Duration-dependent decline of serum serotonin in Parkinson's disease: a motor-phenotype-stratified case-control study from the South Caucasus

Background. Serotonergic degeneration is an early feature of Parkinson's disease (PD), but its trajectory with advancing disease and its relation to dominant motor phenotype remain incompletely characterised, and no PD serotonergic data have been reported from the South Caucasus. We tested the hypothesis that peripheral serum 5-hydroxytryptamine (5-HT) declines monotonically with PD duration and is most depressed in bradykinesia-predominant disease.

Methods. In a single-centre case-control study (Batumi, Georgia), 50 adults with clinically diagnosed PD (26 women, 24 men; age 40–71 years) were compared with 20 sex-matched healthy controls. Patients on SSRIs, SNRIs, MAOIs or tryptophan supplementation were excluded. Patients were stratified by predominant motor phenotype and by disease duration (≤1, 2–5, 6–10, >10 years). Fasting morning serum 5-HT was quantified by enzyme-linked immunosorbent assay. Welch's t-test, one-way ANOVA with Tukey correction, Pearson correlation with 95% CI and Cohen's d were used; significance was set at p < 0.05.

Results. Serum 5-HT declined monotonically with PD duration (Pearson r = –0.62; 95% CI –0.77 to –0.42; p < 0.001). Patients with duration ≤1 year showed values comparable to controls; those with duration >10 years showed the lowest values. Bradykinesia-predominant patients (n = 24; 48%) showed the largest reduction (2.54 ± 0.15 vs control 6.57 ± 0.44 µmol/L; 61% lower; Cohen's d = 12.2; p < 0.001); tremor-predominant patients (n = 6) showed the smallest decrement. A stable-course subgroup showed a 24% reduction (d = 1.4; p < 0.05). Patients in the lowest 5-HT tertile reported depressive symptoms more frequently than those in the highest tertile (≈68% vs 25%; Fisher's exact p < 0.01).

Conclusions. In this first South-Caucasus PD serotonergic dataset, serum 5-HT showed a duration-dependent decline paralleling stage-dependent central serotonergic attrition demonstrated by ¹¹C-DASB PET, and a motor-phenotype gradient consistent with preferential involvement of akinetic-rigid disease. Within the constraints of a small single-centre cohort and a peripheral biomarker, the findings extend the serotonergic literature to a previously unrepresented population and inform the design of a planned multicentre Georgian study with MDS-UPDRS, PDQ-39, and validated depression instruments.

Keywords  Parkinson's disease; serotonin; 5-hydroxytryptamine; non-motor symptoms; depression; case-control studies; Georgia (Republic); South Caucasus