Arabic version of the Global Mental Health Assessment Tool-Primary Care version (GMHAT/PC): a validity and feasibility study.

Mental health services are far from satisfactory in the Eastern Mediterranean Region. The Global Mental Health Assessment Tool-Primary Care version (GMHAT/PC) is a semi-structured, computerized clinical assessment tool that was developed to assist health workers in making quick, convenient and comprehensive standardized mental health assessments. A study was carried out in the United Arab Emirates to evaluate the validity and feasibility of the Arabic version of the GMHAT/PC. Mental health nurses administered the GMHAT/PC Arabic version to 50 patients in mental health and rehabilitation settings and their GMHAT/PC diagnosis was compared with the psychiatrist's independent ICD-10 based clinical diagnosis on the same patients. The nurses found GMHAT/PC easy to administer in an average of 16 minutes. The GMHAT/PC-based diagnosis had a good agreement with the psychiatrist's diagnosis (kappa = 0.91) and a high sensitivity (97%) and specificity (94%).

The role of pterins in depression and the effects of antidepressive therapy.

Urinary excretion of neopterins (N) and biopterins (B) was measured in 48 patients with depression before and after treatment with placebo, antidepressants, or electroconvulsive therapy (ECT), and in 26 healthy control subjects. Patients prior to and after treatment had a significantly greater neopterin/biopterin (N:B) ratio than control subjects. There was a significant correlation between N:B ratios and the severity of depression and plasma cortisol. As a raised N:B ratio implies failure to convert neopterin to biopterin, it is possible that reduced availability of tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, serotonin and dopamine, may exert rate-limiting control over the synthesis of monoamines implicated in the pathogenesis of depressive illness.

Hormonal aspects of postpartum depression.

Plasma cortisol, prolactin, oestrogen, progesterone, thyroxine, thyrotrophin (TSH) were collected from 23 pregnant, 70 postpartum women at 7 days postpartum, and 38 non-gravid controls. Sixty two postpartum women were screened for depression by the Edinburgh Postnatal Depression Scale (EPDS) on day 7 after delivery and 34 of them were assessed by the Present State Examination (PSE) at 8 +/- 2 weeks after delivery. Postpartum women had a significantly greater level of cortisol, prolactin, thyroxine and oestrogen than non-puerperal women. Postpartum women with current depression (EPDS > or = 11) had significantly lower plasma prolactin levels than those without depression and those who developed depression within 6-10 weeks after delivery (PSE level > or = 5) had significantly lower plasma prolactin and significantly greater progesterone levels than those who were not depressed. There were significant correlations between age and plasma cortisol and prolactin levels. Higher thyroxine levels predicted greater severity of concurrent symptoms of depression (total EPDS score) whilst higher progesterone and lower prolactin levels predicted the occurrence of depression (total PSE score) 6-10 weeks after delivery. Women who breastfed had significantly lower EPDS and total PSE scores and higher plasma prolactin levels than those who did not breastfed their infants whilst women who had previous episodes of depression had significantly greater EPDS and PSE scores, lower prolactin and higher TSH levels than those who had not suffered from previous episodes of depression.

Platelet 5-HT uptake sites, labelled with [3H] paroxetine, in controls and depressed patients before and after treatment with fluoxetine or lofepramine.

Platelet [3H] paroxetine binding was measured in 73 depressed patients and in 64 healthy volunteers. No differences were found in Bmax or Kd either overall, or when the 61 depressed subjects who had never received psychotropic drugs were analysed separately. Within the depressed group, no differences in Bmax or Kd were found between subgroups divided on the basis of endogenicity, suicidal thoughts or severity of depression. None of the subgroups differed significantly from controls. Forty of the depressed subjects were retested after 6 weeks' treatment with fluoxetine (n = 22) or lofepramine (n = 18). Treatment was not associated with any change in Bmax but a similar and significant increase in Kd was noted following treatment with either antidepressant. Neither pre- nor post-treatment platelet binding parameters appeared to relate to clinical response to treatment.

The efficacy of low-dose lithium: clinical, psychological and biological correlates.

