A Test of the Transdiagnostic Dopamine Hypothesis of Psychosis Using Positron Emission Tomographic Imaging in Bipolar Affective Disorder and Schizophrenia

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Title: A Test of the Transdiagnostic Dopamine Hypothesis of Psychosis Using Positron Emission Tomographic Imaging in Bipolar Affective Disorder and Schizophrenia
Author(s): Jauhar, S
Nour, MM
Veronese, M
Rogdaki, M
Bonoldi, I
Azis, M
Turkheimer, F
McGuire, P
Young, AH
Howes, OD
Item Type: Journal Article
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 ([18F]-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 (Kicer) 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 (Kicer) (F2,57 = 6.80, P = .002). Kicer 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 Kicer between the bipolar and schizophrenia groups. Kicer 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 Kicer 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.
Publication Date: 11-Oct-2017
Date of Acceptance: 31-Jul-2017
URI: http://hdl.handle.net/10044/1/56382
DOI: https://dx.doi.org/10.1001/jamapsychiatry.2017.2943
ISSN: 2168-622X
Publisher: American Medical Association
Start Page: 1206
End Page: 1213
Journal / Book Title: JAMA Psychiatry
Volume: 74
Issue: 12
Copyright Statement: This is an open access article distributed under the terms of the CC-BY License. © 2017 Jauhar S et al.JAMA Psychiatry
Keywords: Science & Technology
Life Sciences & Biomedicine
Psychiatry
MULTIPLE-TREATMENTS METAANALYSIS
ULTRA-HIGH RISK
SYNTHESIS CAPACITY
IN-VIVO
COMPARATIVE EFFICACY
ANTIPSYCHOTIC-DRUGS
MENTAL-DISORDERS
MANIA
PET
BRAIN
Adult
Bipolar Disorder
Case-Control Studies
Cross-Sectional Studies
Dihydroxyphenylalanine
Dopamine
Dopamine Agents
England
Female
Fluorine Radioisotopes
Humans
Male
Positron-Emission Tomography
Psychiatric Status Rating Scales
Psychotic Disorders
Reproducibility of Results
Schizophrenia
Humans
Fluorine Radioisotopes
Dopamine
Dihydroxyphenylalanine
Dopamine Agents
Positron-Emission Tomography
Case-Control Studies
Cross-Sectional Studies
Reproducibility of Results
Bipolar Disorder
Psychotic Disorders
Schizophrenia
Psychiatric Status Rating Scales
Adult
England
Female
Male
Science & Technology
Life Sciences & Biomedicine
Psychiatry
MULTIPLE-TREATMENTS METAANALYSIS
ULTRA-HIGH RISK
SYNTHESIS CAPACITY
IN-VIVO
COMPARATIVE EFFICACY
ANTIPSYCHOTIC-DRUGS
MENTAL-DISORDERS
MANIA
PET
BRAIN
Publication Status: Published
Open Access location: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2656683
Appears in Collections:Clinical Sciences
Imaging Sciences



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