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OBJECTIVES: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well-characterized individuals with BD in North America, Europe, and Australia. METHODS: Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta-analyses with generalized linear mixed methods were conducted to identify prescription patterns. RESULTS: This study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD-I (60%; vs. BD-II = 33%). Cross-sectionally, mood-stabilizing anticonvulsants (44%), second-generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First-generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD-II (47%) compared to BD-I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort. CONCLUSIONS: Mood-stabilizing anticonvulsants, second-generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first-generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence-based guidelines to help improve treatment practices in BD.
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Antipsicóticos , Transtorno Bipolar , Humanos , Feminino , Masculino , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/diagnóstico , Lítio/uso terapêutico , Anticonvulsivantes/uso terapêutico , Austrália/epidemiologia , Antipsicóticos/uso terapêutico , Antidepressivos/uso terapêuticoRESUMO
OBJECTIVES: Although there is a common clinical assumption that bipolar disorder with psychotic features reflects greater severity than bipolar disorder without psychosis, the existing empirical literature is mixed. This study investigated the phenomenology of psychosis as well as demographic, clinical, functional, and neuropsychological features in a large, cross-sectional sample of participants with bipolar disorder divided by history of psychosis. METHODS: In a large single study, 168 affective-only bipolar disorder (BP-A) participants and 213 bipolar disorder with a history of psychosis (BP-P) participants completed a comprehensive clinical diagnostic interview and neuropsychological testing. t tests, chi-square tests, and Bayes factors were used to investigate group differences or lack thereof. RESULTS: The prevalence of psychosis in this sample (53%) was similar to published reports. Nearly half of BP-P participants experienced grandiose delusions, and relatively few endorsed "first-rank" hallucinations of running commentary or two or more voices conversing. There were no demographic or neuropsychological differences between groups. BP-A participants experienced greater chronicity of affective symptoms and a greater degree of rapid cycling than BP-P participants; there were no other clinical differences between groups. CONCLUSIONS: Overall, these results contradict the conventional notion that bipolar disorder with psychotic features represents a more severe illness than bipolar disorder without a history of psychosis. The presence of psychosis does not appear to be associated with poorer clinical/functional outcome or suggest a greater degree of neuropsychological impairment; conversely, the absence of psychosis was associated with affective chronicity and rapid cycling. Nosological and treatment implications are discussed.
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Transtorno Bipolar , Transtornos Psicóticos , Adulto , Sintomas Afetivos/diagnóstico , Teorema de Bayes , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Estudos Transversais , Gerenciamento Clínico , Feminino , Humanos , Entrevista Psicológica/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prevalência , Prognóstico , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologiaRESUMO
OBJECTIVES: Deficits in social cognition predict poor functional outcome in severe mental illnesses such as schizophrenia and autism. However, research findings on social cognition in bipolar disorder (BD) are sparse and inconsistent. This study aimed to characterize a critical social cognitive process-eye gaze perception-and examine its functional correlates in BD to inform psychopathological mechanisms. METHODS: Thirty participants with BD, 37 healthy controls (HC), and 46 psychiatric controls with schizophrenia (SZ) completed an eye-contact perception task. They viewed faces with varying gaze directions, head orientations, and emotion, and made eye-contact judgments. Psychophysics methods were used to estimate perception thresholds and the slope of the perception curve, which were then compared between the groups and correlated with clinical and functional measures using Bayesian inference. RESULTS: Compared with HC, patients with BD over-perceived eye contact when gaze direction was ambiguous, and this self-referential bias was similar to that in SZ. Patients with BD had lower thresholds (i.e., needed weaker eye-contact signal to start perceiving gaze as self-directed) but a similar slope compared with HC. Regression analyses showed that steeper slope predicted better socio-emotional functioning in HC and SZ, but not in BD. CONCLUSIONS: The psychopathology of social dysfunction was fundamentally different between BD and SZ in this modest sample. Eye gaze perception in BD was characterized by a self-referential bias but preserved perceptual sensitivity, the latter of which distinguished BD from SZ. The relationship between gaze perception and broader socio-emotional functioning in SZ and HC was absent in BD.
