Association of gut dysbiosis with first­episode psychosis (Review).

The gut­microbiota­brain axis is a complex bidirectional communication system linking the gastrointestinal tract to the brain. Changes in the balance, composition and diversity of the gut­microbiota (gut dysbiosis) have been found to be associated with the development of psychosis. Early­life stress, along with various stressors encountered in different developmental phases, have been shown to be associated with the abnormal composition of the gut microbiota, leading to irregular immunological and neuroendocrine functions, which are potentially responsible for the occurrence of first­episode psychosis (FEP). The aim of the present narrative review was to summarize the significant differences of the altered microbiome composition in patients suffering from FEP vs. healthy controls, and to discuss its effects on the occurrence and intensity of symptoms in FEP.

Typhoid fever presenting as acute psychosis in a young adult: case report and literature review of typhoid psychosis.

The rarity of acute psychosis in typhoid fever can result in delayed and misdiagnosis of the condition. We report a case of a 20-year-old man who presented with fever and acute psychotic symptoms. This was associated with headache, dizziness, and body weakness. There were no other significant symptoms. Neurological examination revealed reduced muscle tone of bilateral lower limbs but otherwise unremarkable. The computed tomography (CT) scan of his brain showed no abnormality. Blood specimens for microbiological culture grew Salmonella Typhi. This isolate was susceptible to chloramphenicol, ampicillin, ceftriaxone, ciprofloxacin, and trimethoprim-sulfamethoxazole. He was treated with intravenous ceftriaxone for one week and responded well. He was discharged with oral ciprofloxacin for another week. The repeated blood and stool for bacterial culture yielded no growth of Salmonella Typhi.

The Gut Microbiome and Treatment-Resistance in Schizophrenia.

The effect of antipsychotic medication is poor in 30-40% of patients with schizophrenia; treatment resistance is usually met with shifts to new drugs or drug augmentation strategies or a trial of clozapine. The purpose of this review was to examine the potential role of intestinal bacteria in the bioavailability of antipsychotic medication and the possibility that parenterally administered antipsychotics might be able to overcome treatment resistance. Databases were searched with appropriate terms to locate relevant papers dealing with the effect of antipsychotic drugs on the gut microbiome and the effect of bacterial metabolizing enzymes on antipsychotic drugs. Also searched were papers addressing the various current parenteral formulations of antipsychotic drugs. Sixty-five recent pertinent papers were reviewed and the results are suggestive of the premise that there is a drug refractory form of psychosis for which the composition of gut bacteria is responsible, and that parenteral drug administration could overcome the problem.

Psychosis in Borrelia burgdorferi infection - part II: case reports. / Zaburzenia psychotyczne w przebiegu zakazenia Borrelia burgdorferi ­ czesc II: opisy przypadków.

In the second part of the article case reports of three patients were presented. All patientswere treated for Borrelia infection and all of them developed psychotic disorders. History of each patient was different, as well as the probability of causal relationship between neuroborreliosis and psychosis. The first case concerns a female patient with no former psychiatric history, who developed psychotic episode secondary to neuroborreliosis. Psychotic disorders resolved after antibiotic treatment. In the second case, a male patient was previously twice hospitalized in psychiatric ward due to psychosis. During the third psychiatric hospitalization suspicion of Lyme neuroborreliosis (LNB) was propounded. Patient's health state improved after combined therapy with antibiotics and antipsychotic drugs. Direct causal relationship between neuroborreliosis and psychosis is ambiguous. The third case concerns a male patient who was initially treated for LNB and tick-borne encephalitis in an infectious diseases ward. During the hospitalization he developed the first in life episode of mania with psychotic features. Second episode of psychosis occurred after a tick bite and a vaccination against tick-borne encephalitis. In this case, coexistence of many diverse factors results in many difficulties in estimating of the probability of the relationship between LNB and episode of mania with psychotic features. Referring to the part I of the article, diagnostic difficulties and differential diagnosis were discussed, as well as the causal relationship between borreliosis and psychosis in each case was estimated.

Differences in gut microbiome composition between persons with chronic schizophrenia and healthy comparison subjects.

