Neuroendocrine evidence of normal hypothalamus-pituitary dopaminergic function in Huntington's disease.

OBJECTIVES: In addition to neuronal loss in striatum and cerebral cortex that characterizes Huntington's disease (HD), hypothalamic atrophy has also been found only in certain areas, probably not including dopaminergic functions. METHODS: We assessed the reactivity of the hypothalamus-pituitary dopaminergic system by measuring the acute prolactin (PRL) responses to 5 mg i.m. haloperidol in male and female HD patients and in female subjects with expanded CAG repeats in the Huntington gene before disease onset, as well as in a group of healthy males. RESULTS: The responses of the male patients were similar to those of a group of male healthy volunteers. Females gave higher PRL responses, with no differences in the response patterns of female patients and females at risk for HD. PRL elevations were not related to severity of illness, or to presence of dementia, depression, or psychotic features. CONCLUSIONS: The results implicate a normal dopaminergic input from hypothalamus to pituitary and preserved pituitary dopamine receptors, indicating that hypothalamic atrophy in HD does not affect mechanisms involved in PRL secretion by haloperidol.

Plasma homovanillic acid and prolactin in Huntington's disease.

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.

Plasma testosterone, dehydroepiandrosterone sulfate, and cortisol in female patients with Huntington's disease.

OBJECTIVE: The neuronal loss in several brain regions that characterize the progression of Huntington's disease (HD), is expected to influence the activities of hypothalamus-adrenal and hypothalamus-gonadal axes, and the changes may relate to common features of the disease, like depression and dementia. While in male HD patients low plasma testosterone levels have been reported, information on female patients is lacking. METHODS: We assessed the plasma levels of the androgens total testosterone (TT) and dehydroepiandrosterone sulfate (DHEAS), as well as of cortisol in 41 female patients with HD, confirmed by determination of the CAG repeat number in the IT-15 gene, and searched for associations to the disease symptomatology. We also included a group of 18 females with expanded CAG repeat number in the HD gene (subjects at risk), and a group of 66 age-matched healthy females. Hormone levels of the pre- and post-menopausal subgroups were also compared separately. RESULTS: Significant negative correlations to age were found for TT and DHEAS in both control (age range 20-71 years) and patient (age range 26 to 78 years) groups, and the calculated decline per year was around 1% for TT and 1.5% for DHEAS. There were no significant differences in hormone levels among patients, subjects at risk and controls, either in premenopausal or in postmenopausal state. The subgroup of patients with depression in their symptomatology had significantly lower TT and DHEAS levels compared to patients without depression, or to controls. CONCLUSIONS: While TT and DHEAS seem to decline with age in female patients with HD to the same extend as for healthy females, the presence of depression, but not dementia, in their symptomatology, is connected to lower ovary-adrenal androgen levels.

Illness behaviour in neurological inpatients with psychiatric morbidity.

OBJECTIVE: The aim of the present study was to examine whether psychiatric morbidity can influence the type of illness behaviour of neurological inpatients. METHODS: For this purpose, we compared neurological inpatients with and without psychiatric disorders (DSM-IIIR criteria) for the seven scales of Illness Behaviour Questionnaire (IBQ) and searched for possible differences between the two patient subgroups. RESULTS: Of the 105 neurological inpatients who participated in the study, 54 (51.4%) were diagnosed as having some type of psychiatric disorder. These patients scored significantly higher than patients without psychiatric morbidity in the scale of Irritability. A suggestive trend for higher scores in the scales of Hypochondriasis, Disease Conviction, and Affective Disturbance, and significantly lower score in the scale of Denial, in patients with psychiatric morbidity, were also found. CONCLUSION: The present study has shown that neurological inpatients with psychiatric morbidity tend to develop more intense illness behaviour than those without. The effect of psychiatric morbidity on certain components of illness behaviour in neurological patients can be taken into account when therapeutic strategies are planned.

Plasma testosterone in male patients with Huntington's disease: relations to severity of illness and dementia.

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms and by a progressive loss among other, of dopaminergic receptors in striatum, cortex, and hypothalamus. Central dopaminergic activity has been implicated in the regulation of sex hormones. Several features of testosterone deficiency, such as reduced muscle mass, depressive mood, and cognitive impairment, are often present in HD patients, but data on their testosterone levels are lacking. We assessed plasma levels of testosterone, LH, and FSH in 42 male patients with HD, confirmed by molecular genetic analysis, and searched for differences from age-matched healthy male subjects and for relations to CAG repeat number, age, age range, 26 to 76 (mean, 50.7 +/- 12.3) years; duration of illness range, 1 to 23 (mean, 6.7 +/- 6.3) years; and CAG repeat numbers from 40 to 65 (45.1 +/- 3.8). Disease symptomatology was assessed using the Unified Huntington's Disease Rating Scale. Testosterone and LH levels of the patients were significantly lower compared to the levels of 44 age-matched (mean age, 48.9 +/- 13.0, range, 26-76 years) healthy men. Severity of illness was negatively related to plasma testosterone levels. Further, low testosterone levels were associated with dementia but not with depression or psychotic features. Clinical studies with selected HD patients are needed to evaluate possible beneficial effects of androgen substitution therapy on cognitive functions, depression, muscle mass and strength, general well-being, and, eventually, neuroprotective effects.