The clinical and therapeutic potentials of dehydroepiandrosterone and pregnenolone in schizophrenia.

Neurosteroids such as dehydroepiandrosterone (DHEA), pregnenolone (PREG), and their sulfates (DHEAS and PREGS) display multiple effects on the central nervous system. Specifically, neurosteroids have various functions associated with neuroprotection, response to stress, mood regulation, and cognitive performance. In addition, neurosteroid levels are altered in stress-related neuropsychiatric disorders. This review focuses on the alterations of these neurosteroids in schizophrenia and on their association with clinical and neurocognitive manifestations. As described henceforth, findings from clinical studies have revealed that PREG, DHEA, and their sulfates might be involved in the pathophysiology of schizophrenia, and in some of its manifestations. Clinical trials for the evaluation of these neurosteroids face challenges in terms of experimental design, dosing strategy, data analysis, and interpretation. The review concludes with a list of suggested topics for future research. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Phospholipid patterns of erythrocytes in schizophrenia: relationships to symptomatology.

The phospholipid composition of red blood cells (RBC) from 32 haloperidol-treated schizophrenic patients, classified according to the positive and negative syndrome scale (PANSS) as showing either predominantly positive or predominantly negative symptoms, was determined and compared with that of normal controls. While the levels of phosphatidylcholine and phosphatidylserine were similar in all three groups, sphingomyelin (SM) and phosphatidylethanolamine (PE) were, respectively, increased and decreased in RBCs of schizophrenic patients. In both patient groups, the SM/PE ratios correlated directly with the PANSS negative symptom scale scores and inversely with the positive symptom scale scores. However, the inverse changes in the contents of SM and PE were much more expressed in the negative group. It is suggested that a main source of that difference is a higher activity of the polyunsaturated acid-selective phospholipase A(2) in the negative syndrome patients than in the positive syndrome and control groups.

Suicidal ideation and suicide attempts among immigrant adolescents from the former Soviet Union to Israel.

OBJECTIVE: A community survey was conducted to examine suicidal ideation and suicide attempts, behavior problems, psychological distress, social support, and adjustment difficulties in a sample of adolescents. METHOD: Four hundred six Russian-born Jewish immigrants to Israel, aged 11 to 18 years, were selected to match the age and sex distribution of the total immigrant adolescent population. Two indigenous samples of Jewish adolescents in Russia (n = 203) and in Israel (n = 104) were matched with immigrants for comparison. Parameters of interest were measured with self-administered questionnaires. RESULTS: The 6-month prevalence rate of suicidal ideation in the immigrant sample (10.9%) was significantly higher than that for Russian controls (3.5%) but not for Israeli natives (8.7%). There were few gender differences in suicidal ideation and suicide attempts. Older adolescents reported suicidal ideation 2 times more frequently than their younger counterparts. Suicide ideators scored significantly higher than nonideators on all scales of psychological distress and behavior problems. They rated higher sources of immigration difficulties concerning language, physical health, personality characteristics, and family problems but had less socioeconomic and intercultural problems of migration and lower social support from the family but not from other sources. CONCLUSIONS: Results clearly support the migration-convergence hypothesis of suicide risk among adolescents.

Suicide ideation among recent immigrants to Israel from the former Soviet Union: an epidemiological survey of prevalence and risk factors.

This paper reports results of a national community survey of self-reported suicide ideation and attempts and their relation to psychological distress, depression, social support, and adjustment difficulties in a sample of recent immigrants from the former Soviet Union (FSU) to Israel. Using a door-to-door sampling procedure, a sample of 788 Russian-born Jewish immigrants, ages 18-74 years, was selected to match the age and sex structure of the total immigrant population. An indigenous sample of Jews in Russia (n = 411) was matched with the immigrants for comparison. Parameters of interest were measured with the Demographic Inventory, Talbieh Brief Distress Inventory, Beck Depression Inventory, and Multidimensional Scale of Perceived Social Support. The 1-month prevalence rate of suicide ideation in the immigrant sample (15.1%) was found to be significantly higher than that in Russian controls (6.6%). A total of 5.5% of immigrants but only 0.5% of controls had made a suicide attempt at some time in their lives. Risk factors for suicide ideation included younger age, living without a spouse, low level of social support, being a physician or teacher, a history of immigration from the Baltic countries or Moscow, or duration of stay in Israel from 2 to 3 years. The strongest risk factors were higher level of psychological distress and symptoms such as depression, hostility, and paranoid ideation. These findings can be used as a point of departure for the development of community-based suicide prevention programs for recent immigrants.

Genetic epidemiological study of schizophrenia: two modes of sampling.

The ascertainment of probands according to place of residence in hospitals or in the community has enabled our sampling to be representative of whole subpopulations of patients. Probands from psychiatric hospitals are characterized by biased clinical parameters. Our sampling procedure provides important preliminary results which appear to be contradictory to those produced by conventional sampling methods.

[Genetic epidemiology of schizophrenia in the population of the Tomsk region. Study of clinical polymorphism factors]. / Geneticheskaia épidemiologiia shizofrenii v populiatsii Tomskoi Oblasti. Izuchenie faktorov klinicheskogo polimorfizma.