Intestinal microbiome and gut-brain axis have been receiving increasing attention for their role in the regulation of brain/behavior and possible biological basis of psychiatric disorders. Several recent clinical studies have linked the microbiome with neuropsychiatric conditions, although the literature on schizophrenia is quite limited. This study investigated gut microbiome composition in 50 individuals, including 25 persons with chronic schizophrenia and 25 demographically-matched non-psychiatric comparison subjects (NCs). Stool samples were collected and assayed using 16S rRNA sequencing of the V4 region. Examination of unweighted UniFrac and Bray-Curtis dissimilarity revealed significant community-level separation in microbiome composition between the two subject groups. At the phylum level, Proteobacteria were found to be relatively decreased in schizophrenia subjects compared to NCs. At the genus level, Anaerococcus was relatively increased in schizophrenia while Haemophilus, Sutterella, and Clostridium were decreased. Within individuals with schizophrenia, abundance of Ruminococcaceae was correlated with lower severity of negative symptoms; Bacteroides was associated with worse depressive symptoms; and Coprococcus was related to greater risk for developing coronary heart disease. Our findings provide evidence of altered gut microbial composition in persons with chronic schizophrenia and suggest a need for larger and longitudinal studies of microbiome in schizophrenia.

First-presentation with psychotic behavior to the Emergency Department: Meningitis or not, that is the question.

INTRODUCTION: Meningitis is a potentially life threatening medical emergency. Psychotic behavior may be a presenting feature in patients with meningitis. We aimed to determine the value of various clinical and laboratory features at ruling-out meningitis in the patient presenting with a first-episode of psychotic behavior. METHODS: Medical records of 159 subjects presenting to a tertiary academic hospital over a 6-month period with one or more psychotic features for the first time were prospectively gathered. Pathological cerebrospinal fluid findings as well as clinical and other laboratory findings were tabulated and discussed retrospectively. RESULTS: Cerebrospinal fluid was obtained in 153/159 (96.2%) subjects. Meningitis was confirmed in twenty-eight (18.3%) subjects. Of these, a) one or more clinical feature of meningitis (headache, neck stiffness, photophobia or focal neuropathy) was present in 21 subjects (75.0%), b) visual hallucinations in 15 subjects (53.6%), c) pyrexia >37.5 °C in 7 subjects (25.0%), d) CRP >10 mg/L in 21 subjects (75.0%), e) HIV seropositive status in 19 subjects (67.9%) and f) an absence of illicit substances on urinalysis in 23 subjects (82.1%). Various combinations of these variables, where the presence of ≥1 variable was regarded as positive, were unable to rule-out meningitis in all study subjects. CONCLUSION: The absence of these six parameters; alone or in various combinations, was unable to rule-out meningitis in all patients presenting to our ED with a first-episode of psychotic behavior. When the underlying etiology of psychotic behavior is not obvious, the clinician should adopt a low threshold to perform a lumbar puncture.

Gut microbiome and magnetic resonance spectroscopy study of subjects at ultra-high risk for psychosis may support the membrane hypothesis.

BACKGROUND: The microbiota-gut-brain axis and membrane dysfunction in the brain has attracted increasing attention in the field of psychiatric research. However, the possible interactive role of gut microbiota and brain function in the prodromal stage of schizophrenia has not been studied yet. METHODS: To explore this, we collected fecal samples and performed Magnetic Resonance Spectroscopy (MRS) scans in 81 high risk (HR) subjects, 19 ultra-high risk (UHR) subjects and 69 health controls (HC). Then we analyzed the differences in gut microbiota and choline concentrations in the anterior cingulate cortex (ACC). RESULTS: Presences of the orders Clostridiales, Lactobacillales and Bacteroidales were observed at increase levels in fecal samples of UHR subjects compared to the other two groups. The composition changes of gut microbiota indicate the increased production of Short Chain Fatty Acids (SCFAs), which could activate microglia and then disrupt membrane metabolism. Furthermore, this was confirmed by an increase of choline levels, a brain imaging marker of membrane dysfunction, which is also significantly elevated in UHR subjects compared to the HR and HC groups. CONCLUSION: Both gut microbiome and imaging studies of UHR subjects suggest the membrane dysfunction in the brain and hence might support the membrane hypothesis of schizophrenia.

Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response.

The effects of gut microbiota on the central nervous system, along its possible role in mental disorders, have received increasing attention. Here we investigated differences in fecal microbiota between 28 patients with first-episode psychosis (FEP) and 16 healthy matched controls and explored whether such differences were associated with response after up to 12months of treatment. Numbers of Lactobacillus group bacteria were elevated in FEP-patients and significantly correlated with severity along different symptom domains. A subgroup of FEP patients with the strongest microbiota differences also showed poorer response after up to 12months of treatment. The present findings support the involvement of microbiota alterations in psychotic illness and may provide the basis for exploring the benefit of their modulation on treatment response and remission.

