Sunday, January 31, 2010

MY MYSTERIOUS LOST MONTH OF MADNESS: a case of Anti-nmdar Encephalitis Acute Psychosis

My mysterious lost month of madness

I was a happy 24-year-old suddenly stricken by paranoia & seizures. Was I going crazy?

To read Susannah's article go here.

Susannah's story was featured on MSNBC's Medical Mysteries Series.

Dr. Souhel Najjar is the Neurologist who determined the underlying cause to Susannah's psychosis was anti-NMDAR Encephalitis.

Street: 223 East 34th Street
City/state/zip: New York NY 10016
Country: US
Phone: +1 646 558 0807
Fax: +1 646 358 7166


Epileptic Disord. 2009 Sep;11(3):267-9. Epub 2009 Aug 28.

Anti-NMDA receptor encephalitis: a video case report.
Labate A, Irani SR, Vincent A, Gambardella A, Piane EL, Cianci V, Aguglia U.

Institute of Neurology, University Magna Graecia, Catanzaro, Italy.
This report concerns a 26-year-old Italian woman who was given the diagnosis of anti-NMDAR encephalitis after the incidental identification of an ovarian tumour. Neuropsychiatric symptoms and hyperkinetic movements are very commonly seen as initial symptoms of paraneoplastic encephalitis. Interestingly, our patient showed stereotypical movements predominantly located to lower limbs, mimicking a psychogenic seizure. This latter feature further extends the clinical spectrum of dyskinetic movements of anti-NMDAR encephalitis.

PMID: 19713171 [PubMed - indexed for MEDLINE]


Epileptic Disord. 2009 Sep;11(3):261-5. Epub 2009 Sep 7.
Complex partial status epilepticus revealing anti-NMDA receptor encephalitis.

Bayreuther C, Bourg V, Dellamonica J, Borg M, Bernardin G, Thomas P.

Department of Neurology, University of Nice Sophia-Antipolis, Pasteur Hospital, Nice, France.
Encephalitis with anti-NMDA receptor antibodies is a recently-recognised form of paraneoplastic encephalitis characterized by a prodromal phase of unspecific illness with fever resembling viral disease, followed by memory loss, psychiatric features, seizures, disturbed consciousness, prominent abnormal movements and autonomic imbalance. Association with ovarian teratoma is common. Neurological outcome can be good, especially when surgery is performed at an early stage. Here, we report a case of anti-NMDA receptor encephalitis associated with ovarian teratoma presenting with inaugural complex partial status epilepticus. The nature of abnormal movements at early stages was unclear and abnormal movements were misinterpreted as the recurrence of partial epileptic seizures. Despite its rarity, all clinicians treating epilepsy and movement disorders should be familiar with anti-NMDA receptor encephalitis, that appears to be a very severe but curable disease.

PMID: 19736168 [PubMed - indexed for MEDLINE]


Med J Aust. 2009 Sep 7;191(5):284-6.
Acute psychiatric illness in a young woman: an unusual form of encephalitis.

Parratt KL, Allan M, Lewis SJ, Dalmau J, Halmagyi GM, Spies JM.
Department of Neurology, Royal Prince Alfred Hospital, Sydney, NSW.

A 21-year-old woman was admitted to hospital with a diagnosis of acute psychotic mania, but developed, over approximately 6 weeks, seizures, delirium, catatonia, movement disorder and autonomic dysfunction. She was found to have antibodies to N-methyl-D-aspartate (NMDA) NR1-NR2 receptors in both serum and cerebrospinal fluid, consistent with anti-NMDA-receptor encephalitis, a severe, potentially lethal but treatment-responsive encephalitis often associated with ovarian tumour. With aggressive immunotherapy and bilateral oophorectomy, she recovered over a period of 14 months from her initial presentation. No ovarian tumour was identified.
PMID: 19740054 [PubMed - indexed for MEDLINE]


Med Mal Infect. 2009 Nov 24. [Epub ahead of print]

[Anti-NMDA-receptor encephalitis.]
[Article in French]
de Broucker T, Martinez-Almoyna L.

Service de neurologie, hôpital Delafontaine, 2, rue du Dr-Delafontaine, 93200 Saint-Denis, France.

