Original Article
Childhood anxious/withdrawn behaviour and later anxiety disorder: a network outcome analysis of a population cohort
- Nathan J. Monk, Geraldine F. H. McLeod, Roger T. Mulder, Janet K. Spittlehouse, Joseph M. Boden
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- Published online by Cambridge University Press:
- 24 August 2021, pp. 1343-1354
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Background
Several previous studies have identified a continuity between childhood anxiety/withdrawal and anxiety disorder (AD) in later life. However, not all children with anxiety/withdrawal problems will experience an AD in later life. Previous studies have shown that the severity of childhood anxiety/withdrawal accounts for some of the variability in AD outcomes. However, no studies to date have investigated how variation in features of anxiety/withdrawal may relate to continuity prognoses. The present research addresses this gap.
MethodsData were gathered as part of the Christchurch Health and Development Study, a 40-year population birth cohort of 1265 children born in Christchurch, New Zealand. Fifteen childhood anxiety/withdrawal items were measured at 7–9 years and AD outcomes were measured at various interviews from 15 to 40 years. Six network models were estimated. Two models estimated the network structure of childhood anxiety/withdrawal items independently for males and females. Four models estimated childhood anxiety/withdrawal items predicting adolescent AD (14–21 years) and adult AD (21–40 years) in both males and females.
ResultsApproximately 40% of participants met the diagnostic criteria for an AD during both the adolescent (14–21 years) and adult (21–40 years) outcome periods. Outcome networks showed that items measuring social and emotional anxious/withdrawn behaviours most frequently predicted AD outcomes. Items measuring situation-based fears and authority figure-specific anxious/withdrawn behaviour did not consistently predict AD outcomes. This applied across both the male and female subsamples.
ConclusionsSocial and emotional anxious/withdrawn behaviours in middle childhood appear to carry increased risk for AD outcomes in both adolescence and adulthood.
Metabolic syndrome among young adults at high and low familial risk for depression
- Shimrit Daches, Miklós Vértes, Karen Matthews, Edit Dósa, Eniko Kiss, Ildikó Baji, Krisztina Kapornai, Charles J. George, Maria Kovacs
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- Published online by Cambridge University Press:
- 02 August 2021, pp. 1355-1363
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Background
Our study examined whether the early-onset depression phenotype among young adults (probands) is associated with the metabolic syndrome (MetS) and its components, and if MetS characterizes unaffected but high-risk siblings of probands.
MethodsWe studied three groups of young adults (Mage = 25 years, s.d. = 3.84 years): probands with histories of childhood onset depression – i.e. early-onset phenotype – (n = 293), their unaffected siblings (high-risk siblings, n = 273), and healthy controls (n = 171). Participants completed a full psychiatric interview, physical and laboratory assessments, and self-rating scales. MetS was defined using the criteria of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001).
ResultsEarly-onset depression phenotype and being a high-risk sibling were associated with higher MetS composite scores relative to that of controls, but did not differ from one another. With regard to MetS components: Probands and siblings had similarly larger waist circumference and lower HDL than did controls, while siblings and controls had lower triglyceride levels than did probands but did not differ from one another. Groups did not differ on glucose levels and SBP.
ConclusionsOur study extends the literature on the association between MetS and depression and underscores the importance of depression phenotypes: failure to account for the clinical heterogeneity of depression may partly underlie the inconsistent findings regarding its relation to MetS. The results also suggest that, in depression-prone populations, MetS may predate and possibly function as a risk factor for eventual depression.
Moral injury and substance use disorders among US combat veterans: results from the 2019–2020 National Health and Resilience in Veterans Study
- Shira Maguen, Brandon Nichter, Sonya B. Norman, Robert H. Pietrzak
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- Published online by Cambridge University Press:
- 19 August 2021, pp. 1364-1370
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Background
Exposure to potentially morally injurious events (PMIEs) is associated with increased risk for substance use disorders (SUDs), although population-based studies remain limited. The goal of this study was to better understand the relationships between PMIE exposure and lifetime and past-year alcohol use disorder (AUD), drug use disorder (DUD), and SUD.
MethodsData were analyzed from the 2019–2020 National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 1321 combat veterans. Multivariable analyses examined associations between three types of PMIE exposure (perpetration, witnessing, and betrayal), and lifetime and past-year AUD, DUD, and SUD, adjusting for sociodemographic variables, combat exposure severity, prior trauma, and lifetime posttraumatic stress disorder and major depressive disorder.
