Trends in Maori mental health in Otago.

OBJECTIVE: This paper outlines the methods used, and preliminary descriptive data collected, in a study on a cohort of Maori and non-Maori patients admitted to the inpatient psychiatric services in Otago between 1990 and 1992. METHOD: The notes of 42 Maori and 217 non-Maori first admissions to psychiatric inpatients were reviewed. Information concerning this admission was entered onto a database and analysed. RESULTS: The Maori admission rate was 4 per 1000 compared with 1 per 1000 for non-Maori people. This was higher than expected based on Otago population figures. Rates of family psychiatric history did not differ between Maori and non-Maori. Although Maori were found to have higher rates of social welfare support and were more likely to have no academic qualifications the differences were not significant. The sources of referral for Maori admissions were more likely to be from the law, and Maori were more likely to have had prior psychiatric inpatient treatment. The most common diagnosis for Maori and non-Maori was depressive disorders, and suicidal behaviour was common. CONCLUSIONS: Maori are overrepresented among first psychiatric inpatient admissions in Otago. They appear to be a more disadvantaged group with respect to financial support, academic qualifications and other health problems. The most common diagnosis did not differ between Maori and non-Maori cohorts.

Familial bipolar disorder: preliminary results from the Otago Familial Bipolar Genetic Study.

OBJECTIVE: This paper outlines the methodologies used, and preliminary descriptive data collected, on a cohort of familial bipolar disorder (BPD) probands and first-degree relatives taking part in a descriptive and genetic study into familial BPD in New Zealand. METHOD: Fifty-five bipolar probands and 67 first-degree relatives were interviewed using the modified Diagnostic Interview for Genetic Studies (DIGS) and Family Interview for Genetic Studies (FIGS). Data was also collated from other sources. Blood samples were taken for DNA genomic analysis. RESULTS: New Zealand families in which BPD segregates proved willing participants in this familial based genetic research. The methodologies used were acceptable. High rates of comorbidity were found in probands (27.3% met DSM-IV criteria for panic disorder/sub-threshold panic disorder; 12.7% for phobic disorder; 1.8% for obsessive-compulsive disorder; 9.1% for alcohol-related disorders and 7.3% for an eating disorder) and relatives (major depression 34.3%; panic disorder/sub-threshold panic disorder 12.0%; phobias 11.9% and alcohol-related disorders 11.9%). The polarity of index BPD illness was related to age of onset and frequency of comorbidity. Suicidal behaviour was common. CONCLUSIONS: Psychiatric genetic research in New Zealand families is highly feasible. Emerging trends in the familial transmission of BPD include high rates of comorbidity, illness patterns based on polarity of index episode and frequent suicidal behaviour. Such trends will be delineated further as numbers accrue, perhaps enabling identification of more homogenous phenotypic subgroups than currently produced by diagnostic schemes.

Moderate dieting causes 5-HT2C receptor supersensitivity.

Dieting is a widespread behaviour in developed countries, which in predisposed individuals can lead to the development of clinical eating disorders such as bulimia nervosa and anorexia nervosa. We studied the effect of moderate dieting in healthy women on the prolactin response to the serotonin (5-HT) receptor agonist, m-chlorophenylpiperazine (mCPP), a measure of the sensitivity of post-synaptic 5-HT2C receptors. Dieting significantly increased the prolactin response to mCPP and lowered plasma concentrations of the 5-HT precursor, tryptophan. We propose that dieting in women is associated with the development of functional supersensitivity of 5-HT2C receptors, probably in response to lowered levels of brain 5-HT. Alterations in brain 5-HT neurotransmission could play a part in dieting-induced dysregulation of eating and the development of clinical eating disorders in predisposed individuals.

Dieting decreases plasma tryptophan and increases the prolactin response to d-fenfluramine in women but not men.

We studied the effect of 3 weeks of moderate calorie restriction on 5-HT-mediated prolactin (PRL) release in healthy volunteers using the 5-HT-releasing agent d-fenfluramine. In women, dieting significantly lowered plasma total and free tryptophan (TRP) and increased the PRL response to d-fenfluramine. None of these measures were altered in men who dieted. These findings add to the data indicating that dieting alters brain 5-HT function in women, perhaps as a consequence of reducing the availability of plasma TRP.

m-Chlorophenylpiperazine decreases food intake in a test meal.

We studied the effect of the 5-HT receptor agonist, m-chlorophenylpiperazine (mCPP) (0.4 mg/kg), on food intake in 12 healthy female volunteers, in a double-blind placebo controlled design. Compared to placebo, mCPP significantly lowered food intake in a test meal. Treatment with mCPP also caused significant increases in ratings of nausea and light-headedness, though these effects had remitted by the time of the test meal. The results suggest that activation of brain 5-HT2C receptors may lower food intake in humans; it is also possible, however, that the hypophagic effect of mCPP in the present study could be a consequence of its adverse subjective side effects.

Attenuation of the prolactin-stimulating and hyperthermic effects of nefazodone after subacute treatment.

The acute administration of the antidepressant drug nefazodone (100 mg orally) to healthy male volunteers increased prolactin concentrations in plasma and elevated oral temperature. After repeated treatment with 100 mg of nefazodone twice daily for 7 days, these effects were attenuated. We propose that the ability of nefazodone given acutely to increase prolactin concentrations and oral temperature is mediated via metabolism to the 5-hydroxytryptamine1C (5-HT1C) receptor agonist meta-chlorophenylpiperazine. The attenuation of these effects after subacute treatment could be due to an adaptive down-regulation of 5-HT1C receptors or to direct blockade of 5-HT1C receptors by nefazodone and its metabolite hydroxynefazodone (OH-nefazodone), the concentrations in plasma of which increase substantially during the 7-day treatment period.

Effect of acute tryptophan depletion on mood and appetite in healthy female volunteers.

Twelve healthy female subjects received the following three drinks in a double-blind, semi-balanced, cross over design: (a) 50 g of amino acids without L-tryptophan (LTP); (b) 50 g of amino acid with LTP (balanced); (c) plain water. Compared to both the balanced amino acid mixture and plain water, the LTP drink significantly lowered plasma total and free tryptophan at 4.5 h. However, compared to the two control conditions, there was no effect of the LTP drink on subjective ratings of mood or hunger. Similarly, the LTP drink did not alter significantly either total calorie intake or the macronutrient content of a test meal 5 h after drink ingestion.

Neuroendocrine and temperature effects of nefazodone in healthy volunteers.

The effects of a novel antidepressant, nefazodone (50 mg, 100 mg, and 200 mg orally) on neuroendocrine function and temperature were assessed using a single-blind, crossover design in eight healthy male volunteers. Nefazodone significantly increased plasma levels of prolactin (PRL) and raised oral temperature. There was also a trend towards an increase in plasma cortisol. These results are consistent with an acute facilitatory effect of some aspects of 5-HT neurotransmission, perhaps mediated through nefazodone's metabolism to its major metabolite, m-chlorophenylpiperazine (mCPP).

Lithium and 5-HT1A receptor sensitivity: a neuroendocrine study in healthy volunteers.

The effect of lithium administration (800 mg daily for 7 days) on the neuroendocrine and temperature responses to the 5-HT1A receptor agonist, gepirone, was studied in eight healthy male volunteers. Gepirone (20 mg orally) significantly increased plasma levels of prolactin, growth hormone, corticotropin and cortisol, and lowered oral temperature. None of these responses was significantly altered by lithium treatment. The results suggest that the ability of short-term lithium treatment to increase 5-HT-mediated neuroendocrine responses in humans is unlikely to be related to changes in the sensitivity of pre- or post-synaptic 5-HT1A receptors.