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We investigated (a) whether polygenic risk for schizophrenia predicts different trajectories of social development among those who have not developed psychoses and (b) whether possible associations are PRSSCZ-specific or evident also for any polygenic risk for mental disorders, e.g. for major depression.
Participants came from the population-based Young Finns Study (n = 2377). We calculated a polygenic risk score for schizophrenia (PRSSCZ) and for major depression (PRSDEP). Diagnoses of psychotic disorders were derived from the hospital care register. Social development from adolescence to middle age was measured by (a) perceived social support from friends, family, and a close other, (b) perceived sociability, and (c) family structure (partnership status, number of children, age of first-time parenthood).
Among those without manifest psychoses, high PRSSCZ predicted lower experienced support from friends (B = −0.04, p = 0.009–0.035) and family (B = −0.04, p = 0.009–0.035) especially after early adulthood, and also lower perceived sociability (B = −0.05, p = 0.010–0.026). PRSSCZ was not related to family structure. PRSDEP did not predict any domain of social development.
Individuals at high PRSSCZ (not converted to psychosis) seem to experience a lower preference to be with others over being alone. Individuals with high (v. low) PRSSCZ seem to have a similar family structure in terms of partnership status or number of children but, nevertheless, they experience less support from their family. Among those not converted to psychosis in a typical age period, high PRSSCZ may predict a ‘later risk phase’ and reduced functional resilience when approaching middle age.
The present study investigated the psychopathological processes of post-traumatic stress disorder (PTSD) following the network approach to psychopathology. The directed acyclic graph model was employed to analyse a large longitudinal data-set of Chinese children and adolescents exposed to a destructive earthquake. It was found that intrusion symptoms were first activated by trauma exposure, and subsequently activated other PTSD symptoms. The data are consistent with the idea that symptoms may form a self-sustaining dynamic network by interacting with each other to promote or maintain the chronicity of PTSD. The findings advance the current understanding about the psychopathological processes of PTSD, and inform further research and clinical practices on post-traumatic psychopathology.
In this article, we examine the relationship between important types of policies for asylum permit holders in the Netherlands and the improvement in their command of Dutch. As far as asylum policy is concerned, we find that participation in activities in the asylum seekers reception centre – and in particular, following Dutch language classes – contribute to an improvement in Syrian asylum permit holders’ command of Dutch. On the other hand, a prolonged period of stay and frequent relocations between reception centres are not favourable. Asylum permit holders who have successfully completed the civic integration programme have a better command of the language than asylum permit holders who are still undergoing the programme. An important finding is that there seems to be a sort of double deficit in the area of civic integration: not only do the elderly and lower educated make less progress in learning Dutch, but they are also the ones more likely to receive a dispensation from the civic integration requirement, which places them at a further disadvantage. Third, we find that early participation in the labour market or as a volunteer is also beneficial for language proficiency.
Although common, little is known about the potential impacts of sibling victimization, and how best to ameliorate these. We explored longitudinal associations between sibling victimization and mental health and wellbeing outcomes, and promotive and risk factors that predicted better or worse outcomes following victimization. Data were from >12,000 participants in the Millennium Cohort Study, a longitudinal UK birth cohort, who reported on sibling victimization at age 11 and/or 14 years. We identified potential risk and promotive factors at family, peer, school, and neighborhood levels from age 14 data. Mental health and wellbeing outcomes (internalizing and externalizing problems, mental wellbeing, self-harm) were collected at age 17. Results suggested that over and above pre-existing individual and family level vulnerabilities, experiencing sibling victimization was associated with significantly worse mental health and wellbeing. Having no close friends was a risk factor for worse-than-expected outcomes following victimization. Higher levels of school motivation and engagement was a promotive factor for better-than-expected outcomes. This indicates that aspects of the school environment may offer both risk and promotive factors for children experiencing sibling victimization at home. We argue that effective sibling victimization interventions should be extended to include a focus on factors at the school level.
Magnetic resonance imaging (MRI) studies on major depressive disorder (MDD) have predominantly found short-term electroconvulsive therapy (ECT)-related gray matter volume (GMV) increases, but research on the long-term stability of such changes is missing. Our aim was to investigate long-term GMV changes over a 2-year period after ECT administration and their associations with clinical outcome.
In this nonrandomized longitudinal study, patients with MDD undergoing ECT (n = 17) are assessed three times by structural MRI: Before ECT (t0), after ECT (t1) and 2 years later (t2). A healthy (n = 21) and MDD non-ECT (n = 33) control group are also measured three times within an equivalent time interval. A 3(group) × 3(time) ANOVA on whole-brain level and correlation analyses with clinical outcome variables is performed.