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Transtorno Bipolar , Fixação Ocular , Esquizofrenia/diagnóstico , Comportamento Social , Percepção Social , Adulto , Teorema de Bayes , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Diagnóstico Diferencial , Inteligência Emocional , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
OBJECTIVES: Altered social behavior during mood episodes in bipolar disorder often has detrimental and long-lasting interpersonal consequences. Abnormal face processing may play a role in linking brain functions to clinical symptoms and behavior. This study aimed to understand configural face processing in bipolar disorder as a function of basic communicative attributes of the face and mood symptoms using event-related brain potentials (ERPs). METHODS: Forty-two participants with bipolar I disorder (BP) and 43 healthy controls (HC) viewed face stimuli varying in emotion (neutral or fearful), head orientation (forward or deviated), and gaze direction (direct or averted) while ERPs were recorded. Configural face processing was indexed by the N170 wave. RESULTS: BP participants had comparable overall N170 amplitude and peak latency to HC, although timing was more variable in the BP group. Abnormal N170 modulations by communicative face attributes were observed in BP: exaggerated sensitivity to emotion (fearful > neutral) in the left hemisphere, and reduced sensitivity to gaze-head incongruency (where N170 is normally larger in response to faces with incongruent than congruent gaze and head direction) in the right hemisphere. The former was not associated with mood symptoms, suggesting a heightened trait-like sensitivity to negative emotions. The latter was correlated with greater manic symptoms, indicating that an impaired perceptual sensitivity to faces with features signaling incongruent social attention may underlie social deficits observed during mania. CONCLUSIONS: These findings suggest a pathophysiological role of altered configural face processing in the phenomenology of bipolar disorder, and call for further investigations to evaluate its potential as a biomarker and treatment target.
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Background and Hypothesis: Individuals with schizophrenia (SZ) and bipolar disorder (BD) show disruptions in self-referential gaze perception-a social perceptual process related to symptoms and functioning. However, our current mechanistic understanding of these dysfunctions and relationships is imprecise. Study Design: The present study used mathematical modeling to uncover cognitive processes driving gaze perception abnormalities in SZ and BD, and how they relate to cognition, symptoms, and social functioning. We modeled the behavior of 28 SZ, 38 BD, and 34 controls (HC) in a self-referential gaze perception task using drift-diffusion models (DDM) parameterized to index key cognitive components: drift rate (evidence accumulation efficiency), drift bias (perceptual bias), start point (expectation bias), threshold separation (response caution), and non- decision time (encoding/motor processes). Study Results: Results revealed that aberrant gaze perception in SZ and BD was driven by less efficient evidence accumulation, perceptual biases predisposing self-referential responses, and greater caution (SZ only). Across SZ and HC, poorer social functioning was related to greater expectation biases. Within SZ, perceptual and expectancy biases were associated with hallucination and delusion severity, respectively. Conclusions: These findings indicate that diminished evidence accumulation and perceptual biases may underlie altered gaze perception in patients and that SZ may engage in compensatory cautiousness, sacrificing response speed to preserve accuracy. Moreover, biases at the belief and perceptual levels may relate to symptoms and functioning. Computational modeling can, therefore, be used to achieve a more nuanced, cognitive process-level understanding of the mechanisms of social cognitive difficulties, including gaze perception, in individuals with SZ and BD.
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BACKGROUND: Individuals with schizophrenia (SZ) experience impairments in social cognition that contribute to poor functional outcomes. However, mechanisms of social cognitive dysfunction in SZ remain poorly understood, which impedes the design of novel interventions to improve outcomes. This pre-registered project (https://doi.org/10.17605/OSF.IO/JH5FC) examines the representation of social cognition in the brain's functional architecture across early and chronic SZ. METHODS: The study contains two parts: a confirmatory and an exploratory portion. In the confirmatory portion, we identified resting-state connectivity disruptions evident in early and chronic SZ. We performed a connectivity analysis using regions associated with social cognitive dysfunction in early and chronic SZ to test whether aberrant connectivity observed in chronic SZ (N=47; HC=52) was also present in early SZ (N=71, HC=47). In the exploratory portion, we assessed the out-of-sample generalizability and precision of predictive models of social cognition. We used machine learning to predict social cognition and established generalizability with out-of-sample testing and confound control. RESULTS: Results reveal decreases between left inferior frontal gyrus and intraparietal sulcus in early and chronic SZ, which are significantly associated with social and general cognition and global functioning in chronic SZ and with general cognition and global functioning in early SZ. Predictive modeling reveals the importance of out-of-sample evaluation and confound control. CONCLUSION: This work provides insights into the functional architecture in early and chronic SZ and suggests that IFG-IPS connectivity could be a prognostic biomarker of social impairments and a target for future interventions (e.g. neuromodulation) focused on improved social functioning.
