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Regionally specific volume deficits along the hippocampal long axis in early and chronic psychosis.
McHugo M, Talati P, Woodward ND, Armstrong K, Blackford JU, Heckers S
(2018) Neuroimage Clin 20: 1106-1114
MeSH Terms: Adult, Aged, Bipolar Disorder, Dentate Gyrus, Early Diagnosis, Female, Hippocampus, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Psychotic Disorders
Show Abstract · Added March 26, 2019
Previous studies in psychosis patients have shown hippocampal volume deficits across anterior and posterior regions or across subfields, but subfield specific changes in volume along the hippocampal long axis have not been examined. Here, we tested the hypothesis that volume changes exist across the hippocampus in chronic psychosis but only the anterior CA region is affected in early psychosis patients. We analyzed structural MRI data from 179 patients with a non-affective psychotic disorder (94 chronic psychosis; 85 early psychosis) and 167 heathy individuals demographically matched to the chronic and early psychosis samples respectively (82 matched to chronic patients; 85 matched to early patients). We measured hippocampal volumes using Freesurfer 6-derived automated segmentation of both anterior and posterior regions and the CA, dentate gyrus, and subiculum subfields. We found a hippocampal volume deficit in both anterior and posterior regions in chronic psychosis, but this deficit was limited to the anterior hippocampus in early psychosis patients. This volume change was more pronounced in the anterior CA subfield of early psychosis patients than in the dentate gyrus or subiculum. Our findings support existing models of psychosis implicating initial CA dysfunction with later progression to other hippocampal regions and suggest that the anterior hippocampus may be an important target for early interventions.
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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Enhancing Psychosis-Spectrum Nosology Through an International Data Sharing Initiative.
Docherty AR, Fonseca-Pedrero E, Debbané M, Chan RCK, Linscott RJ, Jonas KG, Cicero DC, Green MJ, Simms LJ, Mason O, Watson D, Ettinger U, Waszczuk M, Rapp A, Grant P, Kotov R, DeYoung CG, Ruggero CJ, Eaton NR, Krueger RF, Patrick C, Hopwood C, O'Neill FA, Zald DH, Conway CC, Adkins DE, Waldman ID, van Os J, Sullivan PF, Anderson JS, Shabalin AA, Sponheim SR, Taylor SF, Grazioplene RG, Bacanu SA, Bigdeli TB, Haenschel C, Malaspina D, Gooding DC, Nicodemus K, Schultze-Lutter F, Barrantes-Vidal N, Mohr C, Carpenter WT, Cohen AS
(2018) Schizophr Bull 44: S460-S467
MeSH Terms: Datasets as Topic, Humans, Information Dissemination, Intersectoral Collaboration, Models, Theoretical, Psychotic Disorders, Schizophrenia, Schizotypal Personality Disorder
Show Abstract · Added April 15, 2019
The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural equation modeling approaches. In the last 50 years, efforts in both psychiatry and psychological science have moved toward (1) a dimensional model of psychopathology (eg, the current Hierarchical Taxonomy of Psychopathology [HiTOP] initiative), (2) an integration of methods and measures across traits and units of analysis (eg, the RDoC initiative), and (3) powerful, impactful study designs maximizing sample size to detect subtle genomic variation relating to complex traits (the Psychiatric Genomics Consortium [PGC]). These movements are important to the future study of the psychosis spectrum, and to resolving heterogeneity with respect to instrument and population. The International Consortium of Schizotypy Research is composed of over 40 laboratories in 12 countries, and to date, members have compiled a body of schizotypy- and psychosis-related phenotype data from more than 30000 individuals. It has become apparent that compiling data into a protected, relational database and crowdsourcing analytic and data science expertise will result in significant enhancement of current research on the structure and biological substrates of the psychosis spectrum. The authors present a data-sharing infrastructure similar to that of the PGC, and a resource-sharing infrastructure similar to that of HiTOP. This report details the rationale and benefits of the phenotypic data collective and presents an open invitation for participation.
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Role of mitochondria and energy metabolism in schizophrenia and psychotic disorders.
Konradi C, Öngür D
(2017) Schizophr Res 187: 1-2
MeSH Terms: Animals, Energy Metabolism, Humans, Mitochondria, Psychotic Disorders, Schizophrenia
Added March 14, 2018
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6 MeSH Terms
Mapping Thalamocortical Functional Connectivity in Chronic and Early Stages of Psychotic Disorders.
