Causal association between kynurenine and depression investigated using two-sample mendelian randomization.

As research progresses, the intricate metabolic connections between depression and tryptophan, as well as kynurenine (KYN), have become increasingly evident. In studies investigating the relationship between KYN and depression, the conclusions reached thus far have been inconsistent. Therefore, we propose employing a two-sample mendelian randomization (MR) approach to further elucidate the relationship between KYN and depression. We utilized extensive data from large-scale genome-wide association studies to identify single nucleotide polymorphisms that act as instrumental variables for kynurenine and depression in European ancestry populations, ensuring compliance with MR assumptions. We employed five MR algorithms, namely, weighted median, MR-Egger, inverse variance weighted (IVW), simple mode, and weighted mode, with IVW as the primary analysis method. Sensitivity tests were conducted using Cochran's Q test, MR-Egger intercept test, MR Pleiotropy Residual Sum and Outlier, and Leave-one-out analysis.The IVW analysis revealed that each standard deviation increase in kynurenine corresponded to a 1.4-fold increase in the risk of depression (OR = 1.351, 95% CI 1.110-1.645, P = 0.003). The direction of the effect size (positive or negative) was consistent with the findings from the other four algorithms. Sensitivity tests indicated no heterogeneity or horizontal pleiotropy among the instrumental variables. Elevated levels of kynurenine have a causal relationship with an increased risk of developing depression.

Relationship between gene-environment interaction and obsessive-compulsive disorder: A systematic review.

BACKGROUND: Gene-environment interaction (G × E) refers to the change of genetic effects under the participation of environmental factors resulting in differences in genetic expression. G × E has been studied in the occurrence and development of many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD). AIM: A systematic review was conducted to investigate the role of G × E plays in OCD. This review explored the relationship between G × E and the susceptibility to OCD occurrence, disease progression, and treatment response. METHODS: This systematic literature search was performed using Web of Science, PubMed, Cochrane Library, and CNKI. Seven studies were selected, which included seven genes (BDNF, COMT, MAO, 5-HTT, SMAD4, PGRN, and SLC1A1) polymorphisms, polygenic risk score (PRS), and two environmental factors (childhood trauma and stressful life events). RESULTS: Information from this systematic review indicated that G × E increased the susceptibility to OCD, played a crucial role in the clinical characteristics, and had an inconsistent impact on treatment response of OCD. FUTURE DIRECTIONS: The multi-omics studies and the inclusion of G × E in future GWAS studies of OCD should be drawn more attention, which may contribute to a deeper understanding of the etiology of OCD as well as guide therapeutic interventions for the disease.

Association of HTR3B gene polymorphisms with depression and its executive dysfunction: a case-control study.

BACKGROUND: Previous studies have shown that depression was associated with HTR3B gene. The aim of this study was to investigate the relationship between polymorphisms of the HTR3B gene and depression and its executive dysfunction in Chinese Han population. METHODS: A total of 229 patients with depressive disorder and 202 healthy controls were enrolled. Six Single nucleotide polymorphism sites (SNPs) including rs10789970, rs4938056, rs12421126, rs1176744, rs2276305 and rs12795805 were genotyped by Snapshot. Clinical features were collected using a general demographic questionnaire. The 24-item Hamilton Depression Scale (HAMD) was used to assess the symptoms' severity of the patients. The patients' executive function was assessed using a series of cognitive tests including Maze Test, Symbolic Coding Test, Spatial Span Inverse Order Test, Linking Test, and Emotional Management Test. RESULTS: The genotypic and allelic distributions of rs1176744 in HTR3B gene were significantly different (χ2 = 11.129, P = 0.004, χ2 = 9.288, P = 0.002, respectively) between patients and controls. The A allele was positively correlated with depression. The proportion of A carriers was significantly higher and that of C carriers was lower in patients than those in controls. Patients had significantly lower scores of Spatial Span Inverse Order Test in carriers of A allele at locus rs1176744 and higher scores in carriers of C alleles at locus rs1176744 and rs12795805. CONCLUSIONS: The polymorphisms of HTR3B gene may be associated with depression in Chinese Han population. The A allele of rs1176744 may increase the risk of developing depression and executive dysfunction while C alleles of rs1176744 and rs12795805 may be the protective factors for executive dysfunction in patients with depression.

Modulation of turbulent Rayleigh-Bénard convection under spatially harmonic heating.

We numerically study turbulent Rayleigh-Bénard (RB) convection under spatial temperature modulation, where the bottom temperature varies sinusoidally around a mean value in space. Both two- and three-dimensional simulations are performed over the Rayleigh number range 10^{7}≤Ra≤10^{10} and the wave number range 1≤k≤120 at fixed Prandtl number Pr=0.7. It is demonstrated that spatial temperature modulation with small wave numbers can enhance the global heat transfer (characterized by the Nusselt number Nu) in the turbulent regime, while Nu is close to that in standard RB convection in the case of large wave numbers. Further, we propose two characteristic modulation length scales: one is the penetration depth δ_{k} above which spatial modulation is negligible, the other is the inversion depth δ_{k2} below which there exists a stable inverse temperature gradient. Based on the relative thickness of the thermal boundary layer (BL) δ_{th} compared with these two length scales, the underlying modulation mechanism is physically explained and three regimes are identified: (1) an unperturbed BL regime (δ_{k}<δ_{th}), in which the modulation effect does not penetrate through the thermal BL and Nu is nearly unchanged; (2) a partially modulated BL regime (δ_{k2}<δ_{th}<δ_{k}), in which hot spots trigger more plume emissions from the thermal BL, resulting in Nu enhancement; and (3) a fully modulated BL regime (δ_{th}<δ_{k2}), in which the stable temperature inversion over the cold phases begins to affect convective flows, which alters the trend of Nu enhancement.