Molecular Psychiatry (2017) 22, 666–679; doi:10.1038/mp.2017.16 published online 14 March 2017

The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment

A H Ashok1,2,3,4, T R Marques1,2,3,4, S Jauhar1,2,3,4, M M Nour1,2,3, G M Goodwin5, A H Young4,6 and O D Howes1,2,3,4

  1. 1Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UK
  2. 2Psychiatric Imaging Group, Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK
  3. 3Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK
  4. 4South London and Maudsley NHS Foundation Trust, Camberwell, London, UK
  5. 5Department of Psychiatry, University of Oxford and Oxford Health NHS Trust, Warneford Hospital, Oxford, UK
  6. 6Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

Correspondence: Professor OD Howes, Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, Du Cane Road, London W12 0NN, UK. E-mail:

Received 25 July 2016; Revised 10 December 2016; Accepted 9 January 2017
Advance online publication 14 March 2017



Bipolar affective disorder is a common neuropsychiatric disorder. Although 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, functional magnetic resonance and molecular 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 homoeostasis 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.