The stability and change of etiological influences on depression, anxiety symptoms and their co-occurrence across adolescence and young adulthood

Background. Depression and anxiety persist within and across diagnostic boundaries. The manner in which common v. disorder-specific genetic and environmental influences operate across development to maintain internalizing disorders and their co-morbidity is unclear. This paper investigates the stability and change of etiological influences on depression, panic, generalized, separation and social anxiety symptoms, and their co-occurrence, across adolescence and young adulthood. Method. A total of 2619 twins/siblings prospectively reported symptoms of depression and anxiety at mean ages 15, 17 and 20 years. Results. Each symptom scale showed a similar pattern of moderate continuity across development, largely underpinned by genetic stability. New genetic influences contributing to change in the developmental course of the symptoms emerged at each time point. All symptom scales correlated moderately with one another over time. Genetic influences, both stable and time-specific, overlapped considerably between the scales. Non-shared environmental influences were largely time- and symptom-specific, but some contributed moderately to the stability of depression and anxiety symptom scales. These stable, longitudinal environmental influences were highly correlated between the symptoms. Conclusions. The results highlight both stable and dynamic etiology of depression and anxiety symptom scales. They provide preliminary evidence that stable as well as newly emerging genes contribute to the co-morbidity between depression and anxiety across adolescence and young adulthood. Conversely, environmental influences are largely time-specific and contribute to change in symptoms over time. The results inform molecular genetics research and transdiagnostic treatment and prevention approaches

A longitudinal twin and sibling study of the hopeless theory of depression in adolescence and young adulthood

Background Maladaptive cognitive biases such as negative attributional style and hopelessness have been implicated in the development and maintenance of depression. According to the hopelessness theory of depression, hopelessness mediates the association between attributional style and depression. The aetiological processes underpinning this influential theory remain unknown. The current study investigated genetic and environmental influences on hopelessness and its concurrent and longitudinal associations with attributional style and depression across adolescence and emerging adulthood. Furthermore, given high co-morbidity between depression and anxiety, the study investigated whether these maladaptive cognitions constitute transdiagnostic cognitive content common to both internalizing symptoms. Method A total of 2619 twins/siblings reported attributional style (mean age 15 and 17 years), hopelessness (mean age 17 years), and depression and anxiety symptoms (mean age 17 and 20 years). Results Partial correlations revealed that attributional style and hopelessness were uniquely associated with depression but not anxiety symptoms. Hopelessness partially mediated the relationship between attributional style and depression. Hopelessness was moderately heritable (A = 0.37, 95% confidence interval 0.28–0.47), with remaining variance accounted for by non-shared environmental influences. Independent pathway models indicated that a set of common genetic influences largely accounted for the association between attributional style, hopelessness and depression symptoms, both concurrently and across development. Conclusions The results provide novel evidence that associations between attributional style, hopelessness and depression symptoms are largely due to shared genetic liability, suggesting developmentally stable biological pathways underpinning the hopelessness theory of depression. Both attributional style and hopelessness constituted unique cognitive content in depression. The results inform molecular genetics research and cognitive treatment approaches

A genetically informed cross-lagged analysis of autistic-like traits and affective problems in early childhood

A genetically informed cross-lagged model was applied to twin data to explore etiological links between autistic-like traits and affective problems in early childhood. The sample comprised 310 same-sex twin pairs (143 monozygotic and 167 dizygotic; 53% male). Autistic-like traits and affective problems were assessed at ages 2 and 3 using parent ratings. Both constructs were related within and across age (r = .30-.53) and showed moderate stability (r = .45-.54). Autistic-like traits and affective problems showed genetic and environmental influences at both ages. Whereas at age 2, the covariance between autistic-like traits and affective problems was entirely due to environmental influences (shared and nonshared), at age 3, genetic factors also contributed to the covariance between constructs. The stability paths, but not the cross-lagged paths, were significant, indicating that there is stability in both autistic-like traits and affective problems but they do not mutually influence each other across age. Stability effects were due to genetic, shared, and nonshared environmental influences. Substantial novel genetic and nonshared environmental influences emerge at age 3 and suggest change in the etiology of these constructs over time. During early childhood, autistic-like traits tend to occur alongside affective problems and partly overlapping genetic and environmental influences explain this association

Monoclonal gammopathy of renal significance (MGRS): Real-world data on outcomes and prognostic factors

Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis-related to MGRS (MGRS-A) was present in 180 patients; nonamyloidosis MGRS (MGRS-NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0–121.0). Patients with MGRS-A had a shorter overall survival than patients with MGRS-NA (HR = 0.41, 95%CI: 0.25–0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04–115.96; p < 0.0001), one-fourth of patients with ≥VGPR were renal nonresponders. In MGRS-A, factors associated with poor prognosis included elevated levels of creatinine, beta-2-microglobulin, and hemodialysis at diagnosis. In MGRS-NA, only age >65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS

Integrating the Hierarchical Taxonomy of Psychopathology (HiTOP) Into Clinical Practice