Woodward ND, Heckers S
(2016) Biol Psychiatry 79: 1016-25
MeSH Terms: Adult, Affective Disorders, Psychotic, Cerebellum, Cerebral Cortex, Cognitive Dysfunction, Connectome, Executive Function, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Motor Cortex, Nerve Net, Prefrontal Cortex, Psychotic Disorders, Schizophrenia, Thalamus, Young Adult
Show Abstract · Added February 15, 2016
BACKGROUND - There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state functional magnetic resonance imaging has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis.
METHODS - Resting-state functional magnetic resonance imaging was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early-stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions of interest (ROIs) on the basis of connectivity with six a priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxelwise seed-based analyses to further localize thalamic dysconnectivity.
RESULTS - ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early-stage psychosis patients. PFC hypoconnectivity and motor cortex hyperconnectivity correlated in patients, suggesting that they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypoconnectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described executive control network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory.
CONCLUSIONS - Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment.
Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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19 MeSH Terms
Schizotypy and clinical symptoms, cognitive function, and quality of life in individuals with a psychotic disorder.
Brosey E, Woodward ND
(2015) Schizophr Res 166: 92-7
MeSH Terms: Adult, Bipolar Disorder, Cognition, Cognition Disorders, Female, Humans, Male, Neuropsychological Tests, Psychiatric Status Rating Scales, Psychotic Disorders, Quality of Life, Schizotypal Personality Disorder, Self Report
Show Abstract · Added February 15, 2016
BACKGROUND - Schizotypy is a range of perceptual experiences and personality features related to risk and familial predisposition to psychosis. Despite evidence that schizotypy is related to psychosis vulnerability, very little is known about the expression of schizotypal traits in individuals with a psychotic disorder, and their relationship to clinical symptoms, cognition, and psychosocial functioning.
METHODS - 59 healthy subjects and 68 patients with a psychotic disorder (47 schizophrenia spectrum disorder; 21 bipolar disorder with psychotic features) completed four schizotypy scales, the Perceptual Aberration Scale, the Revised Physical and Social Anhedonia Scales, and the Schizotypal Personality Questionnaire, a brief neuropsychological assessment, and a self-report measure of quality of life. Clinical symptoms of psychosis were quantified in patients with the Positive and Negative Syndrome Scale (PANSS).
RESULTS - Psychosis patients scored higher than healthy subjects on all schizotypy scales. Correlations between schizotypy and PANSS scores were modest, ranging from r=.06 to r=.43, indicating that less than 20% of the variance in self-reported schizotypy overlapped with clinical symptoms. After controlling for clinical symptoms, patients with schizophrenia spectrum disorders reported higher levels of cognitive-perceptual disturbances and negative traits than patients with bipolar disorder. Elevated schizotypy was associated with lower cognitive functioning and self-reported quality of life.
CONCLUSIONS - Schizotypal personality traits are markedly elevated in psychotic disorders, especially schizophrenia spectrum disorders, relatively weakly correlated with positive and negative psychotic symptoms, and associated with greater cognitive impairment and lower quality of life. Assessing schizotypy in patients with psychosis may be useful for predicting functional outcome and differential diagnosis.
Copyright © 2015 Elsevier B.V. All rights reserved.
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13 MeSH Terms
Brain Structure in Neuropsychologically Defined Subgroups of Schizophrenia and Psychotic Bipolar Disorder.
Woodward ND, Heckers S
(2015) Schizophr Bull 41: 1349-59
MeSH Terms: Adult, Atrophy, Bipolar Disorder, Brain, Cognition Disorders, Female, Gray Matter, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Psychotic Disorders, Schizophrenia, White Matter, Young Adult
Show Abstract · Added February 15, 2016
BACKGROUND - Neuropsychological impairment is heterogeneous in psychosis. The association of intracranial volume (ICV) and total brain volume (TBV) with cognition suggests brain structure abnormalities in psychosis will covary with the severity of cognitive impairment. We tested the following hypotheses: (1) brain structure abnormalities will be more extensive in neuropsychologically impaired psychosis patients; (2) psychosis patients with premorbid cognitive limitations will show evidence of hypoplasia (ie, smaller ICV); and (3) psychosis patients with evidence of cognitive decline will demonstrate atrophy (ie, smaller TBV, but normal ICV).
