Gut microbiome and psychiatric disorders

Several pieces of evidence show that gut microbiota can impact psychiatric disorders. However, no mechanism behind the relationship has been identified. Host genetics and their diets have a significant impact on the gut microbiota. More advanced studies are needed to find the mechanism and develop new therapeutic strategies

Valutazione del rischio genetico di comportamento suicidario nel disturbo bipolare: analisi di 737 pedigrees

Suicide is a significant cause of mortality in patients with major affective disorders(MAD). Suicidal acts are typically more lethal in MAD. A large contribution to the suicide risk derives from the presence of family history of suicidal behavior. Other clinical factors, such as treatment with lithium can reduce the suicide risk in patients with MAD. In this work the results of the distribution of suicidal behavior in a large sample of families with bipolar-spectrum disorder, and its relation to family history of MAD and bipolar disorder (BD) are presented. Methods: The lifetime prevalence of completed and attempted suicides was analyzed in 737 families of probands with MAD with 4,919 first-degree relatives (affected and unaffected). Cox proportional hazard regression models and logistic regression models were used to investigate the role of several clinical covariates on the risk of MAD, BD and suicidal behavior. Results: The lifetime prevalence of suicidal behavior (attempted and completed suicides) in 737 probands was at 38.4 ± 3.0%. Among the clinical variables, lithium treatment was associated with a decreased risk of suicidal behavior in probands (p =0.007). Family history of suicidal behavior contributed significantly to the joint risk of MAD and suicidal behavior (p = 0.0006) in first-degree relatives. Conclusions: These findings suggest that the liability to suicidal behavior has significant contribution from partially overlapping genetic factors underlying MAD and suicidal behavior itself. Even in the presence of high genetic risk for suicidal behavior, lithium treatment seems to decrease significantly the suicide rates

Cutaneous adverse reaction during lithium treatment: a case report and updated systematic review with meta-analysis

OBJECTIVES: To present a new case of adverse cutaneous reaction during lithium treatment and to update the systematic review and meta-analysis of the incidence of this adverse reaction. METHODS: We conducted a systematic search (performed in September 2016) for peer-reviewed articles in English indexed in Medline (2011-present). Meta-analytical estimates were obtained using the "Metafor" package. CASE PRESENTATION: Ms. H., a 31-year-old Caucasian woman with BD1, was admitted to the inpatient unit for a full-blown psychotic episode and treated with carbamazepine 400 mg q.d., lithium carbonate 450 mg q.d., and risperidone 4 mg q.d. with clinical improvement. After 12 days from the start of psychopharmacological treatment, she manifested a cutaneous reaction that motivated the stop of carbamazepine treatment, as well as the increase in lithium carbonate dose (750 mg q.d.). Risperidone dose remained unvaried. Since the skin lesion persisted after 8 days from withdrawal of carbamazepine, the private practitioner stopped also lithium carbonate treatment (de-challenge), maintaining risperidone treatment. The cutaneous reaction resolved spontaneously after six days from withdrawal of lithium carbonate. Subsequently, the worsening of psychopathological conditions motivated a new admission during which lithium carbonate was reintroduced (16 days after its suspension) (re-challenge). On the following day, we observed an itching erythematous maculopapular rash involving the trunk, the four limbs, and the oral mucosa. CONCLUSIONS: Our case of an erythematous maculopapular rash during lithium treatment was the first to present a challenge-de-challenge-re-challenge sequence that suggests causality. Although meta-analysis does not point to an increased rate of adverse skin reaction during lithium treatment, clinicians should not neglect to monitor cutaneous symptoms during lithium treatment

Pharmacogenomics of Mood Stabilizers in the Treatment of Bipolar Disorder

Bipolar disorder (BD) is a chronic and often severe psychiatric illness characterized by manic and depressive episodes. Among the most effective treatments, mood stabilizers represent the keystone in acute mania, depression, and maintenance treatment of BD. However, treatment response is a highly heterogeneous trait, thus emphasizing the need for a structured informational framework of phenotypic and genetic predictors. In this paper, we present the current state of pharmacogenomic research on long-term treatment in BD, specifically focusing on mood stabilizers. While the results provided so far support the key role of genetic factors in modulating the response phenotype, strong evidence for genetic predictors is still lacking. In order to facilitate implementation of pharmacogenomics into clinical settings (i.e., the creation of personalized therapy), further research efforts are needed

The Impact of Alexithymia on Treatment Response in Psychiatric Disorders: A Systematic Review

Treatment of psychiatric disorders relies heavily on a trial and error approach, often prolonging the time required to obtain symptomatic improvements. The identification of reliable predictors of treatment response is instrumental to enact an individualized approach. Alexithymia represents a personality trait reflecting an intrinsic difficulty in recognizing the emotional components of subjective experiences. Thus, its modulating role on treatment outcome has gathered substantial attention during the past years. In the present paper, we aimed at exploring the available evidence for Alexithymia role in influencing the treatment outcome on a wide range of psychiatric conditions by means of a systematic review

The impact of phenotypic and genetic heterogeneity on results of genome wide association studies of complex diseases

Phenotypic misclassification (between cases) has been shown to reduce the power to detect association in genetic studies. However, it is conceivable that complex traits are heterogeneous with respect to individual genetic susceptibility and disease pathophysiology, and that the effect of heterogeneity has a larger magnitude than the effect of phenotyping errors. Although an intuitively clear concept, the effect of heterogeneity on genetic studies of common diseases has received little attention. Here we investigate the impact of phenotypic and genetic heterogeneity on the statistical power of genome wide association studies (GWAS). We first performed a study of simulated genotypic and phenotypic data. Next, we analyzed the Wellcome Trust Case-Control Consortium (WTCCC) data for diabetes mellitus (DM) type 1 (T1D) and type 2 (T2D), using varying proportions of each type of diabetes in order to examine the impact of heterogeneity on the strength and statistical significance of association previously found in the WTCCC data. In both simulated and real data, heterogeneity (presence of "non-cases") reduced the statistical power to detect genetic association and greatly decreased the estimates of risk attributed to genetic variation. This finding was also supported by the analysis of loci validated in subsequent large-scale meta-analyses. For example, heterogeneity of 50% increases the required sample size by approximately three times. These results suggest that accurate phenotype delineation may be more important for detecting true genetic associations than increase in sample size