A Test of the Transdiagnostic Dopamine Hypothesis of Psychosis Using Positron Emission Tomographic Imaging in Bipolar Affective Disorder and Schizophrenia
Sameer Jauhar,Sameer Jauhar,Matthew M. Nour,Matthew M. Nour,Mattia Veronese,Maria Rogdaki,Ilaria Bonoldi,Ilaria Bonoldi,Matilda Azis,Federico Turkheimer,Philip McGuire,Philip McGuire,Allan H. Young,Oliver D. Howes,Oliver D. Howes,Oliver D. Howes +15 more
TLDR
Findings are consistent with a transdiagnostic role for dopamine dysfunction in the pathoetiology of psychosis and suggest dopamine synthesis capacity as a potential novel drug target for bipolar disorder and schizophrenia.Abstract:
Importance The dopamine hypothesis suggests that dopamine abnormalities underlie psychosis, irrespective of diagnosis, implicating dopamine dysregulation in bipolar affective disorder and schizophrenia, in line with the research domain criteria approach. However, this hypothesis has not been directly examined in individuals diagnosed with bipolar disorder with psychosis. Objectives To test whether dopamine synthesis capacity is elevated in bipolar disorder with psychosis and how this compares with schizophrenia and matched controls and to examine whether dopamine synthesis capacity is associated with psychotic symptom severity, irrespective of diagnostic class. Design, Setting, and Participants This cross-sectional case-control positron emission tomographic study was performed in the setting of first-episode psychosis services in an inner-city area (London, England). Sixty individuals participated in the study (22 with bipolar psychosis [18 antipsychotic naive or free], 16 with schizophrenia [14 antipsychotic naive or free], and 22 matched controls) and underwent fluorodihydroxyphenyl-l-alanine ([ 18 F]-DOPA) positron emission tomography to examine dopamine synthesis capacity. Standardized clinical measures, including the Positive and Negative Syndrome Scale, Young Mania Rating Scale, and Global Assessment of Functioning, were administered. The study dates were March 2013 to November 2016. Main Outcomes and Measures Dopamine synthesis capacity (Ki cer ) and clinical measures (Positive and Negative Syndrome Scale, Young Mania Rating Scale, and Global Assessment of Functioning). Results The mean (SD) ages of participants were 23.6 (3.6) years in 22 individuals with bipolar psychosis (13 male), 26.3 (4.4) years in 16 individuals with schizophrenia (14 male), and 24.5 (4.5) years in controls (14 male). There was a significant group difference in striatal dopamine synthesis capacity (Ki cer ) ( F 2,57 = 6.80, P = .002). Ki cer was significantly elevated in both the bipolar group (mean [SD], 13.18 [1.08] × 10 −3 min −1 ; P = .002) and the schizophrenia group (mean [SD], 12.94 [0.79] × 10 −3 min −1 ; P = .04) compared with controls (mean [SD], 12.16 [0.92] × 10 −3 min −1 ). There was no significant difference in striatal Ki cer between the bipolar and schizophrenia groups. Ki cer was significantly positively correlated with positive psychotic symptom severity in the combined bipolar and schizophrenia sample experiencing a current psychotic episode, explaining 27% of the variance in symptom severity (n = 32, r = 0.52, P = .003). There was a significant positive association between Ki cer and positive psychotic symptom severity in individuals with bipolar disorder experiencing a current psychotic episode (n = 16, r = 0.60, P = .01), which remained significant after adjusting for manic symptom severity. Conclusions and Relevance These findings are consistent with a transdiagnostic role for dopamine dysfunction in the pathoetiology of psychosis and suggest dopamine synthesis capacity as a potential novel drug target for bipolar disorder and schizophrenia.read more
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References
More filters
Journal ArticleDOI
Diagnostic and Statistical Manual of Mental Disorders
Vijay A. Mittal,Elaine F. Walker +1 more
TL;DR: An issue concerning the criteria for tic disorders is highlighted, and how this might affect classification of dyskinesias in psychotic spectrum disorders.
Journal ArticleDOI
The Positive and Negative Syndrome Scale (PANSS) for Schizophrenia
TL;DR: Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
Journal ArticleDOI
A rating scale for mania: reliability, validity and sensitivity.
TL;DR: The MRS score correlated highly with an independent global rating, and with scores of two other mania rating scales administered concurrently, and also correlated with the number of days of subsequent stay in hospital.
Book
Structured clinical interview for DSM-IV axis II personality disorders : SCID-II
TL;DR: The Structured Clinical Interview for DSM-IV Axis II personality disorders (SCID-II) as mentioned in this paper is an efficient, user-friendly instrument that will help researchers and clinicians make standardized, reliable, and accurate diagnoses of the 10 DSM-III personality disorders as well as depressive personality disorder, passive-aggressive personality disorder and personality disorder not otherwise specified.
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