Visual hallucinations from retinal detachment misdiagnosed as psychosis.

J Psychiatr Pract. 2011 Mar;17(2):133-6.

Brda D, Tang EC.

*New York State Psychiatric Institute and Columbia University Department of Psychiatry †Columbia University College of Physicians & Surgeons.

Abstract

Hallucinations are a common presenting symptom in schizophrenia and other psychotic disorders. In particular, auditory hallucinations, such as hearing voices, are the most common type of hallucination described in schizophrenia, while visual hallucinations are less frequently seen. Hallucinations are also present in disorders that are not primarily psychotic in nature, including mood disorders, substance-induced disorders, and psychosis due to a general medical condition. However, it is extremely important to rule out general medical causes of hallucinations, as they are often treatable and reversible, and if left untreated, the underlying non-psychiatric disorders causing them can lead to irreversible damage. We present a case in which a 48-year-old woman with schizophrenia began to complain of visual disturbances. Because of her delusional interpretation of these disturbances, they were initially attributed to psychosis, but the disturbances were in fact found to be the result of a retinal detachment. (Journal of Psychiatric Practice. 2011;17:133-136).

PMID: 21430493 [PubMed - in process

[Acute psychotic disorders related to bupropion: review of the literature].

Encephale. 2010 Dec;36(6):461-71. Epub 2010 Mar 15.

[Article in French]
Javelot T, Javelot H, Baratta A, Weiner L, Messaoudi M, Lemoine P.

Service "Les Hortensias", centre psychothérapique Nord Dauphiné, 100, avenue du Médipôle, 38307 Bourgoin-Jallieu cedex, France. javelot.thierry@cp-nord-dauphine.fr



Abstract

RATIONALE AND OBJECTIVES: Bupropion, or amfebutamone, is an atypical antidepressant also used during tobacco cessation. From a structural standpoint, it resembles amphetamine drugs with psychostimulant effects, and endogenous monoamines. From a pharmacological standpoint, bupropion, and two of its most important active metabolites, inhibit dopamine and norepinephrine reuptake. It has recently been discovered that bupropion may act as a non-competitive cholinergic nicotinic receptor antagonist, and that it may inhibit the activation of reward systems triggered by nicotine. Buproprion's efficacy as a smoking cessation aid has been demonstrated by numerous clinical trials that have compared its effects with those of placebo and other nicotinic substitutes. In 2001, buproprion SR received marketing authorization in France as a smoking cessation aid, under the name ZYBAN®. Tobacco addiction indeed remains a major public health issue. Among patients with psychiatric conditions, chronic tobacco consumption is frequent. The development of non-nicotinic drugs may therefore enhance therapeutic possibilities. However, the psychotropic effects of these molecules should be taken into account. We have recently reported the case of a patient with schizoaffective disorder, who presented two acute bupropion-induced psychotic episodes. We have also undertaken an exhaustive bibliographical research on this subject. The aim of the present study is to present the information available to us, in order to suggest aetiopathogenic hypotheses and therapeutic proposals.

Acute psychosis due to the interaction of legal compounds--ephedra alkaloids in 'vigueur fit' tablets, caffeine in 'red bull' and alcohol.

Med Sci Law. 2001 Oct;41(4):331-6.

Tormey WP, Bruzzi A.

Department of Chemical Pathology, Beaumont Hospital, Dublin, Ireland.

Abstract

A short-lasting episode of acute psychosis in a 32-year-old male which followed the consumption of alcohol, caffeine and 'vigueur fit' tablets containing ephedra alkaloids is reported. Less than two days after the event, a urine sample contained 22 microg/ml of ephedrine and 5 microg/ml of pseudoephedrine. Despite detailed pharmacological evidence being given at a jury trial, he was convicted of assault and trespass and was fined pounds sterling 16,000. An earlier incident involving misbehaviour on an aircraft again involving alcohol and ephedrine resulted in a conviction and a court order to provide twice weekly urine tests for alcohol for a period of six months. He stopped taking the alkaloid tablets after the second incident. There was no history of aberrant behaviour in this man outwith the period when taking these tablets. Ephedra alkaloids may cause psychosis and their effects can be exaggerated by interaction with caffeine and ethanol. To protect the public, the use of stimulant drugs in over-the-counter weight control programmes should be prescription only and the package insert should include a warning on the dangers of concomitant use of ethanol.

