Schizophrenia risk factors

In addition to the genes implicated in schizophrenia, a number of environmental risk factors have been implicated in the disease.These include effects during foetal development (famine and maternal infection during pregnancy) as well as during childhood and adulthood. These factors are compiled in this table. Starvation and viral infection activate the eif2alpha kinases eg EIF2AK2 gcn2 and leading to inhibition of the translation initiation factor eif2b, and the arrest of protein synthesis. EIF2B is paricularly important in the control of oligodendrocyte function, and activation of these pathways by some of the risk factors might be related to the oligodendrocyte cell death observed in schizophrenia. Further details Ongoing clinical trails, worldwide, can be interrogated at ClinicalTrials.Gov a service of the US National Institutes of Health

	Risk factor (links to Wikipedia and Pubmed)	PolygenicBlog on the relationships between genes and risk factors
	Prenatal
	Maternal Famine as a risk factor for offspring St Clair et al, 2005 Prenatal Rubella infection (first trimester) as a risk factor for offspring Brown et al, 2000 Measles, varicella zoster and polio (Schizophrenia births) Torrey et al, 1988 Maternal Rubella, Herpes simplex, Influenza as a risk factor for offspring Brown, 2005 Yolken, 2004 Maternal poliovirus infection during second trimester of pregnancy as a risk factor for offspring Suvisaari et al, 1999 Elevated maternal IL-8 levels during second trimester as a risk factor for offspring Brown et al, 2004 Maternal Herpes Infection (HSV-2) as a risk factor for offspring Buka et al, 2007 Fever during prenancy as a risk factor for offspring Torrey et al, 2000 Maternal bleeding during pregnancy and low male birthweight as a risk factor for offspring (interpeted as placental insufficiency)Hultman et al, 1999 Pre-eclampsia and obstetric complications as a risk factor for offspringDalman et al, 1999 Winter birth Bembeneck, 2005 A higher risk of psychosis in offspring is associated with antenatal maternal depression Maki et al, 2010 Lower placental weight, lower birth weight and smaller head circumference at 12 months predicts elevated positive schizotypal traits in women Lahti et al, 2009 Rhesus incompatibility / Hollister et al, 1996 Postnatal Vitamin D supplementation associated with reduced risk .McGrath et al, 2004 Low maternal folate and high homocysteine plasma levels Picker and Coyle, 2005 Unwanted pregnancy reported as a schizophrenia risk factor in the offspring McNeil et al, 2009 Prenatal exposure to maternal urinary tract infection, pyelonephritis.Clarke et al, 2009 Variability of age of onset correlates with latitude . Shaner at al, 2007 A higher risk of schizophrenia in colder climates especially in areas with low fish consumption, darker skin and high infant mortality: All possibly related to prenatal vitamin D defficiency .Kinney et al, 2009
	Childhood
	Childhood meningitis Abrahao et al, 2005 Mumps or cytomegalovirus infection in children (0-12 years) Dalman et al, 2008 Yolken and Torrey, 2008 CNS infection during childhood: particularly Coxsackie B5 virus Rantakallio et al, 1997 Cat ownership (between ages 1-13) Viral zoonoses/ Torrey et al, 2000 Associated with Dog roundworm Toxocariasis (Toxocara.Canis) Kaplan et al, 2008 Childhood Trauma Morgan and Fisher, 2007
	Adult Infections
	Herpes viral infection (HSV-1) (seropositivity in adults)Prasad et al, 2007 Seropositivity to Herpes virus HHV-6: Negative association with HSV-2 and cytomegalovirus and positive asociation with HSV-1 in various subpopulations (Adults)Niebuhr et al, 2008 Borna disease virus (seropositivity in adults)Terayama et al, 2003 Elevated endogenous retrovirus transcripts (HERV-W) in blood of first episode schizophrenics: Yao et al, 2008 .Huang et al, 2010 Presence of measles virus antibodies in patients with recent onset of psychosis Dickerson et al, 2010 Coronavirus seropositivity has been associated with Schizophrenia Severance et al, 2009 Elevated incidence of schizophrenia and other psychiatric disorders in prison inmates infected with HIV with or without Hepatitis B or Hepatitis C .Baillargeon et al, 2008 Toxoplasmosis (T.Gondii) seropositivity in adults .Mayoclinic.com Toxoplasmosis information .Torrey et al, 2006 Yolken and Torrey, 2008 Association with Psoriasis vulgaris in a limited number of patients Miyaoka et al, 2000 Ixodes Tick infestation and Lyme disease (Borrelia burgdorferi) (Geographical and seasonal correlation) Fritzsche, 2002 Chlamydial infection especially C.Psittaci (PCR detection in adults) Fellerhoff et al, 2007 Lactate dehydogenase virus (Brain antigen post-mortem) Dvorakova et al, 1990 Leptospirosis (Weil's disease): adult infection Semiz et al, 2005 High fever can precede psychosis in adults Malhotra et al, 1998 Subacute sclerosing panencephalitis caused by the measles virus has been associated with Psychosis in a number of studies Prashanth et al, 2007 Increased incidence of antibodies reactive to gag encoded proteins of Mason-Pfizer monkey virus (MPMV), baboon endogenous virus (BaEV) and simian retrovirus type 5 (SRV-5) in sera of first episode adult schizophrenics.Lillehoj et al, 2000 Increased levels of alpha defensins in schizophrenic patients suggesting infection Craddock et al, 2008
	Association with other diseases
	Inverse association with rheumatoid arthritis .Gorwood et al, 2004 Torrey and Yolken Autoimmune disease prior to onset: Thyrotoxicosis, celiac disease, acquired hemolytic anemia, interstitial cystitis, and Sjogren's syndrome: Eaton et al, 2006 Inverse association with Type 1 Diabetes .Juvonen at al, 2007 Comorbidity with Type II Diabetes .Bellivier, 2005 Psychosis associated with Porphyria : (Madness of King George)Sassa, 2005 High plasma homocysteine levelsHaidemenos et al, 2007 Low Vitamin B12 levels: Vitamin B12 Deficiency can itself produce psychosis Kale at al, 2010 .Rajkumar and Jebaraj, 2008
	Substance abuse and social
	Alcohol abuse associated with early psychosis Tucker, 2009 Cannabis use Boydell et al, 2006 Living in an urban environment Krabbendam and Van Os, 2005 Living in areas of high social deprivation Agius and Ward, 2009 Lead exposure .Opler and Susser, 2005

Last update: September 1, 2010