First admissions for psychosis in Turku. A time trend study.

Patients over 15 years of age from Turku hospitalized for psychosis for the first time during the years 1949-50, 1959-60 or 1969-70 were investigated. The incidence of hospitalized psychoses (per 100,000 inhabitants) was 115, 136 and 160, respectively. The increase in incidence was greater in women than in men. The incidence remained approximately the same in patients aged 30 to 59, but increased in the younger and older groups. The incidence of functional psychoses increased; in schizophrenia, however, it declined, while in paranoid and effective psychoses it increased. In organic psychoses, the admission frequency of psychoses of old age rose in the 1950's, but declined in some measure in the 1960's. The incidence of psychosis increased for single persons. The ratio of the incidence between single and married persons rose in men, whereas in women it fell. This was particularly pronounced in schizophrenics. The incidence of psychosis was highest in unskilled laborers. The overrepresentation of schizophrenia and paranoid psychoses seemed to have become more pronounced in this occupational group.     

Premorbid abnormalities in mania,schizomania, acute schizophrenia and chronic schizophrenia

The aim of this study was to examine the hypothesis that differences in outcome among affective and non-affective psychoses are associated with differences in the degree of developmental deviance. We conducted a retrospective survey of first contact cases treated over a 20-year period in a psychiatric hospital serving a catchment area in South London. All patients with non-depressive functional psychoses residing in the catchment area who received their first psychiatric treatment between 1965 and 1984 were included in the study. Cases were classified according to the relative chronicity of their illness into four non-overlapping groups: mania, schizomania, acute schizophrenia and chronic schizophrenia. There was a linear trend in the association between illness chronicity and proxy measures of developmental deviance, such as premorbid unemployment, single status and poor academic achievement. Compared to individuals with mania, schizophrenic patients had a 3–6 times increased risk of premorbid abnormality. For patients with schizomania and acute schizophrenia, the risk was 1.5–3 times greater than for manic subjects. We conclude that the prevalence of premorbid abnormalities is highest among chronic schizophrenia, but similar disturbances also occur, to a lesser degree, in less disabling affective and non-affective psychotic disorders.MRC Social Psychiatry Unit, Institute of Psychiatry     

The Kraepelinian dichotomy: preliminary results of a 15-year follow-up study on functional psychoses: focus on negative symptoms

In a 15-year follow-up study, we used a comparative approach to assess course and outcome for all functional psychoses. The presented results focus on negative symptoms and refer to a sample of 76 patients with schizophrenia, 38 patients with a schizoaffective disorder and 32 patients with an affective disorder according to ICD-9. These patients were assessed at their first psychiatric hospitalization and 15 years later. In summary, the findings indicate that the course and outcome of schizophrenia is less favorable than that of affective and schizoaffective disorders. Negative symptoms occurred in all functional psychoses, but were more frequent and prominent in the schizophrenic group than in the other two diagnostic groups at any time of assessment. Narrower concepts of negative symptoms, conceptualized as the deficit syndrome, seem to be specific for schizophrenia and appear quite rarely in patients with affective psychoses. Overall, our study supports Kraepelin's original hypothesis that bifurcated the psychoses into the affective psychoses and schizophrenia, whereby the latter have a more deleterious long-term course and outcome.     

On schizophrenic psychoses.

The author traces the history of the concept of schizophrenic psychoses from Kraepelin's differentiation of dementia praecox from other mental illness and Bleuler's formulation of schizophrenia through the delimitation of the definition of schizophrenia to current thought on the etiology, treatment, and outcome of schizophrenic psychoses. He stresses the importance of our knowledge of both psychological and hereditary factors and urges that rather than searching only for a single, causal metabolic error we also accept the possibility that schizophrenia occurs in highly human, spiritual spheres and consider the schizophrenogenic influences in the lives and personalities of individual patients.     

Why has the incidence of schizophrenia in Danish psychiatric institutions decreased since 1970?