Analyses yield a significant group × time interaction (pFWE < 0.001) resulting from significant volume increases from t0 to t1 and decreases from t1 to t2 in the ECT group, e.g., in limbic areas. There are no effects of time in both control groups. Volume increases from t0 to t1 correlate with immediate and delayed symptom increase, while volume decreases from t1 to t2 correlate with long-term depressive outcome (all p ⩽ 0.049).
Volume increases induced by ECT appear to be a transient phenomenon as volume strongly decreased 2 years after ECT. Short-term volume increases are associated with less symptom improvement suggesting that the antidepressant effect of ECT is not due to volume changes. Larger volume decreases are associated with poorer long-term outcome highlighting the interplay between disease progression and structural changes.
Borderline personality disorder (BPD) and eating disorders are highly comorbid, but the shared course of symptoms and associated risks remain poorly understood. The aim of this study was to examine joint symptom trajectories, temporal precedence, risk factors, and population attributable fractions (PAFs) in a community sample of adolescents, using a developmental psychopathology and psychosocial framework.
Across five years (age 14–18 years), adolescents (n = 544, 56% girls) reported on BPD features and disordered eating behavior. Sociodemographic, interpersonal, and clinical risks were assessed in childhood (age 10–13 years). We used a person-centered approach to examine latent class growth analyses, joint trajectory models, and calculated PAFs.
Three-class solutions were found for both disordered eating and BPD features (low, moderate, high), creating nine joint trajectories. High levels of disordered eating were a stronger indicator of high levels of BPD features than was the reverse. Girls and LGBTQ+ youth were most likely to be in a high symptom trajectory. Bullying perpetration and clinical hyperactivity were unique risks for BPD features. Bullying victimization contributed the largest PAF to disordered eating and BPD features.
We identified several novel and clinically relevant findings related to temporality, risks, screening, and the treatment of adolescent eating problems and BPD.
This study examines whether transition to caregiving within or outside the household is associated with changes in suicidal ideation and whether this depends on the type of caregiver relationship, the age or gender of the caregiver, or the welfare system.
Ten European countries.
Data from the Survey of Health, Ageing, and Retirement in Europe were used (waves 1, 2, 4, 5, and 6) including participants aged ≥40 years (pooled Observations = 171,848).
Suicidal ideation was measured using the Euro-D scale. Caregiving was measured as care inside and outside the household, and for different recipients. Fixed effects logistic regression analyses, adjusted for health and sociodemographic factors, were used.
Transitioning into caregiving inside the household was associated with higher odds of suicidal ideation, in particular if they transitioned into care for partners or parents and within Southern and Bismarckian welfare systems. Transitioning into caregiving outside the household was not associated with suicidal ideation, except among those transitioning into caregiving for non-relatives (higher odds of suicidal ideation), and among male and older caregivers (lower odds of suicidal ideation). Suicide ideation was higher among caregivers in Southern compared to Bismarckian or Scandinavian welfare systems.
Informal caregiving is associated with suicidal ideation among caregivers inside but not among all caregivers outside the household. The caregiver’s characteristics, the care relationship, and the welfare system play an important role. Preventing suicidal ideation requires interventions that focus on informal caregivers and consider their individual and contextual factors.
Few studies have examined associations between gender non-conformity (GNC) in childhood or adolescence and mental health outcomes later in life. This study examined associations between (1) GNC and mental health over multiple time points in childhood and adolescence, and (2) GNC in childhood and/or adolescence and mental health in adulthood.
Second generation participants from the Raine Study, a longitudinal cohort from Perth, Western Australia. Data were collected between 1995 and 2018, comprising seven waves: ages 5 (N = 2236), 8 (N = 2140), 10 (N = 2048), 14 (N = 1864), 17 (N = 1726), 22 (N = 1236) and 27 (N = 1190) years. History of GNC, v. absence of this history, was based on responses to item 110 from the Child Behaviour Checklist (CBCL)/Youth Self Report (YSR) (‘wishes to be of opposite sex’). The CBCL/YSR were used to measure internalising and externalising symptoms. Items 18 (‘deliberate self-harm [DSH] or attempts suicide’) and 91 (‘talks/thinks about killing self’) were used as measures of suicidal ideation (SI) and DSH. For adults, Depression, Anxiety and Stress Subscales and Kessler Psychological Distress Scale assessed mental health.
