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Risk Factors for and Causes of Schizophrenia

Alcohol Dependence Increases Relapse: In a small 2 year retrospective study, schizophrenic patients whe were also alcoholics were more likely to relapse. Gerding, Med Univ South Carolina, APA 5/30/98 Toronto

Autoimmune Diseases More Common in Schizophrenia: In a study of all 7,704 schizophrenics in Denmark from 1981 to 1998 and their parents vs. matched controls, a history of any autoimmune disease was associated with a 45% increase in risk for schizophrenia. Thyrotoxicosis, celiac disease, acquired hemolytic anemia, interstitial cystitis, and Sjogren's syndrome had higher prevalence rates among patients with schizophrenia than among comparison subjects and also among family members. Eaton WW, et al. Johns Hopkins. . Am J Psychiatry 2006 Mar;163(3):521-8.

Autoantibodies Increased in Schizophrenia: 15% schizophrenics vs. 3% normals were found to have 60 kDa autoantibodies to neuroblastoma or heat shock protein. Studies characterizing 60 kda autoantibodies in subjects with schizophrenia. Wang XF, Wang D, et al. Biol Psychiatry 2003 Mar 1;53(5):361-75

Auto-Immune Possible in Some: Platelets from schizophrenic patients have autoantibodies (PAA) which cross-react with brain antigens. Accordingly, treatment of schizophrenia with an immunosuppressant might be of potential benefit. In a recent case study, a chronic schizophrenic patient treated with azathioprine has demonstrated a clear psychiatric improvement preceded by a decrease in PAA level. Study of PAA in 40 schizophrenic patients found 14 had high levels. 11 of these were given azathioprine 3 weeks and two improved. Neuropsychobiology 1997;36(4):172-6

Birth Weight: Low or High Predictive of Schizophrenia: Swedish male conscripts born in 1973-1980 for whom linked birth, census, hospital admission, and adult height and weight data were available. 246,655 subjects. 3.4-year follow-up beginning at age 18 years, 80 subjects developed schizophrenia and 124 developed other nonaffective psychoses. A reverse J-shaped association was found between gestation-adjusted birth weight and schizophrenia. The hazard ratios were 7.03 for males of low birth weight (<5.5#) and 3.37 for those of high birth weight (>8.8#). Birth weight was not strongly related to other nonaffective psychoses. Taller males had a reduced risk of psychosis. Gestational diabetes may play a role. U Bristol. Patterns of fetal and childhood growth and the development of psychosis in young males: a cohort study. Gunnell D, Rasmussen F, Fouskakis D, Tynelius P, Harrison G. Am J Epidemiol. 2003 Aug 15;158(4):291-300

Borna Disease Virus: One in three healthy people are infected with BDV, which attacks the central nervous system, but nearly 100 per cent of people with severe mood disorders have the virus, found a study in 2001. Keizo Tomonaga, Osaka U, inserted a gene for a single protein produced by BDV into mouse embryos. Mice which grew up to express the viral protein in their brains were more aggressive and hyperactive. Only glial cells expressed the BDV protein. These non-neuronal cells are involved in forming and maintaining nerve junctions in the brain. Major psychiatric disorders such as schizophrenia are also characterized by the dysfunction of these special support cells. Proceedings of the National Academy of Sciences  7/8/03.

Cat Ownership a Risk Factor; Also Birth Complications, Fever in Pregnancy: The University of Maryland Survey Research Center studied 264 randomly selected mothers of children with schizophrenia, schizoaffective disorder, or bipolar disorder and 528 mothers of matched controls. For five of the 19 major variables, there were statistically significant differences between cases and controls: fever during pregnancy, complications during delivery, city or suburban residence at birth, cat ownership between birth and age 13, and breast-feeding. Stanley Foundation, The antecedents of psychoses: a case-control study of selected risk factors. Fuller Torrey E, Rawlings R, Yolken RH. Schizophr Res. 2000 Nov 30;46(1):17-23 (see Toxoplasmosis below). Rheumatoid arthritis also higher in cat owners and rheumatoid arthritis and schizophrenia inversely related suggesting an immunity in patients suffering from one of the diseases to the other. The schizophrenia-rheumatoid arthritis connection: infectious, immune, or both? Torrey EF, Yolken RH. Brain Behav Immun. 2001 Dec;15(4):401-10

Celiac Disease a Risk Factor: In a Danish study of 7,997 schizophrenic patients, Denmark's national patient register was used to determine if the schizophrenic patients or their parents were previously treated for celiac disease. The prevalence of celiac disease among schizophrenics was 1.5 cases per 1,000 compared to 0.5 cases per 1,000 in the larger control group. After adjusting for other factors, the risk of schizophrenia was three times greater with a history of celiac disease. Crohn's disease and ulcerative colitis were not associated with schizophrenia. BMJ 2/21/04