From The Danish Psychiatric Register five cohorts of all first-admitted patients to Danish psychiatric institutions from the years 1970, 1973, 1976, 1979, and 1980 have been followed, and trends in age-standardized rates of schizophrenia investigated. The first-admission rates have decreased in both sexes, significantly in males. In addition, the cumulated schizophrenia rates for the cohorts, including those of patients diagnosed as schizophrenics only at a later admission within periods of 2 and 5 years, decreased. This decrease is significant at 2 years of observation in both sexes and at 5 years in females. The decreasing first-admission rates might be explained partly by changes in diagnostic habits. The differential diagnoses of schizophrenia (paranoid states (ICD-8:297), paranoid reactive psychoses (298.3), unspecified psychoses (298.9 and 299), and borderline states (ICD-8 Danish version: 301.83] are increasingly used as first-admission diagnosis for patients later to be diagnosed as schizophrenic, possibly owing to a tendency to avoid the diagnosis of schizophrenia, when treatment of a patient is possible. A method of calculating the hospital incidence of schizophrenia approaching the real incidence better than the incidence of first-admission diagnoses is suggested.     

Neurotrophic factors and the pathophysiology of schizophrenic psychoses.

The aim of this review is to summarize the present state of findings on altered neurotrophic factor levels in schizophrenic psychoses, on variations in genes coding for neurotrophic factors, and on the effect of antipsychotic drugs on the expression level of neurotrophic factors. This is a conceptual paper that aims to establish the link between the neuromaldevelopment theory of schizophrenia and neurotrophic factors. An extensive literature review has been done using the Pub Med database, a service of the National Library of Medicine, which includes over 14 million citations for biomedical articles back to the 1950s. The majority of studies discussed in this review support the notion of alterations of neurotrophic factors at the protein and gene level, respectively, and support the hypothesis that these alterations could, at least partially, explain some of the morphological, cytoarchitectural and neurobiochemical abnormalities found in the brain of schizophrenic patients. However, the results are not always conclusive and the clinical significance of these alterations is not fully understood. It is, thus, important to further neurotrophic factor research in order to better understand the etiopathogenesis of schizophrenic psychoses and, thus, potentially develop new treatment strategies urgently needed for patients suffering from these devastating disorders.     

Some remarks on etiological aspects of early-onset schizophrenia

Neurophysiological, neuropsychological, neuroanatomical, and neuroradiological findings in schizophrenic psychoses demonstrate that subcortical (e.g., mesolimbic and diencephalic regions) as well as neocortical structures (e.g., dorsolateral prefrontal cortex, superior temporal and inferior parietal cortices) are involved. Special significance is accorded to the neuroanatomical connection between limbic structures and the dorsolateral prefrontal cortex. Here myelinization begins relatively late in humans, during the second and third decade of life - a particularly vulnerable period for schizophrenic onset. The nature of prepsychotic behavioral abnormalities in patients with early-onset schizophrenia as well as the existence of typical cognitive dysfunctions preceding the manifestation of psychotic symptoms points to the importance of a dynamic imbalance of neocortical-subcortical interactions in the etiology of schizophrenia. Based on the crucial importance of the prefrontal-hippocampal circuitry a stimulus barrier model of schizophrenic psychoses is elaborated, which integrates recent neurobiological findings as well as results of research in modern developmental psychology. One of the implications of this model is the multidimensional treatment of schizophrenic patients.     

Late life psychosis

Psychoses in late life are serious psychiatric disorders. They include schizophrenia (both late onset schizophrenic patients and the more prevalent early onset schizophrenic patients living into middle and old age), delusional disorder, psychosis in patients with dementia, psychosis in patients with depression, and miscellaneous psychoses. This article reviews some of the more recent and interesting findings in late life psychoses. A need for further research is stressed.     

PROGNOSIS OF PARANOID STATES IN RELATION TO THE CLINICAL FEATURES

Scandinavian psychiatrists acknowledge endogenous psychoses which are neither schizophrenic nor manic-depressive, i.e., above all the “reactive psychoses” and the “schizophreniform psychoses”, both of which differ from schizophrenia in their features as well as in their good prognoses. These Scandinavian diagnoses bear relationships to psychoses, which I separate from schizophrenia. In the present paper, paranoid states are discussed with regard to their clinical pictures and their good prognoses. Among these are the “cycloid psychoses”. Patients suffering from these diseases recover from every phase, though most of the German psychiatrists consider them schizophrenic. Among the cycloid psychoses, the “anxiety happiness psychosis” shows ideas of reference on the one hand and ecstatic ideas on the other. In “inhibited confusion psychosis”, the patients are suffering from ideas of reference and ideas of significance; in “excited confusion psychosis”, from misidentifications of persons. The other symptoms which occur - anxiety, happiness, stupor, incoherent pressure of speech - confirm the cycloid psychoses and disprove schizophrenias. Besides the already mentioned psychoses, there is a monopolar psychosis, “suspicious depression”, in which ideas of reference and ideas of guilt mix. It is extremely important, not only for theoretical but also practical reasons, to separate from schizophrenia paranoid states which terminate in complete recovery from every phase.     

