Risk Factors of Anxiety Disorders in Children

Anxiety disorders are common; lifetime prevalence for the group of disorders is estimated to be as high as 25%. The main question is What is the relative contribution of genetics and environment to etiology of anxiety disorders? The anxiety disorders are not, from a genetic perspective, etiologically homogeneous. Structural equation modeling provides estimates of variance in liability to a disorder that is attributable to additive genetic, common familial environmental, and individual-specific environmental factors. Familial aggregation that largely results from genetic risk factors has been documented for all of the major anxiety disorders. Genes predispose to two broad groups of disorders dichotomized as panic-generalized-agoraphobic anxiety versus specific phobias. The candidate genes are the ones encoding the central and peripheral nervous system receptors and transporters. Trauma in childhood disposes to further anxiety disorders through the hyperactivity of the HPA axis and the hypersecretion of CRF. Traumatic experience in developmental age leads to neurobiochemical changes in brain, typical for panic disorder or PTSD. Behavioral inhibition in early childhood is a predictor of further anxiety disorders. Some types of parental behaviors and family environment can lead to them, as well as improper interactions between parents and child

Potential Effects of the COVID-19 Pandemic on Children and Adolescents with Separation Anxiety Disorder

Children with separation anxiety disorder (SAD) experience unrealistic fear of being separated from their significant caregivers (mostly parents). The occurrence of pathological separation anxiety is determined by many factors: parental attitudes, their mental and physical health, but also the way of perceiving the environment, traumatic events in the child’s family and life, as well as genetic and individual effects. Pandemic situation and related isolation caused change in the current lifestyle. Both psychological (i.e. the novelty of the social situation, negative information in the mass media, fear of their own live and their loved ones) and daily-life routine disturbances (i.e. the closure of schools and restrictions of contacts with peers, limited contacts with distant family members, remote work of parents) generate difficulties for children and can contribute anxiety among children with SAD. Paradoxically, despite the fact that children and adolescents are at home, the COVID-19 pandemic may intensify SAD, exacerbating factors underlying separation anxiety. It turns out that family social isolation can escalate conflicts. This, in turn, adversely affects relationships between family members and can reduce children’s sense of security. Due to pandemic problematic access to specialized health care, especially personal contact with a psychotherapist, children with SAD suffer from insufficient professional help

Concomitant inhibition of the thioredoxin system and nonhomologous DNA repair potently sensitizes Philadelphia‐positive lymphoid leukemia to tyrosine kinase inhibitors

Abstract Breakpoint cluster region‐Abelson (BCR::ABL1) gene fusion is an essential oncogene in both chronic myeloid leukemia (CML) and Philadelphia‐positive (Ph+) B‐cell acute lymphoblastic leukemia (B‐ALL). While tyrosine kinase inhibitors (TKIs) are effective in up to 95% of CML patients, 50% of Ph+ B‐ALL cases do not respond to treatment or relapse. This calls for new therapeutic approaches for Ph+ B‐ALL. Previous studies have shown that inhibitors of the thioredoxin (TXN) system exert antileukemic activity against B‐ALL cells, particularly in combination with other drugs. Here, we present that peroxiredoxin‐1 (PRDX1), one of the enzymes of the TXN system, is upregulated in Ph+ lymphoid as compared to Ph+ myeloid cells. PRDX1 knockout negatively affects the viability of Ph+ B‐ALL cells and sensitizes them to TKIs. Analysis of global gene expression changes in imatinib‐treated, PRDX1‐deficient cells revealed that the nonhomologous end‐joining (NHEJ) DNA repair is a novel vulnerability of Ph+ B‐ALL cells. Accordingly, PRDX1‐deficient Ph+ B‐ALL cells were susceptible to NHEJ inhibitors. Finally, we demonstrated the potent efficacy of a novel combination of TKIs, TXN inhibitors, and NHEJ inhibitors against Ph+ B‐ALL cell lines and primary cells, which can be further investigated as a potential therapeutic approach for the treatment of Ph+ B‐ALL