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Vitamin D and schizophrenia

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Genes Kegg pathways for Schizophrenia genes

Multiple genes of small effect, whose risk promoting ability is conditioned by other genes and risk factors: 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
• and:- Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes
• 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

More info on most of these genes can be found here Recent genes will be linked from this page.

GWAS ACSM1 ADM AGBL1 ANK3 ANXA1 ASTN2 ATP5SL BTN2A2 BTN3A1 BTN3A2 ,BUCS1 C3orf39 C6orf10 C6orf105 CACNG5 CCDC60 CEACAM21 COL25A1 CNTN5 CNTNAP2 CSF2RA CTXN3 CYCSP44 DAOA ENPP4 ELAVL2 ERC2 FAM69A FAM110B FXR1 GABRR1 GPC1 GRIA2 HIST1H2AG, HIST1H2BJ HLA-DQA1 IFLTD1 IFT88 IGSF22 IL3RA KCNJ3 LOC393076 LRRFIP1 LRRIQ3 MHC MIR137 MSRA MYO18B NALCN NAP5 NKAPL NOTCH4 NPAS3 NRGN NRP1 PARD3 PLAA PTBP2 SLC12A2 SLC17A1 SLC17A3 SLCO6A1 PGBD1 PHF8 POU3F2 PRSS16, POM121L2, PPARG PTPRU PTPRN2 RELN RIN2 ROBO1 ROBO2 RYR2 TCF4 TMEM212 TNIK TRAF3 TSPAN18 VIPR2 VRK2 ZKSCAN4 ZNF184 ZNF804A

Pre GWAS: See SZGene Allen et al, 2008 See also The Genetic Association database at NIH ... Genotator at Harvard University and HUGE navigator

• Glutamate: DAO DAOA GRIA1 GRIA3 GRIA4 GRID1 GRIK2 GRIK3 GRIK4 GRIN1 GRIN2A GRIN2B GRIN2D GRM1 GRM3 GRM4 GRM5 GRM7 GRM8 SLC1A1 .SLC1A2 SLC1A3 SLC1A4 SLC1A6 SLC6A5 SLC17A6 SLC17A7 SRR KMO
• GABA: GABBR1 GABRA1 GABRA6 GABRB2 GABRG2 GABRP GAD1 SLC6A12
• Channels: CACNA1C CACNA1F CACNG2 KCNH2 KCNN3 NALCN
• Dopamine:DRD1 DRD2 DRD3 DRD4 DRD5 COMT MAOA MAOB PAH PITX3 SLC6A3 SLC18A1 SLC18A2 TH TYR
• Serotonin: HTR1A HTR1B HTR2A HTR2C HTR3B HTR3E HTR4 HTR5A HTR6 HTR7 SLC6A4 TDO2 TPH1 TPH2
• Acetylcholine: CHRFAM7A CHRM5 CHRNA4 CHRNA7 CHRNB2 CHAT
• Synaptic: DLG1 DLG2 DLG4 GAP43 HOMER1 HOMER2 PICK1 SHANK1 SHANK3 SNAP25 SNAP29 SYN2 SYN3 SYNGR1 SYT11 STX18 STX1A
• Glutathione: CBS GCLC GCLM GLO1 GSTA1 GSTM1 GSTT1 GSTZ1 GSS
• Growth factor:BDNF CNTF CSF2RA CSF2RB EGF EGFR EGR2 EGR3 EGR4 ERBB2 ERBB3 ERBB4 FGF1 FGF14 FGF18 FGFR1 GDNF GFRA1 GFRA2 GFRA3 IGF2 NRG1 NRG2 NRG3 NTF3 NTRK1 NTRK3 PDGFB PDGFRB
• Chemokine/Cytokine: CCR5 IL10 IL10RA IL12B IL18 IL18R1 IL18RAP IL1A IL1B IL1RN IL2 IL3 IL3RA IL4 IL6 IL6R IL9 IL28B IL31RA LIF LTA TNF TNF TNFRSF1B
• Immune C1QB :C3 C4A C4B CD4 CLU CTLA4 EBF3 HLA-A HLA-B HLADQA1 HLA-DQA2 HLA-DRB1 DRB1*04 IFNG IGH@ MICB TPP2
• Oxidative stress/mitochondrial ATP5G3 ATP6 ATP6V1D CYTB MT-RNR1 ND2 ND4 NDUFV2 NQO2 SOD2 UCP2 SLC25A27
• Folate /homocysteine MSRA MTHFD1 MTHFR
• Myelin: MAG MBP . MOG MYT1L .NOTCH NOTCH4 RTN4 RTN4R QK1
• Circadian: CLOCK PER3 TIMELESS
• Structural: COL3A1 COL5A2 MYH9 MYL12A MYL12B MYO18B MYO9B
• Adhesion CDH4 CHL1 CNTN1 CNTNAP2 ITGA3 JAM3 L1CAM NRXN1 PCDH8
• DISC1 ATF4 DISC1 CIT FEZ1 GSK3B MAP1A NDE1 NDEL1 PCNT PDE4B TNIK TSNAX

