Urvakhsh Meherwan Mehta

Mirror neuron dysfunction in schizophrenia and its functional implications: A systematic review

Dysfunctional mirror neuron activity (MNA) has been posited to underlie diverse symptoms of schizophrenia (e.g., ego-boundary disturbances, negative symptoms, social cognition impairments and catatonic symptoms). In this paper, we systematically review studies that have empirically compared putative MNA in schizophrenia patients and healthy subjects using different neurophysiological probes. Majority of the studies (n=9) reported reduced MNA in patients. Two each reported either increased MNA or mixed (both increased and decreased) results, while only one study reported normal findings. Reduced MNA was associated with greater negative symptoms and theory of mind deficits. The neurophysiological technique, task paradigms used, specific brain regions studied and laterality did not influence these findings. Further, we propose an overarching model to understand the heterogeneous symptom dimensions of schizophrenia, in which an inherent mirror system deficit underlying persistent negative symptoms, social cognition impairments and self-monitoring deficits triggers a pathological metaplastic reorganization of this system resulting in aberrant excessive MNA and the phasic catatonic symptoms, affective instability and hallucinations. Despite being preliminary in nature, evidence of abnormal MNA in schizophrenia reported necessitates more detailed investigation. Future research directions of using this model within the Research Domain Criteria framework of the National Institute of Mental Health are discussed.

Schizophrenia patients experience substantial social cognition deficits across multiple domains in remission

Knowledge about SC (social cognition) during remission would inform us whether such deficits are trait- or state-markers of the disorder, as well as highlight its relevance for rehabilitation. We aimed to compare SC deficits and their relative independence from NC (neuro-cognition) deficits in remitted schizophrenia patients and matched health controls using comprehensive, culturally sensitive standardized tools. 60 schizophrenia patients meeting modified standardized criteria for remission and 60 age, gender and education matched healthy controls were compared on culturally validated tests of SC-Social Cognition Rating Tool in Indian Setting (SOCRATIS) & Tool for Recognition of Emotions in Neuropsychiatric Disorders (TRENDS) to assess theory of mind, attributional bias, social perception and emotion recognition and NC-(attention/vigilance, speed of processing, visual and verbal learning, working memory and executive functions). Patients had deficits in both SC and NC compared to healthy controls. Deficits in SC were largely independent of NC performance, and SC deficits persisted after adjusting for deficits in NC function. The effect sizes (Cohens d) for SC deficits ranged from 0.37 to 2.23. All patients scored below a defined cut-off in at least one SC domain. SC deficits are likely to be state-independent in schizophrenia, as they are present in remission phase of the illness. This supports their status as a possible composite-endophenotype in schizophrenia.

Validation of Social Cognition Rating Tools in Indian Setting (SOCRATIS): A new test-battery to assess social cognition

Social cognition is a cognitive domain that is under substantial cultural influence. There are no culturally appropriate standardized tools in India to comprehensively test social cognition. This study describes validation of tools for three social cognition constructs: theory of mind, social perception and attributional bias. Theory of mind tests included adaptations of, (a) two first order tasks [Sally-Anne and Smarties task], (b) two second order tasks [Ice cream van and Missing cookies story], (c) two metaphor-irony tasks and (d) the faux pas recognition test. Internal, Personal, and Situational Attributions Questionnaire (IPSAQ) and Social Cue Recognition Test were adapted to assess attributional bias and social perception, respectively. These tests were first modified to suit the Indian cultural context without changing the constructs to be tested. A panel of experts then rated the tests on likert scales as to (1) whether the modified tasks tested the same construct as in the original and (2) whether they were culturally appropriate. The modified tests were then administered to groups of actively symptomatic and remitted schizophrenia patients as well as healthy comparison subjects. All tests of the Social Cognition Rating Tools in Indian Setting had good content validity and known groups validity. In addition, the social cure recognition test in Indian setting had good internal consistency and concurrent validity.

Neurocognitive predictors of social cognition in remitted schizophrenia

Knowledge of how specific neurocognition (NC) abilities predict social cognition (SC) in schizophrenia has potential to guide novel integrated cognitive-remediation therapies. The scope of studies conducted in this field is limited as they have not examined a comprehensive set of SC domains and they employ small sample sizes of heterogeneous patient groups. We studied a broad range of NC (sustained attention, processing speed, verbal/visual memory and visual processing/encoding, cognitive flexibility and planning) and SC [different levels of theory of mind (ToM)], attributional bias, emotion recognition and social perception] abilities in 170 remitted schizophrenia patients. Multivariate regression analyses revealed attention and planning as predictors of 1st order ToM. Memory encoding was the strongest predictor of 2nd order ToM. Faux-pas recognition, social perception and emotion recognition were influenced by a combination of cognitive flexibility and memory encoding abilities. Overall, NC predicted anywhere between ~4% and 40% of variance observed in specific SC sub-dimensions of attributional bias (4%), 1st order (19%) and 2nd order (12%) theory of mind, faux-pas recognition (28%), social perception (29%) and emotion recognition (39%). Individual SC abilities are predicted by distinctive as well as shared NC abilities. These findings have important implications for integrated cognitive remediation.