METHODS - One hundred thirty-one individuals with psychosis and 97 healthy subjects underwent structural magnetic resonance imaging and neuropsychological testing. Patients were divided into neuropsychologically normal and impaired groups. Impaired patients were further subdivided into deteriorated and compromised groups if estimated premorbid intellect was average or below average, respectively. ICV and TBV were compared across groups. Localized brain volumes were qualitatively examined using voxel-based morphometry.
RESULTS - Compared to healthy subjects, neuropsychologically impaired patients exhibited smaller TBV, reduced grey matter volume in frontal, temporal, and subcortical brain regions, and widespread white matter volume loss. Neuropsychologically compromised patients had smaller ICV relative to healthy subjects, and neuropsychologically normal and deteriorated patient groups, but relatively normal TBV. Deteriorated patients exhibited smaller TBV compared to healthy subjects, but relatively normal ICV. Unexpectedly, TBV, adjusted for ICV, was reduced in neuropsychologically normal patients.
CONCLUSIONS - Patients with long-standing cognitive limitations exhibit evidence of early cerebral hypoplasia, whereas neuropsychologically normal and deteriorated patients show evidence of brain tissue loss consistent with progression or later cerebral dysmaturation.
© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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15 MeSH Terms
The course of neuropsychological impairment and brain structure abnormalities in psychotic disorders.
Woodward ND
(2016) Neurosci Res 102: 39-46
MeSH Terms: Bipolar Disorder, Brain, Cognition Disorders, Humans, Neuropsychological Tests, Psychotic Disorders, Schizophrenia, Schizophrenic Psychology
Show Abstract · Added February 15, 2016
Neuropsychological impairment and abnormalities in brain structure are commonly observed in psychotic disorders, including schizophrenia and bipolar disorder. Shared deficits in neuropsychological functioning and abnormalities in brain structure suggest overlapping neuropathology between schizophrenia and bipolar disorder which has important implications for psychiatric nosology, treatment, and our understanding of the etiology of psychotic illnesses. However, the emergence and trajectory of brain dysfunction in psychotic disorders is less well understood. Differences in the course and progression of neuropsychological impairment and brain abnormalities among psychotic disorders may point to unique neuropathological processes. This article reviews the course of neuropsychological impairment and brain structure abnormalities in schizophrenia and bipolar disorder.
Copyright © 2014. Published by Elsevier Ireland Ltd.
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8 MeSH Terms
Childhood sexual abuse increases risk of auditory hallucinations in psychotic disorders.
Sheffield JM, Williams LE, Blackford JU, Heckers S
(2013) Compr Psychiatry 54: 1098-104
MeSH Terms: Adult, Adult Survivors of Child Abuse, Child, Child Abuse, Sexual, Hallucinations, Humans, Middle Aged, Psychiatric Status Rating Scales, Psychotic Disorders, Risk Factors, Schizophrenia, Schizophrenic Psychology, Surveys and Questionnaires
Show Abstract · Added February 12, 2015
BACKGROUND/AIMS - Previous studies point to an association between childhood sexual abuse (CSA) and auditory hallucinations (AH). However, methodological issues limit the strength of these results. Here we compared childhood abuse between psychotic disorder patients and healthy control subjects using a reliable measure of abuse, and assessed the relationship between CSA and AH.
METHODS - 114 psychotic disorder patients and 81 healthy control subjects were administered the Structured Clinical Interview of the DSM-IV (SCID) and the Childhood Trauma Questionnaire (CTQ). We compared the severity of abuse between groups, and tested the relationship between different types of childhood abuse and specific psychotic symptoms.
RESULTS - Psychotic patients reported more childhood abuse than controls (p<.001). Psychotic patients with a history of AH reported significantly more sexual, emotional, and physical abuse than patients without a history of AH (p<.05). Emotional and physical abuse, in the absence of sexual abuse, did not lead to a higher rate of AH. Finally, reports of childhood abuse did not increase the risk of any form of hallucination other than AH or of any form of delusion.
CONCLUSIONS - These results suggest that childhood abuse, especially childhood sexual abuse, shapes the phenotype of psychotic disorders by conferring a specific risk for AH.
Copyright © 2013 Elsevier Inc. All rights reserved.