PMID: 11693229 [PubMed - indexed for MEDLINE]

Caffeine and psychiatric symptoms: a review.

J Okla State Med Assoc. 2004 Dec;97(12):538-42.

Broderick P, Benjamin AB.

University of Oklahoma, 2312 North Indiana Avenue, Oklahoma City, Oklahoma 73106, USA.

Abstract

Caffeine is a widely used psychoactive substance that has the potential to contribute to many psychiatric symptoms. This review article aims to address the specific research studies and case reports that relate caffeine to psychiatric symptoms. Caffeine can cause anxiety symptoms in normal individuals, especially in vulnerable patients, like those with pre-existing anxiety disorders. Caffeine use is also associated with symptoms of depression due to either a self-medication theory, or a theory that caffeine itself causes changes in mood. Psychosis can be induced in normal individuals ingesting caffeine at toxic doses, and psychotic symptoms can also be worsened in schizophrenic patients using caffeine. Sleep and symptoms of ADHD may be altered by caffeine as well. Prevention of caffeine-induced psychiatric symptoms is possible by recognizing, educating, and treating patients using a tapering approach.

PMID: 15732884 [PubMed - indexed for MEDLINE]

Psychiatric side effects attributed to phenylpropanolamine.

Pharmacopsychiatry. 1988 Jul;21(4):171-81.

Lake CR, Masson EB, Quirk RS.

Dept. of Psychiatry, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

Abstract

Phenylpropanolamine (PPA) is a sympathomimetic drug similar in structure to amphetamine which, in the United States, is present in over 130 medications, primarily decongestants, cough/cold remedies, and anorectic agents. We have reviewed 37 cases (published in North America and Europe since 1960) that received diagnoses of acute mania, paranoid schizophrenia, and organic psychosis and that were attributed to PPA product ingestion. Of the 27 North American case reports, more reactions followed the ingestion of combination products than preparations containing PPA alone; more occurred after ingestion of over-the-counter products than those obtained by prescription or on-the-street; and more of the cases followed ingestion of recommended doses than overdoses. Groups at particular risk appear to be those with a past or family psychiatric history, children under the age of 6 and post-partum women. Failure to recognize PPA as an etiological agent in the onset of symptoms usually led to a diagnosis of schizophrenia or mania, lengthy hospitalization, and treatment with substantial doses of neuroleptics or lithium. While generally safe at recommended doses, PPA can be hazardous to susceptible individuals and we urge physicians to be alert to the potential for PPA related psychiatric reactions. We have compiled an alphabetized table (Table 1: Prescription and Over-the-Counter Products Containing Phenylpropanolamine) allowing busy clinicians quick access to those drugs containing PPA.

PMID: 3060884 [PubMed - indexed for MEDLINE]

Vitamin D Deficiency and Schizophrenia

Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S247-57.

Developmental vitamin D deficiency causes abnormal brain development.

Eyles DW, Feron F, Cui X, Kesby JP, Harms LH, Ko P, McGrath JJ, Burne TH.

Queensland Brain Institute, The University of Queensland, Brisbane, Qld 4072, Australia. Eyles@uq.edu.au

There is now clear evidence that vitamin D is involved in brain development. Our group is interested in environmental factors that shape brain development and how this may be relevant to neuropsychiatric diseases including schizophrenia. The origins of schizophrenia are considered developmental. We hypothesised that developmental vitamin D (DVD) deficiency may be the plausible neurobiological explanation for several important epidemiological correlates of schizophrenia namely: (1) the excess winter/spring birth rate, (2) increased incidence of the disease in 2nd generation Afro-Caribbean migrants and (3) increased urban birth rate. Moreover we have published two pieces of direct epidemiological support for this hypothesis in patients. In order to establish the "Biological Plausibility" of this hypothesis we have developed an animal model to study the effect of DVD deficiency on brain development. We do this by removing vitamin D from the diet of female rats prior to breeding. At birth we return all dams to a vitamin D containing diet. Using this procedure we impose a transient, gestational vitamin D deficiency, while maintaining normal calcium levels throughout. The brains of offspring from DVD-deficient dams are characterised by (1) a mild distortion in brain shape, (2) increased lateral ventricle volumes, (3) reduced differentiation and (4) diminished expression of neurotrophic factors. As adults, the alterations in ventricular volume persist and alterations in brain gene and protein expression emerge. Adult DVD-deficient rats also display behavioural sensitivity to agents that induce psychosis (the NMDA antagonist MK-801) and have impairments in attentional processing. In this review we summarise the literature addressing the function of vitamin D on neuronal and non-neuronal cells as well as in vivo results from DVD-deficient animals. Our conclusions from these data are that vitamin D is a plausible biological risk factor for neuropsychiatric disorders and that vitamin D acts as a neurosteroid with direct effects on brain development.