Anti-NMDA-receptor encephalitis has been described only recently among other causes of paraneoplastic and auto-immune limbic encephalitis. Its frequency is probably underestimated. The very characteristic clinical presentation, the severity of symptoms frequently leading to the intensive care unit, the therapeutic implications of the diagnosis whatever the cause, paraneoplastic or not and, once treated, the possibility of a full recovery or mild sequels in the majority of cases justify a surveillance either in neurology wards or in infectious, psychiatric, intensive care, or pediatric units. The authors review the history of this disease, the available epidemiological data, the characteristic clinical presentation of patients, the differential diagnosis, and the suggested treatment according to an up-to-date literature review.
PMID: 19942390 [PubMed - as supplied by publisher]


Dev Med Child Neurol. 2009 Dec 23. [Epub ahead of print]
Severe childhood encephalopathy with dyskinesia and prolonged cognitive disturbances: evidence for anti-N-methyl-d-aspartate receptor encephalitis.
Poloni C, Korff CM, Ricotti V, King MD, Perez ER, Mayor-Dubois C, Haenggeli CA, Deonna T.

Department of Paediatrics, Child Neurology, University Hospital Lausanne, Lausanne, Switzerland.

Aim We report four cases of acquired severe encephalopathy with massive hyperkinesia, marked neurological and cognitive regression, sleep disturbance, prolonged mutism, and a remarkably delayed recovery (time to full recovery between 5 and 18mo) with an overall good outcome, and its association with anti-N-methyl-d-aspartate (anti-NMDA) receptor antibodies. Method We reviewed the four cases retrospectively and we also reviewed the literature. Results Anti-NMDA receptor antibodies (without ovarian teratoma detected so far) were found in the two children tested in this study. Interpretation The clinical features are similar to those first reported in 1992 by Sebire et al.,(1) and rarely recognized since. Sleep disturbance was not emphasized as part of the disorder, but appears to be an important feature, whereas coma is less certain and difficult to evaluate in this setting. The combination of symptoms, evolution (mainly seizures at onset), severity, paucity of abnormal laboratory findings, very slow recovery, and difficult management justify its recognition as a specific entity. The neuropathological substrate may be anatomically close to that involved in encephalitis lethargica, in which the same target functions (sleep and movement) are affected but in reverse, with hypersomnolence and bradykinesia. This syndrome closely resembles anti-NMDA receptor encephalitis, which has been reported in adults and is often paraneoplastic.
PMID: 20041934 [PubMed - as supplied by publisher]


Eur J Clin Microbiol Infect Dis. 2009 Dec;28(12):1421-9. Epub 2009 Aug 29.
Anti-NMDA receptor encephalitis: report of ten cases and comparison with viral encephalitis.
Gable MS, Gavali S, Radner A, Tilley DH, Lee B, Dyner L, Collins A, Dengel A, Dalmau J, Glaser CA.
Department of Psychiatry, University of California San Francisco, Fresno, CA, USA.
The California Encephalitis Project (CEP), established in 1998 to explore encephalitic etiologies, has identified patients with N-methyl-D-aspartate receptor (NMDAR) antibodies, the likely etiology of their encephalitis. This study compares the presentation of such patients to those with viral encephalitis, so that infectious disease clinicians may identify individuals with this treatable disorder. Patients were physician-referred, and standardized forms were used to gather demographic, clinical, and laboratory data. Features of anti-NMDAR+ patients were compared with the viral encephalitides of enteroviral (EV), rabies, and herpes simplex-1 (HSV-1) origins. Sixteen cases with confirmed viral etiologies were all negative on NMDAR antibody testing. Ten anti-NMDAR+ patients were profiled with a median age of 18.5 years (range 11-31 years). None were Caucasian. They had a characteristic progression with prominent psychiatric symptoms, autonomic instability, significant neurologic abnormalities, and seizures. Two had a teratoma, and, of the remaining eight, four had serologic evidence of acute Mycoplasma infection. The clinical and imaging features of anti-NMDAR+ patients served to differentiate this autoimmune disorder from HSV-1, EV, and rabies. Unlike classic paraneoplastic encephalitis, anti-NMDAR encephalitis affects younger patients and is often treatable. The association of NMDAR antibodies in patients with possible Mycoplasma pneumoniae infection warrants further study.
PMID: 19718525 [PubMed - in process]