Chlamydial Intracellular Infections May Play a Role:  Neurotrophins like neurotrophin3 (NT-3) and brain-derived neurotrophic factor (BDNF), involved in processes of neuroplasticity, are also secreted by immune cells, but only by subpopulations of immune cells. Chlamydiaceae could cause disbalancement of immune cell sub-populations and, in some individuals with a vulnerable disposition, symptoms of mental illness. Based on previous observations of persisting IgA titers in some patients with mental illness, the researchers hypothesize that the intracellular parasites Chlamydiaceae are main pathogenic factors in schizophrenia. Using nested PCR researchers found a significant prevalence of the intracellular parasites Chlamydophila psittaci, C. pneumoniae and Chlamydia trachomatis (9/18, 50%), as compared to controls (8/115, 6.97%). Treatment with in vitro-activated immune cells together with antibiotic modalities showed sustained mental improvements in patients that did not depend on treatment with antipsychotic drugs. High risk of schizophrenia and other mental disorders associated with chlamydial infections: hypothesis to combine drug treatment and adoptive immunotherapy. Fellerhoff B, et al. Ludwig Maximilians-Universitaet Muenchen, Germany. Med Hypotheses. 2005;65(2):243-52

Chlamydophila and Chlamydial Infections: More Evidence: This study analyzes the frequencies of three types of Chlamydiaceae in schizophrenic patients (n=72), random controls (n=225) and hospital-patient controls (n=36), together with HLA-A genotypes. Using PCR analysis of blood, chlamydial infection was found in 40% of schizophrenic vs. 6.7% of control patients, odds ratio = 9.43, especially with Chlamydophila psittaci (OR=24.39). Schizophrenic carriers of the HLA-A10 genotype were clearly most often infected with Chlamydophila, especially C. psittaci (OR=50.00). Chlamydophila infections represent the highest risk factor yet found to be associated with schizophrenia. Associations between Chlamydophila infections, schizophrenia and risk of HLA-A10. Fellerhoff B, et al. Ludwig-Maximilans University of Munich, Germany. Molecular Psychiatry, 14 November 2006.

CNS Viral Illness in Childhood Not Related to Schizophrenia: 320 Finnish with illness before 15 had not greater incidence of later schizophrenia vs. controls. Childhood central nervous system viral infections and adult schizophrenia. Suvisaari J, Mautemps N, et al. Am J Psychiatry. 2003 Jun;160(6):1183-5

Complexin I and II Presynaptic Secretary Proteins Decreased: Neuroimaging and postmortem evidence indicates synaptic terminals are abnormal in schizophrenia, implicating abnormalities of proteins involved in the presynaptic secretory machinery, including the modulator proteins complexin I and complexin II. Using immunocytochemistry to study complexin I and complexin II proteins in hippocampus in 12 subjects with schizophrenia and 12 subjects with no known neuropsychiatric disorder, the absolute values and ratio of the hippocampal presynaptic proteins complexin II-complexin I were lower in subjects with schizophrenia. Disturbances in the complexin proteins in subjects with schizophrenia were greater than those observed for vesicular gamma-aminobutyric acid or vesicular glutamate transporters. The lower complexin II-complexin I ratio in several hippocampal subfields in subjects with schizophrenia was inversely correlated with the severity of antemortem cognitive impairment. The hippocampal complexin II-complexin I ratio is higher in rats trained in a memory task compared with untrained rats. Treatment of rats with antipsychotic drugs or with the psychotomimetic drugs amphetamine or ketamine did not alter the complexin II-complexin I ratio. Hippocampal complexin proteins and cognitive dysfunction in schizophrenia. Sawada K, Barr AM, et al. Kochi Medical School, Japan. Arch Gen Psychiatry. 2005 Mar;62(3):263-72.

Cytomegalovirus Associated with Deficit Schizophrenia: In a study of 88 patients with deficit schizophrenia and 235 nondeficit schizophrenia patients, serum antibodies to cytomegalovirus were twice as common in deficit schizophrenia (odds ratio = 2.01, p = .006). This association remained significant after covarying for positive psychotic symptoms and demographic features known to be associated with cytomegalovirus seropositivity and after correcting for multiple comparisons. No other human herpesvirus was significantly associated with deficit versus nondeficit categorization. Deficit Schizophrenia: Association With Serum Antibodies to Cytomegalovirus. Dickerson F, et al. Sheppard Pratt, Baltimore. Schizophr Bull. 2005 Sep 15

Diet: High Sugar and Milk Linked to Worse 2-Year National Outcome for Schizoprenia: A higher national dietary intake of refined sugar and dairy products predicted a worse 2-year outcome of schizophrenia. A high national prevalence of depression was predicted by a low dietary intake of fish and seafood. International variations in the outcome of schizophrenia and the prevalence of depression in relation to national dietary practices: an ecological analysis. Peet M. Sheffield, UK. . Br J Psychiatry. 2004 May;184:404-8. Ed: This is very preliminary. Still, avoiding sugar is a smart thing to do.  