COMMON INFECTIOUS AETIOLOGIES FOR MULTIPLE SCLEROSIS, SCHIZOPHRENIA AND CHRONIC FATIGUE SYNDROME

Med Hypotheses. 2009 Jun;72(6):736-9. Epub 2009 Mar 6.

On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics.
Frykholm BO.
aion.terapi@yahoo.com

Close similarities in the courses of multiple sclerosis and schizophrenia laid the theoretical ground for attempting to find a common infectious aetiology for the two diseases. Chlamydia pneumoniae, which belongs to the rickettsial family of microorganisms has been linked to both diseases. It is postulated that since rickettsial microorganisms are ubiquitous in human populations they and the human species normally live in peaceful coexistence. In rare cases, for unknown reasons, varieties of them may become aggressive and pathogenic. The kynurenic acid hypothesis of schizophrenia has attracted much attention. It also seems to have initiated a paradigmatic shift from the hitherto prevailing serological research approach to one which focuses on immunological factors. An open clinical pilot study in which, during 2006, eight female and five male patients with psychotic symptoms were treated with a combination of antibiotics is presented, to which, in the beginning of 2007 two female patients suffering from severe and long standing chronic fatigue syndrome were added. On one year follow-up, six out of the eight female patients showed stable excellent treatment results, whereas two were rated as showing significant treatment results. Four of the five men who entered the study were suffering from chronic schizophrenia, whereas the fifth, was a case of severe acute catatonic schizophrenia. Two of the male patients showed significant treatment results, whereas three of them were rated as having had a slight to moderate improvement. No less than three of the women had suffered their first episode of psychosis after giving birth to their first (and only) child. This finding, as these women all responded excellently to treatment with antibiotics, indicates that post partum psychosis could be regarded as an infectious complication of childbirth of, as to the causative agent, unknown aetiology. High priority ought therefore be given to initiate controlled clinical trials with antibiotic treatment of this serious condition. The otherwise promising results of the pilot study seem to warrant further and controlled clinical trials with treatment with antibiotics of patients with psychotic symptoms. As the second patient with psychotic symptoms to enter the study, had a long standing history of chronic fatigue, where an initial treatment with the antidepressant fluoxetine had only worsened her condition, whereas ninety days of treatment with antibiotics, combined with vitamin B injections, effected a complete recovery, the author decided, when two patients with long standing and incapacitating chronic fatigue syndromes sought the clinic in February and March 2007, to include them in the study. The first of them, after sixty days of treatment with antibiotics showed excellent treatment results on follow-up one year later, whereas the second, who also took the combination of antibiotics for sixty days, was rated as having shown a significant improvement.

PMID: 19269110 [PubMed - indexed for MEDLINE]

Calcification of the basal ganglia presenting as a schizophreniform psychosis

Postgrad Med J 1972;48:636-639 doi:10.1136/pgmj.48.564.636
Case report
Calcification of the basal ganglia apparently presenting as a schizophreniform psychosis
Peter Hall

Abstract
A patient with gross basal ganglia calcification is described, whose condition was associated with severe psychotic symptoms and in whom the clinical picture was not typical of hypoparathyroidism, pseudohypoparathyroidism or pseudo-pseudohypoparathyroidism.
Calcification of the basal ganglia may occur in a variety of infections, toxic and metabolic disorders, particularly hypoparathyroidism, pseudohypoparathyroidism, toxoplasmosis and some anoxic conditions (Moskowitz, Winickoff & Heinz, 1971).

Though there is doubt as to the precise diagnosis in the present case, familial calcification appears to be the most probable.

Basal ganglia calcification, idiopathic 1: Abnormal calcium deposits in the part of the brain called the basal ganglia. Type 1 results in psychiatric, cognitive or neurological problems associated with the calcification

TOXOPLASMOSIS MASQUERADING AS A PSYCHOTROPIC SIDE EFFECT

J Clin Psychiatry. 1978 Jul;39(7):631-2.

Toxoplasmosis masquerading as a psychotropic side effect.
Pariser SF, Zunich J, Pinta ER.