Ann Gen Hosp Psychiatry. 2003 Jun 13;2(1):6.
Psychotic mania in glucose-6-phosphate-dehydrogenase-deficient subjects.
Bocchetta A.
Bernard B, Brodie Department of Neurosciences, University of Cagliari, Italy.
BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been associated with acute psychosis, catatonic schizophrenia, and bipolar disorders by previous inconclusive reports. A particularly disproportionate rate of enzyme deficiency was found in manic schizoaffective patients from 662 lithium patients surveyed in Sardinia. The purpose of this study was to describe clinical characteristics which may be potentially associated with G6PD deficiency.
METHODS: Characteristics of episodes, course of illness, family pattern of illness, laboratory tests, and treatment response of 29 G6PD-deficient subjects with a Research Diagnostic Criteria diagnosis of manic schizoaffective disorder were abstracted from available records. RESULTS: The most peculiar pattern was that of acute recurrent psychotic manic episodes, mostly characterized by loosening of associations, agitation, catatonic symptoms, and/or transient confusion, concurrent hyperbilirubinemia, positive psychiatric family history, and partial response to long-term lithium treatment.
CONCLUSIONS: A relationship between psychiatric disorder and G6PD deficiency is to be searched in the bipolar spectrum, particularly among patients with a history of acute episodes with psychotic and/or catatonic symptoms or with transient confusion.
PMID: 12844366 [PubMed - as supplied by publisher]


Ciprofloxacin-Induced Mania in an Elderly Male

ISSN: 1524-7929 VOLUME: 17 PUBLICATION DATE: Jan 08 2009
Issue Number: 1 Jan 09
author: Linda Sohn, MD, MPH

Author Affiliations: Dr. Sohn is Associate Director, Sepulveda VA Nursing Home Care Unit, VA Greater Los Angeles Health Care System, and Assistant Clinical Professor, UCLA School of Medicine/Geriatrics, CA.

Ciprofloxacin is a broad-spectrum fluoroquinolone antibiotic. The newer drugs in this class differ from earlier agents with increased potency, broader spectrum of antibacterial activity, and pharmacokinetics that permit treatment of systemic bacterial infections. The fluoroquinolone antibiotics have a relatively benign side-effect profile, but there have been case reports of behavioral changes in patients after initiation of this class of antibiotics.

We present a case of mania after ciprofloxacin antibiotic use. Elderly patients are especially at risk for adverse effects of medications. Multiple medical comorbidities, polypharmacy, and the potential of drug-drug interactions all increase the risk. Changes in mood or behavior such as mania are a serious adverse effect that can occur. Adverse drug reactions after the addition of a new medication always need to be considered.


Summary: Clinical Toxicology
1986, Vol. 24, No. 5, Pages 429-439 , DOI 10.3109/15563658608992605

Acute Manic Psychosis Following the Dermal Application of N,N-Diethyl-M-Toluamide (deet) in an Adult

J. W. Snyder‌, R. O. Poe‌, J. F. Stubbins‌ and L. K. Garrettson‌
Departments of Pharmacology and Toxicology, Eastern Virginia Medical School, Norfolk, Virginia, 23501
Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, Virginia, 23501
Medicinal Chemistry Medical College of Virginia Virginia Commonwealth University, Richmond, Virginia, 23298
Pediatrics and Pharmaceutics Medical College of Virginia Virginia Commonwealth University, Richmond, Virginia, 23298

Extensive animal testing and 30 years of human experience have established the general safety of DEET when applied episodically to skin or bedclothes. Local and systemic toxic and allergic reactions to DEET have been observed in man. Three weeks prior to admission, for the purpose of self-medication, a 30 year old man began daily applications of the insect repellant, DEET followed by a 1-2 hour period in a light-bulb heated box. Sedation and incoherence were noted for short periods following each application session. Aggressiveness and psychotic ideation led to hospital admission where he displayed psychomotor hyperactivity, rapid and pressured speech, tangentiality, flight of ideas, and grandiose delusions. Treatment was begun with haloperidol. Clinical improvement was complete within 6 days, atypical for classic endogenous mania. Drug and metabolites were identified in the urine more than 2 weeks after the last drug application.
References PDF (437 KB) PDF Plus (201 KB)

Saturday, January 30, 2010


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]


Am J Psychiatry. 2008 Jan;165(1):99-106. Epub 2007 Dec 17.

