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.

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.

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.

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.

A Comparison of Self-Reported Impulsivity in Gambling Disorder and Bipolar Disorder.

The present study investigated self-reported impulsivity in gambling disorder (GD) and bipolar disorder (BD). Participants with GD (n = 31), BD (n = 19), and community controls (n = 68) completed diagnostic interviews and symptom severity and functioning assessments. Participants also completed the UPPS-P Impulsive Behavior Scale composed of five dimensions including urgency (i.e., acting rashly under conditions of negative or positive emotion), lack of perseverance (i.e., inability to maintain focus), lack of premeditation (i.e., inability to consider negative consequences), and sensation seeking (i.e., tendency to pursue novel and exciting activities). Multivariate analysis of variance showed overall significant differences among the diagnostic groups on the UPPS-P subscales. Follow-up analyses of variance showed that the groups differed on all subscales except sensation seeking. The gambling and bipolar groups had significantly higher levels of self-reported impulsivity on all subscales when compared to controls. In addition, the BD group showed higher levels of positive urgency when compared to the GD group. Positive and negative urgency showed the strongest association with GD and BD. Impaired emotion regulation mechanisms may underlie self-reported impulsivity in both disorders. Lack of premeditation and perseverance may be related to dysfunctional cognitive processes.

Violent video game players and non-players differ on facial emotion recognition.

Violent video game playing has been associated with both positive and negative effects on cognition. We examined whether playing two or more hours of violent video games a day, compared to not playing video games, was associated with a different pattern of recognition of five facial emotions, while controlling for general perceptual and cognitive differences that might also occur. Undergraduate students were categorized as violent video game players (n = 83) or non-gamers (n = 69) and completed a facial recognition task, consisting of an emotion recognition condition and a control condition of gender recognition. Additionally, participants completed questionnaires assessing their video game and media consumption, aggression, and mood. Violent video game players recognized fearful faces both more accurately and quickly and disgusted faces less accurately than non-gamers. Desensitization to violence, constant exposure to fear and anxiety during game playing, and the habituation to unpleasant stimuli, are possible mechanisms that could explain these results. Future research should evaluate the effects of violent video game playing on emotion processing and social cognition more broadly.

A magnetic resonance imaging family study of cortical thickness in schizophrenia.

Schizophrenia is associated with abnormalities in cortical thickness, including both thicker and thinner cortices than controls. Although less reliably than in patients, non-psychotic relatives of schizophrenia patients have also demonstrated both thicker and thinner cortices than controls, suggesting an effect of familial or genetic liability. We investigated cortical thickness in 25 schizophrenia patients, 26 adult non-psychotic first-degree biological relatives, and 23 community controls using the automated program FreeSurfer. Contrary to hypotheses, we found relatives of schizophrenia patients had greater cortical thickness in all lobes compared to patients and controls; however, this finding was not as widespread when compared to controls. In contrast, schizophrenia patients only demonstrated a thinner right fusiform region than controls and relatives. Our finding of greater thickness in adult biological relatives could represent a maladaptive abnormality or alternatively, a compensatory mechanism. Previous literature suggests that the nature of abnormalities in relatives can vary by the age of relatives and change across the developmental period. Abnormalities in patients may depend on lifestyle factors and on current and previous anti-psychotic medication use. Our results speak to the need to study various populations of patients and relatives across the lifespan to better understand different developmental periods and the impact of environmental factors. © 2015 Wiley Periodicals, Inc.

Impaired recognition of happy facial expressions in bipolar disorder.

BACKGROUND: The ability to accurately judge facial expressions is important in social interactions. Individuals with bipolar disorder have been found to be impaired in emotion recognition; however, the specifics of the impairment are unclear. This study investigated whether facial emotion recognition difficulties in bipolar disorder reflect general cognitive, or emotion-specific, impairments. Impairment in the recognition of particular emotions and the role of processing speed in facial emotion recognition were also investigated. METHODS: Clinically stable bipolar patients (n = 17) and healthy controls (n = 50) judged five facial expressions in two presentation types, time-limited and self-paced. An age recognition condition was used as an experimental control. RESULTS: Bipolar patients' overall facial recognition ability was unimpaired. However, patients' specific ability to judge happy expressions under time constraints was impaired. CONCLUSIONS: Findings suggest a deficit in happy emotion recognition impacted by processing speed. Given the limited sample size, further investigation with a larger patient sample is warranted.

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.

The hierarchical taxonomy of psychopathology and the search for neurobiological substrates of mental illness: A systematic review and roadmap for future research.

Understanding the neurobiological mechanisms involved in psychopathology has been hindered by the limitations of categorical nosologies. The Hierarchical Taxonomy of Psychopathology (HiTOP) is an alternative dimensional system for characterizing psychopathology, derived from quantitative studies of covariation among diagnoses and symptoms. HiTOP provides more promising targets for clinical neuroscience than traditional psychiatric diagnoses and can facilitate cumulative integration of existing research. We systematically reviewed 164 human neuroimaging studies with sample sizes of 194 or greater that have investigated dimensions of psychopathology classified within HiTOP. Replicated results were identified for constructs at five different levels of the hierarchy, including the overarching p-factor, the externalizing superspectrum, the thought disorder and internalizing spectra, the distress subfactor, and the depression symptom dimension. Our review highlights the potential of dimensional clinical neuroscience research and the usefulness of HiTOP while also suggesting limitations of existing work in this relatively young field. We discuss how HiTOP can be integrated synergistically with neuroscience-oriented, transdiagnostic frameworks developed by the National Institutes of Health, including the Research Domain Criteria, Addictions Neuroclinical Assessment, and the National Institute on Drug Abuse's Phenotyping Assessment Battery, and how researchers can use HiTOP to accelerate clinical neuroscience research in humans and other species. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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).

More pronounced deficits in facial emotion recognition for schizophrenia than bipolar disorder.

Schizophrenia and bipolar disorder are typically separated in diagnostic systems. Behavioral, cognitive, and brain abnormalities associated with each disorder nonetheless overlap. We evaluated the diagnostic specificity of facial emotion recognition deficits in schizophrenia and bipolar disorder to determine whether select aspects of emotion recognition differed for the two disorders. The investigation used an experimental task that included the same facial images in an emotion recognition condition and an age recognition condition (to control for processes associated with general face recognition) in 27 schizophrenia patients, 16 bipolar I patients, and 30 controls. Schizophrenia and bipolar patients exhibited both shared and distinct aspects of facial emotion recognition deficits. Schizophrenia patients had deficits in recognizing angry facial expressions compared to healthy controls and bipolar patients. Compared to control participants, both schizophrenia and bipolar patients were more likely to mislabel facial expressions of anger as fear. Given that schizophrenia patients exhibited a deficit in emotion recognition for angry faces, which did not appear due to generalized perceptual and cognitive dysfunction, improving recognition of threat-related expression may be an important intervention target to improve social functioning in schizophrenia.

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.

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.

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.

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.

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.