Thyrotrophin response to thyrotrophin-releasing hormone in unipolar and bipolar affective illness

The plasma levels of thyrotrophin (TSH) and the response of this hormone to 200 microgram of thyrotrophin-releasing hormone (TRH) were studied in 27 unipolar and 24 bipolar depressive patients before and after amitriptyline treatment as well as in 42 normal controls. There was no significant difference in basal TSH levels between any of the groups studied according to diagnosis, menopausal status and antidepressant treatment. Before treatment, the TSH response to TRH was significantly lower in the unipolar and bipolar depressive patients than in normal controls. The TSH response to TRH did not differ significantly between the unipolar and bipolar depressives. When menopausal status was taken into account, the TSH response to TRH was significantly blunted in the unipolar postmenopausal patients when compared to postmenopausal controls. In the bipolar group, the premenopausal depressive patients had a significantly lower TSH response to TRH than premenopausal controls. After amitriptyline treatment, the TSH response to TRH, which was impaired before treatment in the bipolar premenopausal patients, improved significantly. However, no significant difference in the TSH response to TRH could be demonstrated after treatment in the unipolar postmenopausal patients in whom the TSH response was blunted before treatment. Our findings suggest that the differential TSH response to TRH in unipolar and bipolar patients may constitute biological markers of endocrine dysfunction in clinical subgroups of affective disorders.     

A linkage study of manic-depressive disorder with HLA antigens, blood groups, serum proteins and red cell enzymes

Families with a two-generational history of affective disorder and well and ill sibs were selected from a population of bipolar manic-depressive patients and typed for HLA antigens, blood groups, serum proteins and red cell enzymes. Segregation of specific HLA alleles was not associated with affective illness across family pedigrees. Further, no significant associations were found between affective disorder and ABO, Rh, MNSs blood groups or Hp, EsD, C3, Gc or PGM. Using the lod score method of Morton (1955) for determining linkage, these data indicated that close linkage is unlikely for affective disorder and HLA alleles, haptoglobin, Rh factor, or ABO blood groups.     

Concordance of atopic and affective disorders

The personal and family history of bronchial asthma and/or hay fever was obtained from a series of 82 psychiatric patients. We report a significantly higher incidence of atopic disorders in affective patients (16/48) than in schizophrenic patients (2/34) (chi-square = 8.754, P less than 0.005). There was also a significantly higher incidence of atopic disorders among the first-degree relatives of patients with affective disorders (48/356) than among the first-degree relatives of patients with schizophrenia (10/182) (chi-square 8.501, P less than 0.005).     

Assortative mating in affective disorders

Assortative mating was determined in 170 spouses of patients with major affective illness (bipolar and unipolar). An increase in affective disorders was found in both wives of affected men and husbands of affected women. The data suggest that assortative mating is present in the familial transmission of affective disorder.     

Major histocompatibility antigen expression in the liver in acquired immunodeficiency syndrome

Human leukocyte antigen (HLA) class I molecules are normally detected on most nucleated cells, but not on hepatocytes, while the expression of HLA class II antigens is mainly restricted to certain cell types of the immune system. This normal distribution pattern may be altered in human liver in a variety of disorders, particularly in infectious and immune diseases. In view of multiple infections and severe immune alterations in acquired immunodeficiency syndrome (AIDS), we studied the expression of HLA class I and class II antigens in liver obtained at autopsy from ten patients with AIDS and eight control patients, using a panel of monoclonal antibodies and the indirect immunofluorescence method. In spite of viral bacterial, and fungal infections, HLA class I antigens were detected on hepatocytes in only two patients with AIDS. Human leukocyte antigen class II antigens were found unexpectedly on bile duct epithelium in five of ten patients with AIDS and in one of eight control patients. The aberrant HLA class II antigen expression on bile ducts does not appear to be linked to bile duct damage or infection with cytomegalovirus or other agents, but may be related to immune alterations in patients with AIDS.     

HLA antigen frequencies and natural history in Alternaria-sensitive and perennial nonallergic asthmatics

The frequency of HLA-A, -B, and -C loci antigens in random populations of Alternaria-sensitive (N = 100) and perennial nonallergic asthmatics (N = 87) were compared with age- (±5 yr) and sex-matched controls from the same geographic region. There was no association between HLA antigens as measured by frequency analyses and Alternaria-sensitive or perennial nonallergic asthma. Moreover there was no association between HLA antigens and the age of onset of asthma, associated allergic disorders, various environmental factors provoking asthma, total serum IgE levels, and Alternaria-specific IgE antibody.     