Selected infectious agents and risk of schizophrenia among U.S. military personnel.
Niebuhr DW, Millikan AM, Cowan DN, Yolken R, Li Y, Weber NS.

Department of Epidemiology, Division of Preventive Medicine, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20901.

OBJECTIVE: A number of studies have reported associations between Toxoplasma gondii (T. gondii) infection and the risk of schizophrenia. Most existing studies have used small populations and postdiagnosis specimens. As part of a larger research program, the authors conducted a hypothesis-generating case control study of T. gondii antibodies among individuals discharged from the U.S. military with a diagnosis of schizophrenia and serum specimens available from both before and after diagnosis.
METHOD: The patients (N=180) were military members who had been hospitalized and discharged from military service with a diagnosis of schizophrenia. Healthy comparison subjects (3:1 matched on several factors) were members of the military who were not discharged. The U.S. military routinely collects and stores serum specimens of military service members. The authors used microplate-enzyme immunoassay to measure immunoglobulin G (IgG) antibody levels to T. gondii, six herpes viruses, and influenza A and B viruses and immunoglobulin M (IgM) antibody levels to T. gondii in pre- and postdiagnosis serum specimens.
RESULTS: A significant positive association between the T. gondii IgG antibody and schizophrenia was found; the overall hazard ratio was 1.24. The association between IgG and schizophrenia varied by the time between the serum specimen collection and onset of illness.
CONCLUSION: The authors found significant associations between increased levels of scaled T. gondii IgG antibodies and schizophrenia for antibodies measured both prior to and after diagnosis.
PMID: 18086751 [PubMed - indexed for MEDLINE]


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.

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]


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


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.

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]


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]


Korean J Parasitol. 2009 Jun;47(2):125-30. Epub 2009 May 27.

Seroprevalence of Toxoplasma gondii infection and characteristics of seropositive patients in general hospitals in Daejeon, Korea.

Shin DW, Cha DY, Hua QJ, Cha GH, Lee YH.
Department of Infection Biology, Research Institute for Medical Science, College of Medicine, Chungnam National University, Daejeon, Korea.

To figure out the epidemiological status and relevance with other diseases in toxoplasmosis, we checked serum IgG antibody titers of 1,265 patients and medical records of seropositive patients. Seropositive rates were 6.6% by latex agglutination test (LAT) and 6.7% by ELISA. No significant differences were detected between sexes and age groups. The peak seroprevalence was detected in the 40-49-year-old age group. According to clinical department, Toxoplasma-positive rates were high in patients in psychiatry, ophthalmology, health management, emergency medicine, and thoracic surgery. Major coincidental diseases in seropositive cases were malignant neoplasms, diabetes mellitus, arthritis, chronic hepatitis B, chronic renal diseases, schizophrenia, and acute lymphadenitis, in the order of frequency. In particular, some patients with chronic hepatitis B and malignant neoplasms had high antibody titers. These results revealed that the seroprevalence of toxoplasmosis in a general hospital-based study was similar to that in a community-based study, and T. gondii seropositivity may be associated with neoplasms, diabetes, and other chronic infections.
PMID: 19488418 [PubMed - indexed for MEDLINE]


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.

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]


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]


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.
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 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:
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.


