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Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in brain serotonin synthesis. The TPH2 gene has frequently been investigated in relation to psychiatric morbidity. The aim of the present review is to integrate results from association studies between TPH2 single nucleotide polymorphisms (SNPs) and various psychiatric disorders, which we furthermore quantified with meta-analysis. We reviewed 166 studies investigating 69 TPH2 SNPs in a broad range of psychiatric disorders, including over 30,000 patients. According to our meta-analysis, TPH2 polymorphisms show strongest associations with mood disorders, suicide (attempt) and schizophrenia. Despite small effect sizes, we conclude that TPH2 SNPs in the coding and non-coding areas (rs4570625, rs11178997, rs11178998, rs10748185, rs1843809, rs4290270, rs17110747) are each associated with one or more psychopathological conditions. Our findings highlight the possible common serotonergic mechanisms of the investigated psychiatric disorders. Yet, the functional relevance of most TPH2 polymorphisms is unclear. Characterizing how exactly the different TPH2 variants influence the serotonergic neurotransmission is a next necessary step in understanding the psychiatric disorders where serotonin is implicated. [ABSTRACT FROM AUTHOR]

Background: Some authors have hypothesized that Treatment-Resistant Unipolar Depression (TRD-UP) should be considered within the bipolar spectrum disorders and that hidden bipolarity may be a risk factor for TRD-UP. However, there are neither studies comparing clinical and sociodemographic data of patients with TRD-UP versus Bipolar (BP) disorders nor are there any examining differences versus Bipolar type I (BP-I) and Bipolar type II (BP-II). Methods: Charts analysis was conducted on 194 patients followed at the Mood Disorders Clinic of the McGill University Health Center. Sociodemographic, clinical features and depression scales were collected from patients meeting DSM-IV criteria for TRD-UP (n = 100) and BP (n = 94). Binary logistic regression analysis was conducted to examine clinical predictors independently associated with the two disorders. Results: Compared to BP, TRD-UP patients exhibited greater severity of depression, prevalence of anxiety and panic disorders, melancholic features, Cluster-C personality disorders, later onset of depression and fewer hospitalizations. Binary logistic regression indicated that higher comorbidity with anxiety disorders, higher depression scale scores and lower global assessment of functioning (GAF) scores, and lower number of hospitalizations and psychotherapies differentiated TRD-UP from BP patients. We also found that the rate of unemployment and the number of hospitalizations for depression was higher in BP-I than in BP-II, while the rate of suicide attempts was lower in BP-I than in BP-II depressed patients. Conclusions: These results suggest that TRD-UP constitutes a distinct psychopathological condition and not necessarily a prodromal state of BP depression. [ABSTRACT FROM AUTHOR]