Genetics of resilience: Implications from genome‐wide association studies and candidate genes of the stress response system in posttraumatic stress disorder and depression

Abstract

Resilience is the ability to cope with critical situations through the use of personal and socially mediated resources. Since a lack of resilience increases the risk of developing stress-related psychiatric disorders such as posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), a better understanding of the biological background is of great value to provide better prevention and treatment options. Resilience is undeniably influenced by genetic factors, but very little is known about the exact underlying mechanisms. A recently published genome-wide association study (GWAS) on resilience has identified three new susceptibility loci, DCLK2, KLHL36, and SLC15A5. Further interesting results can be found in association analyses of gene variants of the stress response system, which is closely related to resilience, and PTSD and MDD. Several promising genes, such as the COMT (catechol-O-methyltransferase) gene, the serotonin transporter gene (SLC6A4), and neuropeptide Y (NPY) suggest gene × environment interaction between genetic variants, childhood adversity, and the occurrence of PTSD and MDD, indicating an impact of these genes on resilience. GWAS on PTSD and MDD provide another approach to identifying new disease-associated loci and, although the functional significance for disease development for most of these risk genes is still unknown, they are potential candidates due to the overlap of stress-related psychiatric disorders and resilience. In the future, it will be important for genetic studies to focus more on resilience than on pathological phenotypes, to develop reasonable concepts for measuring resilience, and to establish international cooperations to generate sufficiently large samples. K E Y W O R D S depression, genetic risk factors, posttraumatic stress disorder, resilience, vulnerability

Neuropeptide Y Is an Immunomodulatory Factor: Direct and Indirect

“…The level of plasma NPY is significantly increased in patients with depression ( 139 ), and the NPY gene can be used as a risk gene for severe depression ( 140 ). However, NPY expression in the brain decreases overall during depression ( 13 ).…”

Genome Wide Analysis for Growth at Two Growth Stages in A New Fast-Growing Common Carp Strain (Cyprinus carpio L.)

“…Mixed lineage kinase dual leucine zipper kinase (DLK) regulates the JNKbased stress response pathway 45 . Overexpression of IMPACT in yeast cells inhibited growth under all stress conditions that require GCN2 (eIF-2-alpha kinase) and GCN1 for cell survival, probably by the IMPACT promoting the dissolution of the GCN2-GCN1 complex 46 . Serine/threonine-protein kinase PLK2-like (PLK2-like) is involved in catalysis of the following reaction in response to stress: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate 47 .…”

Association of Personal Anxiety with Dopamine Receptor D4 (DRD4), DAT Genes Polymorphism

“…As in the case of the DRD4 gene, VNTR polymorphic variants of the DAT gene can be associated with some pathological conditions in the pathogenesis, which play the main role in dopamine metabolism disorders [30]. In the studied population, the homozygous 10/10 genotype of the DAT gene prevailed -more than 50%, less often the 9/10 genotype was found slightly more than 36%, and finally, the third place was occupied by the 9/9 genotype -3.7%.…”