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.
The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia.
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]

Friday, January 29, 2010


Nippon Rinsho. 1994 May;52(5):1311-7.
[Manic-depressive symptom associated with endocrine and metabolic disorders]
[Article in Japanese]
Yamada T.
Kashiwa City Hospital.
In an attempt to study "manic-depressive" affairs associated with endocrine and mental disorders, our clinical data are analyzed before and after appropriate treatment in Cushing's disease, Cushing's syndrome, hyperthyroid Graves' disease and primary hypothyroidism. Although our data do not provide definite findings on manic-depressive affairs associated with Cushing's disease and syndrome, review data by others indicated a high incidence of depression under untreated condition and its disappearance after appropriate treatment. In contrast, patients with adrenocortical insufficiency did have a depression but this was cleared after supplemental therapy. In hyperthyroid Graves' disease, a number of emotional and mental instability and irritability were noticed before the treatment, but these abnormalities all disappeared after appropriate treatment for 3-6 months. In contrast, patients with primary hypothyroidism did show lethargy and apathy, and these abnormalities disappeared after appropriate treatment. From the data accumulated, it is concluded that adrenal steroid and thyroid hormone do affect the functions of nervous system and, as a result, cause a number of clinical symptoms. The exact biochemical processes underlying these abnormalities are not known and remains for further investigations.
PMID: 8007407 [PubMed - indexed for MEDLINE]


Gen Hosp Psychiatry. 2005 Mar-Apr;27(2):133-9.

Mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease.

Bunevicius R, Velickiene D, Prange AJ Jr.

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7160, USA.

OBJECTIVE: To evaluate the prevalence of mood and anxiety disorders in women with treated hyperthyroidism caused by Graves' disease and to compare them with the prevalence of such findings in women without past or present thyroid disease.
METHODS: Thirty inpatient women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease and 45 women hospitalized for treatment of gynecologic disorders such as abnormal vaginal bleeding, benign tumors or infertility were evaluated for the prevalence of mood and anxiety diagnoses using a standard Mini-International Neuropsychiatric Interview and for mood and anxiety ratings using the Profile of Mood States (POMS). At the time of assessment, it was discovered that 14 of 30 women with treated hyperthyroidism caused by Graves' disease were still hyperthyroid, while 16 women were euthyroid.
RESULTS: Significantly greater prevalence of social anxiety disorder, generalized anxiety disorder, major depression and total mood and anxiety disorders, as well as higher symptom scores on the POMS, was found in hyperthyroid women with Graves' disease in comparison with the control group. A prevalence of total anxiety disorder, as well as history of mania or hypomania and lifetime bipolar disorder, but not lifetime unipolar depression, was more frequent in both the euthyroid and the hyperthyroid subgroups of study women in comparison with the control group.
CONCLUSIONS: These results confirm a high prevalence of mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease. Hyperthyroidism plays a major role in psychiatric morbidity in Graves' disease.
PMID: 15763125 [PubMed - indexed for MEDLINE]

Neuropsychiatric Symptoms and Occupational Exposure to Chemicals

Human Exposure Assessment and Relief From Neuropsychiatric Symptoms: Case Study of a
Stephen J. Genuis, MD, FRCSC, DABOG and Shelagh K. Genuis, BScOT, MLIS
From the Department of Obstetrics and Gynecology (SJG), University of Alberta, Canada (SKG)
Correspondence: Address correspondence to Dr. Stephen Genuis, 2935–66 Street, Edmonton Alberta, Canada T6K 4C1 (E-mail:

Human exposure assessment and the results of implementing ‘precautionary avoidance’ suggested a relationship between a hairdresser’s neuropsychiatric symptoms and occupational exposure to potentially hazardous chemicals. A variety of investigations in response to patient complaints of depression, emotional instability and various physical symptoms revealed no objective abnormality; the CH2OPD2 mnemonic (community, home, hobbies, occupation, personal habits, diet and drugs) recommended by the Ontario College of Family Physicians was used as a first-line screening tool to assess potential environmental exposure to toxins. After occupational leave of absence, the patient reported cessation of symptoms. Environmental causes for familiar medical problems are frequently undiagnosed; it is recommended that, where appropriate, a screening tool for evaluation of environmental exposure to toxics be incorporated into primary care assessment and management of patients.


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.