Child and adolescent GNC was associated with elevated internalising and externalising behaviours and increased odds of DSH. A history of GNC was also associated with vulnerability for severe psychological distress in adulthood in some symptom scales.
GNC over the child and adolescent period is associated with significant emotional and behavioural difficulties, and psychological distress. A history of GNC in childhood and/or adolescence also predicts poorer mental health in adulthood on multiple symptom domains.
Mental health problems are elevated in autistic individuals but there is limited evidence on the developmental course of problems across childhood. We compare the level and growth of anxious-depressed, behavioral and attention problems in an autistic and typically developing (TD) cohort.
Latent growth curve models were applied to repeated parent-report Child Behavior Checklist data from age 2–10 years in an inception cohort of autistic children (Pathways, N = 397; 84% boys) and a general population TD cohort (Wirral Child Health and Development Study; WCHADS; N = 884, 49% boys). Percentile plots were generated to quantify the differences between autistic and TD children.
Autistic children showed elevated levels of mental health problems, but this was substantially reduced by accounting for IQ and sex differences between the autistic and TD samples. There was small differences in growth patterns; anxious-depressed problems were particularly elevated at preschool and attention problems at late childhood. Higher family income predicted lower base-level on all three dimensions, but steeper increase of anxious-depressed problems. Higher IQ predicted lower level of attention problems and faster decline over childhood. Female sex predicted higher level of anxious-depressed and faster decline in behavioral problems. Social-affect autism symptom severity predicted elevated level of attention problems. Autistic girls' problems were particularly elevated relative to their same-sex non-autistic peers.
Autistic children, and especially girls, show elevated mental health problems compared to TD children and there are some differences in predictors. Assessment of mental health should be integrated into clinical practice for autistic children.
Cross-sectional studies have shown that the COVID-19 pandemic has had a significant impact on the mental health of healthcare staff. However, it is less well understood how working over the long term in successive COVID-19 waves affects staff well-being.
To identify subpopulations within the health and social care staff workforce with differentiated trajectories of mental health symptoms during phases of the COVID-19 pandemic.
The COVID-19 Staff Wellbeing Survey assessed health and social care staff well-being within an area of the UK at four time points, separated by 3-month intervals, spanning November 2020 to August 2021.
Growth mixture models were performed on the depression, anxiety and post-traumatic stress disorder longitudinal data. Two class solutions provided the best fit for all models. The vast majority of the workforce were best represented by the low-symptom class trajectory, where by symptoms were consistently below the clinical cut-off for moderate-to-severe symptoms. A sizable minority (13–16%) were categorised as being in the high-symptom class, a group who had symptom levels in the moderate-to-severe range throughout the peaks and troughs of the pandemic. In the depression, anxiety and post-traumatic stress disorder models, the high-symptom class perceived communication from their organisation to be less effective than the low-symptom class.
This research identified a group of health service staff who reported persistently high mental health symptoms during the pandemic. This group of staff may well have particular needs in terms of the provision of well-being support services.
Traditionally, depression phenotypes have been defined based on interindividual differences that distinguish between subgroups of individuals expressing distinct depressive symptoms often from cross-sectional data. Alternatively, depression phenotypes can be defined based on intraindividual differences, differentiating between transitory states of distinct symptoms profiles that a person transitions into or out of over time. Such within-person phenotypic states are less examined, despite their potential significance for understanding and treating depression.
The current study used intensive longitudinal data of youths (N = 120) at risk for depression. Clinical interviews (at baseline, 4, 10, 16, and 22 months) yielded 90 weekly assessments. We applied a multilevel hidden Markov model to identify intraindividual phenotypes of weekly depressive symptoms for at-risk youth.
Three intraindividual phenotypes emerged: a low-depression state, an elevated-depression state, and a cognitive-physical-symptom state. Youth had a high probability of remaining in the same state over time. Furthermore, probabilities of transitioning from one state to another did not differ by age or ethnoracial minority status; girls were more likely than boys to transition from a low-depression state to either the elevated-depression state or the cognitive-physical symptom state. Finally, these intraindividual phenotypes and their dynamics were associated with comorbid externalizing symptoms.