Determinants of survival in children with brain tumors.

A study was conducted in metropolitan Baltimore to examine time trends in survival and factors which influence survival of children with brain tumors. One hundred eighty-four cases diagnosed from 1960 to 1975 were identified; 76.5% occurred in white children and 48% were girls. Five-year survival rates were 35% for children diagnosed in 1960-64, 34% in 1965-69, and 49% in 1970-74. Girls had consistently better survival rates than boys. White children experienced consistently better survival rates than blacks. Of those who survived the first year, children with supratentorial tumors had better five-year survival rates (46%) than those which with infratentorial tumors (27%). Of those who survived the first year, children with astrocytomas had better survival rates than those with other types of tumors.     

Patterns of psychiatric hospitalizations in schizophrenic psychoses within the Northern Finland 1966 Birth Cohort

We report patterns of hospitalization in schizophrenic psychoses by age 34 in a longitudinal population-based cohort. We test the predictive ability of various demographic and illness-related variables on patterns of hospitalization, with a special focus on the length of the first psychiatric hospitalization. All living subjects of the Northern Finland 1966 Birth Cohort with DSM-III-R schizophrenia (n=88) and other schizophrenia spectrum cases (n=27) by the year 1997 in the Finnish Hospital Discharge Register were followed for an average of 10.5 years. Measures of psychiatric hospitalization included time to re-hospitalization (as continuous and as re-hospitalization within 2 years) and the number of hospital episodes. Length of the first hospitalization, other illness-related and various socio-demographic predictors were used to predict hospitalization patterns. After adjusting for gender, age at first admission and number of hospital days a short (1-14 days) first hospitalization (reference >30 days; adjusted odds ratio 6.39; 95% CI 2.00-20.41) and familial risk of psychosis (OR 3.36; 1.09-10.39) predicted re-hospitalization within 2 years. A short first hospitalization also predicted frequent psychiatric admissions defined as the first three admissions within 3 years (OR 13.77; 3.92-48.36). A short first hospitalization was linked to increased risk of re-hospitalizations. Although short hospitalization is recommended by several guidelines, there may be a group of patients with schizophrenic psychoses in which too short a hospitalization may lead to inadequate treatment response.     

Onset of acute psychotic states in India: a study of sociodemographic,seasonal and biological factors

This is a comparative study of patients with acute-onset, non-affective, non-organic, remitting psychoses and with non-remitting or schizophrenic psychoses in India. Two groups of patients with acute remitting and non-remitting or schizophrenic psychoses were compared with regard to the following variables: month of onset of psychosis; presence of stress, particularly fever, within 4 weeks preceding the onset of psychosis; childbirth within 12 weeks preceding the onset of psychosis; gender differences. It was found that the acute remitting psychoses showed an overrepresentation of females, a higher frequency of associated stress preceding the onset of psychosis, more often had onset during the summer months, i.e. between May and September, and had fever and childbirth preceding the onset of psychosis in a significantly higher proportion of patients, compared to acute non-remitting psychoses or schizophrenia. The implications of the findings which point towards biological factors in the aetiology of acute remitting psychoses are discussed.     

Gender differences in affective, schizoaffective, and schizophrenic disorders. A review

The authors review the literature on sex differences in four DSM-III diagnoses: schizophrenia, schizoaffective psychoses, unipolar and bipolar affective disorders. The findings indicate that (1) gender differences occur most frequently in schizophrenic patients: schizophrenic women exhibit a less deteriorated course of illness; (2) sex differences in affective disordered patients support the unipolar-bipolar subtype distinction; and (3) sex differences are less compelling but also less studied in schizoaffective disorder. Theories attempting to explain sex differences in schizophrenia are reviewed.     