ABCA1 ABCA13 ABCB1 ACE ACSL6 ACSM1 . ADA ADAM12 ADCYAP1 ADH1B ADIPOR2 ADORA1 ADRA1A ADSS AGA AGAP1 AGBL1 AHI AKT1 ALDH1A2 ALDH3B1 ALK ALOX12 AMACR ANK3 ANKAR ANKK1 ANXA7 APBA2 APC APOE APOL2 AR ARHGAP18 ARHGEF10 . ARL17 ARRB1 . ARVCF ASAH1 ASNSD1 ASTN1 ASTN2 ATE1 ATF2 ATF6 ATG9 ATM ATN1 ATXN1 ATXN3 ATXN8OS AVP . B3GAT1 B3GAT2 BAK1 BCL9 BLOC1S3 BMP6 BRD1 BTN2A2 BTN3A1 BTN3A2 BZRP C6orf217 C10orf120 C11orf41 C18orf1 CAG CALR CAPZA2 CAV1 CBX2 CCDC102B CCDC60 CCKAR CDC27 CDC42, CDC42SE2 CDKN2A CEACAM21 CENTG2 CFB CHGA CHGB CHI3L1 CHN1 CHN2 CLDN5 CLINT1 CMYA5 CNP CNR1 CPLX2 CPXM2 CREB3L1 CRH CRHR1 CSMD1 CSMD2 CSPG5 CTNND2 CTXN3 CYP1A2 CYP2D6 CYP3A4 CYP3A5 DAAM1 DAAM2 DBH DDR1 DDX31 DGCR2 DGCR5 DGCR6 . DGKH . DGKI DIRC1 DKK4 DLX1 DNMT3B DPYSL2 DNAJC9 DOCK4 DTNBP1 DUSP12 DYM DYNC2H1 EFNB2 EIF2S1 ELOVL2 ELP3 EML5 ENAH ENO2 ENTH ESD ESR1 EVPL FABP7 FAM71D FBP1 FBXL21 FBXL7 FBXO38 FLJ46361 FLNB FOLH1 FOXP2 FXR1 FXYD2 FXYD6 FYN FZD3 GALNT2 GALNT7 GC GDF8 GJA8 GLG1 GLT8D1 GLO1 GNAL GNAO1 GNAS GNB1L GNB3 GNL3 GNPAT GOPC GPC1 GPHN GPR78 GPR85 GTF2A1L GTF3C4 GULP1 HDAC3 HDAC4 HINT1 HIPK3 HIST1H2AG HIST1H2AH HIST1H2BJ HMBS HMX3 HP HRH2  HSPA1B HSPA1L HSPA12A HSPA1B HSPA1L HTF9C IMP5 IMPA2 IMPAD1 INTS6 IPO5 ITIH3 JARID2 KIAA1267 KIF2A KIF17 KLF5 KLF6 KLH1AS KPNA3  KPNB3 KREMEN1 LAMA1 LARGE LG2 LGI1 LHPP LMX1A LMX1B LOC220433 LOC730216 LPL LRRC37A LOC387895 LRRC37A2 LRRTM1 MAD1L1 MAGI2 MAGI3 MAMDC1 MAN2A1, MAP4 MAP6 MAPK14 MAPK8IP2 MAPT MC5R MCHR1 MCHR2 MCP-2, MCTP2 