Blunted brain responses to neutral faces in healthy first-degree relatives of patients with schizophrenia: an image-based fMRI meta-analysis.

Schizophrenia is characterized by the misattribution of emotional significance to neutral faces, accompanied by overactivations of the limbic system. To understand the disorder's genetic and environmental contributors, investigating healthy first-degree relatives is crucial. However, inconsistent findings exist regarding their ability to recognize neutral faces, with limited research exploring the cerebral correlates of neutral face processing in this population. Thus, we here investigated brain responses to neutral face processing in healthy first-degree relatives through an image-based meta-analysis of functional magnetic resonance imaging studies. We included unthresholded group-level T-maps from 5 studies comprising a total of 120 first-degree relatives and 150 healthy controls. In sensitivity analyses, we ran a combined image- and coordinate-based meta-analysis including 7 studies (157 first-degree relatives, 207 healthy controls) aiming at testing the robustness of the results in a larger sample of studies. Our findings revealed a pattern of decreased brain responses to neutral faces in relatives compared with healthy controls, particularly in limbic areas such as the bilateral amygdala, hippocampus, and insula. The same pattern was observed in sensitivity analyses. These results contrast with the overactivations observed in patients, potentially suggesting that this trait could serve as a protective factor in healthy relatives. However, further research is necessary to test this hypothesis.

Principles and procedures for revising the hierarchical taxonomy of psychopathology.

Quantitative, empirical approaches to establishing the structure of psychopathology hold promise to improve on traditional psychiatric classification systems. The Hierarchical Taxonomy of Psychopathology (HiTOP) is a framework that summarizes the substantial and growing body of quantitative evidence on the structure of psychopathology. To achieve its aims, HiTOP must incorporate emerging research in a systematic, ongoing fashion. In this article, we describe the historical context and grounding of the principles and procedures for revising the HiTOP framework. Informed by strengths and shortcomings of previous classification systems, the proposed revisions protocol is a formalized system focused around three pillars: (a) prioritizing systematic evaluation of quantitative evidence by a set of transparent criteria and processes, (b) balancing stability with flexibility, and (c) promoting inclusion over gatekeeping in all aspects of the process. We detail how the revisions protocol will be applied in practice, including the scientific and administrative aspects of the process. Additionally, we describe areas of the HiTOP structure that will be a focus of early revisions and outline challenges for the revisions protocol moving forward. The proposed revisions protocol is designed to ensure that the HiTOP framework reflects the current state of scientific knowledge on the structure of psychopathology and fulfils its potential to advance clinical research and practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Modeling relations between event-related potential factors and broader versus narrower dimensions of externalizing psychopathology.

The organization of the Hierarchical Taxonomy of Psychopathology (HiTOP) model provides unique opportunities to evaluate whether neural risk measures operate as indicators of broader latent liabilities (e.g., externalizing proneness) or narrower expressions (e.g., antisociality and alcohol abuse). Following this approach, the current study recruited a sample of 182 participants (54% female) who completed measures of externalizing psychopathology (also internalizing) and associated traits. Participants also completed three tasks (Flanker-No Threat, Flanker-Threat, and Go/No-Go tasks) with event-related potential (ERP) measurement. Three variants of two research domain criteria (RDoC)-based neurophysiological indicators-P3 and error-related negativity (ERN)-were extracted from these tasks and used to model two latent ERP factors. Scores on these two ERP factors independently predicted externalizing factor scores when accounting for their covariance with sex-suggesting distinct neural processes contributing to the broad externalizing factor. No predictive relation with the broad internalizing factor was found for either ERP factor. Analyses at the finer-grained level revealed no unique predictive relations of either ERP factor with any specific externalizing symptom variable when accounting for the broad externalizing factor, indicating that ERN and P3 index general liability for problems in this spectrum. Overall, this study provides new insights about neural processes in externalizing psychopathology at broader and narrower levels of the HiTOP hierarchy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Are Brain Responses to Emotion a Reliable Endophenotype of Schizophrenia? An Image-Based Functional Magnetic Resonance Imaging Meta-analysis.

