The environment and susceptibility to schizophrenia

Abstract

In the present article the putative role of environmental factors in schizophrenia is reviewed and synthesized. Accumulating evidence from recent studies suggests that environmental exposures may play a more significant role in the etiopathogenesis of this disorder than previously thought. This expanding knowledge base is largely a consequence of refinements in the methodology of epidemiologic studies, including birth cohort investigations, and in preclinical research that has been inspired by the evolving literature on animal models of environmental exposures. This paper is divided into four sections. In the first, the descriptive epidemiology of schizophrenia is reviewed. This includes general studies on incidence, prevalence, and differences in these measures by urban–rural, neighborhood, migrant, and season of birth status, as well as time trends. In the second section, we discuss the contribution of environmental risk factors acting during fetal and perinatal life; these include infections [e.g. rubella, influenza, Toxoplasma gondii (T. gondii), herpes simplex virus type 2 (HSV-2)], nutritional deficiencies (e.g., famine, folic acid, iron, vitamin D), paternal age, fetal/neonatal hypoxic and other obstetric insults and complications, maternal stress and other exposures [e.g. lead, rhesus (Rh) incompatibility, maternal stress]. Other putative neurodevelopmental determinants, including cannabis, socioeconomic status, trauma, and infections during childhood and adolescence are also covered. In the third section, these findings are synthesized and their implications for prevention and uncovering biological mechanisms, including oxidative stress, apoptosis, and inflammation, are discussed. Animal models, including maternal immune activation, have yielded evidence suggesting that these exposures cause brain and behavioral phenotypes that are analogous to findings observed in patients with schizophrenia. In the final section, future studies including new, larger, and more rigorous epidemiologic investigations, and research on translational and clinical neuroscience, gene–environment interactions, epigenetics, developmental trajectories and windows of vulnerability, are elaborated upon. These studies are aimed at confirming observed risk factors, identifying new environmental exposures, elucidating developmental mechanisms, and shedding further light on genes and exposures that may not be identified in the absence of these integrated approaches. The study of environmental factors in schizophrenia may have important implications for the identification of causes and prevention of this disorder, and offers the potential to complement, and refine, existing efforts on explanatory neurodevelopmental models.

Environmental factors during adolescence associated with later development of psychotic disorders – A nested case-control study

“…In addition to the strong genetic component environmental risk factors also play an important role (Van Os and Kapur, 2009;Ripke et al, 2011). In schizophrenia, this is supported by studies showing geographical variations in incidence (McGrath et al, 2004) and increased risks associated with pregnancy/delivery complications, urbanicity, migration, cannabis use and early traumatic experiences (Cantor-Graae, 2007;Schlossberg et al, 2010;Brown, 2011).…”

Mismatch Negativity Encoding of Prediction Errors Predicts S-ketamine-Induced Cognitive Impairments

“…This approach is inspired by the general notion that the development of psychiatric disease may result from the interplay between the (genetically determined) susceptibility of an individual and the expose to environmental stressors (Brown, 2011), and follows previous studies, which examined whether physiological markers can predict the individual degree of psychotic symptoms in drug-induced psychosis and schizophrenia (Corlett et al, 2006;Honey et al, 2008;Krystal et al, 2003;Umbricht et al, 2002). Here, we found that the MMN slope under placebo showed a negative correlation with the subsequent ketamine-induced extent of cognitive impairments across subjects; in contrast, no comparable relationship was found for psilocybin.…”

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

“…There is evidence that prenatal maternal immune activation (MIA) (Brown and Derkits, 2010), perinatal hypoxia (Cannon et al, 2002;Schmidt-Kastner et al, 2012), adolescent cannabis use (Arseneault et al, 2004;Henquet et al, 2008), stress (Norman and Malla, 1993), obstetric complications (Dalman et al, 1999), urbanicity (Vassos et al, 2012), migrant status (Cantor-Graae and Selten, 2005), advanced paternal age (Malaspina, 2001), and others (Brown, 2011;Tandon et al, 2008) interact with predisposing genetics to increase risk for illness.…”