ResultsPerpetration was associated with increased odds of lifetime AUD (OR 1.15; 95% CI 1.01–1.31) and lifetime SUD (OR 1.18; 95% CI 1.03–1.35). Witnessing was associated with greater odds of past-year DUD (OR 1.20; 95% CI 1.04–1.38) and past-year SUD (OR 1.14; 95% CI 1.02–1.28). Betrayal was associated with past-year AUD (OR 1.20; 95% CI 1.03–1.39). A large proportion of the variance in past-year AUD was accounted for by betrayal (38.7%), while witnessing accounted for 25.8% of the variance in past-year DUD.
ConclusionsExposure to PMIEs may be a stronger contributor to SUDs among veterans than previously known. These findings highlight the importance of targeted assessment and treatment of moral injury among veterans with SUDs, as well as attending to specific types of morally injurious experiences when conceptualizing and planning care.
Longitudinal symptomatic interactions in long-standing schizophrenia: a novel five-point analysis based on directed acyclic graphs
- Giusi Moffa, Jack Kuipers, Giuseppe Carrà, Cristina Crocamo, Elizabeth Kuipers, Matthias Angermeyer, Traolach Brugha, Mondher Toumi, Paul Bebbington
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- Published online by Cambridge University Press:
- 05 August 2021, pp. 1371-1378
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Background
Recent network models propose that mutual interaction between symptoms has an important bearing on the onset of schizophrenic disorder. In particular, cross-sectional studies suggest that affective symptoms may influence the emergence of psychotic symptoms. However, longitudinal analysis offers a more compelling test for causation: the European Schizophrenia Cohort (EuroSC) provides data suitable for this purpose. We predicted that the persistence of psychotic symptoms would be driven by the continuing presence of affective disturbance.
MethodsEuroSC included 1208 patients randomly sampled from outpatient services in France, Germany and the UK. Initial measures of psychotic and affective symptoms were repeated four times at 6-month intervals, thereby furnishing five time-points. To examine interactions between symptoms both within and between time-slices, we adopted a novel technique for modelling longitudinal data in psychiatry. This was a form of Bayesian network analysis that involved learning dynamic directed acyclic graphs (DAGs).
ResultsOur DAG analysis suggests that the main drivers of symptoms in this long-term sample were delusions and paranoid thinking. These led to affective disturbance, not vice versa as we initially predicted. The enduring relationship between symptoms was unaffected by whether patients were receiving first- or second-generation antipsychotic medication.
ConclusionsIn this cohort of people with chronic schizophrenia treated with medication, symptoms were essentially stable over long periods. However, affective symptoms appeared driven by the persistence of delusions and persecutory thinking, a finding not previously reported. Although our findings as ever remain hostage to unmeasured confounders, these enduring psychotic symptoms might nevertheless be appropriate candidates for directly targeted psychological interventions.
The combined impact of Type D personality and depression on cardiovascular events after acute myocardial infarction
- Yini Wang, Xueqin Gao, Zhenjuan Zhao, Ling Li, Guojie Liu, Hui Tao, Xi Yu, Bo Yu, Ping Lin
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- Published online by Cambridge University Press:
- 02 August 2021, pp. 1379-1389
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Background
Type D personality and depression are the independent psychological risk factors for adverse outcomes in cardiovascular patients. The aim of this study was to examine the combined effect of Type D personality and depression on clinical outcomes in patients suffering from acute myocardial infarction (AMI).
MethodsThis prospective cohort study included 3568 patients diagnosed with AMI between February 2017 and September 2018. Type D personality and depression were assessed at baseline, while the major adverse cardiac event (MACE) rate (cardiac death, recurrent non-fatal myocardial infarction, revascularization, and stroke) and in-stent restenosis (ISR) rate were analyzed after a 2-year follow-up period.
ResultsA total of 437 patients developed MACEs and 185 had ISR during the follow-up period. The Type D (+) depression (+) and Type D (+) depression (−) groups had a higher risk of MACE [95% confidence interval (CI) 1.74–6.07] (95% CI 1.25–2.96) and ISR (95% CI 3.09–8.28) (95% CI 1.85–6.22). Analysis of Type D and depression as continuous variables indicated that the main effect of Type D, depression and their combined effect were significantly associated with MACE and ISR. Moreover, Type D (+) depression (+) and Type D (+) depression (−) emerged as significant risk factors for MACE and ISR in males, while only Type D (+) depression (+) was associated with MACE and ISR in female patients.