BACKGROUND: Impaired emotion processing constitutes a key dimension of schizophrenia and a possible endophenotype of this illness. Empirical studies consistently report poorer emotion recognition performance in patients with schizophrenia as well as in individuals at enhanced risk of schizophrenia. Functional magnetic resonance imaging studies also report consistent patterns of abnormal brain activation in response to emotional stimuli in patients, in particular, decreased amygdala activation. In contrast, brain-level abnormalities in at-risk individuals are more elusive. We address this gap using an image-based meta-analysis of the functional magnetic resonance imaging literature. METHODS: Functional magnetic resonance imaging studies investigating brain responses to negative emotional stimuli and reporting a comparison between at-risk individuals and healthy control subjects were identified. Frequentist and Bayesian voxelwise meta-analyses were performed separately, by implementing a random-effect model with unthresholded group-level T-maps from individual studies as input. RESULTS: In total, 17 studies with a cumulative total of 677 at-risk individuals and 805 healthy control subjects were included. Frequentist analyses did not reveal significant differences between at-risk individuals and healthy control subjects. Similar results were observed with Bayesian analyses, which provided strong evidence for the absence of meaningful brain activation differences across the entire brain. Region of interest analyses specifically focusing on the amygdala confirmed the lack of group differences in this region. CONCLUSIONS: These results suggest that brain activation patterns in response to emotional stimuli are unlikely to constitute a reliable endophenotype of schizophrenia. We suggest that future studies instead focus on impaired functional connectivity as an alternative and promising endophenotype.

An introduction to the basic elements of the caste system of India.

Oppression, systemic bias, and racism have unfortunately long been part of the human experience. This paper is a review of basic elements of the Indian caste system, understanding its impact on the daily lives of different caste members, the role of colonialism in perpetuating the caste system, the Indian reservation system for mitigating disadvantages created by the caste system, and how categorization and labels can affect individual identity. This paper then discusses the global relevance of the caste system and its impact on mental health and psychological functioning. In India, the caste system is a comprehensive, systematized, and institutionalized form of oppression of members of the lower castes, particularly the Dalits. Formalized during the British colonial period, the caste system brings together two related Indian concepts of varna and jati to create four social orders and multiple subunits. Sitting outside the traditional four orders are the Dalits, who experience social, economic, and religious discrimination due to an inherited status related to traditionally polluting occupations. Since the caste system extends beyond India to other South Asian countries, as well as to communities around the world that are home to the Indian diaspora, the inequities created by the caste system are a global issue. India's affirmative action system provides important insights to policy makers, as well as researchers in the social sciences for how to counteract the effects of systematized oppression. Collectively, this can aid in a better understanding of the effects of discrimination and oppression on identity, self-esteem, and mental health, and how we can develop more targeted policies and procedures in our own local contexts.

The transdiagnostic relationship of cumulative lifetime stress with memory, the hippocampus, and personality psychopathology.

Stress has a detrimental impact on memory, the hippocampus, and psychological health. Psychopathology research on stress has centered mainly on psychiatric diagnoses rather than symptom dimensions, and less attention has been given to the neurobiological factors through which stress might be translated into psychopathology. The present work investigates the transdiagnostic relationship of cumulative stress with episodic memory and the hippocampus (both structure and function) and explores the extent to which stress mediates the relationship between personality psychopathology and hippocampal size and activation. Cumulative lifetime stress was assessed in a sample of females recruited to vary in stress exposure and severity of personality psychopathology. Fifty-six participants completed subjective and objective tests of episodic memory, a T2-weighted high-resolution magnetic resonance imaging (MRI) scan of the medial-temporal lobe, and functional MRI (fMRI) scanning during a learning and recognition memory task. Higher cumulative stress was significantly related to memory complaints (but not episodic memory performance), lower bilateral hippocampal volume, and greater encoding-related hippocampal activation during the presentation of novel stimuli. Furthermore, cumulative stress significantly mediated the relationship between personality psychopathology and both hippocampal volume and activation, whereas alternative mediation models were not supported. The findings suggest that structural and functional activation differences in the hippocampus observed in case-control studies of psychiatric diagnoses may share cumulative stress as a common factor, which may mediate broadly reported relationships between psychopathology and hippocampal structure and function.