When treating a patient with neuroleptics or tricyclic antidepressants, it is usually assumed that complaints of blurred vision can be ascribed to the anticholinergic side effects of these drugs. The authors present a patient treated with imipramine and trifluoperazine whose complaints of blurred vision led to the diagnosis of toxoplasma chorioretinitis.

PMID: 681294 [PubMed - indexed for MEDLINE]

THE SCHIZOPHRENIA AND TOXOPLASMA GONDIII CONNECTION

Adv Ther. 2008 Jul;25(7):703-9.

The schizophrenia and Toxoplasma gondii connection: infectious, immune or both?
Tamer GS, Dundar D, Yalug I, Caliskan S, Yazar S, Aker A.

Kocaeli University, Medical Faculty, Department of Clinical Microbiology, Kocaeli, Turkey. guldensonmez@hotmail.com

INTRODUCTION: Recent research has suggested a possible link between toxoplasmic agents and schizophrenia. We aimed to assess this by measuring Toxoplasma gondii-associated antibodies in schizophrenia patients and controls

METHODS: We used a commercially available enzyme-linked immunosorbent assay (ELISA) kit to measure the level of immunoglobulin G (IgG) and IgM antibodies in serum samples from schizophrenia patients (n=40) and from a group of non-schizophrenic control subjects (n=37)

RESULTS: Among schizophrenic patients, 16 (40%) showed IgG seropositivity and two (5%) showed IgM seropositivity. Among the control group, five (13.5%) were found have IgG seropositivity and one (2.7%) showed IgM seropositivity. In our study we found that IgG T gondii antibodies were significantly higher in schizophrenia patients compared with controls

CONCLUSIONS: This study supports the theory that toxoplasmic agents may have a role in the aetiology of schizophrenia.

PMID: 18563312 [PubMed - indexed for MEDLINE]

VIRUS ASSOCIATION TO COGNITIVE FUNCTION IN SCHIZOPHRENIA

Schizophr Res. 2008 Dec;106(2-3):268-74. Epub 2008 Sep 17.
Antibodies to cytomegalovirus and Herpes Simplex Virus 1 associated with cognitive function in schizophrenia.

Shirts BH, Prasad KM, Pogue-Geile MF, Dickerson F, Yolken RH, Nimgaonkar VL.
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

BACKGROUND: Cognitive impairment in the form of decreased working memory and executive functions has been recognized as a key deficit in schizophrenia. Neurotropic viruses have been associated with focal gray matter deficits in patients with schizophrenia. We evaluated whether such agents alter cognitive function in schizophrenia.

METHODS: The sample consisted of 329 patients diagnosed with schizophrenia or schizoaffective disorder. We evaluated associations between exposure to selected agents (Herpes Simplex Viruses 1 and 2 (HSV1, HSV2 respectively) cytomegalovirus (CMV) and Toxoplasma gondii) and scores on the Trail Making Test (TMT), controlling for relevant variables.

RESULTS: Serological evidence of exposure to CMV was associated with impaired performance on TMT part A time to completion (p=0.044), a measure of visual search, working memory, and psychomotor speed. Both CMV and HSV1 were significantly associated with increased errors on TMT part B

PARASITIC BRAIN INFECTION, ENDOCANNABINOIDS, AND SCHIZOPHRENIA

Med Hypotheses. 2009 Feb;72(2):220-2. Epub 2008 Nov 7.

Parasitic brain infection, endocannabinoids, and schizophrenia.
Melamede R.
Biology Department, University of Colorado at Colorado, Springs, Colorado Springs, CO 80918, USA. rmelamed@uccs.edu

Cannabis use has often been associated with various forms of psychosis. Today it is well established that everyone produces marijuana-like compounds known as endocannabinoids. The endocannabinoid system is a homeostatic regulator of all body systems including the nervous system. As a result, imbalances in the endocannabinoid system have been considered as possible causes of various forms of mental illness and abnormal behavior. In this paper, a novel hypothesis is presented that suggests that an as yet undefined subset of schizophrenia is caused by an excess of endocannabinoids that are produced to protect the brain in response to infections by agents such as Toxoplasma gondii.

PMID: 18995970 [PubMed - indexed for MEDLINE]

NEUROPSYCHIATRIC DISEASE AND TOXOPLASMA GONDII INFECTION

Neuroimmunomodulation. 2009;16(2):122-33. Epub 2009 Feb 11.
Neuropsychiatric disease and Toxoplasma gondii infection.