Diuretics in 3rd Trimester for Hypertension Quadruples Schizophrenia: Dr. Holger J. Srensen of the University of Copenhagen studied 84 schizophrenic patients from a cohort of 7,881 and found an odds ratio of 4.1 after adjusting for maternal age, maternal schizophrenia, etc. Am J Psychiatry 2003;160:464-468

Downward Drift in Schizophrenia: A German study of the neighborhoods in which schizophrenic patients come from found areas with the highest rates of schizophrenics are characterized by highly unfavorable living conditions, a high percentage of young men, people living alone, students, foreigners, people with a low level of education and a high immigration/emigration rate. The analysis on the individual level, i.e. in the biography of schizophrenics shows that processes of social drift and/or nonstarter take place long before first admission in the prodromal phase and the psychotic prephase of beginning schizophrenia. Probably, these selective processes like downward drift or nonstarting processes, lead to the migration of schizophrenics into unfavorable areas or schizophrenic residents staying in poor areas, while healthy residents leave these districts. Ecological pattern of first admitted schizophrenics in two German cities over 25 years. Loffler W, Hafner H. Soc Sci Med. 1999 Jul;49(1):93-108

Famine Causes Doubling of Schizophrenia: The famine study focused on the Wuhu region of Anhui province in eastern China, one of the hardest-hit areas. The researchers examined data on births and deaths before, during and after the famine of 1959-61 and on psychiatric records from 1971 to 2001. In 1960, in the midst of the famine, there were 13,748 children born in the region; 192 of them developed schizophrenia. That compared with 483 schizophrenics out of 59,088 births in 1956 and 695 out of 83,536 births in 1965. Compared with children born before or after the 1959-61 famine, those born during the disaster faced double the risk of becoming schizophrenic later on. The results are nearly identical to a previous study of a famine in Holland resulting from a Nazi food blockade toward the end of World War II. David St. Clair, et al. University of Aberdeen, Scotland. JAMA 8/3/05.

Fetal Damage Cause for Discordant Monozygotic: Twin study found twin with schiz weighed 1620 g at birth vs 2300. Fromearly childhood, affected twin impaired sociability and intelligence. Hypothesize due to hyoxic damage. Prenatal underdevelopment and schizophrenia: a case report of monozygotic twins. Kunugi H, Urushibara T, Murray RM, Nanko S, Hirose T. Psychiatry Clin Neurosci. 2003 Jun;57(3):271-4

Glutathione Deficiency May Affect Synaptic Plasticity at NMDA Receptor: The metabolism of glutathione, an endogenous redox regulator, is abnormal in schizophrenia. Patients show a deficit in glutathione levels in the cerebrospinal fluid and prefrontal cortex and a reduction in gene expression of the glutathione synthesizing enzymes. This alters short- and long-term synaptic plasticity and affects NMDA receptor function. Neurosci 2005 Dec 1.

Herpes Simplex I Antibodies Associated with Cognitive Impairment in Schiz: 229 out-pt Adults were studied for herpes simplex viruses 1 and 2, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and varicella-zoster virus. Sheppard Pratt. Association of serum antibodies to herpes simplex virus 1 with cognitive deficits in individuals with schizophrenia. Dickerson FB, Boronow JJ, et al. Arch Gen Psychiatry. 2003 May;60(5):466-72

HHV-6, JCV Infects 100% in Glial Cells: Herpes virus-6 (HHV-6) infects worldwide, within the first two years of life, nearly 100% of the human population, infecting predominantly glial cells with a low-level of viral production. It persists latently lifelong, and has been detected in 13% � 74% of normal human brains. The JC virus (JCV) infects more than 70% of the world's population during early childhood, infects mainly glial cells (oligodendrocytes as well as astrocytes), and remains in the latent state without apparent clinical symptoms but shows in vitro the ability to deregulate the cellular function of oligodendrocytes and perhaps astrocytes. The JC virus is spread by urban sewage which might contribute to the urban factor observed in schizophrenia. BMC Psychiatry 2002 2:8

Homocysteine Up in Pregnant Mothers of Schizophrenics: Elevated prenatal homocysteine level is a plausible risk factor for schizophrenia because of its partial antagonism of N-methyl-D-aspartate receptors under physiologic glycine concentrations and its association with abnormal placental function and pregnancy complications. Maternal levels of homocysteine during the third trimester in a nested case-control study of a large birth cohort, born from 1959 through 1967 and followed up for schizophrenia from 1981 through 1997 compared 63 cases of schizophrenia vs. 122 controls using archived maternal serum samples. An elevated homocysteine level was associated with a 139% increase in schizophrenia risk (odds ratio, 2.39; P = .02). If future studies both replicate this association and support a causal link, then the use of folic acid supplementation would merit evaluation. Elevated prenatal homocysteine levels as a risk factor for schizophrenia. Brown AS, et al. Columbia University. . Arch Gen Psychiatry 2007 Jan;64(1):31-9.