The relationships between lithium dosage, affective morbidity, side-effects, thyroid and renal function and biological markers for depression were examined in the context of a prospective double-blind lithium reduction study in patients receiving prophylactic lithium. Unipolar and bipolar patients on such treatment were randomly allocated to two groups over a period of one year, either continuing with their usual dosage of lithium or reducing their lithium dosage by up to 50%. Biological markers investigated included dexamethasone suppression test (DST) and 5-hydroxytryptamine (5-HT) transport into platelets (Vmax). Results showed no association between affective morbidity and lithium dosage/level. There was, however, an association between lower dosage/level of lithium and lower side-effects, including tremor and weight gain, lower TSH levels and lower 24 h urinary volume in these patients. Elderly patients, however, experienced significantly greater morbidity upon reduction of their lithium dosage. There was an association between increased Vmax of 5-HT transport and a reduction in morbidity. DST non-suppression was associated with lower mean weight for the whole year of the study.

The biology of folate in depression: implications for nutritional hypotheses of the psychoses.

Folate deficiency is a common occurrence in psychiatric disorders, whether organic or functional, particularly in depressive illness. We have shown that folate deficiency is a common association of depressive symptoms in a variety of settings including primary endogenous or non-endogenous depression, and in alcoholic, lithium-treated and anorexic patients. Possible pathogenetic mediating mechanisms for this association are methylation and hydroxylation and the implications for nutritional hypotheses of the psychoses are discussed. We suggest that folate deficiency, with or without deficiencies of other nutritional factors such as monoamine precursors, vitamins B6, B12 and C, may predispose to or aggravate psychiatric disturbances, particularly depression and a model for these interactions is proposed.

Dexamethasone suppression and energy balance: a study of anorexic patients.

The performance of the dexamethasone suppression test (DST) was investigated in 45 female anorexic out-patients (cross-sectional study) and in nine female anorexic in-patients (longitudinal study). DST non-suppression was strongly associated with negative energy balance (low body weight and low Ponderal Index) but there was no significant association with the presence of affective or neurotic disturbance in these patients. These findings cast doubt on the value of the DST in the management of depressive illness.

The role of pterins and related factors in the biology of early postpartum depression.

Plasma tryptophan and other putative amino acids, cortisol, folate and vitamin B12 and urinary biopterin (B) and neopterins (N) were measured in three groups of women: 62 women in the early postpartum period, 23 pregnant and 38 non-gravid controls. Sixty-two postpartum women were screened for depression by the Edinburgh postnatal depression scale (EPDS) on day 7 after delivery. Postpartum women had significantly lower tryptophan, vitamin B12 and significantly greater levels of cortisol, folate, neopterins and biopterins than controls. Comparisons between women who were classified on the EPDS as cases and non-cases revealed only a statistically significant difference for lower N:B (P<0.01) and lower folate (P<0.01) ratio in cases than non-cases. Multiple regression analysis showed a significant contribution for low tryptophan to increased EPDS which also showed significant correlations with low methionine, low tyrosine, low N:B ratio and high vitamin B12.

Platelet MAO, personality and response to lithium prophylaxis.

Patients with bipolar affective disorder and who were maintained on long lithium prophylaxis were evaluated retrospectively regarding response to lithium. Good responders to lithium prophylaxis were compared to non-responders and to normal controls on platelet MAO activity, and on psychological variables (Eysenck's extraversion, neuroticism, psychoticism and lie scale; Foulds' extrapunitiveness, intropunitiveness and dominance). Lithium responders, non-responders and normal controls had similar platelet MAO activity. There was a tendency for higher plasma lithium levels to be associated with higher platelet MAO activity in male patients but not in females. Lithium non-responders exhibited significant correlations between their platelet MAO activity and their test scores on psychoticism, and extraversion. Lithium non-responders, compared to responders and normals, showed abnormal personality profiles on neuroticism, and dominance.

Who responds to prophylactic lithium?

Response to prophylactic lithium was studied in relation to clinical and psychological characteristics in a large series of patients with recurrent affective disorders. The findings were that bipolar patients with a family history of mania or depression had more favourable responses than those with no family history of affective disorders. Unipolar patients with more endogenous illnesses and those with pure familial depressive disease had more favourable responses than those with less endogenous illnesses and those with sporadic and depression spectrum diseases. Good responders showed generally less personality disturbance on a variety of measures than fair-to-poor responders. Response to lithium over 6 months in unipolar illness and over the first year in bipolar illness was strongly associated with long-term response.

