently inhibited RA catabolism at clinically relevant concentrations. In PBMC-derived microsomes, we found a large interindividual variability of the sensitivity toward the effects of clozapine. Furthermore, at-RA and retinol serum levels were significantly lower in patients with schizophrenia compared with matched healthy controls. Patients treated with clozapine exhibited significantly higher at-RA serum levels compared with patients treated with other antipsychotics, while retinol levels did not differ between treatment groups. Similarly, in patients without clozapine treatment, mRNA expression of RA-inducible targets CYP26A and STRA6, as well as at-RA/retinol ratio, were significantly reduced. In contrast, clozapine-treated patients did not differ from healthy controls in this regard. Our findings provide the first evidence for altered peripheral retinoid homeostasis in schizophrenia and suggest modulation of RA catabolism as a novel mechanism of action of clozapine, which may be useful in future antipsychotic drug development.

Impact and differences of illness course perception on the desire for social distance towards people with symptoms of depression or schizophrenia in Hanoi, Vietnam.

OBJECTIVES: Public stigma against psychiatric disorders leads to delayed treatment utilization and worsens treatment outcome. This study analyses the impact of expectations regarding the course of illness and attribution as medical illness on the desire for social distance towards schizophrenia and depression in Vietnam. METHODS: In 2013, a survey (n = 771) using unlabelled vignettes either depicting a person with symptoms typical for schizophrenia or major depression was carried out in Hanoi. All respondents had to indicate whether the person was suffering from a medical illness or not. As an indicator of public stigma, the desire for social distance was measured. A possible correlation between expectations towards the course of illness and social distance was evaluated using a linear regression model. RESULTS: 85 % of respondents endorsed that the person depicted in the schizophrenia vignette had a mental illness, compared to only 60 %, who were confronted with the depression vignette. This attribution of mental illness was correlated with higher levels of desire for social distance only in the schizophrenia vignette. While in the case of schizophrenia negative prognostic perceptions were associated with more desire for social distance, in the event of depression, it was only the expectation of lifelong dependency. Moreover, only for depression, positive expectations towards the course of illness correlated with less desire for social distance. CONCLUSION: These results indicate an impact of prognostic expectations on the desire for social distance and support strategies that aim at maintaining social integration and strengthening autonomy.

Mental Health Determinants Among a Psychiatric Outpatient Sample of Vietnamese Migrants in Germany.

Background: Mental health risk-factors for Asian migrants have been studied almost exclusively in the US, Canada, and Australia but not in European countries. Therefore, we aimed to identify sociodemographic, clinical, and migration-surrounding factors associated with experienced mental distress among Vietnamese migrants in Germany. Method: 305 Vietnamese migrants utilizing Germany's first Vietnamese psychiatric outpatient clinic filled out at admission the Brief-Symptom-Inventory 18 (BSI-18) as well as a questionnaire on 22 potential mental health determinants. Using a multiple linear regression model, we identified those sociodemographic, clinical, and migration-surrounding factors that were significantly related to the Global Severity Index (GSI) of the BSI-18. Results: The factors unemployment (B = -6.32, p = 0.014), financial problems (B = -10.71, p < 0.001), no or only little religious involvement (B = -3.23, p = 0.002), no psychiatric precontact (B = -7.35, p = 0.004), previous migration experiences (B = 8.76, p = 0.002), and perceived discrimination (B = 6.58, p = 0.011) were found to significantly increase the level of mental distress according to the BSI-GSI. Conclusion: Based on these results, we were able to construct a mental health risk-profile for Vietnamese migrants in Germany, which aims to detect candidates for psychiatric problems earlier and supply them with customized prevention and therapy options.

The relationship between causal beliefs and desire for social distance towards people with schizophrenia and depression: Results from a survey of young Ghanaian adults.

This study examines attitudes of the young Ghanaian population regarding the relationship between causal beliefs and desire for social distance from people with symptoms of schizophrenia and depression. Respondents (n = 507) were presented with depression and schizophrenia symptoms using unlabeled case vignettes. A factor analysis examined three factors for causal beliefs, and multiple linear regression analysis on the desire for social distance was conducted. The desire for social distance was higher when symptoms in both case-vignettes were attributed to childhood adversities and overall lower when respondents lived in northern regions of Ghana. Only, for vignettes depicting schizophrenia, mental illness attribution was associated with more desire for social distance. Significant gender effects were found for depression vignettes only: female respondents reported significantly more desire for social distance, whereas female gendered vignettes were associated with less desire for social distance by respondents of both genders.

