The dopamine hypothesis of Bipolar Affective Disorder: the state of the art and implications for treatment

Journal article

Bipolar affective disorder is a common neuropsychiatric disorder. Whilst its neurobiological underpinnings are incompletely understood, the dopamine hypothesis has been a key theory of the pathophysiology of both manic and depressive phases of the illness for over four decades. The increased use of antidopaminergics in the treatment of this disorder and new in vivo neuroimaging and post-mortem studies makes it timely to review this theory. To do this, we conducted a systematic search for post-mortem, pharmacological and imaging studies of dopamine function in bipolar disorder. Converging findings from pharmacological and imaging studies support the hypothesis that a state of hyperdopaminergia, specifically elevations in D2/3 receptor availability and a hyperactive reward processing network, underlies mania. In bipolar depression imaging studies show increased dopamine transporter levels, but changes in other aspects of dopaminergic function are inconsistent. Puzzlingly, pharmacological evidence shows that both dopamine agonists and antidopaminergics can improve bipolar depressive symptoms and perhaps actions at other receptors may reconcile these findings. Tentatively, this evidence suggests a model where an elevation in striatal D2/3 receptor availability would lead to increased dopaminergic neurotransmission and mania, whilst increased striatal dopamine transporter (DAT) levels would lead to reduced dopaminergic function and depression. Thus, it can be speculated that a failure of dopamine receptor and transporter homeostasis might underlie the pathophysiology of this disorder. The limitations of this model include its reliance on pharmacological evidence, as these studies could potentially affect other monoamines, and the scarcity of imaging evidence on dopaminergic function. This model, if confirmed, has implications for developing new treatment strategies such as reducing the dopamine synthesis and/or release in mania and DAT blockade in bipolar depression.

Authors: Ashok, A; Marques, T; Jauhar, S; Nour, M; Goodwin, G

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Publishing Group
• Journal: Molecular Psychiatry
• Volume: 22
• Pages: 666–679
• Publication date: 2017-03-14
• Acceptance date: 2017-01-08
• DOI: 10.1038/mp.2017.16
• EISSN: 1476-5578
• ISSN: 1359-4184
• Keywords: mood stabiliser; affective disorders; dopamine; mania; depression; imaging; antidopaminergic; anti-depressant; mechanism; Bipolar affective disorder; etiology