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BACKGROUND: A critical unanswered question about therapeutic transcranial magnetic stimulation is what patients should do during treatment to optimize its effectiveness. Here, we address this lack of knowledge in healthy participants, testing the hypotheses that stimulating the left dorsolateral prefrontal cortex (dlPFC) while participants perform a working memory task will provide stronger effects on subsequent activation, perfusion, connectivity, and performance than stimulating resting dlPFC. METHODS: After a baseline functional magnetic resonance imaging session to localize dlPFC activation and the associated frontoparietal network (FPN) engaged by an n-back task, healthy participants (N = 40, 67.5% female) underwent 3 counterbalanced sessions, separated by several weeks, during which they received intermittent theta burst stimulation (iTBS) followed by magnetic resonance imaging scans as follows: 1) iTBS to the dlPFC while resting passively (passive), 2) iTBS to the dlPFC while performing the n-back task (active), and 3) iTBS to a vertex site, while not engaged in the n-back task and resting passively (control). RESULTS: We found no difference in n-back performance between the 3 conditions. However, FPN activation was reduced while performing the n-back task in the active condition relative to the passive and control conditions. There was no differential activity in the FPN on comparing passive with control conditions, i.e., there was no effect of the site of stimulation. We found no effects of state or site of stimulation on perfusion or connectivity with the dlPFC. CONCLUSIONS: In this study, the state of the brain while receiving iTBS affected FPN activation, possibly reflecting greater efficiency of FPN network activation when participants were stimulated while engaging the FPN.
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Córtex Pré-Frontal , Estimulação Magnética Transcraniana , Humanos , Feminino , Masculino , Estimulação Magnética Transcraniana/métodos , Córtex Pré-Frontal/fisiologia , Córtex Cerebral , Imageamento por Ressonância Magnética , Memória de Curto Prazo/fisiologiaRESUMO
Importance: Alcohol use disorder (AUD) is present in nearly half of individuals with bipolar disorder (BD) and is associated with markedly worsening outcomes. Yet, the concurrent treatment of BD and AUD remains neglected in both research and clinical care; characterizing their dynamic interplay is crucial in improving outcomes. Objective: To characterize the longitudinal alcohol use patterns in BD and examine the temporal associations among alcohol use, mood, anxiety, and functioning over time. Design, Setting, and Participants: This cohort study selected participants and analyzed data from the Prechter Longitudinal Study of Bipolar Disorder (PLS-BD), an ongoing cohort study that recruits through psychiatric clinics, mental health centers, and community outreach events across Michigan and collects repeated phenotypic data. Participants selected for the present study were those with a diagnosis of BD type I (BDI) or type II (BDII) who had been in the study for at least 5 years. Data used were extracted from February 2006 to April 2022, and follow-up ranged from 5 to 16 years. Main Outcomes and Measures: Alcohol use was measured using the Alcohol Use Disorders Identification Test. Depression, mania or hypomania, anxiety, and functioning were measured using the 9-Item Patient Health Questionnaire, the Altman Self-Rating Mania Scale, the 7-item Generalized Anxiety Disorder assessment scale, and the Life Functioning Questionnaire, respectively. Results: A total of 584 individuals (386 females (66.1%); mean [SD] age, 40 [13.6] years) were included. These participants had a BDI (445 [76.2%]) or BDII (139 [23.8%]) diagnosis, with or without a lifetime diagnosis of AUD, and a median (IQR) follow-up of 9 (0-16) years. More problematic alcohol use was associated with worse depressive (ß = 0.04; 95% credibility interval [CrI], 0.01-0.07) and manic or hypomanic symptoms (ß = 0.04; 95% CrI, 0.01-0.07) as well as lower workplace functioning (ß = 0.03; 95% CrI, 0.00-0.06) over the next 6 months, but increased depressive and manic or hypomanic symptoms were not associated with greater subsequent alcohol use. These latter 2 associations were more pronounced in BDII than BDI (mania or hypomania: ß = 0.16 [95% CrI, 0.02-0.30]; workplace functioning: ß = 0.26 [95% CrI, 0.06-0.45]). Alcohol use was not associated with anxiety over time. Conclusions and Relevance: This study found that alcohol use, regardless of diagnostic status, was associated with mood instability and poorer work functioning in BD, but increased mood symptoms were not associated with subsequent alcohol use. Given its prevalence and repercussions, dimensional and longitudinal assessment and management of alcohol use are necessary and should be integrated into research and standard treatment of BD.
