المؤلفون: Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A, Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Díaz-Caneja, Covadonga M, Gurholt, Tiril P, Hegarty, Catherine E, James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G, Karlsgodt, Katherine H, Kochunov, Peter, Lois, Noemi G, Lundberg, Mathias, Myhre, Anne M, Pascual-Diaz, Saül, Piras, Fabrizio, Smelror, Runar E, Spalletta, Gianfranco, Stokkan, Therese S, Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I, Tordesillas-Gutiérrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A, Thompson, Paul M, Agartz, Ingrid

المصدر: Molecular Psychiatry. 28(3)

مصطلحات موضوعية: Brain Disorders, Serious Mental Illness, Pediatric, Biomedical Imaging, Clinical Research, Neurosciences, Mental Health, Schizophrenia, Mental health, Good Health and Well Being, Female, Humans, Male, Adolescent, White Matter, Diffusion Tensor Imaging, Brain, Psychotic Disorders, Anisotropy, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry

الوصف: Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8d58g44gTest

المؤلفون: Millard, Samuel J, Bearden, Carrie E, Karlsgodt, Katherine H, Sharpe, Melissa J

المصدر: Neuropsychopharmacology. 47(3)

مصطلحات موضوعية: Serious Mental Illness, Basic Behavioral and Social Science, Neurosciences, Brain Disorders, Schizophrenia, Behavioral and Social Science, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Mental health, Dopamine, Humans, Psychotic Disorders, Reinforcement, Psychology, Reward, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry

الوصف: Schizophrenia is a severe psychiatric disorder affecting 21 million people worldwide. People with schizophrenia suffer from symptoms including psychosis and delusions, apathy, anhedonia, and cognitive deficits. Strikingly, schizophrenia is characterised by a learning paradox involving difficulties learning from rewarding events, whilst simultaneously 'overlearning' about irrelevant or neutral information. While dysfunction in dopaminergic signalling has long been linked to the pathophysiology of schizophrenia, a cohesive framework that accounts for this learning paradox remains elusive. Recently, there has been an explosion of new research investigating how dopamine contributes to reinforcement learning, which illustrates that midbrain dopamine contributes in complex ways to reinforcement learning, not previously envisioned. This new data brings new possibilities for how dopamine signalling contributes to the symptomatology of schizophrenia. Building on recent work, we present a new neural framework for how we might envision specific dopamine circuits contributing to this learning paradox in schizophrenia in the context of models of reinforcement learning. Further, we discuss avenues of preclinical research with the use of cutting-edge neuroscience techniques where aspects of this model may be tested. Ultimately, it is hoped that this review will spur to action more research utilising specific reinforcement learning paradigms in preclinical models of schizophrenia, to reconcile seemingly disparate symptomatology and develop more efficient therapeutics.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5ht6r5w1Test

المؤلفون: Gurholt, Tiril P, Lonning, Vera, Nerland, Stener, Jørgensen, Kjetil N, Haukvik, Unn K, Alloza, Clara, Arango, Celso, Barth, Claudia, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Dandash, Orwa, Díaz-Caneja, Covadonga M, Edbom, Carl T, van Erp, Theo GM, Fett, Anne-Kathrin J, Frangou, Sophia, Goldstein, Benjamin I, Grigorian, Anahit, Jahanshad, Neda, James, Anthony C, Janssen, Joost, Johannessen, Cecilie, Karlsgodt, Katherine H, Kempton, Matthew J, Kochunov, Peter, Krabbendam, Lydia, Kyriakopoulos, Marinos, Lundberg, Mathias, MacIntosh, Bradley J, Rund, Bjørn Rishovd, Smelror, Runar E, Sultan, Alysha, Tamnes, Christian K, Thomopoulos, Sophia I, Vajdi, Ariana, Wedervang-Resell, Kirsten, Myhre, Anne M, Andreassen, Ole A, Thompson, Paul M, Agartz, Ingrid, ENIGMA-EOP Working Group

المصدر: Human brain mapping. 43(1)

مصطلحات موضوعية: ENIGMA-EOP Working Group, Brain, Hippocampus, Globus Pallidus, Humans, Magnetic Resonance Imaging, Adolescent Development, Affective Disorders, Psychotic, Psychotic Disorders, Schizophrenia, Age of Onset, Adolescent, adolescence, antipsychotics, brain structure, early-onset, intracranial volume, psychosis spectrum, Mental Health, Clinical Research, Serious Mental Illness, Biomedical Imaging, Brain Disorders, Pediatric, Pediatric Research Initiative, Neurosciences, Mental health, Good Health and Well Being, Cognitive Sciences, Experimental Psychology