ConclusionsThese findings suggest that patients complicated with depression and Type D personality are at a higher risk of adverse cardiovascular outcomes. Individual assessments of Type D personality and depression, and comprehensive interventions are required.
Mindfulness-based intervention improves residual negative symptoms and cognitive impairment in schizophrenia: a randomized controlled follow-up study
- Hui Shen, Li Zhang, Yuhuan Li, Denise Zheng, Lizhao Du, Feikang Xu, Chuchen Xu, Yan Liu, Jie Shen, Zezhi Li, Donghong Cui
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- Published online by Cambridge University Press:
- 02 August 2021, pp. 1390-1399
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Background
Residual negative symptoms and cognitive impairment are common for chronic schizophrenia patients. The aim of this study was to investigate the efficacy of a mindfulness-based intervention (MBI) on negative and cognitive symptoms of schizophrenia patients with residual negative symptoms.
MethodsIn this 6-week, randomized, single-blind, controlled study, a total of 100 schizophrenia patients with residual negative symptoms were randomly assigned to the MBI or control group. The 6-week MBI group and the control group with general rehabilitation programs maintained their original antipsychotic treatments. The scores for the Positive and Negative Syndrome Scale (PANSS), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Symptom Checklist 90 (SCL-90) were recorded at baseline and week 6 to assess psychotic symptoms, cognitive performance, and emotional state, respectively.
ResultsCompared with general rehabilitation programs, MBI alleviated the PANSS-negative subscore, general psychopathology subscore, and PANSS total score in schizophrenia patients with residual negative symptoms (F = 33.77, pBonferroni < 0.001; F = 42.01, pBonferroni < 0.001; F = 52.41, pBonferroni < 0.001, respectively). Furthermore, MBI improved RBANS total score and immediate memory subscore (F = 8.80, pBonferroni = 0.024; F = 11.37, pBonferroni = 0.006), as well as SCL-90 total score in schizophrenia patients with residual negative symptoms (F = 18.39, pBonferroni < 0.001).
ConclusionsOur results demonstrate that MBI helps schizophrenia patients with residual negative symptoms improve clinical symptoms including negative symptom, general psychopathology symptom, and cognitive impairment.
Trial registrationChiCTR2100043803.
Risk of suicide in patients who present to hospital after self-cutting according to site of injury: findings from the Multicentre Study of Self-harm in England
- Galit Geulayov, Deborah Casey, Elizabeth Bale, Fiona Brand, Caroline Clements, Bushra Farooq, Nav Kapur, Jennifer Ness, Keith Waters, Anita Patel, Keith Hawton
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- Published online by Cambridge University Press:
- 04 August 2021, pp. 1400-1408
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Background
We compared the risk of death by suicide following hospital presentation for self-harm according to site of self-cut/stab.
MethodWe included 54 999 self-harm presentations (involving 31 419 individuals) to hospitals in the Multicentre Study of Self-harm in England (1/1/2004–31/12/2014), with mortality follow-up to 31/12/2019. Information on method of self-harm was obtained through monitoring in hospitals. Information about mortality was obtained through linkage with NHS Digital. We assessed the association of site of self-cut with death by suicide using mixed effect models.
ResultsIn total, 10 790 (19.6%) hospital presentations involved self-cutting/stabbing, 7489 of which (69.4%) were due to laceration to the arm/wrist alone, 1846 episodes (17.1%) involved cutting elsewhere on the body, and 1455 (13.5%) were due to laceration to unknown site. Controlling for confounders, presentation to a hospital following self-cut/stab to bodily parts other than wrist/arm was associated with greater chance of subsequent suicide relative to presentation after self-poisoning alone [adjusted odds ratio (aOR) 1.75, 95% confidence interval (CI) 1.03–2.96, p = 0.038]. The likelihood of suicide after presentation for cutting/stabbing the wrist/arm alone was comparable to that of patients who had self-poisoned alone. Presentations after laceration involving the neck were associated with a four-fold greater chance of subsequent suicide relative to self-poisoning (aOR 4.09, 95% CI 1.80–9.30, p = 0.001).
ConclusionsPatients who attend hospital after self-cutting/stabbing are a heterogeneous group in terms of characteristics, methods of cutting/stabbing and risk of subsequent suicide. Risk of suicide is greater in individuals who self-cut/stab to parts of the body other than the wrist or arm, especially the neck.