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Consumo de Bebidas Alcoólicas , Transtorno Bipolar , Humanos , Transtorno Bipolar/psicologia , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/complicações , Feminino , Masculino , Adulto , Estudos Longitudinais , Pessoa de Meia-Idade , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/epidemiologia , Alcoolismo/psicologia , Alcoolismo/complicações , Afeto , Michigan/epidemiologia , Ansiedade/epidemiologia , Ansiedade/psicologiaRESUMO
BACKGROUND AND HYPOTHESIS: Corollary discharge (CD) signals are "copies" of motor signals sent to sensory areas to predict the corresponding input. They are a posited mechanism enabling one to distinguish actions generated by oneself vs external forces. Consequently, altered CD is a hypothesized mechanism for agency disturbances in psychosis. Previous studies have shown a decreased influence of CD signals on visual perception in individuals with schizophrenia-particularly in those with more severe positive symptoms. We therefore hypothesized that altered CD may be a trans-diagnostic mechanism of psychosis. STUDY DESIGN: We examined oculomotor CD (using the blanking task) in 49 participants with schizophrenia or schizoaffective disorder (SZ), 36 bipolar participants with psychosis (BPP), and 40 healthy controls (HC). Participants made a saccade to a visual target. Upon saccade initiation, the target disappeared and reappeared at a horizontally displaced position. Participants indicated the direction of displacement. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of pre-saccadic target to inform perception. Thus, multi-level modeling was used to examine the influence of target displacement and saccade landing site on displacement judgements. STUDY RESULTS: SZ and BPP were equally less sensitive to target displacement than HC. Moreover, regardless of diagnosis, SZ and BPP with more severe positive symptoms were more likely to rely on saccade landing site. CONCLUSIONS: These results suggest that altered CD may be a trans-diagnostic mechanism of psychosis.
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Transtorno Bipolar , Transtornos Psicóticos , Esquizofrenia , Humanos , Transtornos Psicóticos/fisiopatologia , Masculino , Feminino , Adulto , Esquizofrenia/fisiopatologia , Pessoa de Meia-Idade , Transtorno Bipolar/fisiopatologia , Movimentos Sacádicos/fisiologia , Percepção Visual/fisiologia , Adulto JovemRESUMO
BACKGROUND: Treatments for cognitive dysfunction in neuropsychiatric conditions are urgently needed. Cognitive training and transcranial direct current stimulation (tDCS) hold promise, and there is growing interest in combined or multimodal treatments, though studies to date have had small samples and inconsistent results. METHODS: A systematic review and meta-analysis was completed. Retained studies included cognitive training combined with active or sham tDCS in a neuropsychiatric population and reported a posttreatment cognitive outcome. Meta-analyses included effect sizes comparing cognitive training plus active tDCS and cognitive training plus sham tDCS in 5 cognitive domains. Risk of bias in included studies and across studies was explored. RESULTS: Fifteen studies were included: 10 in neurodegenerative disorders and 5 in psychiatric disorders (n = 629). There were several tDCS montages, though two-thirds of studies placed the anode over the left dorsolateral prefrontal cortex. A wide variety of cognitive training types and outcome measures were reported. There was a small, statistically significant effect of combined treatment on measures of attention/working memory, as well as small and non-statistically significant effects favoring combined treatment on global cognition and language. There was no evidence of bias in individual studies but some evidence of nonreporting or small-study bias across studies. CONCLUSIONS: These results may provide preliminary support for the efficacy of combined cognitive training and tDCS on measures of attention/working memory. More data are needed, particularly via studies that explicitly align the cognitive ability of interest, stimulation target, training type, and outcome measures.