Treatment recommendation differences for schizophrenia and major depression: a population-based study in a Vietnamese cohort.

BACKGROUND: In Vietnam, the mental health care infrastructure is on the verge of transformation with an increase in the demand for access to adequate and effective mental health care services. Public attitudes towards mental illness, as well as corresponding treatment options influence help-seeking behaviors of patients and caregivers, affecting the course of their treatment. This study assesses attitudes towards treatment options for depression and schizophrenia, as the two most common psychiatric disorders in Vietnam, accounting for at least 75% of all psychiatric inpatients. METHODS: A general population-based survey was conducted in Hanoi, Vietnam between April and August 2013. Participants received a description of a person with symptoms of either depression (n = 326) or schizophrenia (n = 403) and were asked to give recommendations for adequate sources of mental health support and treatment options. Multiple analyses on a single item level compared the likelihood of recommendation between schizophrenia and depression. RESULTS: Overall, respondents recommended health care services, ranging from seeking mental health care professionals, psychotherapists, and psychiatrists for both disorders. Psychotherapy was the most favored treatment method, whereas further treatment options, such as concentration and relaxation exercises, meditation or yoga and psychotropic medication were also endorsed as helpful. For the schizophrenia vignette condition, psychotherapy, visiting a psychiatrist or psychotherapist received stronger endorsement rates as compared to the depression vignette. Furthermore, ECT, Feng Shui-based practices, praying and visiting natural healers were recommended less by respondents for the depression vignette in comparison with the schizophrenia vignette. CONCLUSIONS: The Vietnamese public endorsed evidence-based treatment recommendations from a variety of treatments options. Differences in the treatment recommendations between depression and schizophrenia reflected the perceived severity of each disorder. Further developments of the Vietnamese mental health care system concerning mental health care providers, as well as the legal regulations surrounding the provision of psychotherapy are needed.

Impact of perceived course of illness on the desire for social distance towards people with symptoms of schizophrenia in Hanoi, Vietnam.

In Vietnam, stigmatisation and discrimination of patients with mental illness are highly prevalent. This study explores whether the perception of course of illness of people with symptoms indicating schizophrenia is associated with the desire for social distance in the Vietnamese public. A population-based survey (n = 455) using unlabelled vignettes for schizophrenia was carried out in the Hanoi municipality in 2013. First, a factor analysis was performed to group items indicating perception of prognosis. Second, a linear regression analysis was used to search for correlations between these expectations and desire for social distance. The factor analysis revealed three independent factors of perception of course of illness: (1) loss of social integration and functioning, (2) lifelong dependency on others, and (3) positive expectations towards treatment outcome. Both factors with negative prognostic perceptions (1&2) were associated with more desire for social distance. The results indicate a link between social acceptance and the perceived ability to maintain a social role including a capability of reciprocity within the Vietnamese society. Additionally, these findings highlight the importance of preserving social functioning in any treatment approach for patients with schizophrenia, which includes psychosocial intervention and rehabilitation programs.

Perceived stigmatization and discrimination of people with mental illness: A survey-based study of the general population in five metropolitan cities in India.

BACKGROUND: India faces a significant gap between the prevalence of mental illness among the population and the availability and effectiveness of mental health care in providing adequate treatment. This discrepancy results in structural stigma toward mental illness which in turn is one of the main reasons for a persistence of the treatment gap, whereas societal factors such as religion, education, and family structures play critical roles. This survey-based study investigates perceived stigma toward mental illness in five metropolitan cities in India and explores the roles of relevant sociodemographic factors. MATERIALS AND METHODS: Samples were collected in five metropolitan cities in India including Chennai (n = 166), Kolkata (n = 158), Hyderabad (n = 139), Lucknow (n = 183), and Mumbai (n = 278). Stratified quota sampling was used to match the general population concerning age, gender, and religion. Further, sociodemographic variables such as educational attainment and strength of religious beliefs were included in the statistical analysis. RESULTS: Participants displayed overall high levels of perceived stigma. Multiple linear regression analysis found a significant effect of gender (P < 0.01), with female participants showing higher levels of perceived stigma compared to male counterparts. CONCLUSION: Gender differences in cultural and societal roles and expectations could account for higher levels of perceived stigma among female participants. A higher level of perceived stigma among female participants is attributed to cultural norms and female roles within a family or broader social system. This study underlines that while India as a country in transition, societal and gender rules still impact perceived stigma and discrimination of people with mental illness.