Evidence for nonlikage of genes for HLA and hereditary angioedema

Since the genes for several disorders of the complement system have been found to be linked to the HLA loci on chromosome 6, studies of the inhibitor of the activated first component of complement (Cl INH) and HLA in two families with hereditary angioedema (HAE) were undertaken. A total of 17 individuals were found to be affected in these three-generation families. Evidence was provided against close linkage of the genes for HLA and HAE. Other genetic markers studied were generally noninformative, although evidence was obtained against close linkage of the loci for HAE and ABO and HAE and transferrins. The reliable identification of individuals affected with HAE by Cl INH assay provides potential for establishing linkage relationships in the various phenotypes of this dominantly inherited condition.     

Serological identification of a non-HLA antigen in Oriental populations.

In a routine HLA antibody screening cross-match test using the complement-mediated lymphocytotoxicity (LCT) assay, we discovered an antibody, in a transfused Caucasian woman, recognizing an Oriental restricted antigen that does not appear to be associated with the human leukocyte antigen (HLA) system. The distribution of this 'novel' antigen in Oriental populations and its frequency in the Taiwanese Chinese population are reported.     

Serological identification of a non‐HLA antigen in Oriental populations

In a routine HLA antibody screening cross‐match test using the complement‐mediated lymphocytotoxicity (LCT) assay, we discovered an antibody, in a transfused Caucasian woman, recognizing an Oriental restricted antigen that does not appear to be associated with the human leukocyte antigen (HLA) system. The distribution of this ‘novel’ antigen in Oriental populations and its frequency in the Taiwanese Chinese population are reported.     

Brief communication: HLA antigen frequencies in renal cell carcinoma

HLA-A, B, and C antigen frequencies were studied in 38 Caucasian patients with a history of renal cell carcinomas; 30 were also tested for DR antigen frequencies. The results failed to indicate any significant deviations from normal Caucasian HLA antigen frequency distributions. These results were inconsistent with a previous study that indicated a very significant increase in the frequency of the antigen DR5 among renal cell cancer patients.     

Autoimmunity,HLA, Gm AND Km Polymorphisms in Turner's Syndrome

Considering the high frequency of autoimmune disorders in Turner's syndrome and the close relationship between autoimmunity, HLA and immunoglobulin constant region gene polymorphisms, we studied 46 patients with Turner's syndrome, by determination of autoantibodies, HLA histoglobulins and Gm and Km allotypes. OSA and in particular PCA resulted significantly more frequent in patients than in the controls. A higher frequency of HLA-A31, B38 antigens and of blanks at HLA-A locus was found in Turner's subjects than in the controls. A31 was significantly more frequent in autoantibody positive patients while B38 was more frequent in autoantibody negative Turner's subjects than in the controls. DR4 antigen was present only in autoantibody negative patients. Gm 3; 23; 5* phenotype was significantly less frequent, while Gm 3; 5* phenotype was more frequent in patients than in controls. Our data confirm the higher incidence of autoimmunity disorders in Turner's syndrome than in normal subjects. Particular HLA and immunoglobulin types seem to mark this condition. The increase in the blank frequency at A locus could be explained by the presence of a rare antigen at HLA-A locus or a particularly elevated homozygous condition in these subjects.     

HLA System and Affective Disorders: A Sibship Genetic Study

The authors have investigated HLA-haplotype zygotic assortment in 21 families with multiple cases of affective disorders and in 19 sibling pairs discordant for the disease. The finding of excess similarity between affected sibs stressed the possibility of the existence of genes in the HLA chromosomal region which are involved in the susceptibility to affective disorders. The mode of inheritance of such an hypothesized DS gene was also tested and some theoretical implications are discussed.     

Generic human leukocyte antigen class II (DRB1 and DQB1) alleles in patients with paracoccidioidomycosis.

Human leukocyte antigen (HLA) class II alleles are involved in antigen processing and in the presentation of antigens to T lymphocytes. Few studies have investigated HLA genes in paracoccidioidomycosis. In the present investigation, we analyzed the distribution of the HLA class II alleles DRB1 and DQB1 in 45 healthy volunteers and in 80 patients with paracoccidioidomycosis. The patients presented with various clinical forms of the disease, and allele distribution was evaluated individually in each presentation type. In patients with the unifocal chronic form of the disease, a mild clinical presentation in which lesions are restricted or localized, the HLA allele most commonly seen was DRB1*11 (p<0.039). This suggests that the participation of HLA antigens may influence the outcome of the host-parasite interaction in paracoccidioidomycosis, regulating the immune response to Paracoccidioides brasiliensis antigens.     

Should ‘non-Feighner schizophrenia’ be classified with affective disorder?

