The impact of environmental factors in severe psychiatric disorders

Abstract

During the last decades, schizophrenia has been regarded as a developmental disorder. The neurodevelopmental hypothesis proposes schizophrenia to be related to genetic and environmental factors leading to abnormal brain development during the pre- or postnatal period. First disease symptoms appear in early adulthood during the synaptic pruning and myelination process. Meta-analyses of structural MRI studies revealing hippocampal volume deficits in first-episode patients and in the longitudinal disease course confirm this hypothesis. Apart from the influence of risk genes in severe psychiatric disorders, environmental factors may also impact brain development during the perinatal period. Several environmental factors such as antenatal maternal virus infections, obstetric complications entailing hypoxia as common factor or stress during neurodevelopment have been identified to play a role in schizophrenia and bipolar disorder, possibly contributing to smaller hippocampal volumes. In major depression, psychosocial stress during the perinatal period or in adulthood is an important trigger. In animal studies, chronic stress or repeated administration of glucocorticoids have been shown to induce degeneration of glucocorticoid-sensitive hippocampal neurons and may contribute to the pathophysiology of affective disorders. Epigenetic mechanisms altering the chromatin structure such as histone acetylation and DNA methylation may mediate effects of environmental factors to transcriptional regulation of specific genes and be a prominent factor in gene-environmental interaction. In animal models, gene-environmental interaction should be investigated more intensely to unravel pathophysiological mechanisms. These findings may lead to new therapeutic strategies influencing epigenetic targets in severe psychiatric disorders.

HDAC1 links early life stress to schizophrenia-like phenotypes

“…A number of genes have been associated with the risk to develop schizophrenia (4)(5)(6). In addition to genetic predisposition, environmental factors, such as urbanicity (7), obstetric complications (8), or exposure to early life stress (ELS) (9,10), are known to increase the risk of developing schizophrenia. Such genome-environment interactions are mediated by epigenetic processes, including DNA methylation (DNAme) or histone modifications (11).…”

Are obstetrical complications really involved in the etiology and course of schizophrenia and mood disorders?

“…Data about the role of obstetric complications in major depressive disorder are even more scanty than in bipolar disorder (Schmitt et al, 2014). Three independent studies found that preterm birth was associated with a higher risk of a depressive disorder in adolescence (Patton et al, 2004) or adulthood (Räikkönen et al, 2007;Nosarti et al, 2012).…”

Estados clínicos de alto riesgo para esquizofrenia y otras formas de psicosis: una breve revisión.

“…Muchas de estas alteraciones han sido codificadas desde el nacimiento por genes defectuosos, aunque son desenmascaradas en el tiempo por procesos complejos como la poda neuronal. Es de notar que este último fenómeno, que es fisiológico y se da entre la pubertad y la adolescencia, coincide frecuentemente con la edad de inicio de las primeras alteraciones psicopatológicas presentes en las psicosis (44,45) …”