Public attitude towards restrictions on persons with mental illness in greater Hanoi area, Vietnam.

BACKGROUND AND AIMS: In recent years, there has been a growing awareness of the need to protect human rights in psychiatry. Within the last years, considerable effort has been made to reduce restrictive measures in mental health settings. Reducing restrictive measures within mental health care has also moved increasingly into the focus of public debate. This study aims, for the first time in a Southeast Asian sample, to explore whether socio-demographic factors affect public attitudes toward restrictions on mentally ill people in Hanoi, Vietnam. METHODS: A general population-based survey (self-report questionnaire) was carried out in 2013 in the greater Hanoi area. The survey sample ( N = 813) was recruited according to the latest published census (2009) and micro-census (2013) in Vietnam and Hanoi with regard to the socio-demographic factors gender, age, urbanity, household size and marital status. Multinomial logistic regressions for odds ratios with 95% confidence intervals were calculated to examine the influence of epidemiological variables, like gender and age, on the public attitude toward restrictions imposed on mentally ill people in Vietnam. RESULTS: This study found, for the first time in a large Vietnamese sample, that gender and age were associated with public attitudes toward restrictions on mentally ill people. In detail, significantly fewer men endorsed compulsory admission to a hospital and abortion than Vietnamese women. In addition, endorsement of abortion was significantly higher in older people. CONCLUSION: The results offer some insight into roles of women in the Vietnamese society and might reflect the traditional gender expectations in Vietnamese families. Moreover, the results emphasize the need for supporting female psychiatric patients and their families within their communities and in the Vietnamese society.

Public attitudes towards psychiatrists in the metropolitan area of Hanoi, Vietnam.

OBJECTIVES: Mental health associated stigmatization remains problematic in low and middle-income countries, thus preventing patients from adequate access to psychiatric care. Public attitudes towards psychiatrists have not been examined in many countries, especially not in Vietnam where merely one psychiatrist per 300.000 population is available. The study aims to explore attitudes towards psychiatrists in the Hanoi municipality and to identify socio-demographical factors that influence these attitudes. METHODS: Between April and August 2013, a general population-based survey was carried out in the greater Hanoi area, Vietnam. The sample of 817 participants was stratified according to the latest Vietnamese census (2009) and micro-census (2013) with regards to socio-demographic factors. Multivariate analyses were conducted to determine the influence of these factors on attitudes towards psychiatrists. RESULTS: Gender and religious beliefs significantly influenced public attitudes towards psychiatrists. Male participants reported significantly more negative perception towards psychiatrists compared to female respondents. Participants following a religion reported significantly more negative attitudes toward psychiatrists than those without self-reported religious attainment. CONCLUSIONS: Negative attitudes towards psychiatrists are associated with religious beliefs and gender affiliation in the greater Hanoi area. A strategy that involves religious institutions in raising awareness about mental health issues while considering public's socio-cultural attitudes may pave the way for greater potentialities of adequate psychiatric care, destigmatize the mental health system, and care provider.

Attitude toward psychiatrists and psychiatric medication: A survey from five metropolitan cities in India.

