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Structural alterations within cerebellar circuitry are associated with general liability for common mental disorders.

ABSTRACT: Accumulating mental-health research encourages a shift in focus toward transdiagnostic dimensional features that are shared across categorical disorders. In support of this shift, recent studies have identified a general liability factor for psychopathology-sometimes called the 'p factor'- that underlies shared risk for a wide range of mental disorders. Identifying neural correlates of this general liability would substantiate its importance in characterizing the shared origins of mental disorders and help us begin to understand the mechanisms through which the 'p factor' contributes to risk. Here we believe we first replicate the 'p factor' using cross-sectional data from a volunteer sample of 1246 university students, and then using high-resolution multimodal structural neuroimaging, we demonstrate that individuals with higher 'p factor' scores show reduced structural integrity of white matter pathways, as indexed by lower fractional anisotropy values, uniquely within the pons. Whole-brain analyses further revealed that higher 'p factor' scores are associated with reduced gray matter volume in the occipital lobe and left cerebellar lobule VIIb, which is functionally connected with prefrontal regions supporting cognitive control. Consistent with the preponderance of cerebellar afferents within the pons, we observed a significant positive correlation between the white matter integrity of the pons and cerebellar gray matter volume associated with higher 'p factor' scores. The results of our analyses provide initial evidence that structural alterations in corticocerebellar circuitry supporting core functions related to the basic integration, coordination and monitoring of information may contribute to a general liability for common mental disorders.

SUBMITTER: Romer AL

PROVIDER: S-EPMC5636639 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Structural alterations within cerebellar circuitry are associated with general liability for common mental disorders.

Romer A L AL Knodt A R AR Houts R R Brigidi B D BD Moffitt T E TE Caspi A A Hariri A R AR

Molecular psychiatry 20170411 4

Accumulating mental-health research encourages a shift in focus toward transdiagnostic dimensional features that are shared across categorical disorders. In support of this shift, recent studies have identified a general liability factor for psychopathology-sometimes called the 'p factor'- that underlies shared risk for a wide range of mental disorders. Identifying neural correlates of this general liability would substantiate its importance in characterizing the shared origins of mental disorde ...[more]

PMID: 28397842

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Project description:Multidisciplinary collaboration between clinicians, epidemiologists, neurogeneticists and statisticians on research projects has been encouraged to improve our knowledge of the complex mechanisms underlying the aetiology and burden of mental disorders. The PEGASUS-Murcia (Psychiatric Enquiry to General Population in Southeast Spain-Murcia) project was designed to assess the prevalence of common mental disorders and to identify the risk and protective factors, and it also included the collection of biological samples to study the gene-environmental interactions in the context of the World Mental Health Survey Initiative.The PEGASUS-Murcia project is a new cross-sectional face-to-face interview survey based on a representative sample of non-institutionalised adults in the Region of Murcia (Mediterranean Southeast, Spain). Trained lay interviewers used the latest version of the computer-assisted personal interview of the Composite International Diagnostic Interview (CIDI 3.0) for use in Spain, specifically adapted for the project. Two biological samples of buccal mucosal epithelium will be collected from each interviewed participant, one for DNA extraction for genomic and epigenomic analyses and the other to obtain mRNA for gene expression quantification. Several quality control procedures will be implemented to assure the highest reliability and validity of the data. This article describes the rationale, sampling methods and questionnaire content as well as the laboratory methodology.Informed consent will be obtained from all participants and a Regional Ethics Research Committee has approved the protocol. Results will be disseminated in peer-reviewed publications and presented at the national and the international conferences.Cross-sectional studies, which combine detailed personal information with biological data, offer new and exciting opportunities to study the gene-environmental interactions in the aetiology of common mental disorders in representative samples of the general population. A collaborative multidisciplinary research approach offers the potential to advance our knowledge of the underlying complex interactions and this opens the field for further innovative study designs in psychiatric epidemiology.

Project description:BackgroundConsidering many patients receive care from general hospitals, these healthcare institutions are uniquely situated to address mental and physical health needs. Little is documented, however, on the common current mental disorders diagnosed in patients receiving care in general hospital settings, especially in Puerto Rico. The objective of this study was to characterize the five most common current DSM-5 mental disorder diagnoses made in patients receiving non-psychiatric medical and surgical care from a general hospital system in southern Puerto Rico between January 2015 and December 2019.MethodsOur clinical health psychology team provides integrated psychology consultation-liaison services to select clinical units in general hospitals across the southwestern region of Puerto Rico. The clinical team conducted routine standardized psychological evaluations at patients' bedside, arrived at a current DSM-5 diagnosis if warranted, and documented the diagnosis and other select variables. A retrospective study of cross-sectional data generated from the clinical team's standardized evaluations of 5494 medical patients was implemented. Multinomial logistic regression analyses were used to assess the odds of being diagnosed with a current DSM-5 mental disorder during hospitalization.ResultsOverall, 53% of the entire sample was diagnosed with a mental disorder during hospitalization. Major depressive, neurocognitive, anxiety, substance-related and schizophrenia-spectrum disorders were the most frequently diagnosed. Interestingly, females were 23% less likely to have been diagnosed with major depressive disorder than males (aOR: 0.769, CI [0.650, 0.909], p = 0.002). This is to say males evidenced 1.30 higher odds of being diagnosed with depression compared to their female counterpart. Age, biological sex, civil status, employment status, monthly household income, previous mental disorder and history substance use/abuse history was differentially associated with receiving a current DSM-5 disorder.ConclusionThe integration of clinical health psychology services within a general hospital facilitated our team's work of identifying and treating co-occurring mental disorders among hospitalized patients receiving medical and surgical care. Future studies examining the opportunities and barriers of integrating clinical health psychology services within a general hospital's administrative and clinical infrastructure for rapid identification and treatment of co-occurring mental disorders among medical patients is encouraged.

Dataset Information

Structural alterations within cerebellar circuitry are associated with general liability for common mental disorders.

Publications

Structural alterations within cerebellar circuitry are associated with general liability for common mental disorders.

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