Classification of depressive illness. Clinico-psychological correlates.

347 patients with primary depressive illness were studied. Patients were classified on the Newcastle Diagnostic Scale and their depression was rated on the Hamilton Rating Scale for Depression (HRS) and self-rated on the Beck Depression Inventory (BDI). Clinical and personality factors were studied in relation to classification. Personality was measured by the Eysenck Personality Questionnaire, Fould's Personality Deviance Scale, the Marke-Nyman Temperament Scale and the Crown-Crisp Experimental Index. The frequency distribution of the Newcastle scores of all 347 patients was unequivocally unimodal. Significant positive correlations were obtained between patients' Newcastle scores, age, and HRS scores but not with BDI scores. Patients with non-endogenous depression showed clinical and personality differences compared with those with endogenous depression, and with a group of bipolar depressives.

Problems in validating endogenous depression in the Arab culture by contemporary diagnostic criteria.

This study highlights the difficulties that may be encountered in attempting to apply the clinical construct of endogenous depression derived from western studies to depressed Arab patients. The agreement between 4 operational systems on the diagnosis of endogenous (melancholic) depression is explored in 100 patients with primary depressive disorder in Al-Ain, United Arab Emirates. The symptom characteristics of the 61 patients in whom all diagnostic systems agreed are then described quantitatively and qualitatively. Subjects were evaluated by the Newcastle scale, Hamilton's 21 item depression scale, global assessment of functioning scale, and the operational criteria of the diagnostic systems used. Diagnosis of endogenicity was derived by computer according to the respective criteria. The agreement between DSM-IV, ICD-10, and RDC criteria is moderately high (0.72). When the Newcastle Index is included, it is only moderate (0.58). Disagreements are related to differences in diagnostic criteria. Small differences affect concordance appreciably. DSM-IV agreed with a majority of external validators, differentiating a more homogeneous groups of patients. In the present study, endogenous depression identified by western criteria, was less likely to manifest by guilt feelings, a distinct quality of mood, and loss of libido. The descriptions of patients reveal that the mood component of depression is expressed differently, somatic metaphors are used frequently to express distress, religious elements influence the expression of symptoms, and depression may manifest in behaviours not directly indicative of the disorder. Endogenous depression may be identified in the Arab culture, but considerable variation in its component symptom frequencies and mode of expression needs to be taken in consideration for defining it in terms appropriate to the culture.

Apparent supersensitivity of platelet 5-HT receptors in lithium-treated patients.

An increased 5-HT-induced platelet aggregatory response was seen in bipolar and unipolar patients who were being treated with lithium prophylactically. The responses were not related to the patients' lithium levels or affective morbidity. The results are discussed with reference to the action of antidepressive treatments on 5-HT receptor systems in the platelet and the CNS.

Clinical correlates of response to DST. The Dexamethasone Suppression test in depression: a World Health Organisation collaborative study.

From 9 centres 293 patients took part in the WHO-collaborative study on Dexamethasone-Suppression-Test (DST) in depression to examine the relationship of psychopathological and psychiatric history information to cortisol-levels and suppression/non-suppression status. Differences between the centres were large and significant on nearly all of the measures. The predictor analyses generally suffered from numerically weak correlations with many variables correlating to sex and age. Therefore analyses of the data were adjusted for centre-, sex-, and age-influences. The best predicting features of cortisol were 'fitful, restless sleep', 'change of bodyweight' and 'affective disorders in blood relatives'. The last 2 items together with 'hypersomnia' and 'ideas of insufficiency' were the best predictors of suppression/nonsuppression status. However, statistical evidence did not seem to be strong enough to describe a typical symptom profile of a depressive cortisol suppressor or nonsuppressor.

Neuroendocrine studies in affective disorders. Part 1. Plasma prolactin response to thyrotropin-releasing hormone in affective disorders: effect of ECT.