Henriquez SA, Brett R, Alexander J, Pratt J, Roberts CW.
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, UK.

Toxoplasma gondii infects approximately 30% of the world's population, but causes overt clinical symptoms in only a small proportion of people. In recent years, the ability of the parasite to manipulate the behaviour of infected mice and rats and alter personality attributes of humans has been reported. Furthermore, a number of studies have now suggested T. gondii infection as a risk factor for the development of schizophrenia and depression in humans. As T. gondii forms cysts that are located in various anatomical sites including the brain during a chronic infection, it is well placed anatomically to mediate these effects directly. The T. gondii genome is known to contain 2 aromatic amino acid hydroxylases that potentially could directly affect dopamine and/or serotonin biosynthesis. However, stimulation of the immune response has also recently been associated with mood and behavioural alterations in humans, and compounds designed to alter mood, such as fluoxetine, have been demonstrated to alter aspects of immune function. Herein, the evidence for T.-gondii-induced behavioural changes relevant to schizophrenia and depression is reviewed. Potential mechanisms responsible for these changes in behaviour including the role of tryptophan metabolism and the hypothalamic-pituitary-adrenal axis are discussed. Copyright (c) 2009 S. Karger AG, Basel.

PMID: 19212132 [PubMed - indexed for MEDLINE]

SCHIZOPHRENIA AND EPILEPSY REPORTED TO AFFECT HUMANS COINFECTED WITH T. GONDII

Parasitol Res. 2009 Oct;105(4):893-8. Epub 2009 Jun 23.

Toxoplasma gondii: host-parasite interaction and behavior manipulation.

da Silva RC, Langoni H.
Department of Veterinary Hygiene and Animal Science, College of Veterinary Medicine and Animal Science, São Paulo State University, Campus of Botucatu, Botucatu, São Paulo, Brazil. silva_rcd@yahoo.com.br

Toxoplasma gondii is an obligate intracellular parasite that causes different lesions in men and other warm-blooded animals. Humoral and cellular immune response of the host against the parasite keeps the protozoan in a latent stage, and clinical disease ensues when immunological response is compromised. Brain parasitism benefits the parasite causing behavioral changes in the host, not only in animals but also in humans. Schizophrenia and epilepsy are two neurological disorders that have recently been reported to affect humans coinfected with T. gondii. Further studies based on host-parasite interaction in several wild or domestic warm-blooded species are still necessary in order to better understand parasitism and behavioral changes caused by T. gondii.

PMID: 19548003 [PubMed - indexed for MEDLINE]

TOXOPLASMA GONDI IN MOTHERS AND RISK OF PSYCHOSIS AMONG ADULT OFFSPRING

Microbes Infect. 2009 Nov;11(13):1011-8. Epub 2009 Jul 26.

Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring.
Xiao J, Buka SL, Cannon TD, Suzuki Y, Viscidi RP, Torrey EF, Yolken RH.

The Stanley Division of Developmental Neurovirology, Johns Hopkins School of Medicine, 600 N. Wolfe Street, 1105 Blalock, Baltimore, MD 21287-4933, USA.

Previous studies have shown that maternal antibodies to Toxoplasma measured during pregnancy are associated with an increased risk of schizophrenia and other psychoses in adult offspring. Recently, it has been recognized that different genotypes of Toxoplasma have distinct neuropathogenic potential. The objective of this study was to investigate whether parasite genotype is a contributing factor to disease risk. We have developed an enzyme-linked immunosorbent assay (ELISA) that uses polymorphic polypeptides specific to the three clonal parasite lineages and derived from three dense granule antigens, GRA5, GRA6 and GRA7. We used this assay to measure type-specific antibodies in the sera from 219 pregnant women whose children developed schizophrenia and affective psychotic illnesses in adult life, and 618 matched unaffected control mothers from three cohorts of the Collaborative Perinatal Project. We found that the offspring of mothers with a serological pattern consistent with Toxoplasma type capital I, Ukrainian infection were at significantly increased risk for the development of psychoses as compared with the matched unaffected control mothers (odds ratio=1.94; 95% confidence interval=1.08-3.46; p=0.03). The risk was particularly elevated for affective psychoses (OR=5.24; 95% CI=1.67-16.5; p=0.005). In contrast, we did not find an association between maternal antibodies to other genotypes and risk of psychoses in the offspring. These findings suggest an influence of the parasite genotype on increased risk of psychosis and provide further support for a substantive role of Toxoplasma in the etiology of psychosis.