Identifying these states as well as the transitions between them characterizes how symptoms of depression change over time and provide potential directions for intervention efforts
Political conservatives' opposition to COVID-19 restrictions is puzzling given the well-documented links between conservatism and conformity, threat sensitivity, and pathogen aversion. We propose a resolution based on the Dual Foundations Theory of ideology, which holds that ideology comprises two dimensions, one reflecting trade-offs between threat-driven conformity and individualism, and another reflecting trade-offs between empathy-driven cooperation and competition. We test predictions derived from this theory in a UK sample using individuals' responses to COVID-19 and widely-used measures of the two dimensions – ‘right-wing authoritarianism’ (RWA) and ‘social dominance orientation’ (SDO), respectively. Consistent with our predictions, we show that RWA, but not SDO, increased following the pandemic and that high-RWA conservatives do display more concerned, conformist, pro-lockdown attitudes, while high-SDO conservatives display less empathic, cooperative attitudes and are anti-lockdown. This helps explain paradoxical prior results and highlights how a focus on unidimensional ideology can mask divergent motives across the ideological landscape.
We discuss the single embedded case study design in this chapter. We deliberate how this design is different from multiple and single holistic designs in terms of the levels of analysis and the nature of replication. The selection rationale and sampling are discussed next. Afterwards, we move on to the longitudinal and/or cross-sectional single embedded designs. The strengths and the weaknesses of the design in terms of internal validity, external validity, and the number of variables are discussed subsequently. This chapter also discusses the (mis)conception regarding longitudinal designs and temporal embedded units.
This study examines the relative influence of environmental contexts (family, school, neighborhood) on child behavioral health at ages 3, 5, 9, and 15 years. Path analysis was conducted on a sample of 4,898 urban children from a longitudinal dataset called the Fragile Families and Child Wellbeing Study. Child physical abuse, emotional abuse, maternal depression, substance use, neighborhood social cohesion, neighborhood poverty, school connectedness, and peer bullying had concurrent relationships with child behavior problems at one or more developmental stages. Early childhood abuse (age 3) and school age environmental contexts (age 9) had lasting effects on later behavior problems. Findings underscore the importance of both multilevel contextual factors and developmental timing in determining behavioral health outcomes in children.
Studies on humans that exploit contemporary data-intensive, high-throughput ‘omic’ assay technologies, such as genomics, transcriptomics, proteomics and metabolomics, have unequivocally revealed that humans differ greatly at the molecular level. These differences, which are compounded by each individual’s distinct behavioral and environmental exposures, impact individual responses to health interventions such as diet and drugs. Questions about the best way to tailor health interventions to individuals based on their nuanced genomic, physiologic, behavioral, etc. profiles have motivated the current emphasis on ‘precision’ medicine. This review’s purpose is to describe how the design and execution of N-of-1 (or personalized) multivariate clinical trials can advance the field. Such trials focus on individual responses to health interventions from a whole-person perspective, leverage emerging health monitoring technologies, and can be used to address the most relevant questions in the precision medicine era. This includes how to validate biomarkers that may indicate appropriate activity of an intervention as well as how to identify likely beneficial interventions for an individual. We also argue that multivariate N-of-1 and aggregated N-of-1 trials are ideal vehicles for advancing biomedical and translational science in the precision medicine era since the insights gained from them can not only shed light on how to treat or prevent diseases generally, but also provide insight into how to provide real-time care to the very individuals who are seeking attention for their health concerns in the first place.
The causal impacts of recreational cannabis legalization are not well understood due to the number of potential confounds. We sought to quantify possible causal effects of recreational cannabis legalization on substance use, substance use disorder, and psychosocial functioning, and whether vulnerable individuals are more susceptible to the effects of cannabis legalization than others.
We used a longitudinal, co-twin control design in 4043 twins (N = 240 pairs discordant on residence), first assessed in adolescence and now age 24–49, currently residing in states with different cannabis policies (40% resided in a recreationally legal state). We tested the effect of legalization on outcomes of interest and whether legalization interacts with established vulnerability factors (age, sex, or externalizing psychopathology).
In the co-twin control design accounting for earlier cannabis frequency and alcohol use disorder (AUD) symptoms respectively, the twin living in a recreational state used cannabis on average more often (βw = 0.11, p = 1.3 × 10−3), and had fewer AUD symptoms (βw = −0.11, p = 6.7 × 10−3) than their co-twin living in an non-recreational state. Cannabis legalization was associated with no other adverse outcome in the co-twin design, including cannabis use disorder. No risk factor significantly interacted with legalization status to predict any outcome.
Recreational legalization was associated with increased cannabis use and decreased AUD symptoms but was not associated with other maladaptations. These effects were maintained within twin pairs discordant for residence. Moreover, vulnerabilities to cannabis use were not exacerbated by the legal cannabis environment. Future research may investigate causal links between cannabis consumption and outcomes.
