Reduced Dopamine transporter density linked to clinical Mania reveals PET study

A recent investigation found that decreased dopamine transporter (DAT) density was seen in maniac patients. In those patients with remitted mania, DAT levels were similar to those without bipolar disorder. The study results were published in the journal JAMA Psychiatry. 

Mania is the hallmark of bipolar disorder. Even though the precise changes in the dopaminergic system are not known, dopamine is implicated in the pathophysiology of this disorder. Researchers conducted a study to understand if dopamine transporter (DAT) density in the striatum in patients with BD who are currently having mania and in those with recently remitted mania influences the severity of manic symptoms when compared to healthy control individuals. The study was conducted from November 2001 to February 2007 and the data were analyzed from November 2020 to December 2021.

A cross-sectional study was conducted in a tertiary care referral center for mood disorders in Vancouver, British Columbia, Canada. 26 patients with BD of whom 9 were with current mania and 17 with recently remitted mania were recruited and matched with 21 healthy control individuals. DAT density was measured using positron emission tomography with [11C]d-threo-methylphenidate (MP). Statistical parametric mapping was used to assess the differences between the groups in nondisplaceable binding potential (BPND) for DAT. The main outcome of measurement was DAT density as indexed by BPND for MP across groups; manic symptom severity as measured with the Young Mania Rating Scale (YMRS) and correlated with BPND values in patients with BD. 

Results:

• There were 47 total participants with a mean [SD] age, of 37.8 [14.4] years. Out of which 27 (57.4%) were female. 
• MP BPND was significantly lower in patients with BD in the right putamen and nucleus accumbens as well as left putamen and caudate.
• The reduction in BPND was more extensive and pronounced in patients with current mania, while patients with recently remitted mania had lower BPND in the left striatum but not the right.
• There was a significant negative correlation between YMRS scores and MP BPND in the right striatum in patients with current mania and those with recently remitted mania but not in the left striatum in either group. 

The present study has paved the path for potential implications for drug development for mania. As the study results show that mania was associated with reduced DAT density while remitted mania patients had DAT levels similar to normal individuals. 

Further reading: Yatham LN, Liddle PF, Gonzalez M, et al. A Positron Emission Tomography Study of Dopamine Transporter Density in Patients With Bipolar Disorder With Current Mania and Those With Recently Remitted Mania. JAMA Psychiatry. Published online November 02, 2022. doi:10.1001/jamapsychiatry.2022.3541