Increased markers of inflammation after cannabis cessation and their association with psychotic symptoms.

INTRODUCTION: A dysbalance of the immune system in psychotic disorders has been well investigated. However, despite a higher prevalence of cannabis (THC) consumption in patients with psychosis, few studies have investigated the impact of this use on inflammatory markers. METHODS: One hundred and two inpatients were included in this retrospective study. Leukocytic formula, hsCRP, fibrinogen levels and urinary THC were measured, and comparisons were performed at baseline and after 4 weeks of cannabis cessation between cannabis users (THC+) and non-users (THC-). RESULTS: After cannabis cessation, we found a greater increase in leucocyte level (p < 0.01), monocyte level (p = 0.05) and a statistical trend to a highest increase of lymphocyte level (p = 0.06) between baseline and 4 weeks in the THC+ group as compared to the THC- group. At 4 weeks, highest leucocyte (p = 0.03), lymphocyte (p = 0.04) and monocyte (p < 0.01) counts were found in the THC+ group, whereas at baseline no difference was found. A positive correlation was found between monocyte count at 4 weeks and baseline Positive and Negative Syndrome Scale (PANSS) negative subscore (p = 0.045) and between the variation of monocyte count between baseline and 4 weeks and the PANSS total score at 4 weeks (p = 0.05). CONCLUSION: THC cessation is associated with an increase in inflammatory markers, including white blood cell, lymphocyte and monocyte levels, which correlates with symptomatology of patients with psychosis.

Immune cell subsets in patients with bipolar disorder or schizophrenia with history of childhood maltreatment.

A history of Childhood Maltreatment (CM) has been repeatedly associated with an increased risk of developing bipolar disorders (BD) or schizophrenia (SZ). The impact of severe stress induced by CM has been proposed to be mediated by elevated inflammation reflected by dysregulated inflammatory processes. Little is known about the potential impact of CM on lymphocyte subpopulations or the role of pre-existing infections on CM physiological consequences. This study therefore explored the role of CM and past infection exposure impact on lymphocyte subpopulations to give an indication of their relevance as stressors in the pathoetiology of major mood and psychotic disorders. 118 adult patients with SZ, and 152 with BD were included in the analysis. CM history was assessed by the Childhood Trauma Questionnaire (CTQ), with current and past psychiatric symptomatology also evaluated. Circulating immune cell subsets were analyzed using flow cytometry-based analysis. Past exposure to common infectious stigma including toxoplasma, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were measured by solid phase-enzyme microplate and ELISA immunoassays. The relationship between CM, biological phenotypes (including immune cell subsets distribution and past infectious status) and clinical phenotypes were analyzed using univariate and multivariate analyses. BD patients with, versus without, CM had higher levels of CD3+CD8+ cytotoxic T cells and CMV antibodies along with decreased levels of CD45RA+CCR7+CD8+ naïve CD8+ T cells, and a more severe clinical profile. CMV antibody levels were inversely associated with the CD3 + CD8 + lymphocyte subset level. SZ patients with, versus without, CM, showed lower levels of CD14 + monocytes and no specific clinical characteristics. The accumulation of different types of maltreatment associated with increased body mass index and CMV autoantibodies as well as decreased levels of CD14 + monocytes. In both BD and SZ, further analysis according to the type and the number of CM subtypes showed association with specific changes in lymphocyte cell subsets, clinical profile, and infectious stigma. Adults with BD or SZ exposed to CM exhibit specific immune cell subset profiles, clinical features, and stigma of past infections. In BD, our data indicate an interplay between CM and CMV infections, which may possibly contribute to premature aging and cellular senescence, both of which have previously been shown to associate with mood disorders. Longitudinal studies of CM-exposed patients are required to clarify the interactions of CM and viral infections, including as to the pathophysiological processes driving patient symptomatology.

White blood cells and patients with psychiatric disorders needing seclusion: A retrospective non-interventional study.