The aim of this study was to use longitudinal population-based data to examine the associations between childhood sexual abuse (CSA) and risk for adverse outcomes in multiple life domains across adulthood. In 937 individuals followed from birth to age 45y, we assessed associations between CSA (retrospectively reported at age 26y) and the experience of 22 adverse outcomes in seven domains (physical, mental, sexual, interpersonal, economic, antisocial, multi-domain) from young adulthood to midlife (26 to 45y). Analyses controlled for sex, socioeconomic status, prospectively reported child harm and household dysfunction adverse childhood experiences, and adult sexual assault, and considered different definitions of CSA. After adjusting for confounders, CSA survivors were more likely than their peers to experience internalizing, externalizing, and thought disorders, suicide attempts, health risk behaviors, systemic inflammation, poor oral health, sexually transmitted diseases, high-conflict relationships, benefit use, financial difficulties, antisocial behavior, and cumulative problems across multiple domains in adulthood. In sum, CSA was associated with multiple persistent problems across adulthood, even after adjusting for confounding life stressors, and the risk for particular problems incremented with CSA severity. The higher risk for most specific problems was small to moderate, but the cumulative long-term effects across multiple domains reflect considerable individual and societal burden.
Cognitive symptoms are common during and following episodes of depression. Little is known about the persistence of self-reported and performance-based cognition with depression and functional outcomes.
This is a secondary analysis of a prospective naturalistic observational clinical cohort study of individuals with recurrent major depressive disorder (MDD; N = 623). Participants completed app-based self-reported and performance-based cognitive function assessments alongside validated measures of depression, functional disability, and self-esteem every 3 months. Participants were followed-up for a maximum of 2-years. Multilevel hierarchically nested modelling was employed to explore between- and within-participant variation over time to identify whether persistent cognitive difficulties are related to levels of depression and functional impairment during follow-up.
508 individuals (81.5%) provided data (mean age: 46.6, s.d.: 15.6; 76.2% female). Increasing persistence of self-reported cognitive difficulty was associated with higher levels of depression and functional impairment throughout the follow-up. In comparison to low persistence of objective cognitive difficulty (<25% of timepoints), those with high persistence (>75% of timepoints) reported significantly higher levels of depression (B = 5.17, s.e. = 2.21, p = 0.019) and functional impairment (B = 4.82, s.e. = 1.79, p = 0.002) over time. Examination of the individual cognitive modules shows that persistently impaired executive function is associated with worse functioning, and poor processing speed is particularly important for worsened depressive symptoms.
We replicated previous findings of greater persistence of cognitive difficulty with increasing severity of depression and further demonstrate that these cognitive difficulties are associated with pervasive functional disability. Difficulties with cognition may be an indicator and target for further treatment input.
The aim of the present study was to assess the seasonal relationship between serum 25(OH)D concentration, lean mass and muscle strength. This was a secondary data analysis of a subgroup of 102 postmenopausal women participating in the 2006–2007 D-FINES (Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England) study. The cohort was assessed as two age subgroups: <65 years (n=80) and ≥65 years (n=22). Outcome measures included lean mass (DXA), muscle strength (handgrip dynamometry) and serum 25(OH)D concentration (enzymeimmunoassay). Derived outcomes included appendicular skeletal muscle mass (ASM) and relative appendicular skeletal muscle index (RASM). Sarcopenia status was assessed using the European Working Group on Sarcopenia in Older People 2018 criteria. Non-parametric partial correlation using BMI as a covariate was used to evaluate the study aims. There were no statistically significant associations between total lean mass, ASM or RASM and 25(OH)D in any group at any season. There was a trend for handgrip strength to be positively associated with serum 25(OH)D concentration. There was a trend showing a higher prevalence of sarcopenia in women ≥65 years. Sarcopenia status appeared transient for five women. In conclusion, the present study found no significant association between vitamin D status and functional indicators of musculoskeletal health, which were additionally not affected by season.
This 17-year prospective study applied a social-development lens to the challenge of identifying long-term predictors of adult depressive symptoms. A diverse community sample of 171 individuals was repeatedly assessed from age 13 to age 30 using self-, parent-, and peer-report methods. As hypothesized, competence in establishing close friendships beginning in adolescence had a substantial long-term predictive relation to adult depressive symptoms at ages 27–30, even after accounting for prior depressive, anxiety, and externalizing symptoms. Intervening relationship difficulties at ages 23–26 were identified as part of pathways to depressive symptoms in the late twenties. Somewhat distinct paths by gender were also identified, but in all cases were consistent with an overall role of relationship difficulties in predicting long-term depressive symptoms. Implications both for early identification of risk as well as for potential preventive interventions are discussed.