A positron mission tomography study of dopamine transporter density in patients with bipolar disorder with current mania and those with recently remitted mania

Abstract

IMPORTANCE: Although dopamine is implicated in the pathophysiology of bipolar disorder (BD), the precise alterations in the dopaminergic system remain unknown. OBJECTIVE: To assess dopamine transporter (DAT) density in the striatum in patients with BD with current and recently remitted mania in comparison to healthy control individuals and its correlation with severity of manic symptoms. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study conducted in a tertiary care referral center for mood disorders in Vancouver, British Columbia, Canada, recruited 26 patients with BD (9 with current mania; 17 with recently remitted mania) and 21 matched healthy control individuals. DAT density was measured using positron emission tomography with [11C]d-threo-methylphenidate (MP). The differences between the groups in nondisplaceable binding potential (BPND) for DAT was assessed using statistical parametric mapping. The study was conducted from November 2001 to February 2007 and the data were analyzed from November 2020 to December 2021. MAIN OUTCOMES AND MEASURES: 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: Of 47 total participants (mean [SD] age, 37.8 [14.4] years), 27 (57.4%) were female; 26 individuals had BD (9 with current mania and 17 with recently remitted mania) and there were 21 healthy control individuals. MP BPND was significantly lower in patients with BD in the right putamen and nucleus accumbens (mean reduction [MR] = 22%; cluster level familywise error [FWE]-corrected P < .001) as well as left putamen and caudate (MR = 24%; cluster level FWE-corrected P < .001). 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 (ρ = -0.93; 95% CI, -0.99 to -0.69; P < .001) and those with recently remitted mania (ρ = 0.64; 95% CI, -0.86 to -0.23; P = .005) but not in the left striatum in either group. CONCLUSIONS AND RELEVANCE: These findings indicate that mania was associated with reduced DAT density and remitted mania was associated with DAT levels that approximated those present in individuals without BD. These results have potential implications for drug development for mania.