PMID: 19638313 [PubMed - in process]

SCHIZOPHRENIA AND TOXOPLASMOSIS

Med Sci (Paris). 2009 Aug-Sep;25(8-9):687-91.

[Schizophrenia and toxoplasmosis]
[Article in French]
Dion S, Barbe PG, Leman S, Camus V, Dimier-Poisson I.

Université François Rabelais de Tours, INRA , France. sarah.dion@univ-tours.fr

Schizophrenia is one of the most severe and disabling psychiatric disease that affects about 1 % of the adult worldwide population. Aetiology of schizophrenia is still unknown but genetic and environmental factors are suspected to play a major role in its onset. Recent epidemiologic studies indicate that infectious agents may contribute to some cases of schizophrenia. In particular, several epidemiological, behavioural and neurochemical studies suggested the existence of an association between schizophrenia and past history of primo-infection by the Toxoplasma gondii. However, they are some limitations for this hypothesis among which the lack of correlation between the geographic distribution of both diseases and of direct evidence for the presence of the parasite in schizophrenic patients. Nevertheless the identification of physiopathological mechanisms related to the parasite could provide a better comprehension to the outcome of schizophrenia. Studies on the link between toxoplasmosis and schizophrenia may provide interesting data for the diagnosis and the development of new treatments for this disorder.

PMID: 19765381 [PubMed - indexed for MEDLINE]

TOXOPLASMA GONDI AND SCHIZOPHRENIA

Toxoplasma gondii and Schizophrenia

E. Fuller Torrey* and Robert H. Yolken†*Stanley Medical Research Institute, Bethesda, Maryland, USA; and †Johns Hopkins University Medical Center, Baltimore, Maryland, USA

Suggested citation for this article: Torrey EF, Yolken RH. Toxoplasma gondii and schizophrenia.

Emerg Infect Dis [serial online] Nov 2003 [date cited]. Available from: URL: http://www.cdc.gov/ncidod/EID/vol9no11/03-0143.htm

Recent epidemiologic studies indicate that infectious agents may contribute to some cases of schizophrenia. In animals, infection with Toxoplasma gondii can alter behavior and neurotransmitter function. In humans, acute infection with T. gondii can produce psychotic symptoms similar to those displayed by persons with schizophrenia. Since 1953, a total of 19 studies of T. gondii antibodies in persons with schizophrenia and other severe psychiatric disorders and in controls have been reported; 18 reported a higher percentage of antibodies in the affected persons; in 11 studies the difference was statistically significant. Two other studies found that exposure to cats in childhood was a risk factor for the development of schizophrenia. Some medications used to treat schizophrenia inhibit the replication of T. gondii in cell culture. Establishing the role of T. gondii in the etiopathogenesis of schizophrenia might lead to new medications for its prevention and treatment.

Schizophrenia is a pervasive neuropsychiatric disease of uncertain cause that affects approximately 1% of the adult population in the United States and Europe. An increased occurrence of schizophrenia in family members of affected persons suggests that genetic factors play a role in its etiology, and some candidate predisposing genes have been identified. Environmental factors are also important. Epidemiologic studies, for example, have established that winter-spring birth, urban birth, and perinatal and postnatal infection are all risk factors for the disease developing in later life. These studies have rekindled an interest in the role of infectious agents in schizophrenia, a concept first proposed in 1896 (1). This review focuses on evidence specifically linking infection with Toxoplasma gondii to the etiology of some cases of schizophrenia.

T. gondii is an intracellular parasite in the phylum Apicomplexa. Its life cycle can be completed only in cats and other felids, which are the definitive hosts. However, T. gondii also infects a wide variety of intermediate hosts, including humans. In many mammals, T. gondii is known to be an important cause of abortions and stillbirths and to selectively infect muscle and brain tissue. A variety of neurologic symptoms, including incoordination, tremors, head-shaking, and seizures, have been described in sheep, pigs, cattle, rabbits, and monkeys infected with T. gondii (2).
Humans may become infected by contact with cat feces or by eating undercooked meat. The importance of these modes of transmission may vary in different populations (3). Individual response to Toxoplasma infection is determined by immune status, timing of infection, and the genetic composition of the host and the organism (4).

To read full article go here.

GLUTATHIONE IN THE PATHOPHSIOLOGY OF BIPOLAR DISORDER AND SCHIZOPHRENIA?