الوصف: Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9sk054mxTest

المؤلفون: Jalal, Rhideeta, Nair, Aarti, Lin, Amy, Eckfeld, Ariel, Kushan, Leila, Zinberg, Jamie, Karlsgodt, Katherine H, Cannon, Tyrone D, Bearden, Carrie E

المصدر: Journal of Neurodevelopmental Disorders. 13(1)

مصطلحات موضوعية: Neurosciences, Autism, Behavioral and Social Science, Brain Disorders, Mental Health, Intellectual and Developmental Disabilities (IDD), Clinical Research, Basic Behavioral and Social Science, Pediatric, Aetiology, 2.3 Psychological, social and economic factors, Mental health, Adolescent, Autism Spectrum Disorder, Child, Cognition, DiGeorge Syndrome, Female, Humans, Male, Psychotic Disorders, Social Cognition, Young Adult, 22q11, deletion, Social cognition, Neurocognition, Psychosis, Autism spectrum disorder, 22q11.2 deletion, Psychology

الوصف: Background22q11.2 deletion syndrome (22q11DS) is a common recurrent neurogenetic condition associated with elevated risk for developmental neuropsychiatric disorders and intellectual disability. Children and adults with 22q11DS often exhibit marked social impairment as well as neurocognitive deficits, and have elevated rates of both autism spectrum disorder (ASD) and psychosis. However, the relationship between the basic processes of social cognition and cognitive ability has not been well studied in 22q11DS. Here, we examined differences in social cognition in 22q11DS, relative to multiple groups of idiopathic neuropsychiatric disorders, and typically developing healthy controls (HC). Additionally, we examined differences in intellectual functioning and its relationship to social cognitive abilities. Finally, we examined the relationship between social cognitive abilities and real-world social behavior.MethodsWe examined social cognition and intellectual functioning in 273 participants (mean age = 17.74 ± 5.18% female = 44.3%): 50 with 22q11DS, 49 youth with first episode psychosis (FEP), 48 at clinical high-risk (CHR) for psychosis, 24 participants with ASD, and 102 HC. Social cognition was assessed using The Awareness of Social Inference Test (TASIT), while reciprocal social behavior was assessed via parent/caregiver ratings on the Social Responsiveness Scale (SRS). Participants were also administered the Wechsler Abbreviated Scale of Intelligence, 2nd edition (WASI-II) to assess intellectual functioning.ResultsThe 22q11DS group exhibited significantly lower social cognitive abilities compared to CHR, FEP, and HC groups after controlling for intellectual functioning, but not in comparison to the ASD group. Significant positive correlations were found between social cognition, as measured by the TASIT and IQ across groups. In contrast, no significant relationships were found between TASIT and real-world social behavior (SRS) for any group.ConclusionsOur findings indicate social cognitive deficits are more prominent in 22q11DS than idiopathic neuropsychiatric conditions across the age range, even after adjusting for global intellectual function. These results contribute to our understanding of the intellectual and social vulnerabilities of 22q11DS in comparison to idiopathic neuropsychiatric disorders. Our findings of robust associations between intellectual ability and social cognition emphasizes the importance of accounting for neurocognitive deficits in social skills interventions and tailoring these existing treatment models for 22q11DS and other populations with intellectual impairment.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/119464dfTest

المؤلفون: Leathem, Logan D, Currin, Danielle L, Montoya, Amanda K, Karlsgodt, Katherine H

مصطلحات موضوعية: Brain Disorders, Depression, Behavioral and Social Science, Mental Health, Clinical Research, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Good Health and Well Being, Adult, Anxiety, Emotions, Humans, Loneliness, Psychotic Disorders, Emotion recognition, Social rejection, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry

الوصف: Loneliness is an important predictor of physical and mental health in the general population and in individuals across the psychosis spectrum, including those experiencing subclinical psychotic-like experiences (PLEs). However, the mechanisms underlying loneliness in the psychosis spectrum are not well understood. Emotion processing deficits are well described across the psychosis spectrum, and socioemotional processing biases are critical for the development and maintenance of loneliness through altered social appraisal, including judgements of rejection. Therefore, we propose that PLEs are associated with increased loneliness, and the relationship is mediated by alterations in socioemotional processing. We also explored how this pathway may be affected by mood and anxiety symptoms, which have been associated with loneliness across the psychosis spectrum. As part of the Human Connectome Project, generally healthy adults (n = 1180) reported symptomatology and social functioning and completed the Penn Emotion Recognition Task to assess efficiency in identifying emotions. We found that higher reported PLEs were associated with elevated levels of loneliness and perceived rejection and that these factors were linked by multiple independent pathways. First, anxiety/depression and emotion processing efficiency independently mediated the PLE-loneliness relationship. Second, we found that the association between PLEs and loneliness was serially mediated through inefficient emotion recognition then higher levels of perceived rejection. These separable mechanisms of increased loneliness in subclinical psychosis have implications for treatment and continued study of social functioning in the psychosis spectrum.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4z39184sTest