Similar and contrasting dimensions of social cognition in schizophrenia and healthy subjects

Schizophrenia patients experience substantial impairments in social cognition (SC) and these deficits are associated with their poor functional outcome. Though SC is consistently shown to emerge as a cognitive dimension distinct from neurocognition, the dimensionality of SC is poorly understood. Moreover, comparing the components of SC between schizophrenia patients and healthy comparison subjects would provide specific insights on the construct validity of SC. We conducted principal component analyses of eight SC test scores (representing four domains of SC, namely, theory of mind, emotion processing, social perception and attributional bias) independently in 170 remitted schizophrenia patients and 111 matched healthy comparison subjects. We also conducted regression analyses to evaluate the relative contribution of individual SC components to other symptom dimensions, which are important clinical determinants of functional outcome (i.e., neurocognition, negative symptoms, motivational deficits and insight) in schizophrenia. A three-factor solution representing socio-emotional processing, social-inferential ability and external attribution components emerged in the patient group that accounted for 64.43% of the variance. In contrast, a two-factor solution representing socio-emotional processing and social-inferential ability was derived in the healthy comparison group that explained 56.5% of the variance. In the patient group, the social-inferential component predicted negative symptoms and motivational deficits. Our results suggest the presence of a multidimensional SC construct. The dimensionality of SC observed across the two groups, though not identical, displayed important parallels. Individual components also demonstrated distinct patterns of association with other symptom dimensions, thus supporting their external validity.

Cascading and combined effects of cognitive deficits and residual symptoms on functional outcome in schizophrenia - A path-analytical approach.

Understanding the complex relationship among determinants of real-world functioning in schizophrenia patients in remission is important in planning recovery-oriented interventions. We explored two path-analytical models of functioning in schizophrenia. 170 Schizophrenia patients remitted from positive symptoms underwent fairly comprehensive assessments of cognition - neurocognition (NC) and social cognition (SC), residual symptoms - insight, motivation and other negative symptoms, and socio-occupational functioning. We explored (a) a cascading model, where NC predicted functional outcome through its effects on other determinants and (b) a combined model, incorporating additional direct paths from each of the determinants. The combined model, and not the cascading model demonstrated a good fit. Post-hoc trimming of the combined model by elimination of non-significant paths maintained the goodness-of-fit and was retained as the final model. In addition to the direct paths, this final model demonstrated that (a) NC influenced functioning through SC and insight and (b) SC influenced functioning through motivation and negative symptoms. This suggests that NC and SC may influence functional outcome directly, as well as indirectly, via specific impact on insight, and motivation and negative symptoms respectively.

Negative symptoms mediate the influence of theory of mind on functional status in schizophrenia

We aimed to assess the relationship between social cognition, neurocognition, negative symptoms and functional status in a homogeneous schizophrenia patient group remitted from positive symptoms. Sixty patients underwent assessments of social and neurocognition dimensions recommended by expert panels. A blind rater assessed their functional status. Second order theory of mind (ToM) and negative symptoms had significant correlations with functional status. A bootstrapping analysis used to test for specific mediation models revealed that the effect of second order ToM on functioning was mediated by negative symptoms. Future studies should examine if targeted remediation of ToM improves negative symptoms and thus functioning.

Bridging the schism of schizophrenia through yoga—Review of putative mechanisms

Abstract Schizophrenia patients experience a ‘disconnect’ at multiple levels—neuronal networks, mental processes, and interpersonal relationships. The resultant poor quality-of-life and functional disability are related to the persistent cognitive deficits and negative symptoms, which are rather resistant to conventional antipsychotic medications. Yoga has emerged as an important therapeutic intervention to improve quality-of-life in schizophrenia. Recent preliminary evidence suggests that effects of yoga on cognitive and negative symptoms may drive this benefit. This study attempts to integrate evidence from neuroscience-based research, which focuses on the neuroplasticity-harnessing effects of yoga to bridge the schizophrenia connectopathy. In an overarching model to study putative neurobiological mechanisms that drive therapeutic effects of yoga, it is proposed that (a) various styles of meditation may help in strengthening the lateral and medial prefrontal brain networks, thus improving neurocognition and mentalizing abilities, and (b) learning and performing co-ordinated physical postures with a teacher facilitates imitation and the process of being imitated, which can improve social cognition and empathy through reinforcement of the premotor and parietal mirror neuron system. Oxytocin may play a role in mediating these processes, leading to better social connectedness and social outcomes. Clinical and heuristic implications of this model are further discussed.

Asian Indians in America: The influence of values and culture on mental health

Asian Indians represent a significant portion of the largest growing race of Asians in the past decade in the United States. This selective review examines major cultural themes related to first- and second-generation Asian Indians living in the United States as they impact psychological and psychiatric dysfunction in this population. Specifically, we review the impact of Asian Indian culture on mental health, discuss the impact of acculturation and ethnic identity development on the mental health of Indian-Americans, and focus on typical mental health problems of Asian Indian adolescents, women and elderly in America. Finally, we provide a brief overview of empirically-supported treatment approaches and cultural considerations for additional treatments relevant to this population. This review is intended to provide an important foundation for more systematic empirically-driven investigation into better understanding how Asian Indian cultural themes impact mental health for Indian-Americans, and how to develop effective treatments for these issues in this cultural group.

Association of intracortical inhibition with social cognition deficits in schizophrenia: Findings from a transcranial magnetic stimulation study

Abnormal cortical-inhibition has been hypothesized to underlie social-cognition deficits in schizophrenia. Studies using transcranial magnetic stimulation (TMS) as a neurophysiological probe have demonstrated cortical-inhibition deficits in this group. We compared TMS-measured short- and long-interval intracortical-inhibition (SICI & LICI) in antipsychotic-naïve (n=33) and medicated (n=21) schizophrenia patients and in healthy comparison subjects (n=45). We also studied the association between cortical-inhibition and social-cognition deficits in the patients. Antipsychotic-naïve patients had significant deficits in SICI (i.e., less inhibitory response). In this group, SICI had significant inverse correlations with emotion processing and a global social-cognition score. Impaired intracortical-inhibition may thus contribute to social-cognition deficits in schizophrenia.