Striatal dopamine transporter imaging in Parkinson’s disease drug-naïve patients: focus on sexual dysfunction

Abstract

Introduction Dopamine is involved in sexual behavior, but dopaminergic imaging studies establishing the relationship between nigrostriatal dopaminergic degeneration and sexual dysfunction (SD) in Parkinson’s disease (PD) are lacking. Methods We retrospectively analyzed clinical and 123I-FP-CIT SPECT data of 43 drug-naïve PD patients. Based on the sexual function domain of the Non-Motor Symptoms Scale (NMSS), we identified 23 patients with sexual concerns (WSC), reporting a score ≥ 2 due to hyposexuality, and 20 patients without sexual concerns (NoSC). Dopamine transporter (DAT) uptake was assessed through semi-quantitative analysis in the most and least affected putamen (maP, laP), and most and least affected caudate (maC, laC). Total putamen-to-caudate ratio and total striatal binding ratio (tSBR) were also quantified. Results WSC and NoSC had similar demographic and disease-related characteristics. WSC displayed lower uptake values in maC (p = 0.016), maP (p = 0.004), laC (p = 0.019), laP (p = 0.009), and tSBR (p = 0.006). Pearson correlation analysis revealed, in the WSC group, moderate inverse correlations between the log-transformed SD scores and the uptake in maP (r = − 0.473, p = 0.023), maC (r = − 0.428, p = 0.042), laP (r = -0.437, p = 0.037), and tSBR (r = − 0.460, p = 0.027). After controlling in a two-way ANCOVA model for age and sex, between-group differences,between WSC and NoSC remained statistically significant only for dopaminergic denervation in maP [F(1,38) = 7.478, p = 0.009)], laP [F(1,38) = 4.684, p = 0.037)], and tSBR [F(1,38) = 5.069, p = 0.030]. Conclusion To the best of our knowledge, this is the first study reporting the relationship between the severity of SD and specific patterns of nigrostriatal dopaminergic denervation (especially involving both putamina) in newly diagnosed drug-naïve PD patients.

Striatal dopamine depletion drives disease progression and network topology aberrations specifically by impairing left M1 network

“…Previous studies reported that striatum SBR was associated with autonomic dysfunction in PD patients, 18–21 which was consistent with our findings observed in current study. We revealed FC between left M1 and bilateral middle cingulate gyri mediated the effects of striatal dopamine depletion on autonomic dysfunction, suggesting impaired left M1 subnetwork also contributed to autonomic dysfunction in PD patients.…”

“…70–72 In this study, striatum SBR was negatively associated with SCOPA-AUT scores, which was consistent with previous studies showing autonomic dysfunction in PD was associated with striatal dopamine depletion. 18–21 Cognitive impairment was also one of the most common non-motor features of PD patients 73 and associated with disease progression and outcome. 73–75 Cognitive impairment could occur at the early stage and even prodromal phase of PD.…”

“…5,6 Striatal binding ratio (SBR) in striatum measured by DAT-SPECT has been demonstrated to be associated with motor manifestations, including rigidity, 7,8 resting tremor, 9 and bradykinesia. 8 Apart from its associations with motor symptoms, striatum SBR was also linked to multiple non-motor symptoms, such as RBD, 10 cognitive impairment, 10–13 anxiety, 10 apathy, 14 depression, 15,16 impulse control disorders, 17 sexual dysfunction, 18 urinary dysfunction, 19 cardiovascular dysfunction, 20 gastrointestinal dysfunction, 21 and olfaction loss. 22 Taken together, striatum SBR is an essential indicator of dopaminergic neurodegeneration in PD, which intimately correlated with both motor and non-motor symptoms.…”

Sexual dysfunction precedes motor defects, dopaminergic neuronal degeneration, and impaired dopamine metabolism: Insights from Drosophila model of Parkinson’s disease

“…Drosophila has been widely used as a model animal to study NDDs like PD as they share the same types of neurotransmitter systems like gamma-aminobutyric acid (GABA), glutamate, DA, serotonin, and acetylcholine, and can perform complex behaviors viz., sexual display, social behavior, and learning ( Botella et al, 2009 ). SD in PD seemed to be multifactorial with no single cause identified ( Brown et al, 1990 ) but the involvement of DA remains one of the most important factors ( Heaton, 2000 ; Contaldi et al, 2022 ). However, very little is known about the SD mechanisms involved in sporadic PD.…”

“…Studies have shown that DA in the hypothalamus plays a role in regulating sexual behaviors, however, the detailed mechanism of SD in PD is not known ( Sakakibara et al, 2011 ). A study reported the relationship between the severity of SD and specific patterns of nigrostriatal dopaminergic (DAergic) denervation (especially involving both putamina) in newly diagnosed drug-naïve PD patients ( Contaldi et al, 2022 ). The understanding of the function and regulation of the behavioral circuits involved in mating will have potential implications for the medical treatment of SD in humans ( Emmons and Lipton, 2003 ).…”