Altered activity in functional brain networks involved in lexical decision making in bipolar disorder: An fMRI case-control study.

BACKGROUND: Brain networks involved in language, attentional and response processes are detectable by fMRI during lexical decision (LD). Here, we investigated possible abnormalities in the functional networks involved in LD in patients with bipolar disorder (BD). METHODS: fMRI and behavioural data were compared between BD (n = 25) and control (n = 21), with groups matched for age and sex. The functional brain networks involved in LD were extracted by manipulating the "word-likeness" of LD stimuli and using a multidimensional analysis method. RESULTS: Attentional, response and language processes were captured in separate function-specific brain networks (default mode network, response network, linguistic processing network, respectively) in the BD and control groups, replicating the results of our previous study in an independent group of healthy adults. Behaviourally, the BD group showed higher performance than the control group in the LD task. Activity in the default mode network (DMN) and the linguistic processing network (LPN) did not differ between the groups, but the BD group had higher activation than the control group in the response network (RESP). LIMITATIONS: Due to the small sample, the study is underpowered, capable of only detecting large effects. CONCLUSIONS: The results suggest that BD may be associated with sustained activity in the RESP network, which might contribute to psychomotor dysfunction in BD. Future studies should investigate the possible link between altered RESP activation and psychomotor disturbances in BD, as well as the basis for altered RESP activity in BD.

Excellence, access, and the public good: Building socially responsive admissions practices for health science programs.

The health sciences have a public calling to provide socially responsive health care for all of society, particularly those most in need. This call is reverberating in universities and has particular relevance for health science professions. Despite universities' public mission, admissions practices in the health sciences exhibit a fundamental tension between excellence and access, with excellence defined by rankings and research productivity, and access defined by broader public access both to universities themselves and to the knowledge created there. Health science programs' popularity among students intensifies the exclusivity of admissions processes, at the expense of access. This paper presents both a psychometric and social justice critique of existing admissions criteria and processes. A psychometric perspective demonstrates that admissions processes have inherent bias and fairness issues not limited to reliance on standardized test scores, but extending to measures such as interviews, grade point averages, personal statements, recommendation letters, and CVs. Evaluating admissions criteria using a social justice lens focuses attention on procedural, background, and stake fairness, as well as practices that tend to exclude underrepresented groups. Potential improvements to admissions include applying promising practices from holistic approaches, reducing applicants' financial burden, instituting admissions criteria that more broadly represent all groups, involving underrepresented groups in adjudicating candidate applications, implementing equitable educational strategies, and evaluating the degree to which programs' climate and theoretical underpinnings are conducive to recruiting from underrepresented groups. Finally, to fulfill our public call for social responsiveness, it is essential to frame admissions to health science programs in terms of serving the public good by training candidates from underrepresented groups and by positioning excellence as access.

Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder.

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

Diffusion kurtosis imaging of white matter in bipolar disorder.

White matter pathology likely contributes to the pathogenesis of bipolar disorder (BD). Most studies of white matter in BD have used diffusion tensor imaging (DTI), but the advent of more advanced multi-shell diffusion MRI imaging offers the possibility to investigate other aspects of white matter microstructure. Diffusion kurtosis imaging (DKI) extends the DTI model and provides additional measures related to diffusion restriction. Here, we investigated white matter in BD by applying whole-brain voxel-based analysis (VBA) and a network-based connectivity approach using constrained spherical deconvolution tractography to assess differences in DKI and DTI metrics between BD (n = 25) and controls (n = 24). The VBA showed lower mean kurtosis in the corona radiata and posterior association fibers in BD. Regional differences in connectivity were indicated by lower mean kurtosis and kurtosis anisotropy in streamlines traversing the temporal and occipital lobes, and lower mean axial kurtosis in the right cerebellar, thalamo-subcortical pathways in BD. Significant differences were not seen in DTI metrics following FDR-correction. The DKI findings indicate altered connectivity across cortical, subcortical and cerebellar areas in BD. DKI is sensitive to different microstructural properties and is a useful complementary technique to DTI to more fully investigate white matter in BD.

