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
Toxoplasmosis
Blog
Multiple genes of small effect, whose risk promoting ability is conditioned
by other genes and risk factors (Epistasis, gene/environment interactions).
: For this reason any positive studies are reported.
See also:- The fox and the rabbits, environmental variables and
population genetics.1: Replication problems in association studies
and the untapped power of GWAS. ISRN
Neurology, 2011
eIF2B and oligodendrocyte survival: where nature and nurture meet
in bipolar disorder and schizophrenia? Schiz
Bull, 2007
Schizophrenia susceptibility genes converge on interlinked pathways
related to glutamatergic transmission and long-term potentiation,
oxidative stress and oligodendrocyte viability.Schiz
Res, 2006
Toxoplasmosis and polygenic diseases: Extensive T.Gondii host/pathogen
interactome enrichment in nine psychiatric or neurological disorders
J.Pathogens,
2013
More info on most of these genes can be found here
Recent genes will be linked from this page.
Sponaneous mutations in non familial schizophrenia:
Exome sequencing Xu
et al, 2011 ACOT6 ADAMTS3 ADCY7 CCDC108 CELF2 COL3A1 DGCR2 DPYD
EDEM2 ESAM FAM3D FASTKD5 GIF GPR115 GPR153 INPP5A KLF12 LAMA2 MAGEC1
MTOR NPRL2 OR4C46 PAG1 PITPNM1 PLCL2 PML RB1CC1 RGS12 SAP30BP SLC26A7
SLC26A8 SPATA5 TEKT5 THBS1 TRAK1 TRRAP UGT1A4 VPS35 WDR11 ZNF530 (not
all in the same individuals) LAMA2, DPYD, TRRAP and VPS39
Xu et al, 2012
Autozygosity (two chromosomal segments that are identical
from a common ancestor are inherited from each parent: Relatively common
in inbreeding) has been related to schizophrenia Keller
et al, 2012 Risk factor (links to Wikipedia and Pubmed)
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
But high birthweight and maternal diabetes have been assciated with
subsequent risk Wegelius
et al, 2011
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
The use of aspirin, but not Paracetamol or other analgesics, during
pregnancy has been linked to later psychosis in the offspring Gunawardana
et al, 2010
Breast feeding is less common in those later developing schizophrenia
McCreadie
1997
Maternal obesity prior to and during pregancy was associated with
two- to threefold increased risk of schizophrenia in the adult offspring
Khandaker
et al, 2011
Reduced maternal levels of common viruses during
pregnancy predict offspring psychosis (related to maternal immune
activation ?) Canuti
et al, 2015
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
High prevalence of Kaposi's sarcoma-associated herpesvirus (HHV-8)
in schizophrenia Hannachi
et al, 2013
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
The incidence of previous tuberculosis has been reported to be higher
in schizophrenia patients Ohta
et al, 1988
Enteric fever (salmonella) in the tropics can be associated with
catatonic schizophrenia Khosla
1991
Infectious agents associated with schizophrenia: A meta-analysis
Arias
et al, 2011.
a statistically significant association between schizophrenia
and infection by Human Herpesvirus 2 (OR=1.34; CI 95%: 1.09-1.70;
p=0.05), Borna Disease Virus (OR=2.03; CI 95%: 1.35-3.06; p<0.01),
Human Endogenous Retrovirus W (OR=19.31; CI 95%: 6.74-55.29; p<0.001),
Chlamydophila pneumoniae (OR=6.34; CI 95%: 2.83-14.19; p<0.001),
Chlamydophila psittaci (OR=29.05; CI 95%: 8.91-94.70; p<0.001)
and Toxoplasma gondii (OR=2.70; CI 95%: 1.34-4.42; p=0.005)
Meta-analysis : C. pneumoniae DNA in blood and brain are more common
in schizophrenic patients: greater prevalence of anti-Toxoplasma immunoglobulin
G \Gutiérrez-Fernández
et al, 2015
High antibody titres against an E. coli O-antigen have been observed
in male schizophrenics Krøll,
1986
Psychosis has been observed in chronic brucellosis Annesley,
1968
Chronic otitis, rheumatic fever, severe childhood infections and
maternal problems during pregnancy have been associated with schizophrenia
Polishchuk,
1982
Acute relapse in schizophrenia has been associated with urinary
tract infections Miller
et al, 2013
Antibody levels to several combinations of agents, including casein,
measles, cytomegalovirus, Toxoplasma gondii and the vaccinia virus,
was predictive of an 18-34% increase in the risk of developing schizophrenia
Li
et al, 2013.
Microbiome: modified prevalence of Lactobacillus phage phiadh in
the oral pharynx microbiome (phageome) of schizophrenic patients Yolken
et al, 2015
Previous autoimmune diseases and the number of infections requiring
hospitalization are risk factors for schizophrenia Benros
et al, 2011.
Inceased antibodies to gliadin (gluten component) Jin
et al, 2010
High levels of anti-gliadin IgG in the maternal circulation
associated with risk for the development of nonaffective psychosis
in the offspring Karlsson
et al, 2012
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is associated
with psychosis Iizuka
2008
Association between schizophrenia and diminished risk for duodenal
and gastric ulcers but not for gastrojejunal ulcers Ozdemir
et al, 2007
Associated with polycystic ovary syndrome: Insulin resistance and
elevated testosterone in women contribute to the shared pathogenesis
of PCO and schizophrenia
Matevosyan, 2011
Insomnia is frequent in schizophrenia: association with nocturnal
eating and obesity Palmese
et al, 2011
Psychiatric problems including psychosis and depression are observed
in Cushing syndrome (associated with high cortisol) Hirsch
et al, 2000
Gastrointestinal inflammation related to food antibodies (casein
and gluten) is associated with schizophrenia and may link food antigen
sensitivity and microbial infection as sources of immune activation
in mental illness Severance
et al, 2012.