MDGA1 ME2 MED12 MED15 MEGF10 MET MIM MIR-198 MIR-206 MIR-30E MLC1 MLL3 MMP3 MMP9 MOV10L1 MPP5 MPZL1 MRPL22 MT-haplo MTMR1A MTNR1B MTR MUTED MXRA5 NAALAD2 NBPF10 NCAM1 NCAPD3 NCKAP5 NEK4 NEUROG1 NLGN2 NNMT NOS1 NOS1AP NPAS2 NPAS3 NPTN NPY NRGN NRN1 NSF NTNG1 NTNG2 NUMBL OLFML2B OGG1 OLIG2 OPCML OPRM1 SIGMAR1 ORMDL1 OSGEPL1 OXT PAFAH1B1 PADI2 PADI4 PAWR PAX6 PBRM1 PCK1 PCM1 PDCD1LG2 PDE4A PDE4D PDE7B PDLIM5 PDYN PEMT PFN4 PGAP1 PGBD1 PHOX2A PHOX2B PHTF2 PI4KA PIK3C2G PIK3C3 PIK4B PIP4K2A PIP5K2A PLA2G4 PLA2G4B PLA2G4C PLA2G6 PLAA PLAT PLCB1 PLEK2 PLP1 PLXNA2 PMS1 PNOC PNPLA8 PNPO POM121L2 POU3F2 PPAPDC1A PPARD PPP1R1B PPP3BB PPP3CB PPP3CC PRKAG2 PRKCA PRKCD PRKCH, PRODH PRSS16 PSAP PSEN2 PSKH1 PTBP2 PTGS2 PTK2 PTPN21 PTPRA PTPRM PTPRZ1 RANBP1 RAPGEF6 RASD2 RBP1 RCH2NH2 RELN RFX6 RGS2 RGS4 RGS5 RHD RNLS RNR1 ROBO1 ROBO2 RPGRIP1L RPP21 RPRML RPS4XP16 RPS6KA5 RSRC1 S100B SEMA3D SEMG2 SEPSECS SFRP1 SGCD SH3TC2 SHISA5 SIL1 SIRT1 SIRT5 SKP2 SLC12A2 SLC12A9 SLC15A1 SLC17A1 SLC17A3 SLC22A23 SLC35F3 SLC39A8 SLC40A1 SLCO6A1 SLIT SLIT3 SMARCA2 SMARCC1 SOX10 SP4 SPARCL1 SPRY4 SREBF1 SREBF2 SRD5A2 ST8SIA2 SULT6B1 STH STON1 STON2 SULT4A1 ST8SIA2 TAAR6 TACC2 TAL1 TARBP1 TBP TBX1 TCERG1L TCF4 TCF7L2 TCP1 TF TGIF1 TGM2 TIMP3 TMC4 TMEM108 TNXB TP53 TP53I3 TRAF3IP1 TRIM71 TRMT2A TRPA1 TSKU TSPAN8 TUBA8 TXNDC5 U2AF UFD1L UHMK1 UPF3B USP46 vps34 VDR VRK2 WDFY2 WDR75 WNT3 WNT9B WWC1 XBP1 XRCC1 YWHAE YWHAH ZBED4 ZC3H18 ZDHHC8 ZMYND17 ZNF184 ZNF518A ZNF667 ZNF74 ZNF804A