Neurobiology and the Hierarchical Taxonomy of Psychopathology: progress toward ontogenetically informed and clinically useful nosology
.

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical structural model of psychological symptoms formulated to improve the reliability and validity of clinical assessment. Neurobiology can inform assessments of early risk and intervention strategies, and the HiTOP model has greater potential to interface with neurobiological measures than traditional categorical diagnoses given its enhanced reliability. However, one complication is that observed biological correlates of clinical symptoms can reflect various factors, ranging from dispositional risk to consequences of psychopathology. In this paper, we argue that the HiTOP model provides an optimized framework for conducting research on the biological correlates of psychopathology from an ontogenetic perspective that distinguishes among indicators of liability, current symptoms, and consequences of illness. Through this approach, neurobiological research can contribute more effectively to identifying individuals at high dispositional risk, indexing treatment-related gains, and monitoring the consequences of mental illness, consistent with the aims of the HiTOP framework.
.

La taxonomía jerárquica de la psicopatología (TJP) es un modelo estructural empírico de síntomas psicológicos propuesto para mejorar la confiabilidad y la validez de la evaluación clínica. La neurobiología puede dar cuenta de las evaluaciones de riesgo precoz y estrategias de intervención, y el modelo de TJP tiene un mayor potencial para interactuar con las mediciones neurobiológicas que los diagnósticos categoriales tradicionales dada su mayor confiabilidad. Sin embargo, una complicación es que los correlatos biológicos observados de los síntomas clínicos pueden reflejar varios factores, que van desde el riesgo de la disposición hasta las consecuencias de la psicopatología. En este artículo, se argumenta que el modelo TJP proporciona un marco optimizado para realizar investigaciones sobre los correlatos biológicos de la psicopatología desde una perspectiva ontogenética que distingue entre indicadores de responsabilidad, síntomas actuales y consecuencias de la enfermedad. A través de este enfoque, la investigación neurobiológica puede contribuir de manera más efectiva con la identificación de individuos con un alto riesgo de disposición, el registro de los beneficios del tratamiento y el monitoreo de las consecuencias de la enfermedad mental, de acuerdo con los objetivos del marco de referencia de la TJP.

La taxonomie hiérarchique de la psychopathologie (HiTOP, Hierarchical Taxonomy of Psychopathology) est un modèle empirique et structuré de symptômes psychologiques visant à améliorer la fiabilité et la validité de l'évaluation clinique. L'évaluation sur le risque précoce et les stratégies thérapeutiques peuvent bénéficier des apports de la neurobiologie ; le modèle HiTOP interagit mieux avec les mesures neurobiologiques que les diagnostics catégoriels classiques, en raison de sa plus grande fiabilité. Néanmoins, le fait que les corrélats biologiques observés des symptômes cliniques peuvent refléter différents facteurs qui vont du risque lié à la prédisposition aux conséquences de la pathologie, complique les choses. Dans cet article, nous soutenons que le cadre du modèle HiTOP est optimal pour la recherche sur les corrélats biologiques de la psychopathologie d'un point de vue ontogénétique qui distingue les indicateurs de responsabilité, les symptômes actuels et les conséquences de la maladie. Par cette approche, la recherche neurobiologique permet de mieux identifier les personnes à risque de prédisposition élevé, de mieux répertorier les bénéfices liés au traitement et de surveiller les conséquences de la maladie mentale, selon les objectifs du cadre de l'HiTOP.

A Family Study of Trauma and Coping Strategies in Gambling Disorder.