Curr Med Chem. 2009;16(23):2965-76.

A role for glutathione in the pathophysiology of bipolar disorder and schizophrenia? Animal models and relevance to clinical practice.

Dean OM, van den Buuse M, Bush AI, Copolov DL, Ng F, Dodd S, Berk M.

The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia. oliviad@barwonhealth.org.au

The tripeptide, glutathione (gamma-glutamylcysteinylglycine) is the primary endogenous free radical scavenger in the human body. When glutathione (GSH) levels are reduced there is an increased potential for cellular oxidative stress, characterised by an increase and accruement of reactive oxygen species (ROS). Oxidative stress has been implicated in the pathology of schizophrenia and bipolar disorder. This could partly be caused by alterations in dopaminergic and glutamatergic activity that are implicated in these illnesses. Glutamate and dopamine are highly redox reactive molecules and produce ROS during normal neurotransmission. Alterations to these neurotransmitter pathways may therefore increase the oxidative burden in the brain. Furthermore, mitochondrial dysfunction, as a source of oxidative stress, has been documented in both schizophrenia and bipolar disorder. The combination of altered neurotransmission and this mitochondrial dysfunction leading to oxidative damage may ultimately contribute to illness symptoms. Animal models have been established to investigate the involvement of glutathione depletion in aspects of schizophrenia and bipolar disorder to further characterise the role of oxidative stress in psychopathology. Stemming from preclinical evidence, clinical studies have recently shown antioxidant precursor treatment to be effective in schizophrenia and bipolar disorder, providing a novel clinical angle to augment often suboptimal conventional treatments.

PMID: 19689277 [PubMed - indexed for MEDLINE]

PSYCHOSIS CAUSED BY MICROBIAL AGENTS?

Mol Psychiatry. 2008 May;13(5):470-9. Epub 2008 Feb 12.

Are some cases of psychosis caused by microbial agents? A review of the evidence.

Yolken RH, Torrey EF.

The Stanley Laboratory of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University Medical Center, Baltimore, MD 21287-4933, USA. yolken@mail.jhmi.edu

The infectious theory of psychosis, prominent early in the twentieth century, has recently received renewed scientific support. Evidence has accumulated that schizophrenia and bipolar disorder are complex diseases in which many predisposing genes interact with one or more environmental agents to cause symptoms. The protozoan Toxoplasma gondii and cytomegalovirus are discussed as examples of infectious agents that have been linked to schizophrenia and in which genes and infectious agents interact. Such infections may occur early in life and are thus consistent with neurodevelopmental as well as genetic theories of psychosis. The outstanding questions regarding infectious theories concern timing and causality. Attempts are underway to address the former by examining sera of individuals prior to the onset of illness and to address the latter by using antiinfective medications to treat individuals with psychosis. The identification of infectious agents associated with the etiopathogenesis of schizophrenia might lead to new methods for the diagnosis, treatment and prevention of this disorder.

PMID: 18268502 [PubMed - indexed for MEDLINE]

DECREASED N-3 FATTY ACID LEVELS REPORTED IN PATIENTS WITH SYMPTOMS OF MENTAL ILLNESS

Expert Opin Investig Drugs. 2007 Oct;16(10):1627-38.
Omega-3 fatty acid eicosapentaenoic acid. A new treatment for psychiatric and neurodegenerative diseases: a review of clinical investigations.
Song C, Zhao S.
University of Prince Edward Island, Department of Biomedical Sciences, AVC, 550 University Avenue, Charlottetown, PE, Canada. cai.song@nrc.gc.ca
Decreased n-3 fatty acid levels have been reported in patients with depression, schizophrenia or Alzheimer's disease. Recently, eicosapentaenoic acid (EPA) has been used to treat several psychiatric and neurodegenerative diseases due to its anti-inflammatory and neuroprotective effects. A total of six out of seven clinical trials have shown that EPA significantly improved depressive symptoms when compared with the placebo-treated populations. Several investigations have also reported that EPA could effectively treat schizophrenia. A case report and a clinical trial have shown that EPA was beneficial for the management of most symptoms of Huntington's disease, while a more extensive clinical investigation has demonstrated that EPA could only improve motor functions. Further clinical studies are required to fully explore the effects of EPA on other neurodegenerative diseases. The limitations of previous studies and further research directions have also been discussed.
PMID: 17922626 [PubMed - indexed for MEDLINE]