Longitudinal associations between alcohol use, smoking, genetic risk scoring and symptoms of depression in the general population: a prospective 6-year cohort study
- N. de Boer, J. Vermeulen, B. Lin, J. van Os, M. ten Have, R. de Graaf, S. van Dorsselaer, M. Bak, B. Rutten, A. Batalla, S. Guloksuz, J. J. Luykx
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- Published online by Cambridge University Press:
- 11 August 2021, pp. 1409-1417
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Background
Alcohol consumption, smoking and mood disorders are leading contributors to the global burden of disease and are highly comorbid. Yet, their interrelationships have remained elusive. The aim of this study was to examine the multi-cross-sectional and longitudinal associations between (change in) smoking and alcohol use and (change in) number of depressive symptoms.
MethodsIn this prospective, longitudinal study, 6646 adults from the general population were included with follow-up measurements after 3 and 6 years. Linear mixed-effects models were used to test multi-cross-sectional and longitudinal associations, with smoking behaviour, alcohol use and genetic risk scores for smoking and alcohol use as independent variables and depressive symptoms as dependent variables.
ResultsIn the multi-cross-sectional analysis, smoking status and number of cigarettes per day were positively associated with depressive symptoms (p < 0.001). Moderate drinking was associated with less symptoms of depression compared to non-use (p = 0.011). Longitudinally, decreases in the numbers of cigarettes per day and alcoholic drinks per week as well as alcohol cessation were associated with a reduction of depressive symptoms (p = 0.001–0.028). Results of genetic risk score analyses aligned with these findings.
ConclusionsWhile cross-sectionally smoking and moderate alcohol use show opposing associations with depressive symptoms, decreases in smoking behaviour as well as alcohol consumption are associated with improvements in depressive symptoms over time. Although we cannot infer causality, these results open avenues to further investigate interventions targeting smoking and alcohol behaviours in people suffering from depressive symptoms.
The bidirectional association of 24-h activity rhythms and sleep with depressive symptoms in middle-aged and elderly persons
- Maud de Feijter, Desana Kocevska, M. Arfan Ikram, Annemarie I. Luik
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- Published online by Cambridge University Press:
- 11 August 2021, pp. 1418-1425
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Background
In older populations disturbed 24-h activity rhythms, poor sleep, and depressive symptoms are often lingering and co-morbid, making treatment difficult. To improve insights into these commonly co-occurring problems, we assessed the bidirectional association of sleep and 24-h activity rhythms with depressive symptoms in middle-aged and elderly persons.
MethodsIn 1734 participants (mean age: 62.3 ± 9.3 years, 55% women) from the prospective Rotterdam Study, 24-h activity rhythms and sleep were estimated with actigraphy (mean duration: 146 ± 19.6 h), sleep quality with the Pittsburgh Sleep Quality Index, and depressive symptoms with the Center for Epidemiological Studies Depression scale. Repeated measures were available for 947 participants (54%) over a median follow-up of 6 years (interquartile range = 5.6–6.3). Linear-mixed models were used to assess temporal associations of 24-h activity rhythms and sleep with depressive symptoms in both directions.
ResultsHigh 24-h activity rhythm fragmentation (IV) (B = 1.002, 95% confidence interval (CI) = 0.641–1.363), long time in bed (TIB) (B = 0.111, 95% CI = 0.053–0.169), low sleep efficiency (SE) (B = −0.015, 95% CI = −0.020 to −0.009), long sleep onset latency (SOL) (B = 0.009, 95% CI = 0.006–0.012), and low self-rated sleep quality (B = 0.112, 95% CI = 0.0992–0.124) at baseline were associated with increasing depressive symptoms over time. Conversely, more depressive symptoms at baseline were associated with an increasing 24-h activity rhythm fragmentation (B = 0.002, 95% CI = 0.001–0.003) and TIB (B = 0.009, 95% CI = 0.004–0.015), and a decreasing SE (B = −0.140, 95% CI = −0.196 to −0.084), SOL (B = 0.013, 95% CI = 0.008–0.018), and self-rated sleep quality (B = 0.193, 95% CI = 0.171–0.215) over time.
ConclusionThis study demonstrates a bidirectional association of 24-h activity rhythms, actigraphy-estimated sleep, and self-rated sleep quality with depressive symptoms over a time frame of multiple years in middle-aged and elderly persons.