OBJECTIVE: The objective of this retrospective study was to investigate the peripheral immunological markers using leucocyte count, the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR), and the monocyte to lymphocyte ratio (MLR) in patients with aggressive behavior, during and after seclusion. METHODS: Ninety-nine inpatients were included in this retrospective study. Leucocyte count was measured, and NLR, PLR and MLR were calculated and compared between a group of patients who required seclusion and a group who did not. A multivariate analysis was performed using binary logistic regression, including confounding factors such as age, gender, medication, BMI, smoking status and diagnosis. RESULTS: We found the lowest levels of lymphocytes (P=0.01) and basophils (P<0.01) and the highest NLR (P=0.02) and MLR (P=0.04) in the seclusion group. We also found a restoration of these parameters after the end of the seclusion period. Furthermore, we found a positive correlation between the PANSS negative subscore, and PLR (P=0.05), or MLR (P=0.03) after seclusion, and between the MLR variation across the seclusion period and the PANSS general subscore after the end of seclusion (P=0.04). CONCLUSION: This study shows that NLR and MPR are higher in patients with aggressive symptoms and/or agitation who require seclusion. These immunological markers could be considered as state markers.

Disruption of Conscious Access in Psychosis Is Associated with Altered Structural Brain Connectivity.

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal-occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in long-distance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis.

Natural killer cells in first-episode psychosis: an innate immune signature?

Accumulating evidence majorly implicates immune dysfunction in the etiology of psychotic disorders. In particular, altered numbers and functions of natural killer (NK) cells have been described in psychosis, but interpretation has often been confounded by a number of biases, including treatment. Eighty-one first-episode psychosis (FEP) patients who subsequently received a diagnosis of either schizophrenia (SZ; n = 30) or bipolar disorder (BP; n = 31) over a five-year follow-up period were investigated for their NK cell phenotype and compared to 61 healthy controls (HCs). We found a similar proportion of CD3-CD56+ NK cells in FEP patients and HCs. The frequency of NK cells expressing the late cell activation marker HLA-DR was significantly increased in FEP patients compared to HCs, especially in patients with BP (p < 0.0001) and, to a lesser degree, in patients with SZ (p = 0.0128). Interestingly, the expression of the activating NKG2C receptor, known to be associated with infections, was higher in patients with SZ and BP than in HCs (p < 0.0001) and correlated with HLA-DR expression, altogether defining adaptive NK cells. In terms of NK cell function, we observed a suppressed capacity of SZ-derived NK cells to mount cytotoxic responses in the presence of target cells, while NK cells from patients with BP show an inability to produce IFN-γ, a cytokine pivotal to NK function. This study strongly suggests major dysfunction of NK cells in FEP with functioning impairment correlated with psychotic, manic, and depressive symptoms in subsequently diagnosed patients with SZ and BP.

Cannabis Cessation, Inflammatory Markers and Schizophrenia.

Objective A dysbalance of the immune system in schizophrenia has been largely described but few studies have investigated the impact of cannabis use on inflammatory markers in patients with schizophrenia. The objective of our study was to investigate the impact of cannabis use on high-sensitivity C-reactive protein (hsCRP), fibrinogen levels and leucocytic formula in patients with schizophrenia. Methods: Thirty-eight acutely ill inpatients with schizophrenia were included. Patient hsCRP, fibrinogen levels, leukocytic formula and urinary cannabis were measured at baseline and after four weeks of treatment. Results: After four weeks of cannabis cessation (as confirmed by urinary tests), we found an increase of hsCRP level (p = .016) and lymphocytes (p = .03) in consumers patients whereas no difference was observed in non-consumers patients. As compared to non-consumers patients with schizophrenia, consumers had lower levels of hsCRP (p = .045). Finally, a negative correlation was found between the PANSS score evolution (between baseline and 4 weeks) and baseline hsCRP level. Conclusions: In our study, cannabis cessation raises inflammatory markers though improving clinical symptoms. The investigation and the understanding of interactions between cannabis use and inflammatory markers in patients with schizophrenia is of importance and could in the future be a new target for treatment of psychiatric symptoms linked to inflammation.

Lithium prevents grey matter atrophy in patients with bipolar disorder: an international multicenter study.

BACKGROUND: Lithium (Li) is the gold standard treatment for bipolar disorder (BD). However, its mechanisms of action remain unknown but include neurotrophic effects. We here investigated the influence of Li on cortical and local grey matter (GM) volumes in a large international sample of patients with BD and healthy controls (HC). METHODS: We analyzed high-resolution T1-weighted structural magnetic resonance imaging scans of 271 patients with BD type I (120 undergoing Li) and 316 HC. Cortical and local GM volumes were compared using voxel-wise approaches with voxel-based morphometry and SIENAX using FSL. We used multiple linear regression models to test the influence of Li on cortical and local GM volumes, taking into account potential confounding factors such as a history of alcohol misuse. RESULTS: Patients taking Li had greater cortical GM volume than patients without. Patients undergoing Li had greater regional GM volumes in the right middle frontal gyrus, the right anterior cingulate gyrus, and the left fusiform gyrus in comparison with patients not taking Li. CONCLUSIONS: Our results in a large multicentric sample support the hypothesis that Li could exert neurotrophic and neuroprotective effects limiting pathological GM atrophy in key brain regions associated with BD.