BACKGROUND: Stigmatization and overall scarcity of psychiatrists and other mental health-care professionals remain a huge public health challenge in low- and middle-income countries, more specifically in India. Most patients seek help from faith healers, and awareness about psychiatrists and treatment methods is often lacking. Our study aims to explore public attitudes toward psychiatrists and psychiatric medication in five Indian metropolitan cities and to identify factors that could influence these attitudes. MATERIALS AND METHODS: Explorative surveys in the context of public attitudes toward psychiatrists and psychiatric medication were conducted using five convenience samples from the general population in Chennai (n = 166), Kolkata (n = 158), Hyderabad (n = 139), Lucknow (n = 183), and Mumbai (n = 278). We used a quota sample with respect to age, gender, and religion using the census data from India as a reference. RESULTS: Mean scores indicate that attitudes toward psychiatrists and psychiatric medication are overall negative in urban India. Negative attitudes toward psychiatrists were associated with lower age, lower education, and strong religious beliefs. Negative attitudes toward psychotropic medication were associated with lower age, male gender, lower education, and religion. CONCLUSION: In line with the National Mental Health Policy of India, our results support the perception that stigma is widespread. Innovative public health strategies are needed to improve the image of psychiatrists and psychiatric treatment in society and ultimately fill the treatment gap in mental health.

Acculturation and severity of depression among first-generation Vietnamese outpatients in Germany.

BACKGROUND: Challenges of migration, particularly concerning the process of acculturation are associated with an increased risk of mental illness. Vietnamese migrants constitute the largest Southeast Asian migrant group in Germany, yet there is no data on the relationship between the mental health status and acculturation among this population. AIMS: Therefore, the present study examines the relationship between two well-established dimensions of acculturation, that is, dominant society immersion (DSI) and ethnic society immersion (ESI), the four resulting acculturation strategies (integration, assimilation, separation and marginalization), and severity of depression. METHODS: A sample of N = 113 first-generation Vietnamese outpatients from a psychiatric outpatient clinic for Vietnamese migrants in Germany was studied regarding their self-reported depressive symptoms (Beck Depression Inventory-II (BDI-II)) and acculturation (Stephenson Multigroup Acculturation Scale (SMAS)). RESULTS: Consistent with the hypotheses, patients reported less severe depressive symptoms, when they reported higher orientation toward the German and the Vietnamese society. Moreover, the results showed that integrated patients reported a lower severity of depression compared to marginalized patients, who reported the highest severity of depression. CONCLUSIONS: The findings indicate that among a sample of first-generation Vietnamese patients with depression, an orientation to both, the mainstream society and one's heritage society might serve as a potential resource. The rejection of any orientation to any society is associated with an increased risk for depression.

Cultural differences in symptom representation for depression and somatization measured by the PHQ between Vietnamese and German psychiatric outpatients.

OBJECTIVE: Despite an extensive body of research on somatic symptom presentation among people of East- and Southeast-Asian descent, results are still inconclusive. Examining and comparing symptom presentation in clinically and ethnically well-characterized populations may constitute a step towards understanding symptom presentation between patients with a different cultural background. This study aims to compare Vietnamese and German patients regarding cultural dynamics of symptom presentation upon first admission to a psychiatric outpatient service. METHODS: 110 Vietnamese and 109 German patients seeking psychiatric treatment at two outpatient clinics completed the Patient Health Questionnaire (PHQ). The somatic symptom subscale (PHQ-15), the depression subscale (PHQ-9) and PHQ-subscales examining anxiety and psychosocial stress levels were analyzed and compared for both groups using multivariate analysis of covariance. Regression analysis was utilized to examine the influences of sociodemographic and migration specific factors. RESULTS: Vietnamese and German patients showed comparable Cronbach's alpha for all subscales. Vietnamese patients endorsed significantly higher levels of somatic symptoms overall and on certain items (as pain-related items, dizziness, and fainting spells) despite similar levels of depression severity in comparison with German patients. Vietnamese patients with poor German language skills showed a significantly higher focus on somatic symptoms. CONCLUSION: Raising awareness for cultural dynamics of symptom presentation in patients with depression is indispensable. Cross-cultural symptom assessment using the PHQ seems feasible and expands our understanding of depressive and psychosomatic symptoms when assessed by clinicians.

Migration-Related Stressors and Their Effect on the Severity Level and Symptom Pattern of Depression among Vietnamese in Germany.

