Major depressive disorder has become a prominent cause of disability, as lifetime prevalence has increased to ~15% in the Western world. Pharmacological effects of serotonin (5-hydroxytryptamine, 5-HT) are mediated through 5-hydroxytryptamine receptor (5-HTR) binding. Serotonin regulation of amygdala activity is attained through activation of three 5-HT2 family receptor subtypes, 5-HT2A, 5-HT2B, and 5-HT2C. Specifically, HT2A and the HT2C receptors have similar gross cerebral distribution and function, with higher constitutive activity found in HT2C than in HT2A. We investigated the possible association of 5-HTR gene polymorphisms to specific and non-specific antidepressant treatment responses in treatment-free patients in Siberia. 156 patients, aged between 18–70 years and clinically diagnosed with depressive disorders, were treated with antidepressants for 4 weeks. Patients were genotyped for a subset of 29 SNPs from the following 5-HT Receptor genes: HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B and HTR6. Primary outcome was measured by differences in Hamilton Depression Rating Scale (ΔHAM‐D 17) scores between baseline/week two, week two/week four and baseline/week four. Univariate linear regression was initially conducted to determine the 5-HTR SNPs to be studied within the multiple linear regression. Multiple linear regression analyses over the three time periods were conducted for ΔHAM‐D 17 with independent factors including: age, gender, depression diagnosis, antidepressant treatment and selected 5-HTR SNPs. We found improved ∆HAM-D 17 in patients taking tricyclic antidepressants (0–4 weeks: B = 4.85, p = 0.0002; 0–2 weeks: B = 3.58, p = 0.002) compared to patients taking SSRIs. Over the course of study, significant associations between 5-HT receptors SNPs and antidepressant response were not identified.

Background: Many antidepressants are substrates of P‐glycoprotein, an efflux transporter in the blood‐brain‐barrier encoded by the ABCB1 gene. Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eight polymorphisms in the ABCB1 gene on antidepressant treatment response.Method: 152 patients were included from psychiatric departments of the Mental Health Research Institute in Tomsk. The difference in Hamilton‐Depression‐Rating‐Scale (HAMD‐17)‐scores between baseline and week two, week two and four, and baseline and week four was used to estimate timing of improvement of depression. Associations between the ABCB1 gene‐polymorphisms and reduction in HAMD‐17 score were assessed using independent t‐test and multiple linear regression.Results: Tricyclic antidepressants were associated with a higher reduction of HAMD‐17 score when compared to SSRIs. The SNP rs2235040 A‐allele had a significant positive influence on the ΔHAMD‐17_(0→2W) score but a significant negative influence on the ΔHAMD‐17_(2→4W) score. The rs4148739 G‐allele had a significant negative influence on the ΔHAMD‐17_(0→2W) score but a significant positive influence on the ΔHAMD‐17_(2→4W) score. The SNP rs2235015 T‐allele is significant negatively related to the ΔHAMD‐17_(2→4W) score.Conclusion: ABCB1 Genetic variations appear to affect speed but not magnitude of antidepressant drug response.

Background: Tuberculosis (TB) in children and adolescents is a sentinel event for ongoing transmission. In the Netherlands, epidemiological characteristics of childhood and adolescent TB have not been fully evaluated. Therefore, we aimed to assess TB epidemiology within this population to provide guidance for TB elimination.Methods: A retrospective time-series analysis using national surveillance data from 1993–2018 was performed in children (aged <15 years) and adolescents (aged 15–19 years) with TB. Poisson regression models offset with log-population size were used to estimate notification rates and rate ratios. Trends in notification rates were estimated using average annual percentage changes (AAPC) based on the segmented linear regression analysis.Results: Among 3899 children and adolescents with TB notified during 1993–2018, 2418 (62%) were foreign-born (725 (41.3%) out of 1755 children and 1693 (78.9%) out of 2144 adolescents). The overall notification rate in children was 2.3 per 100 000 person-years, declining steadily during the study period (AAPC −10.9%, 95% CI −12.6–−9.1). In adolescents, the overall notification rate was 8.4 per 100 000 person-years, strongly increasing during 1993–2001 and 2012–2018. Compared to Dutch-born children and adolescents, substantially higher notification rates were observed among African-born children and adolescents (116.8 and 316.6 per 100 000 person-years, respectively). Additionally, an increasing trend was observed in African-born adolescents (AAPC 18.5%, 95% CI 11.9–25.5). Among the foreign-born population, those from countries in the horn of Africa contributed most to the TB caseload.Conclusion: TB notification rate among children was low and constantly declining across different demographic groups. However, heterogeneities were shown in adolescents, with an increasing trend in the foreign-born, particularly those from Africa.