المؤلفون: Barber, Anita D, Hegarty, Catherine E, Lindquist, Martin, Karlsgodt, Katherine H

المصدر: Cerebral Cortex. 31(6)

مصطلحات موضوعية: Genetics, Clinical Research, Neurosciences, Neurological, Brain, Connectome, Databases, Genetic, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Net, Rest, ACE, dynamic connectivity, heritability, resting state networks, static connectivity, Psychology, Cognitive Sciences, Experimental Psychology

الوصف: Recent efforts to evaluate the heritability of the brain's functional connectome have predominantly focused on static connectivity. However, evaluating connectivity changes across time can provide valuable insight about the inherent dynamic nature of brain function. Here, the heritability of Human Connectome Project resting-state fMRI data was examined to determine whether there is a genetic basis for dynamic fluctuations in functional connectivity. The dynamic connectivity variance, in addition to the dynamic mean and standard static connectivity, was evaluated. Heritability was estimated using Accelerated Permutation Inference for the ACE (APACE), which models the additive genetic (h2), common environmental (c2), and unique environmental (e2) variance. Heritability was moderate (mean h2: dynamic mean = 0.35, dynamic variance = 0.45, and static = 0.37) and tended to be greater for dynamic variance compared to either dynamic mean or static connectivity. Further, heritability of dynamic variance was reliable across both sessions for several network connections, particularly between higher-order cognitive and visual networks. For both dynamic mean and static connectivity, similar patterns of heritability were found across networks. The findings support the notion that dynamic connectivity is genetically influenced. The flexibility of network connections, not just their strength, is a heritable endophenotype that may predispose trait behavior.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/54h24152Test

المؤلفون: Patel, Pooja K, Leathem, Logan D, Currin, Danielle L, Karlsgodt, Katherine H

المصدر: Biological Psychiatry. 89(2)

مصطلحات موضوعية: Pediatric, Prevention, Schizophrenia, Serious Mental Illness, Pediatric Research Initiative, Mental Health, Neurosciences, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Mental health, Adolescent, Brain, Humans, Psychotic Disorders, Risk Factors, White Matter, Adolescence, Cannabis, Development, Psychosis, Social function, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry

الوصف: Adolescence is characterized by significant changes in several domains, including brain structure and function, puberty, and social and environmental factors. Some of these changes serve to increase the likelihood of psychosis onset during this period, while others may buffer this risk. This review characterizes our current knowledge regarding the unique aspects of adolescence that may serve as risk factors for schizophrenia spectrum disorders. In addition, we provide potential future directions for research into adolescent-specific developmental mechanisms that impart vulnerability to psychosis and the possibility of interventions that capitalize on adolescents' unique characteristics. Specifically, we explore the ways in which gray and white matter develop throughout adolescence in typically developing youth as well as in those with psychosis spectrum disorders. We also discuss current views on the function that social support and demands, as well as role expectations, play in risk for psychosis. We further highlight the importance of considering biological factors such as puberty and hormonal changes as areas of unique vulnerability for adolescents. Finally, we discuss cannabis use as a factor that may have a unique impact during adolescent neurodevelopment, and subsequently potentially impact psychosis onset. Throughout, we include discussion of resilience factors that may provide unique opportunities for intervention during this dynamic life stage.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4p88v2hhTest

المؤلفون: Karlsgodt, Katherine H

المصدر: Trends in Neurosciences. 43(6)

مصطلحات موضوعية: Biological Psychology, Psychology, Schizophrenia, Clinical Research, Behavioral and Social Science, Neurosciences, Brain Disorders, Mental Health, Biomedical Imaging, Serious Mental Illness, Mental health, Good Health and Well Being, Diffusion Tensor Imaging, Humans, Neuroimaging, Psychotic Disorders, White Matter, diffusion tensor imaging, neuroimaging, psychosis, schizophrenia, spectrum, white matter, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology, Clinical and health psychology

الوصف: Diffusion-weighted imaging (DWI) is a neuroimaging technique that has allowed us an unprecedented look at the role that white matter microstructure may play in mental illnesses, such as psychosis. Psychosis-related illnesses, including schizophrenia, are increasingly viewed as existing along a spectrum; spectrums may be defined based on factors such as stage of illness, symptom severity, or genetic liability. This review first focuses on an overview of some of the recent findings from DWI studies. Then, it examines the ways in which DWI analyses have been extended across the broader psychosis spectrum, or spectrums, and what we have learned from such approaches.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7np4029sTest