The contribution of genetic, constitutional and environmental factors to the clinical polymorphism of schizophrenia was analysed. A sample from 353 pedigrees of the patients suffering from the manifest forms of schizophrenia which inhabited five districts of Tomsk region was studied using multifactorial threshold and single locus diallele models. It is established that the severity of the psychosis is mainly determined by autosomal genetic factors, the proportion of the affective disorders being specified by gonosomal factors. The type of the course of schizophrenia is closely connected with the patients' somatotype. Common environmental influences and peculiarities of personality before onset are linked with no characteristics of the clinical polymorphism studied.

[Effect of psychiatric service resources on detection of mentally ill patients in Siberia and Far East (correlation-regression analysis)]. / Vliianie resursov psikhiatricheskoi sluzhby na vyiavlenie psikhicheski bol'nykh v regionakh Sibiri i Dal'nego Vostoka (korreliatsionno-regressivnyi analiz).

Analysis of the character of the linear relation between the totality and some factors (the number of beds, psychiatrists working at hospitals and on an outpatient basis) that characterize the psychiatric services in 18 regions of Siberia and the Far East over 16 years as well as between the identification of new cases of schizophrenia, epilepsy, alcoholism, neuroses, psychoses and oligophrenia has demonstrated a high efficacy of the totality of factors. The differences have been shown between the regions in respect to the relation of the factors to the disease incidence, explained by the authors by the specificity of the organizational structure of the psychiatric services and by a number of other factors.

[Analysis of the interconnection between susceptibility factors to schizophrenia and epilepsy]. / Analiz vzaimosviazi mezhdu faktorami podverzhennosti shizofrenii i épilepsii.

The results of the genetic-correlative analysis of schizophrenia (681 families) and epilepsy (365 families) are given. The presence of various liabilities to these diseases, having genetic correlation of 0.16-0.19 between them, is shown. From epidemiologic data, elevated frequency of convulsive manifestations in schizophrenics and schizophrenia-like psychosis in epileptic patients was established. Within the limits of the three-component hypothesis of etiology of these diseases ("major genes", environmental factors and constitutional readiness), the relation detected is explained by interaction between constitutional readiness factors.

[Genetic epidemiology of schizophrenia in the population of Tomsk Oblast. Dependence of parameters of the occurrence of schizophrenia among relatives on the method of proband sample formation]. / Geneticheskaia épidemiologiia shizofrenii v populiatsii Tomskoi oblasti. Zavisimost' pokazatelei rasprostranennosti shizofrenii sredi rodstvennikov ot sposoba formirovaniia vyborki probandov.

The program of genetic-epidemiological study of schizophrenia in five districts of the Tomsk region is presented. According to standardized methods, 610 diagnosed patients (epidemiological register) were examined, 74.1% of them being at random registered as probands (452 families of the epidemiological sample). 229 probands of non-epidemiological sample were registered in psychiatric hospitals. Schizophrenia occurrence parameters among first-degree relatives of probands of the non-epidemiological sample were regularly overestimated, as compared to the epidemiological sample. The methodical sources of contradictions in clinico-genealogical studies are discussed; the conclusion about representativeness+ of the probands' epidemiological sample is made.

[Genetico-epidemiologic analysis of the role of constitutional factors in the etiology of epilepsy]. / Genetiko-épidemiologicheskii analiz roli konstitutsional'nykh faktorov v étiologii épilepsii.

Using multifactorial and monolocus models interrelations of a number of constitutional factors of probands (sex, child convulsive reactions, character abnormalities, age at the time of illness onset) with genetic factors of epilepsy occurrence among relatives (365 families) and populations from 5 regions of the Khabarovsk krai (2.88 patients per 1000 subjects) were studied. The dependence of epilepsy manifestation probability in mutant homo- and heterozygotes on sex, convulsive reactions and age characteristics of the proband body reactivity was shown. The notions of double threshold determination of convulsive readiness (the T1 threshold "cuts" a part of population with non-paroxysmal abnormality of the brain bioelectric activity, while the T2 threshold "cuts" that with convulsive reactions) were substantiated, the presence of this causing epilepsy development in individuals with a mutant allele of the major dominant gene. The hypothesis of the ecogenetic interaction of epilepsy main etiologic factors (major gene, environmental factors and constitutional readiness) has been described.

[Genetico-mathematical analysis of manifested schizophrenia with a permanent and attack-like course]. / Genetiko-matematicheskii analiz manifestnoi shizofrenii s nepreryvnyi pristupoobraznym techeniem.

The parameters of multifactorial and monolocal models were evaluated according to the incidence indices of the manifested forms of schizophrenia in three population groups of Tomsk regions among the relatives of probands with permanent and attack-like course of the disease. Higher occurrence of mutant homozygotes and increase of the share of these genotypes were detected in permanent course of the manifested schizophrenia. The authors suggest that the differences in genetical parameters of susceptibility to the disease with permanent and attack-like course are caused by influence of constitutional factors on the mutant genes penetrant ability.

[Isolation of informative factors regarding the development of epilepsy by the method of image recognition]. / Vydelenie informativnoi sovokupnosti vozniknoveniia épilepsii metodom raspoznavaniia obrazov.