Family studies can provide a wealth of information regarding risk factors in psychological disorders. No studies have compared the trauma experiences and coping strategies of problem gamblers with those of their first-degree relatives. Therefore, in this study, childhood trauma and coping strategies were investigated among participants with gambling disorder, their first-degree biological relatives, and community controls. Participants completed diagnostic interviews and symptom severity assessments. Participants also completed the Childhood Trauma Questionnaire (CTQ) which assesses history of abuse and neglect, and the Coping Inventory for Stressful Situations (CISS) which assesses task, emotion, and avoidance oriented coping strategies. Analysis of variance showed that there was a significant effect for group, but not gender, on the CTQ. Multivariate analysis of variance revealed a significant effect for group on coping style. Post-hoc tests showed that probands and relatives were less likely to use task-oriented coping compared to controls, but probands and relatives did not differ from each other on task-oriented coping. Mediation analysis showed that task-oriented coping did not mediate the relation between childhood trauma and gambling severity. By using a family study design, this study was able for the first time to delineate familial and disease-specific effects associated with childhood trauma and coping strategies in gambling disorder.

Attitudes and Beliefs Toward Computerized Cognitive Training in the General Population.

INTRODUCTION: In recent years, computerized cognitive training (CCT) programs have been developed commercially for widespread public consumption. Despite early enthusiasm, whether these programs enhance cognitive abilities in healthy adults is a contentious area of investigation. Given the mixed findings in the literature, researchers are beginning to investigate how beliefs and attitudes toward CCT impact motivation, expectations, and gains after cognitive training. METHOD: We collected survey data from 497 North American participants from Amazon's Mechanical Turk (MTurk). This survey asked novel questions regarding respondents' beliefs about the effectiveness of CCT for improving different domains of cognition, mood, and daily life; beliefs about whether CCT programs are supported by research; and whether impressions of CCT have improved or worsened over time. Exploratory analyses are reported descriptively, while parametric tests were used to analyze a priori hypotheses. RESULTS: Almost half of the surveyed participants had used CCT, and respondents with a self-reported psychological or neurological disorder were more likely to have used CCT platforms than participants without such conditions. Motivations for using CCT included curiosity; to improve or maintain cognition; to prevent cognitive decline; and/or for enjoyment or fun. Participants believed that CCT is somewhat effective for improving mood and cognition across a variety of domains. Greater age and fewer years of education predicted perceived effectiveness of CCT. Finally, participants largely reported unchanged opinions of CCT platforms over time. CONCLUSION: Our study suggests the need for future research regarding the general population's beliefs and attitudes toward CCT, along with knowledge translation for relevant stakeholders.

The relationship between maintenance and manipulation components of working memory and prefrontal and parietal brain regions in bipolar disorder.

BACKGROUND: A domain of cognition that has been found to be impaired in bipolar disorder across mood states is working memory. Working memory can be separated into two components, maintenance and manipulation. Bipolar patients also demonstrate structural brain abnormalities in prefrontal and parietal regions, which are regions associated with working memory processes. Despite the understanding that working memory consists of multiple separable cognitive processes, no study to date has differentiated maintenance and manipulation, and associated them with underlying structural brain regions in bipolar disorder. METHODS: Twenty-six bipolar patients and 24 controls completed a visuospatial working memory task and structural neuroimaging. Prefrontal and parietal gray matter volume, surface area, and cortical thickness were obtained using FreeSurfer. The relationship between working memory performance, structural integrity, symptoms, and functioning were investigated. RESULTS: Bipolar patients were less accurate on the working memory task compared to controls, without a greater deficit in the manipulation condition. Controls had thicker prefrontal and parietal cortices than bipolar patients. In bipolar patients, thicker prefrontal cortices had a small association with greater accuracy on the maintenance condition, as well as greater depression. LIMITATIONS: This study could have benefitted from a larger sample size. CONCLUSIONS: Bipolar patients demonstrated both poorer accuracy on the visuospatial working memory task compared to controls and thinner cortices in areas associated with working memory, namely the prefrontal and parietal cortices. This demonstrates an underlying relationship between brain and behavior in bipolar disorder.

Functional brain networks involved in lexical decision.