OBJECTIVES: Vietnamese in Germany represent a scarcely researched and vulnerable group for mental health problems, especially under exposure to migration-related stressors (MRS). This study analyzes the effect of those MRS on the severity level and symptom pattern of depression. DESIGN: We analyzed the data of 137 depressed Vietnamese patients utilizing Germany's first Vietnamese psychiatric outpatient clinic. Hierarchical linear regression models were applied to investigate how the quantity of MRS influenced (1) the overall severity of self-reported depression symptoms; (2) the cognitive, affective, and somatic BDI-II subscale; and (3) the single BDI-II items of these subscales. RESULTS: A greater number of MRS were related to a higher severity level of depression in general, as well as to a higher level on the cognitive depression subscale in particular. The BDI-II single items pessimism, past failure, guilt feelings, punishment feelings, and suicidal thoughts were particularly associated with a higher quantity of perceived MRS. CONCLUSION: Among depressed Vietnamese migrants in Germany, a higher number of reported MRS were associated with higher overall depression severity. Within the domains of depression, particularly the cognitive domain was linked to perceived MRS. The association between MRS and suicidal thoughts is clinically highly relevant.

Hypothalamic-Pituitary-Adrenocortical Dysfunction in Elderly, Male Marathon Runners: Feedback Sensitivity, Stress Response, and Effects on Verbal Memory.

Animal studies suggest that repeated episodes of elevated glucocorticoids lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) system at a suprapituitary level, and to impaired mnemonic function. We compared cognitive tests, as well as feedback integrity and stress responsivity of the HPA system, between 11 elderly, male marathon runners - a model of repeated HPA system activation - and 10 sedentary controls. The marathon runners had significantly increased baseline, stress, and post-stress ACTH - but not cortisol - concentrations. Also, suppression of ACTH by 3 mg dexamethasone was impaired in the athletes compared to the control subjects, while the ACTH and cortisol response to additional CRH did not differ between the 2 groups. Finally, long-term verbal memory was impaired in the athletes compared to the controls. Regarding the HPA system, these findings are in accordance with an acquired suprapituitary feedback disturbance in marathon runners; however, the similar glucocorticoid concentrations in the 2 groups may be due to reduced adrenal sensitivity to ACTH. Together with impaired verbal memory, these data support the assumption that repeated episodes of HPA system activity may exert negative effects at the level of the hippocampus.

Clozapine-induced agranulocytosis: Evidence for an immune-mediated mechanism from a patient-specific in-vitro approach.

Use of the atypical antipsychotic clozapine (CZP) is compromised by the risk of potentially fatal agranulocytosis/granulocytopenia (CIAG). To address this, we have established a simple, personalized cell culture-based strategy to identify CIAG-susceptible patients, hypothesizing that an immunogenic and possibly haptene-based mechanism underlies CIAG pathophysiology. To detect a putative haptene-induced response to CZP in vitro exposure, a traditional lymphocyte stimulation assay was adapted and applied to patient-specific peripheral blood-derived mononuclear cells (PBMC). 6 patients with a history of CIAG, 6 patients under CZP treatment (without CIAG) and 12 matched healthy controls were studied. In vitro CZP exposure, even at strikingly low levels, resulted in significantly increased proliferation rates only in CIAG patients' PBMC. Other parameters including cell viability and mitogen-induced proliferation were also affected by in vitro CZP exposure, yet there was no significant difference between the groups. This personalized approach is a starting point for further investigations into a putative haptene-based mechanism underlying CIAG development, and may facilitate the future development of predictive testing.

Influence of urbanity on perception of mental illness stigma: a population based study in urban and rural Hanoi, Vietnam.

BACKGROUND AND AIMS: To examine, for the first time in Vietnam, whether urbanity of respondents among other socio-demographic factors affects the public perception of stigma attached to persons with mental illness in Hanoi. METHODS: A general population-based survey was carried out in 2013 in the greater Hanoi area. The perception of stigma attached to people with mental illness was elicited using Link's perceived discrimination and devaluation scale (PDDS) carried out in Vietnamese language. The survey sample (n = 806) was stratified for gender, urban/rural location, age, household size and marital status, in accordance with the 2013 Vietnamese census. RESULTS: Comparing the total score of the PDDS and its single items, we found less perceived stigma and discrimination among the rural population of Hanoi and in respondents who reported religious attainment to either Buddhism or Christianity. Logistic regression analyses found no significant influences of gender, age, household size or marital status regarding the perceived stigma toward persons with mental illness. CONCLUSION: Less negative perception of stigma attached to persons with mental illness that was observed among the rural population in the Hanoi area may be interpreted in the light of possibly more demanding living conditions in modern urban Vietnam with less opportunities for mentally ill patients and points toward a dynamic interaction with rapidly changing living conditions in Asian megacities.