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13 MeSH Terms
Attenuated psychosis syndrome in DSM-5.
Tsuang MT, Van Os J, Tandon R, Barch DM, Bustillo J, Gaebel W, Gur RE, Heckers S, Malaspina D, Owen MJ, Schultz S, Carpenter W
(2013) Schizophr Res 150: 31-5
MeSH Terms: Diagnostic and Statistical Manual of Mental Disorders, Humans, Psychotic Disorders, Risk Factors, Schizophrenia, Schizophrenic Psychology
Show Abstract · Added February 12, 2015
Despite advances in the treatment of schizophrenia over the past half-century, the illness is frequently associated with a poor outcome. This is principally related to the late identification and intervention in the course of the illness by which time patients have experienced a substantial amount of socio-occupational decline that can be difficult to reverse. The emphasis has therefore shifted to defining psychosis-risk syndromes and evaluating treatments that can prevent transition to psychosis in these ultra-high risk groups. To consider the appropriateness of adding psychosis risk syndrome to our diagnostic nomenclature, the psychotic disorders work group extensively reviewed all available data, consulted a range of experts, and carefully considered the variety of expert and public comments on the topic. It was clear that reliable methods were available to define a syndrome characterized by sub-threshold psychotic symptoms (in severity or duration) and which was associated with a very significant increase in the risk of development of a full-fledged psychotic disorder (schizophrenia spectrum, psychotic mood disorder, and other psychotic disorders) within the next year. At the same time, the majority of individuals with "attenuated psychotic symptoms" had one or more other current psychiatric comorbid conditions (usually mood or anxiety disorders, substance use disorder; Fusar-Poli 2012) and exhibited a range of psychiatric outcomes other than conversion to psychosis (significant proportions either fully recover or develop some other psychiatric disorder, with a minority developing a psychotic disorder). Although the reliability of the diagnosis is well established in academic and research settings, it was found to be less so in community and other clinical settings. Furthermore, the nosological relationship of attenuated psychosis syndrome (APS) to schizotypal personality disorder and other psychiatric conditions was unclear. Further study will hopefully resolve these questions. The work group decided to recommend the inclusion of attenuated psychosis syndrome as a category in the appendix (Section 3) of DSM-5 as a condition for further study.
Copyright © 2013 Elsevier B.V. All rights reserved.
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6 MeSH Terms
Schizoaffective Disorder in the DSM-5.
Malaspina D, Owen MJ, Heckers S, Tandon R, Bustillo J, Schultz S, Barch DM, Gaebel W, Gur RE, Tsuang M, Van Os J, Carpenter W
(2013) Schizophr Res 150: 21-5
MeSH Terms: Diagnostic and Statistical Manual of Mental Disorders, Humans, Mood Disorders, Psychotic Disorders
Show Abstract · Added February 12, 2015
Characterization of patients with both psychotic and mood symptoms, either concurrently or at different points during their illness, has always posed a nosological challenge and this is reflected in the poor reliability, low diagnostic stability, and questionable validity of DSM-IV Schizoaffective Disorder. The clinical reality of the frequent co-occurrence of psychosis and Mood Episodes has also resulted in over-utilization of a diagnostic category that was originally intended to only rarely be needed. In the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, an effort is made to improve reliability of this condition by providing more specific criteria and the concept of Schizoaffective Disorder shifts from an episode diagnosis in DSM-IV to a life-course of the illness in DSM-5. When psychotic symptoms occur exclusively during a Mood Episode, DSM-5 indicates that the diagnosis is the appropriate Mood Disorder with Psychotic Features, but when such a psychotic condition includes at least a two-week period of psychosis without prominent mood symptoms, the diagnosis may be either Schizoaffective Disorder or Schizophrenia. In the DSM-5, the diagnosis of Schizoaffective Disorder can be made only if full Mood Disorder episodes have been present for the majority of the total active and residual course of illness, from the onset of psychotic symptoms up until the current diagnosis. In earlier DSM versions the boundary between Schizophrenia and Schizoaffective Disorder was only qualitatively defined, leading to poor reliability. This change will provide a clearer separation between Schizophrenia with mood symptoms from Schizoaffective Disorder and will also likely reduce rates of diagnosis of Schizoaffective Disorder while increasing the stability of this diagnosis once made.
Copyright © 2013 Elsevier B.V. All rights reserved.
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4 MeSH Terms