The plasma prolactin response to thyrotropin-releasing hormone, which is thought to be mediated by central 5-HT mechanisms, has been studied in patients with affective disorders. There was no difference between depressive patients (taken as a whole), bipolar patients undergoing a manic phase and controls in the prolactin response to thyrotropin-releasing hormone. When the depressive patients were divided on a genetic basis into familial pure and sporadic depressive disease it was found that the sporadic patients had an enhanced response. The results do not provide any strong evidence to suggest that central 5-HT mechanisms as measured by the prolactin response to thyrotropin-releasing hormone are abnormal in depressed patients or bipolar patients undergoing a manic phase. Patients after ECT had an increased prolactin response to thyrotropin-releasing hormone which may indicate increased sensitivity of central 5-HT receptors following this treatment.

Neuroendocrine studies in affective disorders. Part 2. Plasma thyroid-stimulating hormone response to thyrotropin-releasing hormone in affective disorders: effect of ECT.

The plasma thyroid-stimulating hormone response to thyrotropin-releasing hormone in controls and patients with affective disorders has been studied. The results of the investigation do not suggest any abnormality of this response in monopolar or unipolar depressed patients or bipolar patients undergoing a manic phase of their illness. No significant difference in this response could be detected between 'sporadic depressive disease' patients and 'familial pure depressive disease' patients, and age- and sex-matched controls. The neuroendocrine response was essentially unchanged after treatment by ECT.

Treatment of bipolar affective illness with zimeldine, a 5-HT uptake inhibitor.

A small group of patients who had been successfully treated with lithium for a number of years were treated with zimeldine in order to determine whether this antidepressant could be substituted for lithium in patients with a bipolar affective illness. The proposed treatment period of 6 months was not reached by any patient due to depression, hypomania, mania or unusual adverse symptoms. The results of this pilot study suggest that bipolar patients being treated with lithium should not then be treated by antidepressants including those which are potent and selective inhibitors of 5-HT uptake.

Single photon emission tomography with 99m Tc-HMPAO in Arab patients with depression.

BACKGROUND: This study investigates the rate of cerebral blood flow (rCBF) in Arab patients wth depression. METHODS: Forty-four patients with DSM-III-R major depressive disorders were studied at rest using single photon emission computerized tomography (SPECT) with 99m Tc-HMPAO in comparison with 20 normal controls. All patients were assessed using the Hamilton Rating Scale for Depression (HRSD). RESULTS: The depressed group showed greater rCBF in left and right posterior frontal and parietal cortical regions than normal controls. Within the depressed group, patients with the least severe illness (HRSD < 20) had significantly lower rCBF than normal controls, whilst those with moderately severe (HRSD 20-29) and severe (HRSD > 30) had significantly greater rCBF in most cortical regions than normal controls. Symptom scores, derived from the HRSD were predicted by rCBF principally increased rCBF in the left frontal cortex. CONCLUSIONS: These results suggest a generalized cerebral activation principally in the frontal cortex which is in contrast to the results of most previous studies but more in line with the results of studies of induced affect and some studies of depression subsyndromes.

5-Methyltetrahydrofolate level in the serum of depressed subjects and its relationship to the outcome of ECT.

Serum 5-MeTHF levels are reported in 26 subjects, before and after completing a course of ECT, and compared to 21 healthy volunteers. 5-MeTHF levels of depressed subjects were significantly lower than controls before and after ECT. There was no difference in 5-MeTHF levels between ECT responders and non-responders but folate deficiency was related to severity of depression before ECT. Serum 5-MeTHF was not related to treatment response and values remained markedly low even after a good response to treatment.

Predictors of response to amine-specific antidepressants.

Discriminant function analysis of data from a double-blind comparative trial of lofepramine (a noradrenaline-specific reuptake inhibitor) and fluoxetine (a serotonin-specific reuptake inhibitor), involving 183 patients was used to identify predictors of response. Psychic anxiety significantly predicted a positive response to antidepressant medication, whereas psychomotor retardation, observed sadness, subjective lassitude and somatic complaints were significant predictors of nonresponse. Age, gender, endogenicity, duration of illness and number of previous episodes were not predictive of response. Significant differences were found between predictors of response to fluoxetine and lofepramine (P < 0.001 all groups). Predictors of response to lofepramine were similar to overall predictors, i.e., psychic anxiety predicted responders whilst observed sadness, psychomotor retardation, lassitude, inability to feel and somatic complaints predicted nonresponders. In contrast, baseline weight loss predicted response to fluoxetine, whereas anxiety, reduced insight and a tendency to blame others significantly predicted nonresponse. Such findings have practical implications for the management of depressive illness.