Homocysteinemia and 677TT MTHFR Gene: Homozygosity for the 677C --> T polymorphism (677TT) in the methylenetetrahydrofolate reductase (MTHFR) gene in 254 well-defined schizophrenic patients and 414 healthy controls found a 60% increased risk of schizophrenia and heterozygosity a 30% increased risk. Plasma homocysteine concentrations in 62 patients with schizophrenia and 432 controls found an increased risk for schizophrenia in the fourth and third quartile versus the lowest quartile [odds ratio (OR) = 3.3; and OR = 3.1; respectively]. Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype, and the risk for schizophrenia: A dutch population based case-control study. Muntjewerff JW, Hoogendoorn ML, et al. Nijmegen, The Netherlands. Am J Med Genet B Neuropsychiatr Genet. 2005 Apr 1;135B(1):69-72

Influenza in 5th Month of Pregnancy Doubles Schizophrenia: French study of 994 schizophrenic adults compared to non-schizophrenic family siblings or other controls. Significantly more schizophrenic subjects than controls (both groups) had been exposed to the influenza virus during the fifth month of pregnancy (OR=2.24). Acta Psychiatr Scand. 2003 May;107(5):331-5

Inhalant Abuse of Volatile Solvents Can Cause Psychosis: Solvent-induced psychosis is very similar in clinical presentation to standard schizophrenia.  Amotivational symptoms are somewhat more common, but delusions, hallucinations, emotional instability are all typical. Symptomatological structure of volatile solvent-induced psychosis: is "solvent psychosis" a discernible syndrome? Wada K, et al. Tokyo, Japan. Nihon Arukoru Yakubuzu Zasshi 2005 Oct;40(5):471-84.

IQ Decline Between Ages 4 and 7 Predictive of Psychosis: A study of 547 children found that the 10% with the largest IQ decline had 7 times as high a level of psychotic symptoms at age 23 as the others. IQ at 4 not predictive, but low IQ at age 7 was also predictive. Kremen, Am J Psychiatry 5/98;155:672-7

IQ Decline by Age 17 Common in Schizophrenia:  In a study of Israeli draftees, 75% of schizophrenics with low IQs (<85) had had an IQ decline of 10 points or more and 23% for those with normal IQs. Arch Gen Psychi 2005 Dec;62(12):1297-304.

IQ: School Performance Deteriorates in Late High School for Schizophrenics: A Swedish study of school records of 76 schizophrenic adult patients and 146 controls found that at age 9, there were no differences in grades. At 12, cases had higher marks in drawing/art and tended to excel in language and religion. At 15, proficiency remained in drawing/art, but cases did worse in gymnastics. As psychotic symptoms started to appear later, a high frequency of school maladaptation was reported. By time of admission, grades were lower and falling. Helling I, et al: School achievements and schizophrenia: a case-control study. Acta Psychiatr Scand 11/2003;108:381-6. Some other studies have found academic problems in primary school for pre-schizophrenic children of schizophrenic parents.

Kynurenic Acid Elevated in Schizophrenia; Antagonist at Glycine NMDA Site: Kynurenic acid is an endogenous glutamate antagonist with a preferential action at the glycine-site of the N-methyl D-aspartate-receptor. In a study of 28 male schizophrenics and 17 male controls, kynurenic acid was found to be 70% higher in the cerebral spinal fluid of the schizophrenic patients. Levels in patients tended to increase with age. It appears that kynurenic acid plays a pathophysiological role in schizophrenia. Karolinska Institute, Sweden. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Erhardt S, Blennow K, Nordin C, Skogh E, Lindstrom LH, Engberg G. Neurosci Lett. 2001 Nov 2;313(1-2):96-8

Late Onset Schizophrenia Prelude for Alzheimers: 27 who developed schizophrenia at age 50 or above, with Mini-Mental State Examination (MMSE) scores were 20 or above. 19 followed-up 5 years later. Compared with those of 34 normal controls, 24 of whom were re-examined after 5 years. Average age of both groups exceeded 70 years. At 1-year follow-up, there was no evidence of decline in either group. At 5 years, however, nine schizophrenia patients were diagnosed with dementia. Five met criteria for Alzheimer's disease, one for vascular dementia, and three for dementia of unknown type. None of the controls had dementia. Over 5 years, mean MMSE scores declined from 25.5 to 19.0 in the schizophrenic patients, but only from 29.7 to 29.2 in the normal subjects (p < 0.001). Schizophrenic individuals who did not develop dementia had global Assessment of Functioning scores increased from 41.4 to 61.6 during follow-up, which was attributed to resolution of psychosis. Given that about half of the patients with schizophrenia did not become demented, the authors maintain that late-onset schizophrenia is a heterogeneous syndrome. Br J Psychiatry 2003;183:213-219.

Meningitis in Childhood Increases Risk of Adult Schizophrenia: In a follow-up study of 190 individuals affected by a meningitis infection the first 4 years of life during an epidemic in Sao Paulo, Brazil, between 1971 and 1974, usign 156 siblings of the meningitis patients who were not affected by meningitis at childhood as controls, there were eight (4.2%) cases of schizophrenia among meningitis victims vs. none in the controls, and 40 (21.0%) cases of life occurrence of psychotic symptoms compared to 12 (7.6%) cases in the control group (P<0.001). There were no differences between the two groups regarding other psychiatric disorders or of neurological soft signs. Childhood meningitis increases the risk for adult schizophrenia. Abrahao AL, et al. University of Sao Paulo, Brazil. World J Biol Psychiatry. 2005;6 Suppl 2:44-8.

More Women with Late Schizophrenia: A study of schizophrenia onset found 41% of women had late onset after 45 vs. 20% of males. J Clin Psychiatry 1/99 60:61-7.