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)
Risk factor (links to Wikipedia and Pubmed)

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
• Prenatal lead exposure has been associated with schizophrenia Opler et al, 2008
• 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 HSV-2 infection- interacting with NMDA receptor polymorphisms DeMontis et al, 2011
• Prenatal Influenza b infection associated with psychosis in the offspring Ellman et al, 2009
• 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
• Low birthweight may predispose to adult psychiatric disorders Abel et al, 2010
• Pre-eclampsia and obstetric complications as a risk factor for offspringDalman et al, 1999
• Winter birth in both southern and northern hemispheres Boyd et al, 1986 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
• But high birthweight and maternal diabetes have been assciated with subsequent risk Wegelius et al, 2011
• Rhesus incompatibility / Hollister et al, 1996
• Postnatal Vitamin D supplementation associated with reduced risk .McGrath et al, 2004
• Prenatal Vitamin D deficiency may contribute to schizophrenia risk McGrath et al, 2010
• Vitamin D deficiency is observed in adult schizophrenics Paartii et al, 2010
• 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
• The use of aspirin 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

• 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

• Herpes viral infection (HSV-1) (seropositivity in adults)Prasad et al, 2007 associated with cognitive decline Yolken et al, 2011
• 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
• Seropositivity to human coronaviruses Severance et al, 2011
• Higher Epstein-Barr virus seropositivity in schizophrenia DeLisi et al, 1986
• 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
• Hepatitis C is often associated with schizophrenia Carney at al, 2006
• 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
• C.Psittacci , C. pneumoniae and Chlamydia trachomatis infections Fellerhoff et al, 2005
• 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
• 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
• Increased levels of alpha defensins in schizophrenic patients suggesting infection Craddock et al, 2008
• 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)
• 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

• A geographical and seasonal correlation with multiple sclerosis Fritzsche, 2002
• Inverse association with rheumatoid arthritis .Gorwood et al, 2004 Torrey and Yolken
• Autoimmune disease prior to onset: Thyrotoxicosis, coeliac disease, acquired hemolytic anemia, interstitial cystitis, and Sjogren's syndrome: Eaton et al, 2006
• Inceased antibodies to gliadin (gluten component) Jin et al, 2010
• 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
• Psychosis associated with some forms of multiple sclerosis Felgenhauer, 1990
• Cancer risk is low in schizophrenia patients Barak et al, 2005
• Brain trauma can increase schizophrenia risk Chen et al, 2010
• 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

Dietary and environmental factors

• Low Vitamin B12 levels: Vitamin B12 Deficiency can itself produce psychosis Kale at al, 2010 .Rajkumar and Jebaraj, 2008
• 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
• Pesticides and disease database

Biochemistry and pathology

• Lateral cerebral ventricle enlargement Weinberger et al, 1979
• Cortical thinning in in prefrontal and temporal cortices Yang et al, 2010
• Oligodendrocyte cell loss RSS feed
• Decreased dentritic spine density in cortical regions RSS feed
• Progressive gray matter loss Video
• Decreased frontal cortex glutathione levels Gawryluk et al, 2011
• Increased frontal cortex kynurenate levels (NMDA antagonist) Wonodi and Schwarcz, 2010.
• N-acetyl cysteine, as a glutathione precursor, has been used with some success to treat schizophrenia Berk et al, 2008 RSS 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
• High plasma homocysteine levels Haidemenos et al, 2007

Substance abuse , drugs and infections inducing psychosis and related symptoms and social

• Alcohol abuse associated with early psychosis Tucker, 2009
• Cannabis use Boydell et al, 2006
• Amphetamine (Releases dopamine. noradrenaline and serotonin) Hermens et al, 2009
• Buproprion (inhibits dopamine and noradrenaline reuptake and is a non-competitive cholinergic nicotinic receptor antagonist) Javelot et al, 2010
• Ketamine (NMDA antagonist) Morgan et al, 2010
• Phencyclidine (NMDA antagonist) Koseki and Nabeshima 2010
• Living in an urban environment Krabbendam and Van Os, 2005
• 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.
• Living in areas of high social deprivation Agius and Ward, 2009
• Lead exposure .Opler and Susser, 2005
• The HIV-1 antiviral efavirenz can induce psychosis Cavalcante et al 2010
• Psychosis is a rare side effect of interferon-alpha therapy Quarantini et al, 2006
• Schizophrenia has been inversely linked to the occurence of geomagnetic storms during gestation Kay, 2004
• Thyrotoxic psychosis Rizvi, 2007
• Viruses inducing psychosis
  • Hepatitis B (case report) Weber et al, 1994
  • HIV-1 AIDS Grehl and Kaschka 1994 assocvieted with high CSF levels of kynurenic acid Atlas et al, 2007 NeuroAIDS RSS feed
  • SARS coronavirus Llee et al, 2004
  • Dengue fever (case-report) Blum et al, 2010
  • Tick-borne encephalitis virus (case-report) Chlabicz et al, 1996
  • Psychosis asociated with Kaposi's sarcoma (Human herpesvirus 8) Gallafent et al, 2005
  • Viral encephalitis can induce psychosis Wilson, 1976
• Schizophrenia has a graded geographical distribution (Map from Wikipedia )
• 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