C. Schotte

Construct validity of the Beck Depression Inventory in a depressive population

This study investigates the construct validity of the Beck Depression Inventory (BDI) in a large population of DSM-III unipolar depressive inpatients. The BDI correlates weakly with the Hamilton scale and differentiates between minor, major and melancholic/psychotic unipolar depressive subgroups. Factor analysis of the BDI resulted in psychological/cognitive (BDIPSY) and somatic/vegetative (BDISOM) subscales. The BDISOM subscale displayed a narrower relationship with the depression construct, as evidenced by a better differential validity and by significant effects for the DST non-suppression response. The present findings generally lend support to the construct validity of the BDI in depressive populations.

An evaluation of basal hypothalamic-pituitary-thyroid axis function in depression: Results of a large-scaled and controlled study

In order to evaluate the function of the hypothalamic-pituitary-thyroid (HPT)-axis in unipolar depression, the authors measured basal 0800h plasma levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) by means of the new, ultrasensitive assays (TSH-IRMA) in 69 healthy controls, 62 minor, 101 simple major, and 57 melancholic depressed subjects. Basal HPT-axis hormone levels of almost all (96.8%) unipolar depressed patients fell within the normal, euthyroid range. None of the major depressed subjects showed subclinical hypothyroidism. It was found that 8.8% of the melancholic subjects exhibited some degree of subclinical hyperthyroidism. Basal TSH-IRMA values were significantly lower in melancholic patients than in healthy controls, minor and simple major depressed patients, and in major vs. minor depressed subjects. FT4 circulating levels were significantly higher in melancholic patients than in all other subjects. Basal TSH-IRMA and FT4 levels were significantly correlated with severity of illness. In depression, there was a significant and negative correlation between basal TSH-IRMA values and FT4 concentrations. No significant gender- or age-related differences in TSH-IRMA or thyroid hormones were detected in depression. It is argued that--in depression research--the assays of basal TSH-IRMA should replace thyrotropin releasing hormone tests.

Immune disorders in depression: higher T helper/T suppressor‐cytotoxic cell ratio

This study investigated the leukocyte T helper and T suppressor‐cytotoxic cell (sub)set profile of minor, simple major and melancholic depressives versus normal controls. Using both monoclonal antibody staining and flow cytometry, we determined the absolute numbers and percentages of the following T cell immune subsets: T helper (CD4+), T virgin (CD4+ CD45+), T memory (CD4 + CD45‐), T suppressor/cytotoxic (CD8 +), CD8 + T suppressor (CD8 + CD57 ‐) and CD8 + T cytotoxic (CD8 + CD57 +) cells. After computing the CD4+/CD8 + ratio, we detected a significantly increased ratio in depressed patients as compared with healthy controls. Depression per se is characterized by a higher percentage of CD4+ and a lower percentage of CD8+CD57‐ cells. Melancholic depressed subjects exhibit a significantly increased number of CD4+ and CD4+ CD45‐ cells. The combined use of various percentages of CD4+ and CD8+ (sub)sets yields a high degree of marker positivity for melancholia: through cumulative evaluation of those percentages, the marker positivity increases to 68% (sensitivity) and the specificity is 95%. These results together with our previous reports may refer to a depression‐related state of T cell activation.

A revised interpretation of the TRH test results in female depressed patients

Thyrotropin secreting hormone (TSH) levels were recorded in baseline conditions and 20 and 60 min after thyrotropin releasing hormone (TRH) administration (200 micrograms i.v.) in 60 depressed females categorized according to DSM-III. Basal TSH (TSHB) and peak TSH responses (TSHP) were measured using ultrasensitive RIA assays. The use of delta max TSH (TSHP minus TSHB) had no advantage over the use of TSHP since both factors were almost linearly (r = 0.98) correlated. TSHP was largely (72% of the variance) predicted by TSHB. It was suggested that TSHP consisted of two components. The first part was a relative deduction from TSHB. The second part was the newly proposed concept of the residual TSH (TRHR). This part was computed by partialling out the relative effects of TSHB on TSHP by means of regression analysis. In clinical practice two relevant factors should be used to evaluate the hypothalamic-pituitary-thyroid (HPT) axis: (1) TSHB reflecting the setpoint of the HPT axis and (2) TSHR reflecting the latent capacity of the HPT axis to respond to overwhelming amounts of exogenous TRH. TSHB was significantly reduced in severely depressed patients (296.X3, 296.X4) as compared with minor depressives (300.40, 309.00). These differences could be attributed to significantly increased free thyroxine levels and to noradrenergic hyperactivity in the severely depressed females. TSHR correlated significantly and negatively with follicle stimulating hormone levels, age, body mass index and the post-dexamethasone cortisol values. TSHR was significantly reduced in the post-menopausal state.

Anthropometric and biochemical assessment of the nutritional state in depression: evidence for lower visceral protein plasma levels in depression

Severe depression is characterized by anorexia and weight loss, symptoms that could endanger the patients nutritional state. In order to investigate the nutritional state of depressed patients we determined the following in 113 healthy controls and depressed inpatients: (1) anthropometric variables such as body weight, ideal body weight (IBW), percentage of IBW, mean arm circumference, triceps skinfold thickness and arm muscle circumference, and (2) biochemical parameters such as albumin (Alb), prealbumin (Prealb), and transferrin (Tf). We were unable to detect any differences in the anthropometric parameters between healthy controls, minor and major depressed patients. Depressed patients exhibited significantly lower Alb and Tf levels than healthy controls. The drop in both plasma proteins was highly sensitive (72%) and specific (92%) for melancholia. These results may point towards the existence of a disorder in protein homeostasis or protein malnutrition without a marasmic component.