Obsessive-Compulsive Disorder: Autoimmunity and Neuroinflammation.

PURPOSE OF REVIEW: Here, we propose to review the immuno-inflammatory hypothesis in OCD given the concurrent incidence of autoimmune comorbidities, infectious stigma, and raised levels of inflammatory markers in a significant subset of patients. A better understanding of the immune dysfunction in OCD may allow stratifying the patients in order to design personalized pharmaco/psychotherapeutic strategies. RECENT FINDINGS: A persistent low-grade inflammation involving both innate and adaptive immune system with coexisting autoimmune morbidities and stigma of infectious events has been prominently observed in OCD. Hence, specific treatments targeting inflammation/infection are a feasible alternative in OCD. This review highlights that OCD is associated with low-grade inflammation, neural antibodies, and neuro-inflammatory and auto-immune disorders. In some subset of OCD patients, autoimmunity is likely triggered by specific bacterial, viral, or parasitic agents with overlapping surface epitopes in CNS. Hence, subset-profiling in OCD is warranted to benefit from distinct immune-targeted treatment modalities.

A Multilevel Functional Study of a SNAP25 At-Risk Variant for Bipolar Disorder and Schizophrenia.

The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant in SNAP25, rs6039769, that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combined in vitro and in vivo approaches in humans to understand the functional impact of the at-risk allele. Thus, we showed in vitro that the rs6039769 C allele was sufficient to increase the SNAP25 transcription level. In a postmortem expression analysis of 33 individuals affected with schizophrenia and 30 unaffected control subjects, we showed that the SNAP25b/SNAP25a ratio was increased in schizophrenic patients carrying the rs6039769 at-risk allele. Last, using genetics imaging in a cohort of 71 subjects, we showed that male risk carriers had an increased amygdala-ventromedial prefrontal cortex functional connectivity and a larger amygdala than non-risk carriers. The latter association has been replicated in an independent cohort of 121 independent subjects. Altogether, results from these multilevel functional studies are bringing strong evidence for the functional consequences of this allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network, which therefore may increase the vulnerability to both early-onset bipolar disorder and schizophrenia.SIGNIFICANCE STATEMENT Functional characterization of disease-associated variants is a key challenge in understanding neuropsychiatric disorders and will open an avenue in the development of personalized treatments. Recent studies have accumulated evidence that the SNARE complex, and more specifically the SNAP25 protein, may be involved in psychiatric disorders. Here, our multilevel functional studies are bringing strong evidence for the functional consequences of an allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network. These results demonstrate a common genetically driven functional alteration of a synaptic mechanism both in schizophrenia and early-onset bipolar disorder and confirm the shared genetic vulnerability between these two disorders.

Neurodevelopmental subtypes of bipolar disorder are related to cortical folding patterns: An international multicenter study.

OBJECTIVES: Brain sulcation is an indirect marker of neurodevelopmental processes. Studies of the cortical sulcation in bipolar disorder have yielded mixed results, probably due to high variability in clinical phenotype. We investigated whole-brain cortical sulcation in a large sample of selected patients with high neurodevelopmental load. METHODS: A total of 263 patients with bipolar disorder I and 320 controls were included in a multicentric magnetic resonance imaging (MRI) study. All subjects underwent high-resolution T1-weighted brain MRI. Images were processed with an automatized pipeline to extract the global sulcal index (g-SI) and the local sulcal indices (l-SIs) from 12 a priori determined brain regions covering the whole brain. We compared l-SI and g-SI between patients with and without early-onset bipolar disorder and between patients with and without a positive history of psychosis, adjusting for age, gender and handedness. RESULTS: Patients with early-onset bipolar disorder had a higher l-SI in the right prefrontal dorsolateral region. Patients with psychotic bipolar disorder had a decreased l-SI in the left superior parietal cortex. No group differences in g-SI or l-SI were found between healthy subjects and the whole patient cohort. We could replicate the early-onset finding in an independent cohort. CONCLUSIONS: Our work suggests that bipolar disorder is not associated with generalized abnormalities of sulcation, but rather with localized changes of cortical folding restricted to patients with a heavy neurodevelopmental loading. These findings support the hypothesis that bipolar disorder is heterogeneous but may be disentangled using MRI, and suggest the need for investigations into neurodevelopmental deviations in the disorder.