Attitude towards psychiatrists: A comparison between two metropolitan cities in India.

BACKGROUND: Few patients in need of mental health care have access to psychiatric care in low and middle income countries. Public attitudes towards psychiatrists have not been adequately studied in most developing countries and especially in India, where on average one trained psychiatrist is available for 300,000 people. The aim of our study was to explore attitudes towards psychiatrists in the general population in two Indian metropolitan cities (Chennai and Kolkata) and to identify factors that could influence these attitudes. SUBJECTS AND METHODS: Explorative surveys in the context of public attitudes towards psychiatrists were conducted in a convenience sample from the general population in Chennai (n=166) and Kolkata (n=158). Sampling was balanced for age, gender and school education. RESULTS: Comparing the two samples using a multivariate analysis, we found more negative attitudes towards psychiatrists in Chennai compared to Kolkata (p<0.0001). Negative attitudes correlated with lower education levels (p<0.001) and stronger religious beliefs (p<0.05) in both cities. CONCLUSION: Attitudes towards psychiatrists differed widely between two large metropolitan cities in India. In line with previous studies, negative attitudes correlated with lower level of education and stronger religious beliefs across both cities. Future studies may identify finer cultural and social factors that play an important role in attitudes towards psychiatrists in a diverse country like India.

Perceived stigma of mental illness: A comparison between two metropolitan cities in India.

PURPOSE: An increasing number of comparative studies are conducted on the stigmatization of persons with mental illness, in particular with regard to regional and diachronic variation. So far, there have been no studies comparing stigmatization of persons with mental illness in two different regions of India. Therefore, we examined the differences in perception of stigma attached to mental illnesses in Kolkata and Chennai, with regard to cultural and geographical differences to better understand the roots and origins of this issue. MATERIALS AND METHODS: Explorative surveys in the context of public attitudes toward people with mental disorders were conducted among conveniently selected members of the general population in Chennai (n = 166) and Kolkata (n = 158) with identical methodology. Link's perceived devaluation-discrimination measure was used. The samples were matched for age, gender, and education. RESULTS: The calculated sum score indicated that respondents from Kolkata had a higher level of perceived discrimination toward persons with mental illness than respondents from Chennai (P = 0.043). Furthermore, regression analysis revealed that lower perceived stigma was associated with stronger religious devotion (P = 0.049) and higher educational attainment (P = 0.001) in both cities. DISCUSSION: The results showed that perceived stigma was higher in Kolkata than in Chennai. The correlation of higher stigma with lower education was in line with the previous research, and interestingly, it was found that higher stigma correlated with weaker religious devotion. Further studies exploring a wider variety of factors may provide us with a better understanding of the roots of perceived stigma in India.

Mirror neuron deficit in schizophrenia: Evidence from repetition suppression.

BACKGROUND: Schizophrenia is associated with impaired cognition, especially cognition in social contexts. The mirror neuron system (MNS) serves as an important neuronal basis for social cognitive skills; however, previous investigations on the integrity of MNS function in schizophrenia remain approximate. METHODS: We employed a repetition suppression paradigm that allows for measuring neuronal responses to gesture observation and gesture execution. Cross-modal repetition suppression, i.e., adaptation between observe/execute and execute/observe conditions, was defined as the decisive experimental condition characterizing the unique sensori-motor properties of mirror neurons. Event-related potentials (ERPs) were assessed in 15 schizophrenia patients and 15 matched controls. RESULTS: We isolated an ERP signature of specific adaptation effects to identical hand gestures. Of critical importance, this ERP signature indicated intact intra-modal adaptive pattern, i.e., observe/observe and execute/execute, of comparable magnitude between groups, but deficient cross-modal adaptation, i.e., observe/execute and execute/observe, in schizophrenia patients. CONCLUSION: Our data provide robust evidence that pure perception and execution of hand gestures are relatively intact in schizophrenia. In contrast, visuo-motor transformation processes mediated by the MNS seem to be specifically disturbed in schizophrenia. These results unambiguously demonstrate MNS deficits in schizophrenia and extend our understanding of the neuronal bases of social dysfunction in this disorder.