Molecular Imaging of Dopamine Abnormalities in Bipolar Disorder and Schizophrenia
This article is based on the talk by Dr Sameet Jauhar at RCPsych2019. Dr Jauhar is currently a Senior Research Fellow at the Department of Psychological Medicine at the Institute of Psychiatry, Psychology and Neuroscience at King’s College, London, and a Consultant Psychiatrist, working within Early Intervention for Psychosis services within South London and Maudsley NHS Foundation
The FDA has licensed several antipsychotic treatments for mania and maintenance treatment in depression which are used in bipolar disorder. [read more on guidelines for bipolar disorder]
Research questions include:
- Is presynaptic dopamine elevated in bipolar disorder?
- How does this compare with schizophrenia and healthy controls?
- Does a relationship exist between presynaptic dopamine and positive psychotic systems irrespective of diagnosis?
A recent study showed elevated dopamine synthesis capacity (DSC) in bipolar and schizophrenia groups and was significantly higher in patients with first-episode psychosis, who then responded to antipsychotic treatment.[Jauhar et al. 2018]
- DSC is associated with positive psychotic symptoms in individuals diagnosed with bipolar disorder or schizophrenia.
The locus of the largest dopaminergic abnormality in schizophrenia is presynaptic, which affects dopamine synthesis capacity, baseline synaptic dopamine levels, and dopamine release. Current drug treatments, which primarily act at D(2/3) receptors, fail to target these abnormalities. [Howes O, 2012]
- Mania is also associated with DSC, although the contribution of dopamine dysregulation to mania is unclear.
- It can be concluded that in bipolar disorder and schizophrenia, psychosis is linked to presynaptic dopamine irrespective of diagnosis. However, there is no clarity regarding mania and non-psychotic mania, and more studies are needed to understand the mechanism of what works in mania.
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. [Ashok A et al., 2017]
- The published literature in schizophrenia is clear, but there is a need for more molecular imaging studies in bipolar disorder and the dopamine system.