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

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]


Neurotoxicology. 2008 Nov;29(6):1147-9. Epub 2008 Jun 24.
Toxic causes of mental illness are overlooked.
Genuis SJ.
While proper brain function requires the complex interaction of chemicals perpetually occupied in purposeful biochemistry, it is well established that certain toxic substances have the potential to disrupt normal brain physiology and to impair neurological homeostasis. As well as headache, cognitive dysfunction, memory disturbance, and other neurological signs and symptoms, disruption of brain function may also manifest as subtle or overt alteration in thoughts, moods, or behaviors. Over the last four decades, there has been the unprecedented development and release of a swelling repertoire of potentially toxic chemicals which have the capability to inflict brain compromise. Although the ability of xenobiotics to induce clinical illness is well established, the expanding public health problem of widespread toxicant exposure in the general population is a relatively new phenomenon that has spawned escalating concern. The emerging area of clinical care involving the assessment and management of accrued toxic substances such as heavy metals, pesticides, plasticizers and other endocrine disrupting or neurotoxic compounds has not been fully appreciated by the medical community and has yet to be incorporated into the clinical practice of many consultants or primary care practitioners.
PMID: 18621076 [PubMed - indexed for MEDLINE]


J Am Osteopath Assoc. 1998 Jul;98(7):373-8.

Neuropsychiatric manifestations of Lyme disease.

Paparone PW.

Lyme Disease Center for South Jersey, Absecon, NJ 08201, USA.
Lyme disease is a multisystem illness that may affect the central nervous system and subsequently produce mild to severe psychiatric disorders. Physicians who treat patient with Lyme disease need to be aware of its neuropsychiatric symptoms, which may emerge months to years after the initial infection. Prompt diagnosis and effective treatment are needed to avoid the debilitating and possibly irreversible mental illness associated with the neurologic involvement of this spirochetal infection. The author reviews the neuropsychiatric manifestations of Lyme disease and provides diagnostic and therapeutic approaches for the management of the central nervous system disease that may cause them.
PMID: 9695456 [PubMed - indexed for MEDLINE]


Psychosomatics. 2005 May-Jun;46(3):259-61.

Acute mania in the setting of severe hypothyroidism.

Stowell CP, Barnhill JW.

Department of Psychiatry, New York-Presbyterian Hospital, Weill-Cornell Medical Center, 525 East 68th St., New York, NY 10021, USA.

Although the associations between depression and hypothyroidism and between mania and hyperthyroidism are well described, mania in the setting of hypothyroidism is unusual. The authors present the case of a patient whose acute mania appears to have been precipitated by hypothyroidism secondary to postpartum thyroiditis. This case underscores the importance of thyroid screening in patients with mood and psychotic disorders, including patients who lack the classical psychiatric features of thyroid dysfunction. Further investigation is required on the nature of the relationship between thyroid function and bipolar disorder and any implications it may have for the diagnosis and treatment of this illness.
PMID: 15883148 [PubMed - indexed for MEDLINE]


Encephale. 2003 Nov-Dec;29(6):560-5.

[Psychiatric manifestations of vitamin B12 deficiency: a case report]

[Article in French]

Durand C, Mary S, Brazo P, Dollfus S.

Centre Esquirol, Service du Professeur S. Dollfus, CHU de Caen, avenue Côte-de-Nacre, 14033 Caen.

