David M. Martin

The TRH test in the diagnosis of major and minor depression.

Abstract (1) The effect of TRH on TSH and GH release was studied in 144 consecutive psychiatric admissions. The magnitude of the TSH response to TRH differentiated unipolar from clinically similar and dissimilar groups. (2) Of 41 patients with unipolar depression, 31 had a ΔTSH of ≤7 μI.U./ml while only 1 of 12 bipolar and 0 of 10 minor depressive patients had a ΔTSH of ≤7 μI.U./ml. (3) A ΔTSH of ≤7 μI.U./ml is a frequent finding in unipolar depression and infrequently associated with other psychiatric diagnoses. (4) The data reported support the hypothesis that patients with a ΔTSH of ≤7 are unipolar depressives. (5) Six of 12 bipolar and 17 of 41 unipolar depressives had a GH response to TRH while none of the patients with a minor depression had a significant GH response. These data suggest that major and minor depressions can be separated on the basis of the TRH-induced GH response test. (6) The magnitude of the TRH-induced TSH response and the presence of a pathological GH response may be extremely useful in differentiating manics from schizophrenics and other similarly appearing patient groups. (7) The TRH test is useful in clinical differential diagnosis of dysphoric states and as a confirmatory laboratory test for major depressive disease and unipolar depression.

TRH-induced TSH response in unipolar, bipolar, and secondary depressions: Possible utility in clinical assessment and differential diagnosis

Abstract (1) The effect of TRH on TSH and GH release was studied in 32 depressed patients. (2) Patients were diagnosed as having a primary (unipolar or bipolar) or secondary depression and rated with Hamilton ratings at the time of TRH testing. (3) The magnitude of the TRH-induced TSH responses significantly differentiated unipolar and bipolar depressed patients who had similar symptoms, cortisol secretion, and Hamilton ratings. (4) GH responses to TRH were only observed in primary affective, depressed patients. (5) The fact that bipolar depressives had augmented TSH responses while unipolar patients had blunted TSH responses supports the clinical differentiation of these patients and suggests that different neurobiological factors may be involved in these clinically similar states. TRH-induced TSH response may ‘switch’ from augmented to blunted as the patients clinical state changes from depressed to manic. (6) The neural mechanism mediating these TRH test data is difficult to discern on the basis of current studies reported in the literature.

Beta-endorphin decline in late luteal phase dysphoric disorder.

The β-endorphin hypothesis of late luteal phase dysphoric disorder (premenstrual syndrome or L2D2) was tested. Twenty-two PMS patients were compared to twenty-two controls. Levels of β-endorphin, ACTH, FSH, LH, cortisol, prolactin and TRH were measured on the first and twentieth days after menses. PMS subjects exhibited a significantly greater drop in the opiate, β-endorphin, (p < .001) than controls. No relationship or significant e was seen with the other hormones/transmitters tested. The symptoms of PMS may be due to noradrenergic rebound following β-endorphin decline. Symptomatic and pharmacological morphine withdrawal and manic phase of bipolar disorder are discussed as possible models for L2D2.

The thyroid-stimulating hormone response to thyrotropin-releasing hormone in mania and bipolar depression

The release of thyroid-stimulating hormone (TSH) from the pituitary after infusion of 500 microgram of thyrotropin-releasing hormone (TRH) was decreased (p < 0.01) in manic patients and increased (p < 0.01) in bipolar depressed patients compared to a control group of patients with personality disorders. These results suggest that the TRH test may be useful in the diagnosis of psychiatric disorders and in the prediction of response to pharmacotherapy. We discuss the role of central monoaminergic systems in changes in the TSH response to TRH.

Symptoms of premenstrual syndrome as a function of beta-endorphin: Two subtypes

1. Forty six women presenting with symptoms of premenstrual syndrome (PMS) were studied. Ages ranged from 21 to 32. All women answered a questionnaire based on DSM-III-R criteria. They then had serum beta-endorphin levels drawn on day 1 and day 20 of their menstrual Cycle. 2. Beta-endorphin levels were compared with symptom presentation. Such symptoms as anxiety, food cravings and physical discomfort were associated with significant decline in beta-endorphin. Other symptoms were found equally distributed in both groups. The existence or absence of beta-endorphin decline in specific PMS subgroup was postulated.