The interactive association of adverse childhood experiences and polygenic susceptibility with depressive symptoms and chronic inflammation in older adults: a prospective cohort study
- Eleonora Iob, Olesya Ajnakina, Andrew Steptoe
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- 05 August 2021, pp. 1426-1436
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Background
Adverse childhood experiences (ACEs) and genetic liability are important risk factors for depression and inflammation. However, little is known about the gene−environment (G × E) mechanisms underlying their aetiology. For the first time, we tested the independent and interactive associations of ACEs and polygenic scores of major depressive disorder (MDD-PGS) and C-reactive protein (CRP-PGS) with longitudinal trajectories of depression and chronic inflammation in older adults.
MethodsData were drawn from the English longitudinal study of ageing (N~3400). Retrospective information on ACEs was collected in wave3 (2006/07). We calculated a cumulative risk score of ACEs and also assessed distinct dimensions separately. Depressive symptoms were ascertained on eight occasions, from wave1 (2002/03) to wave8 (2016/17). CRP was measured in wave2 (2004/05), wave4 (2008/09), and wave6 (2012/13). The associations of the risk factors with group-based depressive-symptom trajectories and repeated exposure to high CRP (i.e. ⩾3 mg/L) were tested using multinomial and ordinal logistic regression.
ResultsAll types of ACEs were independently associated with high depressive-symptom trajectories (OR 1.44, 95% CI 1.30–1.60) and inflammation (OR 1.08, 95% CI 1.07–1.09). The risk of high depressive-symptom trajectories (OR 1.47, 95% CI 1.28–1.70) and inflammation (OR 1.03, 95% CI 1.01–1.04) was also higher for participants with higher MDD-PGS. G×E analyses revealed that the associations between ACEs and depressive symptoms were larger among participants with higher MDD-PGS (OR 1.13, 95% CI 1.04–1.23). ACEs were also more strongly related to inflammation in participants with higher CRP-PGS (OR 1.02, 95% CI 1.01–1.03).
ConclusionsACEs and polygenic susceptibility were independently and interactively associated with elevated depressive symptoms and chronic inflammation, highlighting the clinical importance of assessing both ACEs and genetic risk factors to design more targeted interventions.
Social engagement and allostatic load mediate between adverse childhood experiences and multimorbidity in mid to late adulthood: the Canadian Longitudinal Study on Aging
- Leslie Atkinson, Divya Joshi, Parminder Raina, Lauren E. Griffith, Harriet MacMillan, Andrea Gonzalez
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- Published online by Cambridge University Press:
- 23 August 2021, pp. 1437-1447
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Background
Adverse childhood experiences (ACEs) are associated with multimorbidity in adulthood. This link may be mediated by psychosocial and biological factors, but evidence is lacking. The current study evaluates this mediation model.
MethodWe analyzed data from the Canadian Longitudinal Study of Aging (N = 27 170 community participants). Participants were 45–85 years at recruitment, when allostatic load and social engagement data were collected, and 3 years older at follow-up, when ACEs and multimorbidity data were collected. Structural equation modeling was used to test for mediation in the overall sample, and in sex- and age-stratified subsamples, all analyses adjusted for concurrent lifestyle confounds.
ResultsIn the overall sample, ACEs were associated with multimorbidity, directly, β = 0.12 (95% confidence interval 0.11–0.13) and indirectly. Regarding indirect associations, ACEs were related to social engagement, β = −0.14 (−0.16 to −0.12) and social engagement was related to multimorbidity, β = −0.10 (−0.12 to −0.08). ACEs were related to allostatic load, β = 0.04 (0.03–0.05) and allostatic load was related to multimorbidity, β = 0.16 (0.15–0.17). The model was significant for males and females and across age cohorts, with qualifications in the oldest stratum (age 75–85).
ConclusionsACEs are related to multimorbidity, directly and via social engagement and allostatic load. This is the first study to show mediated pathways between early adversity and multimorbidity in adulthood. It provides a platform for understanding multimorbidity as a lifespan dynamic informing the co-occurrence of the varied disease processes represented in multimorbidity.
A population-wide analysis of the familial risk of suicide in Utah, USA
- Amanda V. Bakian, Danli Chen, Chong Zhang, Heidi A. Hanson, Anna R. Docherty, Brooks Keeshin, Douglas Gray, Ken R. Smith, James A. VanDerslice, David Z. Yu, Yue Zhang, Hilary Coon
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- Published online by Cambridge University Press:
- 10 August 2021, pp. 1448-1457
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Background
The degree to which suicide risk aggregates in US families is unknown. The authors aimed to determine the familial risk of suicide in Utah, and tested whether familial risk varies based on the characteristics of the suicides and their relatives.