Functional magnetic resonance imaging (fMRI)5 studies on lexical decision (LD)6 attempting to isolate the brain network underlying access to lexical representations can be confounded by attentional and response processes. However, manipulating the "wordlikeness" of the LD stimuli can facilitate functional interpretation of each emerging brain network, providing principles for separation of attentional demand from linguistic processing. This is because activation of difficult-to-access lexical representations (for obscure real words), and avoidance of interfering word properties (for wordlike non-words), are both generally attentionally demanding. Therefore, congruent patterns of activation would be predicted for general-attention-responsive networks, but opposing patterns for language-responsive networks. 59 healthy adults performed a LD task, and multidimensional functional connectivity analysis was used to extract three functional brain networks. A linguistic processing network (LPN) was separated from attention/response networks anatomically (LPN included Broca's and Wernicke's areas), but also temporally by showing reduced activation for the most attentionally demanding condition (i.e., wordlike non-words). This demonstrated that during LD in fMRI a network involved in linguistic processing can be disentangled from attention- and response-specific networks, using a combination of experimental design and multidimensional analysis methods.

Manipulating visual scanpaths during facial emotion perception modulates functional brain activation in schizophrenia patients and controls.

Individuals with schizophrenia exhibit deficits in facial emotion processing, which have been associated with abnormalities in visual gaze behavior and functional brain activation. However, the relationship between gaze behavior and brain activation in schizophrenia remains unexamined. Studies in healthy individuals and other clinical samples indicate a relationship between gaze behavior and functional activation in brain regions implicated in facial emotion processing deficits in schizophrenia (e.g., fusiform gyrus), prompting the question of whether a similar relationship exists in schizophrenia. This study examined whether manipulating visual scanpaths during facial emotion perception would modulate functional brain activation in a sample of 23 schizophrenia patients and 26 community controls. Participants underwent functional magnetic resonance imaging (MRI) while viewing pictures of emotional faces. During the typical viewing condition, a fixation cue directed participants' gaze primarily to the eyes and mouth, whereas during the atypical viewing condition gaze was directed to peripheral features. Both viewing conditions elicited a robust response throughout face-processing regions. Typical viewing led to greater activation in visual association cortex including the right inferior occipital gyrus/occipital face area, whereas atypical viewing elicited greater activation in primary visual cortex and regions involved in attentional control. There were no between-groups activation differences in response to faces or interaction between group and gaze manipulation. The results indicate that gaze behavior modulates functional activation in early face-processing regions in individuals with and without schizophrenia, suggesting that abnormal gaze behavior in schizophrenia may contribute to activation abnormalities during facial emotion perception. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Abnormal neural functions associated with motor inhibition deficits in schizophrenia and bipolar disorder.

Deficits in response inhibition have been observed in schizophrenia and bipolar disorder; however, the neural origins of the abnormalities and their relevance to genetic liability for psychosis are unknown. We used a stop-signal task to examine motor inhibition and associated neural processes in schizophrenia patients (n = 57), bipolar disorder patients (n = 21), first-degree biological relatives of patients with schizophrenia (n = 34), and healthy controls (n = 56). Schizophrenia patients demonstrated motor control deficits reflected in longer stop-signal reaction times and elongated reaction times. With the possibility of needing to inhibit a button press, both schizophrenia and bipolar disorder patients showed diminished reductions of the P300 brain response and only the healthy controls demonstrated adjustments in response execution time, as measured by response-locked lateralized readiness potentials. Schizotypal traits in the biological relatives were associated with less P300 modulation consistent with the motor-related anomalies being associated with subtle schizophrenia-spectrum symptomatology in family members. The two patient groups had elongated response selection processes as manifest in the delayed onset of the stimulus-locked lateralized readiness potential. The bipolar disorder group was unique in showing significantly diminished neural responses to the stop-signal to inhibit a response. Antipsychotic medication dosage was related to worse motor inhibition, thus motor inhibition deficits in schizophrenia may be partially explained by the effect of pharmacological agents. Failed modulation of brain processes in relation to response inhibition probability and the lengthening of motor response selection appear to be transdiagnostic abnormalities spanning schizophrenia and bipolar disorder.

The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder.

BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.