Fig. 2. Epidemiologically-validated developmental risk factors for schizophrenia and the convergent processes affecting brain development.

This figure depicts the multiple convergent processes operating across the prominent developmental risk factors for schizophrenia. Almost all exposures increase foetal brain/placental exposure to increased glucocorticoids and inflammatory factors. There are also multiple alterations to early epigenetic factors governing gene expression, with most risk exposures affecting DNA methylation, however certain exposures also affect histone acetylation/methylation and micro RNA production. At a cellular level a surprisingly high number of exposures affect the early ontogeny of dopamine neurons. Effects on the development of other brain cell types i.e. GABA or glutamateric are also affected but reports of alterations to these neurons are far less frequent. Also noted is whether genome-wide environmental interaction (GWEIS) studies have been conducted for these developmental risk exposures. Abbreviations: DA, dopamine; GWEIS, genome wide environment interaction study; HPA, hypo-thalamic pituitary axis; Vit D, vitamin D; Fe²⁺, iron; PUFA, polyunsaturated fatty acids. Increased exposure validated in developing brain/placenta. Weak evidence. X No effect. ? Not studied. Altered DNA methylation. Altered Histone acetylation/methylation. Increased micro-RNA.