BackgroundOver the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).MethodsWe conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).ResultsWe observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10−6). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a ‘neurodevelopmental hub’ on chromosome 8p11.23.ConclusionsThis study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4. Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-017-0137-9) contains supplementary material, which is available to authorized users.
Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association (GWA) study, meta-analysis and follow-up (totaling as many as 18,206 cases and 42,536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7,469 bipolar disorder cases, 1,535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46,160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T], OR = 1.08, P = 6.6 × 10−11). The new variant is located within a 593 kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P = 0.0039 in the public GIANT consortium dataset; P = 0.00047 in 22,651 additional Icelanders).
Ukraine is a newly independent state with a population of about 48 million. It inherited its national health system from the USSR. The Soviet system was conceived as part of a massively expensive socialist planning economy that was generally delivering poor value for money. Some aspects of the Soviet health system were, however, undoubtedly sound and certain public health measures were superior to those in the West. For example, infant mortality, despite possible underreporting, was probably lower in the USSR than in many Western countries (Anderson & Silver, 1986). The health system became increasingly corrupt and inefficient during the final years of the USSR's existence. Since independence, the health system has not been a state priority and has been chronically under-funded. In the past few years of rapid economic development in Ukraine, the share of the state budget allocated to the health system has remained static, leaving Ukraine in a disadvantaged state compared with other European countries (United Nations, 2007).
The article provides up-to-date scientific data on the clinical phenotype of depression in children and adolescents that were exposed to significant psychological trauma as a result of hostilities, terrorism, natural disasters, abuse, physical and sexual violence. The review presents the latest data on the prevalence of depression due to various traumatic factors, comorbidity of mental and neurological disorders, possible mechanisms of their relationship, treatment recommendations. Post-traumatic depressions (PTD) are widespread in children and adolescents and negatively affect the quality of life and significantly increase the risk of suicide and self-harming behavior. The presence of depression worsens the prognosis of post-traumatic stress disorder, the treatment response. Several psychotherapeutic interventions, including cognitive-behavioral therapy and eye-movement desensitization, are effective in the treatment of PTD. Psychopharmacological drugs, in particular antidepressants and mood stabilizers, have limited proven efficacy in PTD in pediatric practice. The use of these drugs in comorbid mental and neurological conditions has a higher level of evidence. Conclusions. Depression in children and adolescents due to psychological trauma remains an understudied topic. Future research should focus on the efficacy of pharmacological approaches to the treatment of posttraumatic depression and comorbid mental and neurological disorders, which is especially important for countries with low access to specialized psychotherapeutic care.
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