Thyroid Stimulating Hormone and Growth Hormone Responses to Thyrotropin Releasing Hormone in Anorexia Nervosa

Ten female patients who satisfied objective criteria for the diagnosis of anorexia nervosa were given 500 ug of thyrotropin releasing hormone. Thyroid stimulating hormone and growth hormone responses were measured in duplicate by radioimmunoassay. These patients had a low normal Δ thyroid stimulating hormone but a delayed peak response. In addition, these patients had pathological growth hormone release in response to thyrotropin releasing hormone infusion. Both delayed peak thyroid stimulating hormone and growth hormone response to thyrotropin releasing hormone have been reported for patients with hypothalamic disorders.

Prevalence of drug and alcohol use in urban Afghanistan: epidemiological data from the Afghanistan National Urban Drug Use Study (ANUDUS)

BACKGROUNDnPrevious attempts to assess the prevalence of drug use in Afghanistan have focused on subgroups that are not generalisable. In the Afghanistan National Urban Drug Use Study, we assessed risk factors and drug use in Afghanistan through self-report questionnaires that we validated with laboratory test confirmation using analysis of hair, urine, and saliva.nnnMETHODSnThe study took place between July 13, 2010, to April 25, 2012, in 11 Afghan provinces. 2187 randomly selected households completed a survey, representing 19u2008025 household members. We completed surveys with the female head of the household about past and current drug use among members of their household. We also obtained hair, urine, and saliva samples from 5236 people in these households and tested them for metabolites of 13 drugs.nnnFINDINGSnOf 2170 households with biological samples tested, 247 (11·4%) tested positive for any drug. Overall, opioids were the most prevalent drug in the biological samples (5·6%), although prescription drugs (prescription pain pills, sedatives, and tranquilliser) were the most commonly reported in the past 30 days in the questionnaires (7·6%). Of individuals testing positive for at least one substance, opioids accounted for more than 50% of substance use in women and children, but only a third of substances in men, who predominantly tested positive for cannabinoids. After controlling for age with direct standardisation, individual prevalence of substance use (from laboratory tests) was 7·2% (95% CI 6·1-8·3) in men and 3·1% (2·5-3·7) in women-with a national prevalence of 5·1% (4·4-5·8) and a prevalence of 5·0% (4·1-5·8) in Kabul. Concordance between laboratory test results and self-reports was high.nnnINTERPRETATIONnThese data suggest the female head of household to be a knowledgeable informant for household substance use. They also might provide insight into new avenues for targeted behavioural interventions and prevention messages.

Nortriptyline plasma levels and clinical response in patients with familial pure unipolar depression and blunted TRH tests

We studied the efficacy of nortriptyline (NT) when given in doses which produce tricyclic antidepressant (TCA) levels within the proposed therapeutic “window” in a select patient group to assess the “window” hypothesis in a group of patients that was biologically homogeneous with respect to the TRH test and clinically homogeneous with respect to RDC, DSM III, and Winokur criteria. Pharmacokinetic and dose differences were controlled for by administering a NT dose-prediction test, giving the indicated dose, allowing levels to reach steady state and changing the dose, if necessary, to maintain NT levels within the range of 90–130 ng/ml. Using this protocol nine of ten patients responded to NT. This rate of response for a severely depressed patient group is comparable to response data for ECT and recent European data using regular NT levels to change doses of NT and assess appropriate NT trial duration.

Clinical Laboratory Aspects of Eating Disorders

Clinical laboratory studies have only recently been applied to the diagnosis and treatment of eating disorders. The most remarkable laboratory investigations in this area have been in etiology and sequelae of anorexia nervosa and bulimia nervosa. Although distinct medical illnesses, both anorexia and bulimia have a spectrum of clinically overlapping symptoms that also may exist with other disorders such as depression, substance abuse, and endocrinopathies. The accurate diagnosis of the specific underlying or coexisting disorders associated with the clinical presentations of anorexia or bulimia is essential for the development of an effective treatment strategy. Clinical laboratory studies routinely provide physicians with a means of objectively assessing the medical status of patients and can also provide invaluable information on the course and medical condition of anorectic and/or bulimic patients. The following provides an overview of the clinical utility and cost effectiveness of a variety of laboratory studies in the diagnosis and management of the anorectic and/or bulimic patient.