Brain Autoimmunity and Intestinal Microbiota: 100 Trillion Game Changers.

T cells play a critical role in autoimmune diseases in the brain, particularly in multiple sclerosis (MS). Since T cells are normally prevented from crossing the blood-brain barrier (BBB), autoimmunity requires prior activation of naturally occurring autoreactive T cells in peripheral tissue. Recently, a critical role for the microbiota in this activation process has emerged. Here, we review the role of gut-associated lymphoid tissues (GALT) as a major site for the phenotypic changes that allow the migration of autoreactive T cells to the brain. Additionally, we examine the involvement of the microbiota in clinical MS as well as other brain disorders such as Parkinson's disease (PD), stroke, and psychiatric disorders.

Revisiting an old foe: The face of psychosis in neurosyphilis.

A delusional, agitated middle-aged man presented to hospital with a tenacious psychotic episode. Upon appropriate therapy for neurosyphilis, dramatic resolution of this brief episode ensued, prompting a literature review of psychosis associated with neurosyphilis.

The importance of not jumping to conclusions: syphilis as an organic cause of neurological, psychiatric and endocrine presentations.

A 66-year-old Caucasian man was admitted to an acute psychiatric ward under section 2 of the Mental Health Act after presenting with auditory hallucinations and partition delusions. He had been known to mental health services since 2005 but had never been treated with psychotropic medication or given a formal psychiatric diagnosis. He was also diagnosed with hypopituitarism of unknown aetiology in 2002. In light of this presentation, his medical history was reviewed in full, hormone levels and a full delirium screen including blood borne virus and syphilis serology was completed to ensure no organic cause had been missed. The treponemal antibody was positive, and he reported no previous syphilis treatment, as such a diagnosis of neurosyphilis was performed. This case demonstrates a patient presenting with two potential complications of syphilis; psychosis and hypopituitarism where screening for this infection had not been previously considered.

Psychosis in neurosyphilis -- clinical aspects and implications.

BACKGROUND: The World Health Organization estimates that 10-12 million new syphilis infections occur each year. Without treatment, years to decades after initial infection, 30% of affected individuals may develop tertiary syphilis, which can manifest as neurosyphilis. The aim of this review is to evaluate the research literature examining the psychopathological manifestations of psychosis in association with neurosyphilis. METHOD: The authors performed a systematic electronic search for published studies (1995-2012). The following databases were used: Medline, Embase and the Cochrane Library as well as the search engines Scopus and Google Scholar. RESULTS: 61 articles were used for detailed analysis. Psychotic symptoms due to neurosyphilis are numerous and can inform differential diagnosis for many psychotic manifestations according to ICD-10 or DSM-IV. CONCLUSION: Due to our results, current epidemiological data, and the difficulties in differential diagnosis of neurosyphilis, routine screening tests are still recommended in the psychiatric field. Long-term psychiatric input, with periodic syphilis titre controls, seems indicated in individuals affected by neurosyphilis with psychiatric symptoms. Furthermore, individuals with mental health problems may be at higher risk of acquiring syphilis.

Brucellar psychosis.

Brucellosis is the most common worldwide zoonotic infection of which psychosis is a rare feature of this disease. Brucellar psychosis should be considered in a patient with unexplained, nonspecific psychological complaints. Its timely diagnosis relies on special attention to the epidemiologic profile of the patient for a possible exposure to the brucella species. This article has presented three cases of brucellar psychosis initially misdiagnosed because the risk factors which made them at risk for the disease were ignored.

Tremor, seizures and psychosis as presenting symptoms in a patient with chronic lyme neuroborreliosis (LNB).