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Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Treino Cognitivo , Córtex Pré-Frontal , Cognição/fisiologia , Memória de Curto Prazo/fisiologiaRESUMO
In this work, we expand the normative model repository introduced in Rutherford et al., 2022a to include normative models charting lifespan trajectories of structural surface area and brain functional connectivity, measured using two unique resting-state network atlases (Yeo-17 and Smith-10), and an updated online platform for transferring these models to new data sources. We showcase the value of these models with a head-to-head comparison between the features output by normative modeling and raw data features in several benchmarking tasks: mass univariate group difference testing (schizophrenia versus control), classification (schizophrenia versus control), and regression (predicting general cognitive ability). Across all benchmarks, we show the advantage of using normative modeling features, with the strongest statistically significant results demonstrated in the group difference testing and classification tasks. We intend for these accessible resources to facilitate the wider adoption of normative modeling across the neuroimaging community.
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Imageamento por Ressonância Magnética , Esquizofrenia , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , NeuroimagemRESUMO
Impaired social cognition is common in bipolar disorder (BD) and predicts poor functional outcomes. A critical determinant of social cognition is the ability to discriminate others' gaze direction, and its alteration may contribute to functional impairment in BD. However, the neural mechanisms underlying gaze processing in BD are unclear. Because neural oscillations are crucial neurobiological mechanisms supporting cognition, we aimed to understand their role in gaze processing in BD. Using electroencephalography (EEG) data recorded during a gaze discrimination task for 38 BD and 34 controls (HC), we examined: theta and gamma power over bilateral posterior and midline anterior locations associated with early face processing and higher-level cognitive processing, and theta-gamma phase-amplitude coupling (PAC) between locations. Compared to HC, BD showed reduced midline-anterior and left-posterior theta power, and diminished bottom-up/top-down theta-gamma PAC between anterior/posterior sites. Reduced theta power and theta-gamma PAC related to slower response times. These findings suggest that altered theta oscillations and anterior-posterior cross-frequency coupling between areas associated with higher-level cognition and early face processing may underlie impaired gaze processing in BD. This is a crucial step towards translational research that may inform novel social cognitive interventions (e.g., neuromodulation to target specific oscillatory dynamics) to improve functioning in BD.
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Transtorno Bipolar , Disfunção Cognitiva , Humanos , Eletroencefalografia , Cognição/fisiologia , Tempo de ReaçãoRESUMO
BACKGROUND: Patients with schizophrenia show abnormal gaze processing, which is associated with social dysfunction. These abnormalities are related to aberrant connectivity among brain regions that are associated with visual processing, social cognition, and cognitive control. In this study, we investigated 1) how effective connectivity during gaze processing is disrupted in schizophrenia and 2) how this may contribute to social dysfunction and clinical symptoms. METHODS: Thirty-nine patients with schizophrenia/schizoaffective disorder (SZ) and 33 healthy control participants completed an eye gaze processing task during functional magnetic resonance imaging. Participants viewed faces with different gaze angles and performed explicit and implicit gaze processing. Four brain regions-the secondary visual cortex, posterior superior temporal sulcus, inferior parietal lobule, and posterior medial frontal cortex-were identified as nodes for dynamic causal modeling analysis. RESULTS: Both the SZ and healthy control groups showed similar model structures for general gaze processing. Explicit gaze discrimination led to changes in effective connectivity, including stronger excitatory, bottom-up connections from the secondary visual cortex to the posterior superior temporal sulcus and inferior parietal lobule and inhibitory, top-down connections from the posterior medial frontal cortex to the secondary visual cortex. Group differences in top-down modulation from the posterior medial frontal cortex to the posterior superior temporal sulcus and inferior parietal lobule were noted, such that these inhibitory connections were attenuated in the healthy control group but further strengthened in the SZ group. Connectivity was associated with social dysfunction and symptom severity. CONCLUSIONS: The SZ group showed notably stronger top-down inhibition during explicit gaze discrimination, which was associated with more social dysfunction but less severe symptoms among patients. These findings help pinpoint neural mechanisms of aberrant gaze processing and may serve as future targets for interventions that combine neuromodulation with social cognitive training.