Paternal Age Over 50 Triples Schizophrenia: Jerusalem Perinatal Study 1964-76 cohort 90,000 at age 21 found 335 with schizophrenia and nonaffective psychoses. Incidence of schizophrenia onset highest in late teens and early 20s. By age 34, cumulative prevalence nearly 1%. 27% of schizophrenia is attributed to advanced paternal age with offspring of >50 triple those <25. Risk did not increase in relation to maternal age. Paternal age not associated with other psychiatric disorders. Malaspina D et al: Advancing paternal age and the risk of schizophrenia. Arch Gen Psyc 01;58:361-7, Columbia U

Paternal Age Effect Confirmed: A study of Swedish youth in the military with a 36 year follow-up of over 50,000 found that for each decade of life past age 20 for the father, the rate of schizophrenia in the off-spring increases by 30%. Stanley Zammit, University of Wales, and Gothenburg University researchers. Brit J Psychiatry 10/2003.

Pregnancy Factors: Low Maternal BMI late in Pregnancy, Low Birth Weight, Short Birth Length, Low Placental Weight: All risk factors for schizophrenia. Wahlbeck, Arch Gen Psychiatry 01;58:48

Premorbid Adjusted Very Important: A 1-year follow-up for 319 emergency admissions diagnosed with primary psychotic disorders and substance-induced psychoses, of those with a baseline diagnosis of primary psychotic disorder, 50% were in remission (6 months with psychosis) at 1 year postintake, while of those with a baseline diagnosis of substance-induced psychosis, 77% were in remission at this time point. Lower Positive and Negative Syndrome Scale (PANSS) symptom levels at baseline, better premorbid functioning, greater insight into psychosis, and a shorter duration of untreated psychosis predicted remission at 1 year in both diagnostic groups. A good Premorbid Adjustment Scale score was especially favorable (OR = 0.13). Predictors of Psychosis Remission in Psychotic Disorders That Co-occur With Substance Use. Caton CL, et al. Columbia University. Schizophrenia Bull 2006 Jul 27.

Rh Incompatibility Risk Factor: babies with Rh positive blood, born to mothers who have Rh negative blood�a condition known as maternal-fetal Rh incompatibility�are at increased relative risk for developing schizophrenia. All of the subjects in Palmer�s study were born prior to the advent of pharmacological means to block an Rh negative mother�s immune response to her Rh positive fetus�the first such product, RhoGAM (RhO [D] immune globulin) was developed in the late 1960s. Christina Palmer, UCLA, Am J Human Genetics 12/02

Seasons & Places: Denmark study of all born 1935-78 found family history important, but also urban birth exerted a powerful impact, followed by births in Feb or March, followed by a family history. Mortensen, Aarhus U, NEJM 2/25/99.

Short Babies at Risk for Schizophrenia: In a huge study of 719,476 Swedes from the age of 16 with 9.9 years of follow-up, there were 736 cases of schizophrenia. There was little evidence of an association between birthweight and schizophrenia (hazard ratio per kg increase in birthweight: 0.90); the HR in babies weighing <2.5 kg compared to 3.5-4.0 kg was 1.29. However, short babies were at an increased risk with 47% less schizophrenia for every 4 extra inches in length (HR per 10 cm increase in birth length: 0.53). In males, low body mass index and short height at age 18 were associated with increased risk. There is some evidence that patterns of risk in relation to fetal growth differ depending on post-natal growth patterns: the increased risk associated with low body mass index was restricted to long babies who became light adults. Cohort study of 720,000 Swedish men and women. Gunnell D, et al. Bristol, UK. Schizophr Res. 2005 Aug 24. Ed: This connection could be in part due to a vitamin D deficiency, since vitamin D supplementation in pregnancy or infancy dramatically lowers the risk of schizophrenia and vitamin D supplementation plays a role in bone formation and calcium absorption.

Smoking 430% Common is Schizophrenia: When comparing current smoking in schizophrenia patients versus the general population, smoking was 430% more common with schizophrenia (OR = 5.3 in a meta-analysis of 42 studies from 20 nations). This study in a country with less smoking found a strong connection to schizophrenia, but none with depression. Smoking is associated with schizophrenia, but not with mood disorders, within a population with low smoking rates: A matched case-control study in Bucaramanga, Colombia. Campo-Arias A, et al. Universidad Autonoma de Bucaramanga, Colombia. Schiz Res 2006 Feb 21.

Social Adversity in Families Linked to More Schizophrenia: In a study of all children born in Sweden in 1963-1983, the risk of developing schizophrenia was increased for all childhood socioeconomic indicators, (from lowest to highest): rented apartments, low socioeconomic status, single-parent households, unemployment, and households receiving social welfare benefits. Those with four measures of adversity had a 2.7-fold higher risk of schizophrenia than those with none. Social adversity in childhood and the risk of developing psychosis: a national cohort study. Wicks S, et al. Stockholm, Sweden. . Am J Psychiatry. 2005 Sep;162(9):1652-7.

