Relationship between Toxoplasma gondii infection and bipolar disorder in a French sample.

BACKGROUND: Prenatal exposure to viruses or parasites with tropism for the central nervous system is one of the risk factors for psychotic disorders. However, the relationship between past exposure to Toxoplasma gondii (T. gondii) and incidence of bipolar disorders (BD) is poorly documented across populations. METHODS: We explored the potential association between T. gondii exposure and BD in France, a country of high prevalence of Toxoplasmosis, comparing the prevalence of serological markers (IgG/IgM class antibodies) for T. gondii infection in 110 BD patients and 106 healthy controls all living in France. In a subgroup of 42 patients and 42 controls we also evaluated the levels of interleukin 6 (IL-6) transcripts, an adjunct marker of inflammation. RESULTS: We found that the sero-positive group for IgG antibodies to T. gondii had a 2.7 fold odds of having BD as compared to the sero-negative group (OR=2.17 CI 95%=1.09-4.36, p=0.028). Despite the fact that BD patients had significantly higher levels of IL-6 than the non-patient controls, no notable association between T. gondii status and IL-6 transcript levels was found. We did not find any clinical or demographic correlates of Toxoplasma exposure in the study population. LIMITATIONS: Our results are to be interpreted with caution because of our small sample size. RESULTS: We confirm the association between seropositive status to T. gondii and bipolar disorders reported in other populations and extend it to French patients. Our data strengthen the importance of early detection of T. gondii infected patients in order to propose specific and adequate treatments.

Neuroimaging biomarkers in bipolar disorder.

There is an urgent need to identify objective biomarkers for the assessment of bipolar disorder, to improve diagnosis and prognostic evaluation. Neuroimaging is a particularly promising approach. We review here the structural and functional neuroimaging studies carried out on bipolar disorder. These studies have led to the development of neurobiological models of bipolar disorder assuming cortical-limbic dysregulation. Dorsal brain structures are thought to decrease in volume and activity in bipolar disorder, reducing inhibition of the ventral-limbic network and enhancing emotional responses. These models also assume abnormal prefrontal-subcortical limbic connectivity. This abnormal connectivity has been identified by both diffusion tensor imaging studies (anatomical connectivity) and functional MRI (functional connectivity). However, studies are currently limited by the heterogeneity of the patients included. Future research should include studies to validate biomarkers for the assessment of bipolar disorder and studies of large and well characterized samples of patients with bipolar disorder.

MRI exploration of pineal volume in bipolar disorder.

BACKGROUND: Circadian rhythm instability and abnormalities of melatonin secretion are considered as trait markers of bipolar disorder. Melatonin is secreted by the pineal gland. We investigated pineal volume in patients with bipolar disorder, and expected to observe smaller than normal pineal glands in cases of bipolar disorder. METHODS: The primary outcome was the total pineal volume measured for each pineal gland with T1 MRI sequence. Twenty patients with bipolar I and II disorder and twenty controls were recruited. Pineal glands with large cysts (type 3) were excluded. RESULTS: After exclusion of individuals with type 3 cysts, 32 subjects were analyzed for total pineal volume (16 patients with bipolar disorder and 16 controls). Total pineal volume did not differ significantly between patients (total pineal volume=115+/-54.3mm(3)) and controls (total pineal volume=110+/-40.5mm(3)). CONCLUSIONS: Contrary to our hypothesis, no difference in total pineal volume between patients with bipolar disorder and healthy subjects was observed. These results indicate that the putative dysfunction of the pineal gland in bipolar disorder could be not directly related to an abnormal volume of the pineal gland.

A meta-analysis of whole-brain diffusion tensor imaging studies in bipolar disorder.

OBJECTIVES: White matter abnormalities are one of the most consistently reported findings in neuroimaging studies of bipolar disorder (BD). We conducted an anatomical likelihood estimation meta-analysis of BD whole-brain diffusion tensor imaging (DTI) studies, with the aim of identifying statistically consistent fractional anisotropy (FA) changes reflecting microstructural modifications to white matter in BD. METHODS: We performed online searches of the PUBMED and EMBASE databases in January 2011. Studies were considered for inclusion if they used diffusion tensor MRI, compared a group of subjects with BD with healthy controls and involved whole-brain white matter analysis of FA. The analyses were conducted in Talairach space, using the activation likelihood estimation technique. We carried out a meta-analysis restricted to studies reporting a lower FA in patients with BD than in healthy controls. RESULTS: Ten studies were included. We identified two significant clusters of decreased FA on the right side of the brain. The first was located in the right white matter, close to the parahippocampal gyrus. Four of the ten studies included contributed to this cluster. The second cluster was located close to the right anterior and subgenual cingulate cortex. These two clusters of decreased FA in BD are crossed by several white matter tracts. CONCLUSIONS: These two clusters of altered FA may underlie the abnormal emotional processing and altered functional limbic connectivity in BD. Explorations based on DTI-based tractography are required to identify the tracts involved in the pathophysiology of BD.