Immunoglobulin sub-class distribution in bipolar disorder and schizophrenia: potential relationship with latent Toxoplasma Gondii infection.

BACKGROUND: Immune dysfunction could play a significant role in the pathogenesis of bipolar disorder (BD) and schizophrenia (SZ), conditions with an underlying pro-inflammatory state. Studies on humoral immune responses (which reflects antibody mediated fight against pathogens) in schizophrenia and bipolar disorder are sparse and often providing contradictory results. The aim of this study was to assess humoral immunity in a group of stable bipolar disorder and schizophrenia patients compared to controls by determining total Immunoglobulins and IgG subclasses and to assess their association with latent Toxoplasma gondii and/or CMV infection. METHODS: 334 subjects (124 BD, 75 SZ and 135 Healthy Controls [HC]) were included and tested for humoral immunity by determining the total immunoglobulins (IgG,A and M) and IgG subclasses (IgG1, IgG2, IgG3, IgG4) and their relationship with latent Toxoplasma gondii infection, an established risk factor for BD and SZ. RESULTS: Although lower levels of IgG, IgG1, IgG2, IgG4 and IgA were found among BD as compared to HC and/or SZ, after adjustment for confounding variables, only low levels of IgG and IgG1 in BD remai- ned significant. Strikingly highest levels of antibodies to T. gondii (but not CMV) infection in BD and SZ were associated with lowest levels of IgG3 and IgG4 levels as compared to controls. CONCLUSIONS: Schizophrenia and bipolar disorder patients with latent T. gondii specific infection may be more vulnerable to changes in immuno-inflammatory processes than controls with similar latent infectious state. Simultaneous sequential immunological monitoring both in steady state and active disease phases in the same BD and SZ patients are warranted to understand the role of Toxoplasma gondii latency in these disorders.

Shape analysis of the cingulum, uncinate and arcuate fasciculi in patients with bipolar disorder.

BACKGROUND: Abnormal maturation of brain connectivity is supposed to underlie the dysfunctional emotion regulation in patients with bipolar disorder (BD). To test this hypothesis, white matter integrity is usually investigated using measures of water diffusivity provided by MRI. Here we consider a more intuitive aspect of the morphometry of the white matter tracts: the shape of the fibre bundles, which is associated with neurodevelopment. We analyzed the shape of 3 tracts involved in BD: the cingulum (CG), uncinate fasciculus (UF) and arcuate fasciculus (AF). METHODS: We analyzed diffusion MRI data in patients with BD and healthy controls. The fibre bundles were reconstructed using Q-ball-based tractography and automated segmentation. Using Isomap, a manifold learning method, the differences in the shape of the reconstructed bundles were visualized and quantified. RESULTS: We included 112 patients and 82 controls in our analysis. We found the left AF of patients to be further extended toward the temporal pole, forming a tighter hook than in controls. We found no significant difference in terms of shape for the left UF, the left CG or the 3 right fasciculi. However, in patients compared with controls, the ventrolateral branch of the left UF in the orbitofrontal region had a tendency to be larger, and the left CG of patients had a tendency to be smaller in the frontal lobe and larger in the parietal lobe. LIMITATIONS: This was a cross-sectional study. CONCLUSION: Our results suggest neurodevelopmental abnormalities in the left AF in patients with BD. The statistical tendencies observed for the left UF and left CG deserve further study.

Corpus callosum area in patients with bipolar disorder with and without psychotic features: an international multicentre study.