Tetrachloroethylene: a Solvent used in Dry Cleaning: Researchers examined the relationship between parental occupation as a dry cleaner and risk for schizophrenia in a prospective population-based cohort of 88,829 offspring followed from birth to age 21-33 years. Of 144 offspring whose parents were dry cleaners, 4 developed schizophrenia: an increased incidence of schizophrenia in offspring of parents who were dry cleaners (RR=3.4, p=0.01). Tetrachloroethylene exposure warrants further investigation as a risk factor for schizophrenia. Tetrachloroethylene exposure and risk of schizophrenia: Offspring of dry cleaners in a population birth cohort, preliminary findings. Perrin MC, et al. Columbia University, New York. Schiz Res 2006 Nov 16.

Toxoplasmosis: Meta-Analysis: An analysis of 42 studies of Toxoplasma gondii antibodies in schizophrenia in 17 countries over 5 decades were identified; 23 met selection criteria. The combined odds ratio (OR) was 2.73 (P < .000001). Seven studies that included only patients with first-episode schizophrenia (OR 2.54) did not differ significantly from 16 studies that included patients in all clinical phases (OR 2.79). Although the OR of 2.73 is modest, it exceeds that for genetic or other environmental factors identified to date and suggests that Toxoplasma is in some way associated with a large number of cases of schizophrenia. If an etiological association can be proven, it would have implications for the design of measures for the prevention and treatment of this disease. Antibodies to Toxoplasma gondii in Patients With Schizophrenia: A Meta-Analysis. Torrey EF, et al. Stanley Medical Research Institute, Chevy Chase, Bethesda, MD. Schiz Bull 2006 Nov 3.

Toxoplasma Antibodies in Schizophrenia Linked to Big Increase in Death Rate in Small Study: Increased rates of exposure to Toxoplasma gondii have been found in individuals with schizophrenia. In a study of IgG class antibodies to Toxoplasma gondii in 358 individuals with schizophrenia, during five years of follow-up, serological evidence of Toxoplasma was associated with a significantly 370% increased risk of dying of natural causes (P = .020) adjusted for age, gender, and other clinical and demographic variables. Toxoplasma gondii in Individuals With Schizophrenia: Association With Clinical and Demographic Factors and With Mortality. Dickerson F, et al. Sheppard Pratt, Baltimore , MD. Schizophrenia Bull 2007 Feb 20.

Toxoplasmosis: High Maternal Titers Linked to Increased Risk of Schizophrenia in Offspring: In a nested case-control design, serological assays for Toxoplasma antibody on maternal serum specimens from pregnancies giving rise to 63 cases of schizophrenia and other schizophrenia spectrum disorders and 123 controls, the adjusted odds ratio of schizophrenia with high maternal Toxoplasma IgG antibody titers was 2.61. There was no association between moderate Toxoplasma Ig antibody titers and the risk of schizophrenia/spectrum disorders. Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring. Brown AS, Schaefer CA, et al. New York State Psychiatric Institute. Am J Psychiatry. 2005 Apr;162(4):767-73. 

Toxoplasma May Be a Significant Cause of Schizophrenia: Kozar in Poland reported antibodies to toxoplamosis in 495 (52%) of 961 psychiatric inpatients compared with 170 (25%) of 681 controls (Bull Inst Mar Trop Med Gdańsk 1953;5:134-45), and Roch and Varela in Mexico found antibodies in 836 (86%) of 973 patients with schizophrenia compared with finding antibodies in 30% of the general population (Rev Invest Salud P�bl (M�x) 1966;26:31-49). Leweke's study collected cerebrospinal fluid (CSF) from the first-episode patients. The level of Toxoplasma antibody in the CSF of untreated patients was significantly higher than the normal controls (p < 0.0001)(Eur Arch Psychiatry Clin Neurosci 2003). An increased rate of immunoglobulin (Ig) M (but not IgG) class antibodies to Toxoplasma gondii in mothers with infants in whom schizophrenia developed later, suggesting that the mothers were experiencing an active infection or that they had persistent IgM antibodies, as described in other studies. T. gondii is of special interest because of its known affinity for brain tissue and its capacity for long-term infection starting in early life. Two studies have reported that adults who have schizophrenia or bipolar disorder had a greater exposure to cats in childhood. In one study, 84 (51%) of the 165 affected versus 65 (38%) of the 165 matched controls had owned a house cat in childhood (p = 0.02)(Schizophr Bull 1995;21:167-71). In the other study, 136 (52%) of the 262 affected versus 219 (42%) of the 522 matched controls owned a cat between birth and age 13 (odds ratio 1.53; p < 0.007)(Schizophr Res 2000;46:17-23). France, which has a high prevalence of Toxoplasma-infected persons, was reported to have first-admission rates for schizophrenia approximately 50% higher than those in England (Br Med J 1993;307:489-92. Ireland has a high rate of toxoplasma-infected people in rural areas (Epid Infect 1990;105:565-70)with high rates of infection in hospital personnel. The area also has a high rate of schizophrenia (Am J Psychiatry 1984;141:966-70). E. Fuller Torrey is the leading researcher in the field. 30-60% of humans have been infected with Toxoplasma.