Decreased incidence of Duchenne muscular dystrophy in western Japan 1956-1980

In 50 patients from 41 families of Duchenne muscular dystrophy (DMD) born between 1956 and 1980 in the San-in area of Japan, the changes in DMD incidence rate were analyzed through five periods of time: 1956-1960, 1961-1965, 1966-1970, 1971-1975 and 1976-1980. The overall incidence decreased from 22.31 X 10(-5) live male births in the first period to 14.51 X 10(-5) in the last. This decrease was mainly related to the group of mothers who were definite carriers (p less than 0.005), and was probably due to genetic counselling of definite carrier families. For a further decrease in the incidence of DMD, the newborn male screening system for creatine phosphokinase (CPK) and appropriate genetic counselling might be effective. From an analysis of 28 families without previous family history, the expected proportion of maternal carriers was 0.57.     

Reactive psychoses and schizophrenia with good prognosis.

Cross-national studies have indicated that American psychiatrists diagnose schizophrenia more often than others. Clinical, genetic, and follow-up studies suggest that many patients diagnosed as having acute schizophrenia might be more appropriately diagnosed as having affective disorder. Forty probands diagnosed in Aarhus, Denmark, as having reactive psychoses are compared with 28 probands diagnosed in St Louis as having schizophrenia with good prognosis. Clinical differences largely reflect diagnostic criteria, with the patients from the St Louis group frequently having diagnosable affective disorder. A smaller proportion, 39% of the patients from St Louis, could be considered for the diagnosis of reactive psychosis. This is additional evidence supporting the use of the diagnostic category, reactive psychoses. Patients ordinarily given the diagnoses acute schizophrenic episode and/or schizo-affective schizophrenia may be more appropriately diagnosed as having (1) affective disorder and (2) reactive psychoses.     

Spatial concentration of the incidence of treated psychiatric disorders in Mannheim

ABSTRACT— The spatial concentration of the incidence of treated psychiatric disorders in Mannheim was determined in 2 ways. The first, the classical zone model according to Neller (1), distinguishes an inner, intermediate and outer zone. This concept was applied to data from an ecological study conducted by Hafner et al. (2) in 1965 and to those derived from the Cumulative Psychiatric Case Register for the years 1974–1980. For the second period of time we developed, in addition, a factor ecological concept. The 23 districts of Mannheim were divided into 5 areas that were as homogeneous as possible in terms of segregation and density. There was a marked increase in the concentration index for schizophrenia in the inner zone, as well as for neuroses and personality disorders between 1974–1980 as compared with 1965. There were strong concentrations in the inner zone during both periods of study for the diagnosis of alcoholism and drug addiction. Although in 1965 there was a visible concentration trend in the inner zone for affective psychoses, it had almost vanished between 1974–1980. Using the factor ecological classification we demonstrated that, with the exception of affective psychoses and neurotic depression, all diseases concentrate in the city areas that, besides being centrally located, are characterized by high population density, poor housing conditions, low social status of the residents and where foreign nationals were segregated in the 1970s.     

Validation of Danish case register diagnosis for schizophrenia

The ABC schizophrenia study aims at investigating sex differences in age of onset, symptoms and course of schizophrenic and paranoid disorders. For this purpose, we used case register data from Denmark and Mannheim and a directly examined sample of first admissions (ABC sample). The Danish case register sample included less clinical diagnoses of schizophrenia and more schizophrenia-related disorders (acute paranoid reaction, paranoid states and borderline schizophrenia) than the Mannheim data (case register and ABC sample). The problem therefore was whether the two datasets are comparable and the results are valid. For this reason a randomized, stratified sample of 116 patients was drawn from the Danish case register sample. The case notes of these 116 patients were requested from the hospitals where the patients had been treated and analyzed by means of a scoring sheet based on the Interview for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS). The use of operationalized diagnoses of the CATEGO program, based on PSE items, which are integrated in IRAOS, demonstrated that the samples of the Danish and the Mannheim case registers and the directly investigated ABC sample have comparable diagnostic distributions. Possible explanations for the differences between the clinical and the CATEGO diagnoses in the Danish case register may be the frequent use of diagnoses of borderline schizophrenia and reactive psychoses (previously called psychogenic psychoses), and above all a more narrow concept of schizophrenia; in Denmark, schizophrenia is diagnosed relatively late, i.e., after the presence of enduring negative symptoms, and thus mostly after the appearance of residual state. These diagnostic preferences may help to explain the fall in first admission rates for schizophrenia – above all in women – in Denmark and the low incidence rates of schizophrenia by first contact within the WHO determinants of outcome study. The earlier hospitalization of men could be replicated as well as the course of treatment (readmissions and discharges) of schizophrenic men and women over 10 years after first admission.     

