Progression of nonmotor symptoms in subgroups of patients with non-dopamine-deficient Parkinsonism.

BACKGROUND: Ten to fifteen percent of Parkinson's disease (PD) patients recruited to clinical trials have scans without evidence of dopaminergic deficit, whose presence represents a heterogeneous patient population. METHODS: A cohort of 41 patients with parkinsonism and scans without evidence of dopaminergic deficit at baseline, were subdivided into groups according to their final clinical diagnoses and nigrostriatal dopamine function assessed after 2 years of study. At follow up, 23 patients had clinically probable PD or unclassified parkinsonism with normal nigrostriatal dopamine imaging ("true" scans without evidence of dopaminergic deficit), nine were diagnosed with another tremulous condition, five had psychogenic parkinsonism, and four had phenoconverted to PD with reduced nigrostriatal dopamine function. We analyzed nonmotor symptoms at baseline and follow-up in subgroups of patients with scans without evidence of dopaminergic deficit in comparison with a random sample of 62 PD patients and 195 healthy controls (HCs). All patients were enrolled in the Parkinson's Progressive Marker's Initiative. RESULTS: Patients who had true scans without evidence of dopaminergic deficit had more severe rapid eye movement sleep disorder, depression, anxiety, and autonomic dysfunction than HCs in addition to more frequent depressive symptoms and worse cardiovascular dysfunction than patients with PD (P = 0.038, P = 0.047, respectively). Patients with true scans without evidence of dopaminergic deficit had normal olfaction that was significantly better than that of patients with PD (P < 0.001). Subgroup analysis of the cohort with scans without evidence of dopaminergic deficit revealed that all patients shared similar nonmotor features irrespective of their final clinical diagnoses. Follow-up of subject groups showed stable nonmotor symptoms over 2 years of study. CONCLUSIONS: At an early symptomatic stage, patients with scans without evidence of dopaminergic deficit and long-standing parkinsonism exhibit nonmotor features that differ from those of patients with PD on mood and cardiovascular and olfactory function, but remain similar to patients with scans without evidence of dopaminergic deficit with alternative final diagnoses.

2D:4D ratio in children at familial high-risk for eating disorders: The role of prenatal testosterone exposure.

OBJECTIVES: Markers of prenatal hormone exposure have been associated with the development of eating disorder (ED) behaviors. Our aim was to determine whether 2D:4D ratio, a marker for in utero testosterone exposure, is associated with risk for ED in a large population-based cohort: the Avon Longitudinal Study of Parents and Children (ALSPAC). METHODS: This is the first study to investigate prenatal testosterone exposure in children at high-risk for ED, using 2D:4D as a marker. We compared children whose mothers reported a lifetime ED (anorexia, bulimia, or both; N = 446) to children whose mothers did not (n = 5,367). RESULTS: Daughters of women with lifetime bulimia nervosa (BN) had lower 2D:4D ratio (B: -0.01, 95% CI: -0.02 to -0.002, P = 0.02), indicating higher prenatal testosterone exposure, than daughters of mothers unaffected by ED. No differences were observed in the male children of women with an ED. CONCLUSIONS: Findings suggest that children at high-risk for BN may be exposed to higher levels of testosterone in utero. Fetal exposure to androgen excess is thought to be causal in the development of polycystic ovary syndrome (PCOS), a disorder which is highly comorbid with binge eating and BN. Future research should investigate the potential role of testosterone exposure in utero as a risk factor for BN and binge eating.