Association with liver diseases, including hepatitis C and alcohol-related
cirrhosis Fuller
et al, 2011
No general association with parental cancers in the offspring ,
but a small increase in risk with maternal lung cancer (possibly related
to smoking rather than cancer ?) Benros
et al, 2013
A higher dietary intake of refined sugar and dairy products predicted
a worse 2-year outcome of schizophrenia.Peet
2004
Adult women with a high intake of fish, omega-3 or omega-6 polyunsaturated
fatty acids and vitamin D had a lower rate of psychosis Hedelin
et al, 2010.
Favourable outcomes associated with a low percentage of total fat,
and of fat from land animals and birds (composed mainly of saturated
fat) High percentage of fat from vegetables, fish and seafood (having
a relatively high content of unsaturated fatty acids) tended to be
associated with a favourable course and outcome Christensen
and Christensen, 1988
Levels of essential trace metals (Iron and Selenium) were reduced
while levels of certain heavy metals (Lead, Chromium and Cadmium)
were raised in schizophrenic patients Arinola
et al, 2010.
Reduced hair concentrations of Zinc and Calcium and increases in
the hair concentration of copper and cadmium have been reported in
schizophrenic patients Rahman
et al, 2009
Mercury related schizophreniforme psychosis Bader
, 1952
N-acetyl cysteine, as a glutathione precursor, has been used with
some success to treat schizophrenia Berk
et al, 2008RSS
feed
A "P lymphocyte" is found in schizophrenics and their
relatives, characterised by high cytoplasmic basophilia and leptochromatic
nuclear structure.The cytoplasm often contains vacuoles and the nuclear
shape is often irregular with one or more nucleoli visible Hirata-Hibi
and Hayashi, 1993
Activated kynurenine metabolism in fibroblasts from bipolar and
schizophrenia patients. Cytokine challenge increases 3-hydroxykynurenine
production Johansson
et al, 2013
A metabolomics plasma study identified higher concentration of ornithine
and lower concentrations of arginine, glutamine, histidine and phosphatidylcholine
ae C38:6 in schizophrenic patients He
et al, 2012
Serum levels of IL1B, IL6 TNF and adiponectin increased in first
episode schizophrenia Song
et al, 2013
Decreased IL10 serum levels in first-episode drug-naïve schizophrenia
(anti-inflammatory cytokine) Xiu
et al, 2014
Pyroglutamic acid, sorbitol and tocopherol-a identified as peripheral
blood mononuclear cells biomarkers Liu
et al, 2014
Shortened telomere length in unremitted schizophrenia subjects Kota
et al, 2014
oxidative stress marker (malondialdehyde levels) increased, and
the levels of antioxidative enzymes (glutathione peroxidase and superoxide
dismutase) decreased in erythrocytes of drug-naive schizophrenic patients
Reyazuddin
et al, 2014
Increased urinary concentrations of biopyrrins in patients with
chronic schizophrenia Miyaoka
et al, 2015
Evidence for toll-like receptor activation ( TLR4 ) in the schizophrenia
prefrontal cortex Garcia-Bueno
et al, 2016
Autoantibodies and antibodies in schizophrenia
Autoantibodies to NMDA receptors and potassium channel complexes
Zandi
et al, 2011
Casein- and/or gluten-IgG binding to C1q reported to be increased
in non-recent onset group of schizophrenia Severance
et al, 2012
IgG antibodies to Saccharomyces cerevisiae in recent onset schizophrenia
patients , correlating with food antigen antibodies (bovine milk casein,
wheat-derived gluten): Anti-food antigen antibodies were correlated
to antibodies against Toxoplasma gondii Severance
et al, 2012
antibodies to surface dopamine D2 and NMDA NR1 receptors in pediatric
patients with psychosis Pathmanandavel
et al, 2014
Antibodies to folate receptor alpha (FOLR1): Folinic acid resultedin
clinical improvement Ramaekers
et al, 2014
Substance abuse , drugs and infections inducing psychosis and
related symptoms and social
Living in an urban environment Krabbendam
and Van Os, 2005 Urban living environments associated with higher
rates of prescription for psychotropic medication for anxiety, depression
and psychosis McKenzie
et al , 2013.
There is a clear gradient of schizophrenia incidence from completely
rural (low ) to urban, (high). Within rural areas high incidences
were related to mining camps, lumbering camps, or fishing villages,
and not farming areas (1880 census data) Torrey
et al, 1997.
Psychosis asociated with Kaposi's sarcoma (Human herpesvirus
8) Gallafent
et al, 2005
Viral encephalitis can induce psychosis Wilson,
1976
Schizophrenia incidence peaks in late adolescence ( puberty ) in
men and women and following menopause in women Markham,
2012
The incidence of schizophrenia doubled in south-east London between
1965 and 1997 Boydell
et al, 2003 perhaps due to migrant trends : Overall, there is
some evidence that the global incidence of schizophrenia may be declining
McGrath
et al, 2004
Schizophrenia has a graded geographical distribution (Map from Wikipedia
)