Toxoplasmosis Infected Had Lower IQ and Novelty Seeking: In a Czech study of 857 military draftees, Those with Toxoplasma antibodies had lower IQs (p=.003) and less education (<.0000). Decreased level of psychobiological factor novelty seeking and lower intelligence in men latently infected with the protozoan parasite Toxoplasma gondii Dopamine, a missing link between schizophrenia and toxoplasmosis? Flegr J, Preiss M, Klose J, Havlicek J, Vitakova M, Kodym P. Biol Psychol. 2003 Jul;63(3):253-68.

Toxoplasmosis: Toxoplasma antibodies were found in 45% of Barcelona cats. It's more common in feral cats or cats raised together with only 28% of single domestic cats positive. Cats are the only hosts that excrete resistant oocysts. J Parasitol. 2003 Oct;89(5):1067-8. 65% of 29 free range chickens were positive in Argentina. J Parasitol. 2003 Oct;89(5):1063-4. 16% of 118 Ohio and Massachusetts chickens from widely scattered farms were positive and cats fed uncooked chicken meat often got infected. J Parasitol. 2003 Oct;89(5):1063-4; Exposure to undercooked meat is a risk factor (RR 1.6). Srp Arh Celok Lek. 2003 Mar-Apr;131(3-4):162-7; 20% of opossums were positive in Brazil. J Parasitol. 2003 Aug;89(4):870-1; 70% of capybaras were positive in a Brazilian study. J Parasitol. 2003 Aug;89(4):850; 0.3% Wyoming wild horses were positives. J Parasitol. 2003 Aug;89(4):716-20; 92% of 55 pigs were infected and passed it on to cats feed undercooked pork. J Parasitol. 2002 Dec;88(6):1234-8; Contact with soil is a risk factor. J Obstet Gynaecol. 2002 May;22(3):296-8; as has been drinking rain water.

Toxoplasmosis Treatment: New and Much Improved: Treatment has been very difficult in view of the intracellular cyst state. About 3,000 infants are born each year in the U.S. with toxoplasmosis, which causes severe eye damage, mental retardation and death. The cost of caring for these children is thought to exceed $500 million per year. In addition to active infections, T. gondii in its latent stage infects the nervous system of an estimated 3 billion people, including about 30 percent of Americans. Although it has long been considered harmless, it causes lifelong infections. The effects of those infections on physical and mental health are still being researched. The new delivery system uses a short chain made up eight connected arginines, a naturally occurring amino acid, to ferry a drug across membranes. In 1996, scientists led by Paul Wender and Jonathan Rothbard at Stanford, discovered that short sequences of arginine could slip easily through biological membranes, either alone or attached to active molecules. T. gondii and related parasites, which cause malaria and cryptosporidia, all rely on unique enzymes not present in other animals, e.g. enoyl reductase required to synthesize fatty acids necessary for growth and reproduction. Triclosan, a common antiseptic used in toothpaste, skin creams and mouthwash, can kill the toxoplasmosis and malaria parasites, in part, from its ability to inhibit enoyl reductase. The arginine chain makes cyst entry of triclosan possible. Rima McLeod, et al. Univ Chicago, Proceedings of the National Academy of Sciences 11/17/03.

Toxoplasmosis Treatment Toxic: AIDS patients often get reactivation of toxoplasmosis due to their immunosuppressed state. Medications to treat the infection include: pyrimethamine, sulfonamide drugs, folinic acid, clindamycin, and trimethoprim-sulfamethoxazole. Pregnant mothers and prenatally infected children are treated with pyrimethamin, sulfadiazin, folinic acid, and spiramycine. Toxicity is a problem. A new and less toxic approach for AIDS patients has been reported: atovaquone suspension (1500 mg twice daily) plus either pyrimethamine (75 mg daily following a 200 mg loading dose) or sulfadiazine (1500 mg 4 times daily) for both acute (6 weeks) and maintenance (42 weeks) therapy for toxoplasmic encephalitis. Clinical Infectious Diseases, 2002. Sulphonamides (30 mg/kg twice daily) in combination with pyrimethamine (0.5 mg/kg twice daily); or clindamycin 10 mg/kg b.i.d. alone have also been reported. Septra DS QD can be used for prophylaxis in AIDS patients positive for toxoplasmosis. 

Untreated Psychosis Increases Long-Term Morbidity: Prolonged durations of untreated psychosis are associated with poorer long-term outcomes. Lieberman JA, Fenton WS. Delayed detection of psychosis: causes, consequences, and effect on public health. [letter; comment.] Am J Psychiatry. 2000;157:1727-1730.

Untreated: Treatment Delay Might Be Harmful: Two studies look at recovery on first episode by number of months before get into treatment. Average is 1-2 years Barnes (Br J Psychiatry 00;177:207) didn�t find any difference in 53 patients. However, (Drake, Brit J Psychiatry 00;177:511) in 248 London patients found long delays associated with poor treatment response.

Violent Teens More Likely to Develop Schizophrenia: In a 9-year register-based followup of all 780 15-19-year-old convicted criminals in Denmark in 1992, 3.3% had been diagnosed with schizophrenia and 4.5% with any psychosis. Conviction of violence in late adolescence was significantly increased the risk of a diagnosis of schizophrenia by 359% (OR = 4.59). Violent behavior can be part of the preschizophrenia phase of young criminals. Violence of young criminals predicts schizophrenia: a 9-year register-based followup of 15- to 19-year-old criminals. Gosden NP, et al. Copenhagen, Denmark. . Schizophr Bull. 2005 Jul;31(3):759-68. Ed: Hopefully, the reseachers controlled for increased drug abuse, head injury, etc.