A complex of factors carrying major information on the epileptogenesis was recognized and their interrelation analyzed. Initial sample comprised 14 signs of the patients' constitutional features (532 individuals) and their relatives' mental health (10858 individuals). A model was constructed to represent the interrelation of the signs using an algorithm of logical-+-mathematical image detection realized on an SM-4 computer. Eight signs were entered into a most informative group. The model helped to formulate new theoretical notions of the relationship of constitutional and hereditary factors in epileptogenesis.

[Correlation-regression analysis of the influence of psychiatric service resources on the dynamics of detected morbidity in the populations of Siberia and the Far East]. / Korreliatsionno-regressionnyi analiz vliianiia resursov psikhiatricheskoi sluzhby na dinamiku vyiavlennoi boleznennosti naseleniia Sibiri i Dal'nego Vostoka.

The authors have demonstrated the existence of linear correlation between the complex of three factors (the number of beds and psychiatrists in hospitals and outpatient clinics) and incidence rate (over a period of 16 years) of neuroses in 11 administrative areas, epilepsy, in 12 areas, psychoses, in 15, oligophrenia, in 17, alcoholism and schizophrenia in all 18 areas of Siberia and the Far East. Correlations of each of the three factors with the morbidity rate varied within a wide range in relation to both administrative areas and individual diseases. The authors draw attention to the importance of supplementing the growth of resources of psychiatric service with new forms and methods of work.

[The role of environmental factors in the etiology of epilepsy (based on data from epidemiological genetic research)]. / Rol' sredovykh faktorov v étiologii épilepsii (po dannym genetiko-épidemiologicheskogo issledovaniia).

Genetic-epidemiological analysis of the role of ante-, peri- and postnatal exogenous adversities in the development of epilepsy was performed on the representative sample of 365 families using the multifactor and single locus models. The relationship was established of the genetic factors with ante- and perinatal factors on the one hand, and with postnatal ones on the other. An ecogenetic hypothesis of the epilepsy etiology was put forward.

[Estimate of the penetrance of genotypes in a monolocus model taking into account environmental factors]. / Otsenivanie penetrantnostei genotipov monolokusnoi modeli s uchetom faktorov sredy.

Based on ITO matrices, a method for parameter estimation of the monolocus diallele model (MDM) of qualitative trait is described, taking account of non-genetic (environmental) factors. The model parameters, probabilities of relatives' affection, constructing the likelihood function and testing hypotheses of the effect of environmental factors on the penetrations of MDM genotypes are outlined. Examples are given, concerning estimation of epilepsy MDM parameters, taking account of two factors-harmfulness of antenatal ontogenesis period and harmfulness which provokes paroxysms.

[Analysis of the diallelic model for the prevalence of epilepsy in families and populations]. / Analiz diallel'noi modeli rasprostranennosti épilepsii v sem'iakh i populiatsiiakh.

The initial data for the analysis have resulted in epidemiologic (547 patients) and genetic-epidemiologic (365 patients) study of patients with diagnosis of epilepsy living in five districts of the Khabarovsk Territory. The population frequency of epilepsy was equal to 0.288%. With the use of data on numbers of sick and healthy first-third-degree relatives, and the method of maximum likelihood, the monolocus diallelic model (MDM) parameters of the family and population epilepsy prevalence were estimated. For each of 9 MDM variants two decisions were obtained, depending on the use of population probability of the feature. The analysis of 8 sets of initial data allowed to ascertain the influence of information about the first-third-degree relatives on parameter estimates. The calculation results are presented for one of initial data sets (set A). Three MDM variants were shown to predict the values of the relative affection probability, these being rather close to frequencies observed. The arguments are presented in favour of quasi-dominant variant with following parameters: frequency of mutant allele in a population - 5.28%, homozygote penetrance - 21.5% and that for heterozygote - 2.6%. According to parameter estimates within this model, the probability of offspring disease in the family with the known number of sick and healthy parents was calculated.

[Multidimensional analysis of the relation between the resources of the psychiatric service and the detection and prevalence of mental patients in regions of Siberia and the Far East]. / Mnogomernyi analiz sviazi resorsov psikhiatricheskoi sluzhby s vyiavleniem i rasprostranennost'iu psikhicheski bol'nykh v regionakh Sibiri i Dal'nego Vostoka.

The article deals with the assessment of the main components and canonic correlations reflecting the relationship between the resources of psychiatric care (a number of beds and psychiatrists providing medical care in hospitals and in other settings) and the rate of identification and incidence of psychoses, schizophrenia, epilepsy, alcoholism, neuroses and oligophrenia in Siberia and Far East over a period of 16 years (from 1965 to 1981 excluding 1978). The first main component covered up to 80.1% of the dispersion range of the identification rate and 94.5% of the incidence rate, the second component covered up to 37.1% and 21% respectively. Canonic correlations proved higher for the incidence rate as against the identification rate. Although there were substantial differences in the studied interrelationship with regard to a number of territories, the main tendency was expressed in a marked linear correlation between a growth in the resources of psychiatric service and the time-course of the rates of the studied pathology.