BACKGROUND: Previous studies have reported MRI abnormalities of the corpus callosum (CC) in patients with bipolar disorder (BD), although only a few studies have directly compared callosal areas in psychotic versus nonpsychotic patients with this disorder. We sought to compare regional callosal areas in a large international multicentre sample of patients with BD and healthy controls. METHODS: We analyzed anatomic T1 MRI data of patients with BD-I and healthy controls recruited from 4 sites (France, Germany, Ireland and the United States). We obtained the mid-sagittal areas of 7 CC subregions using an automatic CC delineation. Differences in regional callosal areas between patients and controls were compared using linear mixed models (adjusting for age, sex, handedness, brain volume, history of alcohol abuse/dependence, lithium or antipsychotic medication status, symptomatic status and site) and multiple comparisons correction. We also compared regional areas of the CC between patients with BD with and without a history of psychotic features. RESULTS: We included 172 patients and 146 controls in our study. Patients with BD had smaller adjusted mid-sagittal CC areas than controls along the posterior body, the isthmus and the splenium of the CC. Patients with a positive history of psychotic features had greater adjusted area of the rostral CC region than those without a history of psychotic features. LIMITATIONS: We found small to medium effect sizes, and there was no calibration technique among the sites. CONCLUSION: Our results suggest that BD with psychosis is associated with a different pattern of interhemispheric connectivity than BD without psychosis and could be considered a relevant neuroimaging subtype of BD.

[Anti-NR1 antibodies in anti-N-methyl-D-aspartate receptor encephalitis and schizophrenia]. / Anticorps anti-NR1 dans l'encéphalite anti-récepteur N-méthyl-D-aspartate et la schizophrénie.

The recent discovery of anti-NMDA receptor antibodies and proof of their pathogenic effects in limbic encephalitides raised many questions among neuroscientist and physicians working in the field of schizophrenia. Indeed, this two conditions share several major clinical, pathophysiological or etiological aspects and some authors tend to consider some forms of schizophrenia as mild-encephalitis cases. Some studies have reported the presence of these antibodies in schizophrenic patient's sera without neurological symptoms. These findings suggest new therapeutic perspectives in some schizophrenic patients, despite a low seroprevalence and pathogenic effects that remain to be demonstrated.

Comparative analysis of anti-toxoplasmic activity of antipsychotic drugs and valproate.

Recent studies have shown a strong link between Toxoplasma gondii infection and psychiatric disorders, especially schizophrenia and bipolar disorders (odd ratio ≈2.7 for each disorder). Antipsychotic drugs and mood stabilizers may have anti-toxoplasmic activity that potentially may be associated with better effectiveness in these disorders, but previous results have been few in number and conflicting. We therefore sought to determine which daily prescribed antipsychotics and mood stabilizer have the best anti-toxoplasmic activity during the development phase of the parasite. In the present study, we examined the effects of commonly used antipsychotic drugs (amisulpride, cyamemazine, fluphenazine, haloperidol, levomepromazine, loxapine, olanzapine, risperidone and tiapride) and one mood-stabilizing agent (valproate) on toxoplasmic activity. We replicated that fluphenazine has a high anti-toxoplasmic activity, but it does not seem to be a phenothiazine-specific class effect: indeed, we found that another first-generation antipsychotic, zuclopenthixol, has a high anti-toxoplasmic activity. Valproate, tiapride and amisulpride have no anti-toxoplasmic activity on parasite growth, and the other antipsychotic drugs showed low or intermediate anti-toxoplasmic activity. As it is not possible to know the intracellular concentrations of antipsychotics in the brain, further clinical studies are warranted to determine whether these in vitro findings have potential implications in treatment of toxo-positive patients with schizophrenia. These findings may be potentially relevant for the choice of the first-line antipsychotic drug or mood stabilizer in previously infected patients.

Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis.

Irritable bowel syndrome (IBS) has been associated with high prevalence of psychological disorders. However, it remains unclear whether IBS and each of its subtypes (predominant diarrhea IBS-D, constipation IBS-C, mixed IBS-M) are associated with higher anxiety and depressive symptoms levels. This study aimed to determine the associations of IBS and each of its subtypes with anxiety and/or depression. We conducted a systematic review and meta-analysis using five electronic databases (PubMed, PsychINFO, BIOSIS, Science Direct, and Cochrane CENTRAL). We selected case-control studies comparing anxiety and depression levels of patients with IBS to healthy controls, using standardized rating scales. Outcomes were measured as random pooled standardized mean differences (SMD). Ten studies were included in our analysis (885 patients and 1,384 healthy controls). Patients with IBS had significant higher anxiety and depression levels than controls (respectively, SMD = 0.76, 95 % CI 0.47; 0.69, p < 0.01, I2 = 81.7 % and SMD = 0.80, 95 % CI 0.42; 1.19, p < 0.01, I2 = 90.7 %). This significant difference was confirmed for patients with IBS-C and -D subtypes for anxiety, and only in IBS-D patients for depression. However, other IBS subtypes had a statistical trend to be associated with both anxiety and depressive symptomatology, which suggests a lack of power due to the small number of studies included. Patients with IBS had significantly higher levels of anxiety and depression than healthy controls. Anxiety and depression symptomatology should be systematically checked and treated in IBS patients, as psychological factors are important moderators of symptom severity, symptom persistence, decisions to seek treatment, and response to treatment.