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Fixação Ocular , Esquizofrenia , Humanos , Interação Social , Encéfalo , Lobo TemporalRESUMO
Interoception refers to the processing, integration, and interpretation of bodily signals by the brain. Interoception is key to not only basic survival, but also motivational and affective functioning. There is emerging evidence suggesting altered interoception in schizophrenia, but few studies have explored potential neural underpinnings. The current study aims to investigate the anatomical connectivity of a previously identified interoception network in individuals with schizophrenia, and the relationship between network structural connectivity and both emotional functioning and clinical symptoms. Thirty-five participants with schizophrenia (SZ) and 36 healthy control participants (HC) underwent diffusion tensor imaging (DTI) and performed tasks measuring emotional functioning. Probabilistic tractography was used to identify white matter tracts connecting key hubs in an interoception network. Microstructural integrity of these tracts was compared across groups and correlated with measures of emotional functioning and symptom severity. Compared with HC, SZ exhibited altered structural connectivity in the interoception network. In HC, the structural connectivity of the network was significantly correlated with emotion recognition, supporting a link between the interoception network and emotional functioning. However, this correlation was much weaker in SZ. These findings suggest that altered interoception may have implications for illness mechanisms of schizophrenia, especially in relation to emotional deficits.
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Interocepção , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagemRESUMO
Individuals with bipolar I disorder (BD) have difficulty inhibiting context-inappropriate responses. However, neural mechanisms of impaired cognitive control over impulsive behaviors, especially in response to emotion, are unclear. Theta-band neural oscillatory activity over midfrontal areas is thought to reflect cognitive control. The current study examined behavioral performance and theta-band activity during inhibition to affective stimuli in BD, relative to healthy control participants (HC). Sixty-seven participants with BD and 48 HC completed a Go/No-Go task with emotional face stimuli during electroencephalography (EEG) recording. Behavior was measured with reaction time, discriminability (d') and response bias (ß). Time-frequency decomposition of EEG data was used to extract event-related theta-band (4-7 Hz) neural oscillatory power and inter-trial phase consistency (ITPC) over midline fronto-central areas. Behavior and theta-band activity were compared between groups, while covarying for age. Participants with BD exhibited slower response execution times on correct Go trials and reduced behavioral discrimination of emotional versus neutral faces, compared to HC. Theta-band power and ITPC were reduced in BD relative to HC. Theta-band power was higher on No-Go trials than Go trials. The magnitude of differences in theta-band activity between Go/No-Go trial types did not differ between groups. Increased theta-band power was associated with faster response execution times, greater discrimination of differing facial expressions, and stronger tendency to respond both across the full sample and within the BD group. Attenuated midline fronto-central theta-band activity may contribute to reduced cognitive control and maladaptive behavioral responding to emotional cues in individuals with BD.
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Transtorno Bipolar , Humanos , Transtorno Bipolar/psicologia , Eletroencefalografia , Emoções/fisiologia , Tempo de Reação , Cognição , Ritmo Teta/fisiologiaRESUMO
BACKGROUND: Response monitoring, as reflected in electroencephalogram recordings after commission of errors, has been consistently shown to be abnormally enhanced in individuals with obsessive-compulsive disorder (OCD). This has traditionally been quantified as error-related negativity (ERN) and may reflect abnormal neurophysiological mechanisms underlying OCD. However, the ERN reflects the increase in phase-locked activities, particularly in the theta-band (4-8 Hz), and does not reflect non-phase-locked activities. To more broadly investigate midfrontal theta activity in a brain region that is essential for complex cognition, this study investigated theta abnormalities during response monitoring in participants with OCD to acheive a better understanding of the mechanism underlying the ERN. METHODS: Electroencephalogram data were recorded from 99 participants with pediatric OCD and 99 sex- and age-matched healthy control participants while they completed the arrow flanker task. Effects of group (OCD, healthy control) and response type (error, correct) on postresponse theta total power and intertrial phase coherence (ITPC) were examined using mixed analysis of covariance and Bayesian analyses controlling for sex and accuracy. RESULTS: Theta total power was larger on error than on correct trials and larger in OCD than healthy control participants, but there was no effect of response type between groups. Theta ITPC was larger on error than correct trials, but there was no group difference or response type difference between the groups. Correlations of theta total power and ITPC with clinical measures were overall small. CONCLUSIONS: Abnormally enhanced midfrontal theta total power, but not ITPC, may reflect ineffective heightened response monitoring or compensatory activity in pediatric OCD.