MethodsA population-based sample of 12 160 suicides from 1904 to 2014 were identified from the Utah Population Database and matched 1:5 to controls based on sex and age using at-risk sampling. All first through third- and fifth-degree relatives of suicide probands and controls were identified (N = 13 480 122). The familial risk of suicide was estimated based on hazard ratios (HR) from an unsupervised Cox regression model in a unified framework. Moderation by sex of the proband or relative and age of the proband at time of suicide (<25 v. ⩾25 years) was examined.
ResultsSignificantly elevated HRs were observed in first- (HR 3.45; 95% CI 3.12–3.82) through fifth-degree relatives (HR 1.07; 95% CI 1.02–1.12) of suicide probands. Among first-degree relatives of female suicide probands, the HR of suicide was 6.99 (95% CI 3.99–12.25) in mothers, 6.39 in sisters (95% CI 3.78–10.82), and 5.65 (95% CI 3.38–9.44) in daughters. The HR in first-degree relatives of suicide probands under 25 years at death was 4.29 (95% CI 3.49–5.26).
ConclusionsElevated familial suicide risk in relatives of female and younger suicide probands suggests that there are unique risk groups to which prevention efforts should be directed – namely suicidal young adults and women with a strong family history of suicide.
Dynamic relationships between depressive symptoms and insulin resistance over 20 years of adulthood
- Che-Yuan Wu, Hugo Cogo-Moreira, Bradley J. MacIntosh, Jodi D. Edwards, Saffire H. Krance, Michael Eid, Pamela J. Schreiner, Lenore J. Launer, Walter Swardfager
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- Published online by Cambridge University Press:
- 07 September 2021, pp. 1458-1467
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Background
Bidirectional longitudinal relationships between depression and diabetes have been observed, but the dominant direction of their temporal relationships remains controversial.
MethodsThe random-intercept cross-lagged panel model decomposes observed variables into a latent intercept representing the traits, and occasion-specific latent ‘state’ variables. This permits correlations to be assessed between the traits, while longitudinal ‘cross-lagged’ associations and cross-sectional correlations can be assessed between occasion-specific latent variables. We examined dynamic relationships between depressive symptoms and insulin resistance across five visits over 20 years of adulthood in the population-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Possible differences based on population group (Black v. White participants), sex and years of education were tested. Depressive symptoms and insulin resistance were quantified using the Center for Epidemiologic Studies Depression (CES-D) scale and the homeostatic model assessment for insulin resistance (HOMA-IR), respectively.
ResultsAmong 4044 participants (baseline mean age 34.9 ± 3.7 years, 53% women, 51% Black participants), HOMA-IR and CES-D traits were weakly correlated (r = 0.081, p = 0.002). Some occasion-specific correlations, but no cross-lagged associations were observed overall. Longitudinal dynamics of these relationships differed by population groups such that HOMA-IR at age 50 was associated with CES-D score at age 55 (β = 0.076, p = 0.038) in White participants only. Longitudinal dynamics were consistent between sexes and based on education.
ConclusionsThe relationship between depressive symptoms and insulin resistance was best characterized by weak correlations between occasion-specific states and enduring traits, with weak evidence that insulin resistance might be temporally associated with subsequent depressive symptoms among White participants later in adulthood.
Disorder-specific cingulo-opercular network hyperconnectivity in pediatric OCD relative to pediatric anxiety
- Hannah C. Becker, Luke J. Norman, Huan Yang, Christopher S. Monk, K. Luan Phan, Stephan F. Taylor, Yanni Liu, Kristin Mannella, Kate D. Fitzgerald
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- Published online by Cambridge University Press:
- 16 August 2021, pp. 1468-1478
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Background
Prior investigation of adult patients with obsessive compulsive disorder (OCD) has found greater functional connectivity within orbitofrontal–striatal–thalamic (OST) circuitry, as well as altered connectivity within and between large-scale brain networks such as the cingulo-opercular network (CON) and default mode network (DMN), relative to controls. However, as adult OCD patients often have high rates of co-morbid anxiety and long durations of illness, little is known about the functional connectivity of these networks in relation to OCD specifically, or in young patients near illness onset.
MethodsIn this study, unmedicated female patients with OCD (ages 8–21 years, n = 23) were compared to age-matched female patients with anxiety disorders (n = 26), and healthy female youth (n = 44). Resting-state functional connectivity was used to determine the strength of functional connectivity within and between OST, CON, and DMN.
ResultsFunctional connectivity within the CON was significantly greater in the OCD group as compared to the anxiety and healthy control groups. