Elizabeth Cantor-Graae

Substance abuse in schizophrenia: a review of the literature and a study of correlates in Sweden

The purpose of the current study is twofold: (a) to provide an overall synthesis of recent research on substance abuse in schizophrenia and (b) to present findings in a Swedish patient sample. Studies conducted since 1990 have found a wide range of abuse prevalence rates, with male gender and younger age as primary correlates. Less certainty exists regarding substance abuse as an independent risk factor for schizophrenia and its further impact on illness course. In a sample of 87 patients attending a psychiatric clinic in Malmö, lifetime prevalence of substance abuse was 48.3%, with abuse debut primarily preceding first contact for psychotic symptoms. Significant correlates of abuse were male gender, family history of substance abuse, and increased rates of hospitalization and criminality, with poorer outcome found in previous as well as current abusers. Alcohol abuse, either solely or in combination with other substances, was the main type of substance abuse. Although the specific factors (social, behavioural, genetic) that predispose schizophrenic patients to substance abuse remain unclear, the predominantly male profile of abusers might suggest a link between substance abuse and the poorer clinical outcome frequently observed, especially in male schizophrenic patients.

The Social Defeat Hypothesis of Schizophrenia: An Update

According to the social defeat (SD) hypothesis, published in 2005, long-term exposure to the experience of SD may lead to sensitization of the mesolimbic dopamine (DA) system and thereby increase the risk for schizophrenia. The hypothesis posits that SD (ie, the negative experience of being excluded from the majority group) is the common denominator of 5 major schizophrenia risk factors: urban upbringing, migration, childhood trauma, low intelligence, and drug abuse. The purpose of this update of the literature since 2005 is to answer 2 questions: (1) What is the evidence that SD explains the association between schizophrenia and these risk factors? (2) What is the evidence that SD leads to sensitization of the mesolimbic DA system? The evidence for SD as the mechanism underlying the increased risk was found to be strongest for migration and childhood trauma, while the evidence for urban upbringing, low intelligence, and drug abuse is suggestive, but insufficient. Some other findings that may support the hypothesis are the association between risk for schizophrenia and African American ethnicity, unemployment, single status, hearing impairment, autism, illiteracy, short stature, Klinefelter syndrome, and, possibly, sexual minority status. While the evidence that SD in humans leads to sensitization of the mesolimbic DA system is not sufficient, due to lack of studies, the evidence for this in animals is strong. The authors argue that the SD hypothesis provides a parsimonious and plausible explanation for a number of epidemiological findings that cannot be explained solely by genetic confounding.

Increased rates of psychosis among immigrants to Sweden: is migration a risk factor for psychosis ?

BACKGROUND Previous studies have shown high rates of psychosis among Afro-Caribbean immigrants to the UK and immigrants to the Netherlands. Rates of schizophrenia-like psychoses (SLP), i.e. schizophrenia or other non-affective psychosis, among the native-born and immigrant populations were assessed in Malmö, the city in Sweden with the highest proportion of immigrants. METHODS All adult patients admitted for in-patient psychiatric treatment in Malmö during the course of a 1-year period (N = 1162) were studied with regard to ethnicity and SLP diagnosis. A smaller sample consisting only of first-onset SLP cases (regardless of in- or out-patient status) was also studied (N = 56). Risks for admission and first-onset were calculated on the basis of current background population figures for Malmö. RESULTS Compared with those who were native-born, immigrants had increased risk for admission for SLP, with a similar tendency for increased risk for first-onset of SLP. Relative risk for SLP admission was most markedly increased in immigrants from East-Africa. Background factors specifically associated with migration (e.g. extreme duress) did not appear to contribute strongly to SLP in immigrants. CONCLUSION While the current results add to the growing body of evidence showing increased risk for psychosis in immigrants, vulnerability to psychosis may have been determined by factors other than the migration process.

Migration and schizophrenia.

Purpose of review An exploration of the evidence that a history of migration is a risk factor for schizophrenia and an evaluation of those studies that seek an explanation for this. Recent findings A meta-analysis found an increased risk for schizophrenia among first-generation and second-generation migrants and found a particularly high risk for migrants from countries where the majority of the population was Black. The latter finding was confirmed and extended by a large first-contact incidence study in the UK, which found excessive risks for schizophrenia and mania in the African–Caribbean and black–African sections of the population. A very high risk of schizophrenia has also been reported for Moroccan males in the Netherlands. The explanation for these findings is uncertain. Social adversity, racial discrimination, family dysfunction, unemployment and poor housing conditions have been proposed as contributing factors. According to one hypothesis, the chronic experience of social defeat disturbs dopamine function in the brain. Summary A personal or family history of migration is a high risk factor for schizophrenia and there is now strong evidence against selective migration as the explanation. There is an increasing interest in the impact of social stressors on brain functioning and on the pathogenesis of schizophrenia.

The Contribution of Social Factors to the Development of Schizophrenia: A Review of Recent Findings

Objective: To investigate recent evidence suggesting that social factors are causally related to the development of schizophrenia. Method: I conducted a sytematic review of MEDLINE to identify possibly relevant studies. The search was limited to peer-reviewed studies and review articles appearing in English-language journals since 1996. Studies were included if they used standardized diagnostic criteria for schizophrenia or standardized assessment instruments for psychotic symptoms. Results: Studies of migrants to western Europe provide compelling support for the notion that social factors contribute to the development of schizophrenia. Findings such as excessively high risk for schizophrenia in second-generation immigrants are difficult to explain solely in terms of biological or genetic factors. A growing number of studies implicate childhood exposure to social adversity as a risk factor for schizophrenia, although few studies have used prospective designs. The increased incidence of schizophrenia risk associated with urban birth and (or) urban upbringing suggests possible social causation, but these findings are more ambiguous. Thus far, no studies have explored actual mechanisms by which exposure to social factors might generate psychotic symptoms, although animal experiments suggest that social defeat or social exclusion may cause dopamine dysregulation or sensitization. Conclusions: The accumulating evidence suggesting a role for social factors in the development of schizophrenia arises primarily from studies of migrants conducted in Europe. The mechanisms by which social factors exert their influence remain unknown. Future investigations of social causation should clarify the temporal relation between exposure to social defeat and (or) social adversity and the development of psychotic symptoms.

Hypothesis: social defeat is a risk factor for schizophrenia?

The increased schizophrenia risks for residents of cities with high levels of competition and for members of disadvantaged groups (for example migrants from low- and middle-income countries, people with low IQ, hearing impairments or a history of abuse) suggest that social factors are important for aetiology. Dopaminergic dysfunctioning is a key mechanism in pathogenesis. This editorial is a selective literature review to delineate a mechanism whereby social factors can disturb dopamine function in the brain. Experiments with rodents have shown that social defeat leads to dopaminergic hyperactivity and to behavioural sensitisation, whereby the animal displays an enhanced behavioural and dopamine response to dopamine agonists. Neuroreceptor imaging studies have demonstrated the same phenomena in patients with schizophrenia who had never received antipsychotics. In humans, the chronic experience of social defeat may lead to sensitisation (and/or increased baseline activity) of the mesolimbic dopamine system and thereby increase the risk for schizophrenia.

Obstetric complications as antecedents of schizophrenia: Empirical effects of using different obstetric complication scales

The new McNeil-Sjöström Scale for obstetric complications (OCs), as well as scales of Lewis et al. (Schizophrenia: Scientific progress. Oxford University Press, 1989) and Parnas et al. (British Journal of Psychiatry, 140, 416-420, 1982), were applied to the OC histories of 70 singleton schizophrenics and 70 demographically-matched controls from the same hospital delivery series, using blindly assessed hospital pregnancy and birth record information. With the McNeil-Sjöström scale, schizophrenics were found to have significantly increased rates of OCs for the total reproduction, as well as for labor-delivery and the neonatal period but not for pregnancy. Significant increases in OCs in these schizophrenics were also found in scores produced by the Lewis et al. scale but not by the Parnas et al. scale. Further application of these three scales to OC data obtained through parental report for 23 monozygotic (MZ) twin pairs discordant and 10 pairs concordant for schizophrenia, as well as seven normal control MZ pairs, showed a significant difference in OC rates across the different twin pair groups, when assessed by the McNeil-Sjöström and Parnas et al. scales, but not by the Lewis et al. scale. The particular scoring system used in a study is thus of considerable importance not only for findings concerning OC histories of schizophrenics vs. controls, but also for the relationship between OCs and other presumed etiological factors in schizophrenia. Among the three scales, the McNeil-Sjöström scale provided the most sensitive assessment of OC history for schizophrenics.

Paternal and maternal age as risk factors for psychosis: findings from Denmark, Sweden and Australia

BACKGROUND While the association between increased maternal age and congenital disorders has long been recognized, the offspring of older fathers are also at increased risk of congenital disorders related to DNA errors during spermatogenesis. Recent studies have drawn attention to an association between increased paternal age and increased risk of schizophrenia. The aim of the current study was to examine both paternal and maternal age as risk factors for the broader category of psychosis. METHOD We used data from three sources examining psychosis: a population-based cohort study (Denmark), and two case-control studies (Sweden and Australia). RESULTS When controlling for the effect of maternal age, increased paternal age was significantly associated with increased risk of psychosis in the Danish and Swedish studies. The Australian study found no association between adjusted paternal age and risk of psychosis. When controlling for the effect of paternal age, younger maternal age was associated with an increased risk of psychoses in the Danish study alone. CONCLUSIONS The offspring of older fathers are at increased risk of developing psychosis. The role of paternally derived mutations and/or psychosocial factors associated with older paternal age warrants further research.

Peer-group support intervention improves the psychosocial well-being of AIDS orphans: Cluster randomized trial

Accumulating evidence suggests that AIDS orphanhood status is accompanied by increased levels of psychological distress such as anxiety, depression, intense guilt, shame, and anger. However, few studies have examined the possible reduction of psychological distress in AIDS orphans through the help of interventions that promote well-being. The objective of the study was to evaluate the effects of a school-based peer-group support intervention combined with periodic somatic health assessments and treatment on the psychosocial well-being of AIDS orphans in the Mbarara District of southwestern Uganda. In a cluster randomized controlled design, 326 AIDS orphans aged 10-15 years were assigned to either peer-group support intervention combined with monthly somatic healthcare (n=159) or control group (n=167) for follow-up assessment. Baseline and 10 week follow-up psychological assessments were conducted in both groups using self-administered Beck Youth Inventories. Complete data were available for 298 orphans. After adjusting for baseline scores, follow-up scores for the intervention group in comparison with controls showed significant improvement in depression, anger, and anxiety but not for self-concept. This study demonstrated that peer-group support intervention decreased psychological distress, particularly symptoms of depression, anxiety and anger. Thus, the use of peer-group support interventions should be incorporated into existing school health programs.

Minor physical anomalies in schizophrenia: Cognitive, neurological and other clinical correlates

Minor physical anomalies (MPAs) are minor congenital malformations which are found with significantly increased frequency among both patients with schizophrenia and their siblings, suggesting the effect of early developmental disturbance in their families. The aim of this study was to explore the relationship between these signs of early dysmorphogenesis and cognitive and neurological dysfunction in the patients and their siblings as well as the clinical characteristics of the patients. Sixty patients with schizophrenia, 21 nonpsychotic siblings and 75 normal comparison subjects were studied. Increased rates of cognitive and neurological dysfunction and high MPA scores were found in both the patients and their siblings. High rates of MPAs were not significantly related to cognitive or neurological dysfunction in the patients or siblings, or to premorbid history or other characteristics of the clinical disease process in the patients. These results suggest that MPAs are possibly markers of general early neuromaldevelopment rather than markers of a specific cognitive/neurological or clinical subtype of schizophrenia.