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Transtorno Obsessivo-Compulsivo , Ritmo Teta , Transtorno Obsessivo-Compulsivo/fisiopatologia , Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Cognição , Fatores de Tempo , Potenciais EvocadosRESUMO
BACKGROUND: Gaze perception is a basic building block of social cognition, which is impaired in schizophrenia (SZ) and contributes to functional outcomes. Few studies, however, have investigated neural underpinnings of gaze perception and their relation to social cognition. We address this gap. METHOD: We recruited 77 SZ patients and 71 healthy controls, who completed various social-cognition tasks. During functional magnetic resonance imaging, participants (62 SZ, 54 controls) completed a gaze-perception task, where they judged whether faces with varying gaze angles were self-directed or averted; as a control condition, participants identified stimulus gender. Activation estimates were extracted based on (a) task versus baseline, (b) gaze-perception versus gender-identification, (c) parametric modulation by perception of stimuli as self-directed versus averted, and (d) parametric modulation by stimulus gaze angle. We used latent variable analysis to test associations among diagnostic group, brain activation, gaze perception, and social cognition. RESULTS: Preferential activation to gaze perception was observed throughout dorsomedial prefrontal cortex, superior temporal sulcus, and insula. Activation was modulated by stimulus gaze angle and perception of stimuli as self-directed versus averted. More precise gaze perception and higher task-related activation were associated with better social cognition. Patients with SZ showed hyperactivation within left pre-/postcentral gyrus, which was associated with more precise gaze perception and fewer symptoms and thus may be a compensatory mechanism. CONCLUSIONS: Neural and behavioral indices of gaze perception were related to social cognition, across patients and controls. This suggests gaze perception is an important perceptual building block for more complex social cognition. Results are discussed in the context of dimensional psychopathology and clinical heterogeneity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Esquizofrenia , Humanos , Cognição Social , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Sistema Nervoso , Mapeamento EncefálicoRESUMO
Recreational cannabis use has recently gained considerable interest as an environmental risk factor that triggers the onset of psychosis. To date, however, the evidence that cannabis is associated with negative outcomes in individuals at clinical high risk (CHR) for psychosis is inconsistent. The present study tracked cannabis usage over a 2-year period and examined its associations with clinical and neurocognitive outcomes, along with medication rates. CHR youth who continuously used cannabis had higher neurocognition and social functioning over time, and decreased medication usage, relative to non-users. Surprisingly, clinical symptoms improved over time despite the medication decreases.
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Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data (n = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (≥5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs.
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Bipolar disorder (BD) is associated with excessive pleasure-seeking risk-taking behaviors that often characterize its clinical presentation. However, the mechanisms of risk-taking behavior are not well-understood in BD. Recent data suggest prior substance use disorder (SUD) in BD may represent certain trait-level vulnerabilities for risky behavior. This study examined the mechanisms of risk-taking and the role of SUD in BD via mathematical modeling of behavior on the Balloon Analogue Risk Task (BART). Three groups-18 euthymic BD with prior SUD (BD+), 15 euthymic BD without prior SUD (BD-), and 33 healthy comparisons (HC)-completed the BART. We modeled behavior using 4 competing hierarchical Bayesian models, and model comparison results favored the Exponential-Weight Mean-Variance (EWMV) model, which encompasses and delineates five cognitive components of risk-taking: prior belief, learning rate, risk preference, loss aversion, and behavioral consistency. Both BD groups, regardless of SUD history, showed lower behavioral consistency than HC. BD+ exhibited more pessimistic prior beliefs (relative to BD- and HC) and reduced loss aversion (relative to HC) during risk-taking on the BART. Traditional measures of risk-taking on the BART (adjusted pumps, total points, total pops) detected no group differences. These findings suggest that reduced behavioral consistency is a crucial feature of risky decision-making in BD and that SUD history in BD may signal additional trait vulnerabilities for risky behavior even when mood symptoms and substance use are in remission. This study also underscores the value of using mathematical modeling to understand behavior in research on complex disorders like BD.