Attention, memory, and motor skills as childhood predictors of schizophrenia-related psychoses: the New York High-Risk Project

OBJECTIVE: Childhood neurobehavioral deficits in offspring of schizophrenic, affectively ill, and psychiatrically normal parents were evaluated as predictors of schizophrenia-related psychoses in adulthood. METHOD: The offspring were tested with neurobehavioral measures at 7-12 years of age and assessed in mid-adulthood for axis I diagnoses. The relationships of childhood deficits in attention, verbal memory, and gross motor skills to adulthood schizophrenia-related psychoses were examined in separate path analyses by using logistic regression equations. Sensitivity and specificity were determined for each of the childhood dysfunctions. RESULTS: For the offspring of schizophrenic parents, childhood deficits in verbal memory, gross motor skills, and attention identified 83%, 75%, and 58%, respectively, of the subjects with schizophrenia-related psychoses; 50% were identified by all three variables combined. False positive rates in subjects who did not develop schizophrenia-related psychoses ranged from 18% for those with deficits in attention during childhood to 28% for those with deficits in memory. The three variables had low deficit rates in the offspring of the other two parental groups and were not associated with other psychiatric disorders in any group. CONCLUSIONS: Schizophrenia-related psychoses in adulthood are distinguished in subjects at risk for schizophrenia by childhood deficits in verbal memory, gross motor skills, and attention. The findings suggest that deficits in these variables are relatively specific to schizophrenia risk and may be indicators of the genetic liability to schizophrenia.     

The genetics of delusional psychoses

In a genetic study of the first-degree relatives of 77 patients with delusional (paranoid) psychoses, the morbidity risks for schizophrenia, affective disorders, and atypical psychoses were evaluated using ICD-9 criteria. The prevalence of schizophrenia was 3.10 percent (4.12 percent with age correction to 40 years and 4.94 percent with age correction to age 60), which is higher than in investigations of paranoid psychoses, but lower than in studies of paranoid schizophrenia. The prevalence figure for affective disorders (age-corrected 3.04 percent for unipolar plus bipolar patients) is also intermediate to those for relatives of paranoid schizophrenics and paranoid psychotics. When the 77 index delusional patients were subdivided into axial syndromes (endogenomorphic-schizophrenic, endogenomorphic-cyclothymic, and organomorphic axial syndromes), two very homogeneous subgroups emerged. The endogenomorphic-schizophrenic subgroup showed high rates of schizophrenic secondary cases, whereas the endogenomorphic-cyclothymic subgroup showed high rates of affectively disordered secondary cases. The third organomorphic subgroup showed a high prevalence of atypical psychoses among first-degree relatives. Thirty-seven of the 77 index patients could not be assigned to any axial syndrome; their first-degree relatives had an increased prevalence of schizophrenia, but affective disorders were no more frequent than in the normal population. These data suggest that the heterogeneous group of paranoid psychoses can be meaningfully subdivided by use of axial syndromes which are viewed as representing "basic" disturbances underlying delusional symptomatology.     

Clozapine: A Clinical Review of Adverse Effects and Management

Clozapine (Clozaril^®) is a novel and unique prototype atypical, tricyclic, dibenzodiazepine-derivative, antipsychotic agent. It has been proven effective and significantly superior to placebo, as well as to conventional neuroleptics, in several placebo-controlled, double-blind studies in treatment-resistant schizophrenia. It has also been found to produce an incidence of extrapyramidal symptoms (EPS) as low as that found with placebo. Approximately 30–60% of all schizophrenic patients who fail to respond to typical antipsychotics may respond to clozapine. It was the first major advance that marked a turning point in the treatment of schizophrenia and other psychotic disorders since the introduction of the typical antipsychotic agents, i.e., chlorpromazine and haloperidol in the 1950s and 1960s, respectively. After its introduction in clinical studies in the United States in the early 1970s, it was withdrawn in 1974, and was not approved for clinical use in the United States until February 1990, because of the risk of agranulocytosis. Its novel pharmacological profile, lack of propensity to cause EPS in both short- and long-term uses, lack of effects on serum prolactin, and ameliorative effects on tardive dyskinesia have resulted in the expansion of its use from refractory schizophrenia to schizoaffective disorders, affective disorders, some neurological disorders, aggression, as well as psychosis in patients with dementia and parkinsonism. This review covers the history, pharmacology, management of side effects, and fetal and neonatal effects of clozapine.