Regional cerebral blood flow in unipolar depression measured with Tc-99m-HMPAO single photon emission computed tomography: Negative findings

Recent studies have reported that patients with unipolar major depression may show a lower whole brain cerebral blood flow (CBF) and reduced regional CBF in frontal, temporal, and parietal lobes. The present study used single photon emission computed tomography (SPECT) with the CBF marker Tc-99m-hexamethylpropyleneamineoxine (HMPAO) to measure the cortical CBF of six individual regions of interest (ROIs), total ROI, and left or right hemispheric total ROI in 43 unipolar depressed subjects and 12 normal control subjects. There were no significant differences in the distribution of Tc-99m-HMPAO uptake into total ROI, right or left global ROI, prefrontal, motor frontal, parietal, temporal, visual cortex, or associative visual cortex between patients with melancholic depression, simple major depression, or minor depression and healthy control subjects. There were also no significant differences in the right-left distribution of uptake between the patients and the control subjects. Hypoperfusion was observed in motor frontal and parietal cortex of patients who had been taking benzodiazepines during the study period. It is concluded that cortical CBF, as assessed with Tc-99m-HMPAO SPECT, is relatively intact in the present sample of patients with severe depression.

A study on the blunted natural killer cell activity in severely depressed patients

Recently, some investigators have established a blunted natural killer cell activity (NKCA) in severely depressed patients. In order to replicate these findings NKC cytotoxicity assays--on fresh cell suspensions in human plasma and fetal calf serum--were performed in healthy controls and depressed inpatients. Instead of the commonly used 51Cr-release assay we have used a fluorescent NKC cytotoxicity assay, which allows a greater sensitivity. We observed a significantly blunted NKCA in melancholic patients as compared with healthy controls and minor depressives, whilst simple major depressives exhibited an intermediate position. NKC cytotoxicity assays in fetal calf serum were significantly and negatively correlated with the severity of illness. We were unable to establish any relationship between NKCA and measures of hypothalamic-pituitary-adrenal-axis function, such as baseline, postdexamethasone plasma cortisol and 24 hr urinary cortisol secretion. In addition, we did not find any effects of dexamethasone administration (1 mg orally) on NKCA.

Clinical subtypes of unipolar depression: Part I. A validation of the vital and nonvital clusters

Cluster analyses were carried out on a sample of 100 depressed females. The study was based on the 14 items relevant to depressive phenomenology of the Structured Clinical Interview for DSM-III-R (SCID). Our findings support the existence of two classes, i.e., a vital (melancholic) vs. a nonvital cluster. The vital cluster is characterized by the following symptoms: a distinct quality of depressed mood, nonreactivity, early morning awakening, anorexia-weight loss, and cognitive and psychomotor disturbances. Patients belonging to the vital cluster exhibit disorders in the hypothalamic-pituitary-adrenal and thyroid axes and a markedly decreased availability of L-tryptophan to the brain. The vital depressives score significantly higher on the Hamilton Rating Scale for Depression as compared to those suffering from nonvital depression. The cluster-analytically derived class of vital depression and the DSM-III subtype of melancholia tend to be quite similar. Our findings support the isolation and the descriptive validity of a vital (melancholic) depressive syndrome.

A significantly increased number and percentage of B cells in depressed subjects: results of flow cytometric measurements

Recently, there have been some reports that depression may be accompanied by indices of polyclonal B cell proliferation. In order to examine whether depression is characterized by an altered B cell subset profile we determined the number and percentage of the following B cells: HLADR+, CD19+, CD20+, and CD21+. We found a significantly increased number of HLADR+ and CD19+ B cells in depressed subjects compared with normal controls. Depressed patients exhibited a significantly higher percentage of HLADR+ and CD21+ B cells than normal controls. The number of CD21+ cells and the percentage of CD19+ cells were higher in melancholics than in normal controls. The increase in the number of the various B cells was highly sensitive (63%) and specific (94%) for melancholia. Our results may indicate B cell proliferation in depression, and particularly in melancholia.

Sex‐linked differences in cortisol, ACTH and prolactin responses to 5‐hydroxy‐tryptophan in healthy controls and minor and major depressed patients

ABSTRACT— Some researchers have found that the administration of 5‐hydroxytryptophan (5‐HTP) results in increased cortisol secretion in major depressives but not in healthy controls. Other authors observed gender‐related differences in cortisol responses to 5‐HTP in major depressives. In order to investigate the pituitary/adrenal responsivity to 5‐HTP, the authors measured cortisol, adrenocorticotropic hormone (ACTH) and prolactin (PRL) in 30 healthy controls and in 90 depressed patients; the hormone levels were determined in baseline conditions and 60, 90 and 120 min after 125 ma L‐5‐HTP (orally, non‐enteric coated). We found [hat healthy men had significantly higher cortisol responses to L‐5‐HTP than healthy women. In the major depressives with melancholia and/or psychotic features these differences were reversed: women exhibited significantly higher cortisol and PRL responses than men. In the female group the most severely depressed patients had increased cortisol and PRL responses to L‐5‐HTP. The amplitudes of the cortisol, ACTH and PRL responses to L‐5‐HTP were significantly and positively correlated. It was concluded that the central serotonergic regulation of ACTH and PRL is significantly different between the sexes and between healthy controls, minor depressives and severely depressed patients.