Psychiatric manifestations are frequently associated with pernicious anemia including depression, mania, psychosis, dementia. We report a case of a patient with vitamin B12 deficiency, who has presented severe depression with delusion and Capgras' syndrome, delusion with lability of mood and hypomania successively, during a period of two Months. Case report - Mme V., a 64-Year-old woman, was admitted to the hospital because of confusion. She had no history of psychiatric problems. She had history of diabetes, hypertension and femoral prosthesis. The red blood count revealed a normocytosis with anemia (hemoglobin=11,4 g/dl). At admission she was uncooperative, disoriented in time and presented memory and attention impairment and sleep disorders. She seemed sad and older than her real age. Facial expression and spontaneous movements were reduced, her speech and movements were very slow. She had depressed mood, guilt complex, incurability and devaluation impressions. She had a Capgras' syndrome and delusion of persecution. Her neurologic examination, cerebral scanner and EEG were postponed because of uncooperation. Further investigations confirmed anemia (hemoglobin=11,4 g/dl) and revealed vitamin B12 deficiency (52 pmol/l) and normal folate level. Antibodies to parietal cells were positive in the serum and antibodies to intrinsic factor were negative. An iron deficiency was associated (serum iron=7 micromol/l; serum ferritin concentration=24 mg/l; serum transferrin concentration=3,16 g/l). This association explained normocytocis anemia. Thyroid function, hepatic and renal tests, glycemia, TP, TCA, VS, VDRL-TPHA were normal. Vitamin B12 replacement therapy was started with hydroxycobalamin 1 000 ng/day im for 10 days and iron replacement therapy. Her mental state improved dramatically within a few days. After one week of treatment the only remaining symptoms were lability of mood, delusion of persecution, Capgras' syndrome but disappeared totally 9 days after the beginning of the treatment. A neurologic examination was possible because of cooperation. All the tendon reflexes of inferior members were absent. The plantars were in flexion and there was a left inferior member hypoesthesia. The cerebral scan and EEG were normal. Fundic biopsy, realized by fibroscopy, revealed fundic atrophia and intestinal metaplasia compatible with Biermers' disease. The iron deficiency exploration concluded diet deficiency. Mme V. appeared euphoric, her speech was very rapid with play on words and overactivity. This hypomania state totally disappeared 3 days after. Six Months after her hospitalisation, she presented an hypothyroidism (TSH=3,780; T3=1,35; T4=1,08). A thyroid hormones replacement was started and she continued to receive Monthly B12 replacement. Discussion - This case report illustrates psychiatric manifestations of Biermers' disease. The clinical arguments in favour are: white woman, more than 60 Years old, no history of psychiatric problems, atypical symptoms (confusional state with psychiatric symptoms), fluctuation of symptoms (severe depression with confusional state, delusion of persecution and Capgras' syndrome; delusion with lability of mood and hypomania), dramatic improvement after 9 days of vitamin B12 replacement therapy. The biological arguments are: anemia, vitamin B12 deficiency, normal folate level, atrophia and fundic metaplasia, positive antibodies to parietal cells in the serum, association between Biermers' disease and autoimmune disease (Haschimoto thyroidite). Psychiatric manifestations can occur in the presence of low serum B12 levels but in the absence of the other well recognized neurological and haematological abnormalities of pernicious anemia. Mental or psychological changes may precede haematological signs by Months or Years. They can be the initial symptoms or the only ones. Verbank et al. described the case of a patient with vitamin B12 deficiency in whom hypomania, paranoia and depression had been successively presented during a period of 5 Years before anemia have been developed. The case of Mme V. is similar in the succession of severe depression with delusion of persecution and Capgras' syndrome, delusion with lability of mood and hypomania, during a period of two Months. This report seems to be the first one of a sequence of several psychiatric states with pernicious anemia during a period of two Months with normocytosis anemia. To illustrate this illness we reviewed the literature regarding psychopathology associated with B12 deficiency. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. The neuropsychiatric severity by vitamin B12 deficiency and the therapeutic efficacy depends on the duration of signs and symptoms. Conclusion - We recommend consideration of B12 deficiency and serum B12 determinations in all the patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. B12 levels should be evaluated with treatment resistant depressive disorders, dementia, psychosis or risk factors for malnutrition such as alcoholism or advancing age associated with neurological symptoms, anemia, malabsorption, gastrointestinal surgery, parasite infestation or strict vegetarian diet. In first intention, B12 deficiency should be researched by serum B12 determination (normal 200-950 pg/ml). Studies of methylmalonic acid and homocysteine showed that they are very sensitive functional indicators of cobalamin status especially when other evidence of cobalamin (B12) deficiency was equivocal. Measurement of methylmalonic acid (normal 73-271 nmol/l) and homocysteine (normal 5,4-13,9 micromol/l) should not replace the measurement of serum cobalamin.

PMID: 15029091 [PubMed - indexed for MEDLINE]


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.
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]

Thursday, January 28, 2010


Lead Levels in the Hair of Bipolar Patients and Normal Controls

Med Hypotheses. 1986 Jun;20(2):151-5.

Lead levels in the hair of bipolar patients and normal controls.
Kanofsky JD, Rosen WA, Ryan PB, Decina P, Fieve RR, Kanofsky PB.

The analysis of hair samples taken from ten symptomatic bipolar patients and from ten normal controls matched for age, sex and race suggest that a relatively high body burden of lead may be associated with episodes of bipolar illness.

PMID: 3637615 [PubMed - indexed for MEDLINE]