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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Childhood maltreatment (CM) is recognized as a non-specific risk factor for Eating Disorders (EDs), but the mechanisms explaining this association have been insufficiently assessed. We aim to explore the psychological pathways through which CM experiences promote ED core symptoms.
Two-hundred-twenty-eight people with EDs, 94 with anorexia nervosa restricting (ANR) type and 134 with binge-purging (BP) symptoms (including 23 with AN purging type and 111 with bulimia nervosa), completed the Eating Disorder Inventory-2, the State-Trait Anxiety Inventory and the Childhood Trauma Questionnaire. The variables provided by these questionnaires were included in a network analysis to identify the shortest pathways between CM nodes and ED core symptoms. Then mediation analysis was performed in order to confirm the mediation role of the nodes included in the shortest pathways from CM to ED core symptoms.
All types of CM experiences were connected to the ED psychopathology through emotional abuse. In the ANR group, interoceptive awareness was included in the shortest path between emotional abuse and drive to thinness and mediated this relationship. In the BP group, the shortest routes between CM and ED core symptoms included both ineffectiveness and interoceptive awareness.
Combining the network analysis approach with the mediation analyses provides for the first time a putative hybrid model, which reveals that all CM types converge towards ED symptoms through emotional abuse and that interoceptive awareness and ineffectiveness mediate these connections in people with ANR and BP symptoms, respectively. These findings may have possible implications for both research and treatment of EDs.
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