Lyme borreliosis is a multisystem disorder caused by Borrelia burgdorferi (Bb). Neurological symptoms such as lymphocytic meningoradiculoneuritis (Bannwart's syndrome), cranial neuritis (II,III,IV,V,VI), encephalitis, transverse myelitis are found in about 10% of cases during the second phase of the disease. In the chronic stage, many months or years after the initial infection, other neurologic complications may occur, such as encephalomyelitis, epileptic crises, cognitive impairment, peripheral neuropathy and psychiatric disturbances such as depression, anxiety, panicc attacks, catatonia, psychosis etc. Some patient continue to experience symptoms of fatigue, insomnia or psychiatric disorder in the post borrelia syndrome. We describe here a patient with a triad of unusual symptoms in chronic LNB including tremor, seizures and psychosis. Standardized medical interview, neurologic examination, neuroimaging, serum and CSF serology as well as EEG and EMNG evaluation were performed. The patient was treated with intravenous ceftriaxone and doxycycline and responded with rapid clinical and functional improvement.Newertheless, he suffered from multiple systemic and neurologic sequelas that influenced his daily activities in post treatment period. Emphasis is placed on the atypical onset and evolution, the difficulties encountered in formulating diagnosis, early treatment and the uncertainties concerning the sequelae after treatment. In patients with non-specific long lasting symptoms in the absence of overt clinical signs suggesting CNS involvement, routine treatment with i.v. ceftriaxone is not to be encouraged.

Psychosis following mycoplasma pneumonia.

Extrapulmonary manifestations of Mycoplasma pneumoniae are well described, including a subset of central nervous system (CNS)-associated syndromes. In pediatric populations, frequencies of CNS sequelae occur in 0.1% to 7% of patients. Neurologic illness associated with M. pneumoniae, such as meningitis, encephalitis, polyradiculitis, Guillain-Barre, and stroke have been reported; however, the incidence of M. pneumoniae-associated organic brain syndrome is rare. We present the case of a 20-year-old midshipman with acute psychosis following resolution of M. pneumoniae pneumonia and review 6 other adult cases found in the literature. M. pneumoniae remains one of the most common causes of respiratory illnesses in the military recruit setting and therefore should always be suspected as an organic cause of mental status changes in young persons such as recruits, cadets, and midshipmen particularly with antecedent respiratory illnesses.

Effect of trifluoperazine, a potential drug for tuberculosis with psychotic disorders, on the growth of clinical isolates of drug resistant Mycobacterium tuberculosis.

The effect of the antipsychotic drug trifluoperazine (TFP) on the in-vitro growth of 50 clinical isolates of Mycobacterium tuberculosis was tested. Of these isolates, 29 were susceptible to all five of the antitubercular drugs isoniazid, rifampicin, streptomycin, ethambutol and pyrazinamide, and 21 were resistant to one or more of the five drugs. The minimum inhibitory concentration (MIC) of TFP was 4 microg/ml for 40% of both the susceptible (12/29) and resistant (8/21) isolates and 8 microg/ml for 55% (16/29) and 48% (10/21) of the susceptible and resistant isolates respectively. Further analysis of the data for resistant isolates indicated that the MIC of TFP was 4 microg/ml and 16 microg/ml respectively for 50% (4/8) and 75% (6/8) of the isolates resistant to one drug only from isoniazid, streptomycin or pyrazinamide. Of the nine isolates resistant to two drugs, isoniazid and streptomycin, the MIC was 4 microg/ml for 33% (3/9) and 16 microg/ml for 80% (7/9). The MIC of TFP for two isolates resistant to the three drugs isoniazid, rifampicin and streptomycin was 8 microg/ml for one and 32 microg/ml for the other. Of two isolates resistant to all five drugs, it is of interest to note that the MIC of TFP was only 4 microg/ml for one but 32 microg/ml for the other. Because the above MICs are for TFP as a single drug, it would be desirable to study the antitubercular activity of the serum of tuberculosis patients with psychotic problems receiving regular antitubercular therapy supplemented with TFP at its recommended and tolerated dose.

Neuropsychiatric manifestations of Lyme disease.

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.

Borna disease virus genome transcribed and expressed in psychiatric patients.

Borna disease virus (BDV) is a neurotropic, negative and single-stranded enveloped RNA virus that persistently infects various domestic animal species. Infection causes disturbances in behaviour and cognitive functions, but can also lead to a fatal neurologic disease. Human infections seemed likely, since serum antibodies were detected in neuropsychiatric patients. Further proof came from our discovery that peripheral blood monocytes carry viral antigens. Here, we present the first data on different viral genomic transcripts in such patients' cells as well as sequence data of transcripts. Both viral markers seem to coincide with acute episodes of mood disorders, thus pointing to a new human virus infection possibly threatening mental health.