Vitamin D: Schizophrenia Not Linked to Vitamin D Deficiency in Turkish Family: In a study of a large, inbred Turkish family with an inherited vitamin D deficiency gene and an increased rate of psychosis in the same extended family, it was found that each disease was inherited separately. Is vitamin D hypothesis for schizophrenia valid? Independent segregation of psychosis in a family with vitamin-D-dependent rickets type IIA. Ozer S, Ulusahin A, Ulusoy S, Okur H, Coskun T, Tuncali T, Gogus A, Akarsu AN Prog Neuropsychopharmacol Biol Psychiatry. 2004 Mar;28(2):255-66

Vitamin D Supplement in Infancy Linked to Dramatically Lower Schizophrenia in Males: In a Finnish study of 9114 newborns followed for 31 years, those given vitamin D supplements in the first year of life, in males, the use of either irregular or regular vitamin D supplements was associated with a reduced risk of schizophrenia (Risk ratio (RR)=0.08; RR=0.12, respectively) compared with no supplementation. In males, the use of at least 2000 IU of vitamin D was associated with a reduced risk of schizophrenia (RR=0.23) compared to those on lower doses. There was no link for females or for other psychiatric difficulties for either sex. Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. McGrath J, et al. Schizophr Res. 2004 Apr 1;67(2-3):237-45

Vitamin D: Schizophrenia May be Increased with Vitamin D Deficiency in Infancy: People who develop schizophrenia in Europe and North America are more likely to be born in the spring, according to an article in the New Scientist. They are also roughly four times as likely to be born to Afro-Caribbean immigrants living in England as they are to have parents of other ethnic origins living in the same areas. Australian Psychiatrist John McGrath found adult rats deprived of vitamin D from conception are more startled than normal by a loud noise preceded by a soft noise. He also found ventricles in the brains of vitamin-deprived baby rats are also unusually large, a feature seen in people with schizophrenia. A U.S. survey suggests vitamin D deficiency affects 12% of women of childbearing age. BBC News 2/7/02.

Vitamin D: Schizophrenics' Mothers Not Deficient in Vitamin D During Pregnancy: There was no significant difference in levels using banked sera in third trimester maternal vitamin D in the sample (cases = 26, controls = 51). Within the subgroup of Afro-Australian individuals (n = 21), there was a trend level difference in the predicted direction. Low maternal vitamin D as a risk factor for schizophrenia: a pilot study using banked sera. McGrath J, Eyles D, Mowry B, Yolken R, Buka S. Schizophr Res. 2003 Sep 1;63(1-2):73-8.

Vitamin D Insufficiency Common in Pregnant Women and Pregnancy Vitamins Not Enough: In utero or early-life vitamin D deficiency is associated with skeletal problems, type 1 diabetes, and schizophrenia. Serum 25-hydroxyvitamin D (25(OH)D) was measured at 4-21 wk gestation and predelivery in 200 European- and 200 African-American pregnant women and in cord blood of their neonates. Over 90% used prenatal vitamins. At delivery, vitamin D deficiency and insufficiency occurred in 29% and 54% of black women and 45% and 47% black neonates, respectively. Ten percent and 56% of European neonates were vitamin D deficient and insufficient, respectively. African-American women had a smaller mean increase in maternal 25(OH)D from winter to summer (16.0 vs. 23.2 nmol/L) and from spring to summer (13.2 nmol/L vs. 27.6 nmol/L) (P<0.01). Pregnant women and neonates residing in the northern US are at high risk of vitamin D insufficiency, even when mothers are compliant with prenatal vitamins. Higher-dose supplementation is needed. High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates. Bodnar LM, et al. University of Pittsburgh. . J Nutr 2007 Feb;137(2):447-52.

Vitamin D Evidence: An increased risk for multiple sclerosis and schizophrenia is observed at increasing latitude and in patients born in winter or spring. Vitamin D-deficient female rats were mated with vitamin D normal males. Pregnant females were kept vitamin D-deficient until birth whereupon they were returned to a control diet. At week 10, vitamin D (DVD) deficiency caused a dysregulation of 36 brain proteins involved in several biological pathways including oxidative phosphorylation, redox balance, cytoskeleton maintenance, calcium homeostasis, chaperoning, PTMs, synaptic plasticity and neurotransmission. A computational analysis of these data revealed that (i) nearly half of the molecules dysregulated in our animal model have also been shown to be misexpressed in either schizophrenia and/or multiple sclerosis and (ii) an impaired synaptic network may be a consequence of mitochondrial dysfunction. Developmental vitamin D deficiency alters brain protein expression in the adult rat: Implications for neuropsychiatric disorders. Almeras L, et al. Universite de la Mediterranee, Marseille, France. Proteomics 2007 Feb 13.

Thomas E. Radecki, M.D., J.D.