المؤلفون: DeRosse, Pamela, Ikuta, Toshikazu, Karlsgodt, Katherine H, Szeszko, Philip R, Malhotra, Anil K

المصدر: Brain Imaging and Behavior. 14(2)

مصطلحات موضوعية: Biological Psychology, Psychology, Neurosciences, Child Abuse and Neglect Research, Pediatric, Violence Research, Biomedical Imaging, Clinical Research, Behavioral and Social Science, Adult, Adverse Childhood Experiences, Anisotropy, Brain, Diffusion Tensor Imaging, Female, Humans, Male, Middle Aged, Nucleus Accumbens, Prefrontal Cortex, Reward, Self-Injurious Behavior, Surveys and Questionnaires, White Matter, Childhood maltreatment, CTQ, DTI, Accumbofrontal tract, Nucleus accumbens, Orbitofrontal cortex, Medical and Health Sciences, Psychology and Cognitive Sciences, Experimental Psychology, Biomedical and clinical sciences, Health sciences

الوصف: The deleterious outcomes associated with exposure to childhood maltreatment (CM) are well known and may be at least partially mediated by self-harm behaviors. It has been suggested that these self-harm behaviors serve as a means of decreasing negative mood states but the effects of CM on health outcomes may be much more sinister. A wealth of data suggest that CM may lead to experience-dependent changes in neural circuits underlying reward processes; processes associated with many harmful behaviors. The present study examined the relationship between a history of CM and the microstructure of a white matter tract that may be central to reward processes. Healthy adults (N = 122) were assessed with a diffusion tensor imaging (DTI) exam and the Childhood Trauma Questionnaire (CTQ). Probabilistic tractography was used to delineate the accumbofrontal "reward" tract, connecting the orbitofrontal cortex and nucleus accumbens, and measures of white matter microstructure were extracted. We then examined whether variation in CTQ scores were associated with variation in the microstructure of this tract as measured by fractional anisotropy (FA). After accounting for the effects of age and sex, the CTQ total score accounted for approximately 6% of the variance of FA in the accumbofrontal tract (F(3, 121) = 5.74; p = .001). Post hoc analyses indicated that the overall severity of CM, rather than a specific type of maltreatment, drove this result. These findings indicate that CM influences white matter microstructure in a fiber tract that is likely central to reward processes and adds to a growing literature implicating CM in long-term health-related outcomes.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1sn0t3rhTest

المؤلفون: Mennigen, Eva, Jolles, Dietsje D, Hegarty, Catherine E, Gupta, Mohan, Jalbrzikowski, Maria, Loohuis, Loes M Olde, Ophoff, Roel A, Karlsgodt, Katherine H, Bearden, Carrie E

المصدر: Schizophrenia Bulletin. 46(2)

مصطلحات موضوعية: Neurosciences, Brain Disorders, Mental Health, Schizophrenia, Serious Mental Illness, Pediatric, Clinical Research, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Adolescent, Adult, Brain, Child, Cohort Studies, Connectome, Female, Humans, Magnetic Resonance Imaging, Male, Nerve Net, Neurodevelopmental Disorders, Psychotic Disorders, Young Adult, dynamic functional network connectivity, psychosis spectrum, independent component analysis, adolescence, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry

الوصف: Psychosis spectrum disorders are conceptualized as neurodevelopmental disorders accompanied by disruption of large-scale functional brain networks. Dynamic functional dysconnectivity has been described in patients with schizophrenia and in help-seeking individuals at clinical high risk for psychosis. Less is known, about developmental aspects of dynamic functional network connectivity (dFNC) associated with psychotic symptoms (PS) in the general population. Here, we investigate resting state functional magnetic resonance imaging data using established dFNC methods in the Philadelphia Neurodevelopmental Cohort (ages 8-22 years), including 129 participants experiencing PS and 452 participants without PS (non-PS). Functional networks were identified using group spatial independent component analysis. A sliding window approach and k-means clustering were applied to covariance matrices of all functional networks to identify recurring whole-brain connectivity states. PS-associated dysconnectivity of default mode, salience, and executive networks occurred only in a few states, whereas dysconnectivity in the sensorimotor and visual systems in PS youth was more pervasive, observed across multiple states. This study provides new evidence that disruptions of dFNC are present even at the less severe end of the psychosis continuum in youth, complementing previous work on help-seeking and clinically diagnosed cohorts that represent the more severe end of this spectrum.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/49b0r42sTest