Narrow definitions of schizophrenia increase homogeneity at the expense of leaving unclassified many patients with shizophrenic symptoms. Family history and follow-up studies indicate that many such patients ought to be classified with those having affective disorders. This study determines morbid risks for affective disorder and schizophrenia in first degree relatives of patients with chart but not research diagnoses of schizophrenia. Comparisons with morbid risk figures for relatives of individuals satisfying research criteria for depression, mania or schizophrenia indicate that the 'non-Feighner schizophrenia' group is probably too heterogenous to be classified entirely as affective disorder or as schizophrenia.     

X-linkage in bipolar affective illness: Perspectives on genetic heterogeneity,pedigree analysis and the X-chromosome map

The search for genetic markers is a powerful strategy in psychiatric genetics. The present article examines four areas relevant to discrepancies among X-linkage studies in bipolar affective disorder. These are questions of ascertainment, analytic methods, the X-chromosome map and genetic heterogeneity. The following conclusions are reached: (a) Positive linkage findings cannot be attributed to ascertainment bias or association between affective illness and colorblindness. (b) The possibility that falsely positive linkage results were obtained by using inappropriate analytic methods is ruled out. (c) Reported linkages of bipolar illness to colorblind and G6PD loci are compatible with known map distances between X-chromosome loci. Linkage to the Xg antigen remains uncertain. (d) The discrepancy among the various data sets on affective illness and colorblindness is best explained by significant linkage heterogeneity among pedigrees informative for the two traits.     

HLA haplotypes and TNF polymorphism do not associate with longevity in the Irish

Polymorphism of the human leukocyte antigen has been implicated in a number of autoimmune disorders including ageing. In the course of the present study, no association of the human leukocyte antigen (HLA)-A1, B8, DR3 haplotype with a male Irish aged population, as previously reported, was observed. Two polymorphic nucleotides in the TNF cluster (G-308A TNF-alpha and G+252A TNF-beta), associated with increased TNF-alpha production, were shown to be in tight linkage disequilibrium with the class I and II HLA loci, generating HLA haplotypes with extended linkage disequilibrium. However, no age-related allele or genotype frequencies were observed for either polymorphic nucleotide.     

HLA-A, B and DR antigens in patients with gonadal dysgenesis

HLA (human leukocyte antigens) antigens A, B, and DR were determined in a series of 50 patients with gonadal dysgenesis (GD), separated into different groups according to karyotype. There were no significant differences in frequency of HLA antigen types between GD patients and the population control. When frequencies of the HLA antigens in the various GD patient groups by karyotype were compared, only one significant difference was found: HLA-A3 was more common among GD patients with isochromosome X than among GD patients with karyotype 45, X (p<0.001, corr. p<0.008). Although GD patients have a higher expectancy for development of autoimmune disorders, and in our 50 patients thyroglobulin and/or microsomal antibodies were detected in 20 (i.e., 40%), we failed to find any increased frequency of specific HLA antigen types known to be associated with juvenile autoimmune thyroiditis.     

The characterization of depressive disorders in serious juvenile offenders

The authors systematically evaluated a selected population of juvenile offenders for the prevalence of affective disorders. Seventy-one (40 male, 31 female) serious juvenile offenders were interviewed using the Schedule for Affective Disorders and Schizophrenia (SADS). They were then diagnosed using the Research Diagnostic Criteria (RDC) and the DSM-III. The Hamilton Rating Scales (HRS), Carroll Self-Rating Scale (CSRS), and Global Rating Scale for Depression (GRS) were also obtained for each subject. Eleven (15%) subjects were diagnosed as having an active major depressive disorder (MDDa), 6 (8%) subjects were diagnosed as having a major depressive disorder in remission (MDDr), and 9 (13%) as having a minor depressive disorder (mDD). The HRS, CSRS, and GRS differentiated the MDDa from the other three groups including MDDr, mDD and all other psychiatric diagnoses. RDC subtypes of depressive disorders were identified in those juvenile offenders with active major depressive disorders (MDDa) and compared to a population of hospitalized adolescents with major depressive disorders. There were significant differences in the distribution of the subtypes identified. Secondary, gitated and endogenous subtypes occured significantly more often. The diagnostic, prognostic and therapeutic significance of these findings are discussed.     

Medical-psychiatric unit patients compared with patients in two other services

Two hundred patients in a medical-psychiatric unit (MPU) were compared with equal numbers seen in a liaison-consultation service (LCS) and in a psychiatric inpatient unit (PIU). Statistically significant (P<.05) differences were found in the three populations. Compared with LCS patients, MPU patients were characterized by a higher prevalence of bipolar affective disorders and schizophrenia, a shorter length of stay, lower social class, lower requirements for medical care, and medical illnesses apparently not causally related to the psychiatric disorder. The findings suggest that the MPU and LCS each serve a specific and definable segment of patients with concomitant physical and psychiatric disorders. The ideal design of an MPU is discussed.