Immunity, inflammation, and bipolar disorder: diagnostic and therapeutic implications.

Bipolar disorder is now known to be associated not only with highly prevalent co-occurring psychiatric and substance use disorders but also with medical comorbidities, such as cardiovascular diseases, diabetes mellitus, obesity and thyroid dysfunction. Inflammatory disturbances repeatedly observed in bipolar disorder, can explain some of the comorbidity between bipolar disorder and medical disorder. This revised perspective of bipolar disorders should promote the development of therapeutic tools. Immuno-inflammatory dysfunction may well represent a significant component of the underlying pathophysiology of the disorder. We therefore propose to review the immuno-inflammatory hypothesis in bipolar disorder considering the co-occurence with autoimmune diseases, immunological and inflammatory markers, as well as immuno-genetic markers which could lead to personalized treatments.

A bipolar disorder patient becoming asymptomatic after adjunctive anti-filiarasis treatment: a case report.

BACKGROUND: Evidence suggests that neurotropic infectious agents might be involved in bipolar disorder. So far, few have been written for the association between parasitic infection and bipolar disorder. Filariasis is a parasitic disease acting ruthlessly via mosquitos and affecting more than 120 million people worldwide. We present here, to our knowledge, the first description of a filariasis infected manic bipolar disorder patient fully improved in terms of psychiatric symptoms by anti-heminthic treatment. CASE PRESENTATION: The patient is a 31 years-old man native of Congo. At inclusion, he presented a severe manic episode with dangerous behaviour unresolved by classic treatments. A diagnosis of filariasis bancrofti infection was made after the discovery of a systemic hypereosinophilia. Therefore, a bi-therapy of anthelmintics was conducted allowing a successful improvement with clear reduction of agitation and aggressive behaviours that could not be attributed to a modification of psychotropic treatments or filarial encephalopathy or acute disseminated encephalomyelitis. CONCLUSION: The ineffectiveness of psychotropic treatment of a manic episode requires the evaluation of co-morbid medical conditions such as infections which can interfere with adequate mood stabilizing medication. Filariasis by inducing chronic inflammation and immunopathologic reactions seems to play a major role in infected affective disorders patients by changing levels of cytokines of the Th1 system or indirectly damaging the brain tissue. The beneficial combination of antihelmintics and mood stabilizers, in this case, could be explained by the potential of such association to downregulate neuroinflammation and excitotoxicity processes.Altogether, these data pinpoint the requirement to explore the parasitic infectious status in case of bipolar disorder patients resistant to classic treatments and originating or living in endemic geographical areas.

The Modulated Role of Toxoplasma gondii on Eosinophils in Psychiatric Disorders after Cannabis Cessation.

The aim of our study was to evaluate the impact of T. gondii status on eosinophils count (EOS), the eosinophil-to-lymphocyte ratio (ELR), and the eosinophil-to-neutrophil-to-lymphocytes ratio (ENLR) before and after cannabis cessation in patients with psychiatric disorders. One hundred and eighty-eight patients were included in the study. T. gondii, EOS, ELR, ENLR, and urinary cannabis were measured at baseline and after 4 weeks of cannabis cessation. Highest levels and increase of PNE (p = 0.02), ENLR levels (p = 0.031) and highest level of ELR (p = 0.03) were found in patients after cannabis cessation only in patients positive for T. gondii serology (Toxo+ group). At four weeks, significant interactions between cannabis and T. gondii status for EOS (p = 0.038), and for ENLR (p = 0.043) levels were found, as well as for the evolution between baseline and 4 weeks for ENLR level (p = 0.049). After cannabis cessation, we found a positive correlation between negative symptoms and EOS levels at 4 weeks in the Toxo+ group. This study shows that the increase of inflammation after cannabis cessation might be modulated by T. gondii seropositivity status in patients after cannabis cessation.