Plasma Homovanillic Acid and Prolactin in Huntington’s Disease

Abstract

Dopaminergic activity is expected to be altered in patients with Huntington's disease (HD) and be related to factors like duration and severity of illness or patients' specific symptomatology like dementia, depression, or psychotic features. We assessed plasma homovanillic acid (pHVA) and plasma prolactin (pPRL), two correlates of dopaminergic activity, in 116 subjects with CAG repeats expansion in the HD gene, 26 presymptomatic (18 females) and 90 with overt symptomatology (43 females). Patients were evaluated using the Unified HD Rating Scale and the Total Functional Capacity Scale. Presence of dementia, depression, and psychotic features were also assessed. The age range of the patients was 22-83 years, duration of illness from 0.5 to 27 years, and CAG repeat number from 34 to 66. A group of 60 age and sex matched healthy subjects served as control group. Plasma PRL in subjects at risk and in neuroleptic-free patients, evaluated separately for males and females, did not differ from controls. Plasma HVA levels did not differ from controls in the group of presymptomatic subjects, but were significantly higher in the patients group. This increase was positively associated mainly with severity of illness and functional capacity of the patients, and not with presence of depression or dementia. Plasma HVA levels may be proven to be a peripheral index of disease progression. Reducing dopaminergic activity may have not only symptomatic, but also neuroprotective effects in HD.

Altered thyrotropic and lactotropic axes regulation in Huntington’s disease

“…the human homologue of the arcuate nucleus in rodents), or the loss of pituitary D 2 receptor expression as described in the R6/2 mice 28 could both underlie the irregular pattern of prolactin secretion in patients with HD. The diminished regularity of prolactin secretion even in our cohort of medication‐free patients with early‐stage HD may also account for the inconsistencies in findings from previous studies on prolactin levels in HD subjects, 7,11,16,17 because the irregular pattern of prolactin release as assessed by a single or a few baseline measurements is unlikely to be properly demonstrated. It remains to be established to what extent the irregular pattern of prolactin secretion in HD could lead to abnormal responses to physiological stimuli of prolactin release, such as stress 8 .…”

“…Compared to thyrotropic axis function, lactotropic axis activity in patients with HD has been investigated more intensively 15 . Nevertheless, as prolactin levels in patients with HD have been reported to be unchanged, 10,16 increased, 11 or even decreased, 17 it still remains unknown whether the lactotropic axis is indeed affected in HD or whether altered prolactin levels are merely a consequence of antidopaminergic medication use in HD. The discordances in findings regarding thyrotropic and lactotropic axes functioning in HD are likely because of the use of a few baseline measurements of hormone levels or long blood sampling intervals which are not adequate to assess either the pulsatile nature of TSH and prolactin secretion or their total daily production rates 18 …”

Environmental enrichment rescues female-specific hyperactivity of the hypothalamic-pituitary-adrenal axis in a model of Huntington's disease

“…The available findings suggest that dopaminergic input from the hypothalamus to the pituitary is not significantly altered in asymptototic HD gene carriers as shown by prolactin and homovanillic acid measures, although differences become apparent post-onset. 42, 43 Previous studies of HD endocrinology have been limited, with findings of reduced HPG axis activity in separate studies examining male 37 and female 38 patients. Interestingly, female testosterone and dehydroepiandrosterone sulphate hormone decline is similar between HD patients and controls, except for those patients with depression, who show significantly lower levels.…”

Variability of Plasma Homovanillic Acid Over 13 Months in Patients with Schizophrenia; Relationship with the Clinical Response and the Wisconsin Card Sort Test

“…measurements vary together or that the peripheral contribution remains relatively stable [17]. Moreover, various authors have found a relationship between the pHVA levels and the severity of certain psychiatric and neurological pathologies [18][19][20][21][22]. Overall, these results suggest that, under controlled conditions, this plasma metabolite may well reflect changes which occur in cerebral dopaminergic activity, especially when measured in response to pharmacological stimuli.…”