Objective: Diagnosis is a cornerstone of clinical practice for mental health care providers, yet traditional diagnostic systems have well-known shortcomings, including inadequate reliability, high comorbidity, and marked within-diagnosis heterogeneity. The Hierarchical Taxonomy of Psychopathology (HiTOP) is a data-driven, hierarchically based alternative to traditional classifications that conceptualizes psychopathology as a set of dimensions organized into increasingly broad, transdiagnostic spectra. Prior work has shown that using a dimensional approach improves reliability and validity, but translating a model like HiTOP into a workable system that is useful for health care providers remains a major challenge. / Method: The present work outlines the HiTOP model and describes the core principles to guide its integration into clinical practice. Results: Potential advantages and limitations of the HiTOP model for clinical utility are reviewed, including with respect to case conceptualization and treatment planning. A HiTOP approach to practice is illustrated and contrasted with an approach based on traditional nosology. Common barriers to using HiTOP in real-world health care settings and solutions to these barriers are discussed. / Conclusions: HiTOP represents a viable alternative to classifying mental illness that can be integrated into practice today, although research is needed to further establish its utility

Attentional control theory in childhood: enhanced attentional capture by non-emotional and emotional distractors in anxiety and depression

Attentional control theory (ACT) proposes that anxiety is associated with executive functioning deficits. The theory has been widely investigated in adults. The current study tested whether symptoms of childhood anxiety and depression were associated with experimentally measured attentional control in the context of non-emotional and emotional stimuli. Sixty-one children (mean age = 9.23 years, range = 8.39 - 10.41) reported their trait anxiety and depression symptoms and completed three visual search tasks. The tasks used a variant of an irrelevant singleton paradigm and measured attentional capture by task-irrelevant non-emotional (color) and emotional (facial expressions) distractors. Significant attentional capture by both non-emotional and emotional distractors was observed, and was significantly correlated with trait anxiety and symptoms of depression. The strength of relationship between attentional capture and the symptoms did not differ significantly for non-emotional and emotional distractors. The results suggest that symptoms of childhood anxiety and depression are associated with poorer attentional control both in the presence of emotional and non-emotional stimuli, supporting ACT in younger populations. This attentional deficit in the context of non-emotional information might be as central to childhood internalizing symptoms as attentional biases often observed on tasks investigating processing of emotional stimuli

Coordination difficulty and internalising symptoms in adults: A twin/sibling study

Increased anxiety and depression symptoms have been reported in individuals with neurodevelopmental disorders, and have been found to be associated with motor coordination difficulties, but little is known about the aetiology of these associations. This study aimed to assess genetic, shared (making twins/siblings alike) and non-shared (individual-specific) environmental influences on the association between poor coordination and symptoms of anxiety and depressed mood using a sample of adult twin and sibling pairs. Participants were asked about their coordination skill and anxiety and depression symptoms. About half of the variance in coordination difficulty was explained by familial (combined genetic and shared environmental) influences, with the remaining variance explained by non-shared environmental influences. Phenotypic associations between coordination and anxiety (r = .46) and depression symptoms (r = .44) were largely underpinned by shared familial liability for the three traits. Non-shared environment accounted for about a third of the phenotypic association. Results suggest that both familial and non-shared environmental influences play a role in the aetiology of coordination difficulty and its association with internalizing symptoms. The current study highlights that both biological and environmental pathways shared between these symptoms should be examined in future research to inform prevention and treatment approaches in clinical settings

Generalised Anxiety Disorder – A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression

Generalised Anxiety Disorder (GAD) is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS), a personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS) was studied for evidence of differential expression using RNA-seq data. Significant differential expression of two exons with the ITM2B gene within the discordant MZ subset was observed, a finding that was replicated in an independent cohort. While previous research has shown that anxiety has a high comorbidity with a variety of psychiatric and neurodegenerative disorders, our analysis suggests a novel etiology specific to AS

The CogBIAS longitudinal study protocol: cognitive and genetic factors influencing psychological functioning in adolescence.

BACKGROUND: Optimal psychological development is dependent upon a complex interplay between individual and situational factors. Investigating the development of these factors in adolescence will help to improve understanding of emotional vulnerability and resilience. The CogBIAS longitudinal study (CogBIAS-L-S) aims to combine cognitive and genetic approaches to investigate risk and protective factors associated with the development of mood and impulsivity-related outcomes in an adolescent sample. METHODS: CogBIAS-L-S is a three-wave longitudinal study of typically developing adolescents conducted over 4 years, with data collection at age 12, 14 and 16. At each wave participants will undergo multiple assessments including a range of selective cognitive processing tasks (e.g. attention bias, interpretation bias, memory bias) and psychological self-report measures (e.g. anxiety, depression, resilience). Saliva samples will also be collected at the baseline assessment for genetic analyses. Multilevel statistical analyses will be performed to investigate the developmental trajectory of cognitive biases on psychological functioning, as well as the influence of genetic moderation on these relationships. DISCUSSION: CogBIAS-L-S represents the first longitudinal study to assess multiple cognitive biases across adolescent development and the largest study of its kind to collect genetic data. It therefore provides a unique opportunity to understand how genes and the environment influence the development and maintenance of cognitive biases and provide insight into risk and protective factors that may be key targets for intervention.This work was supported by the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement no: [324176]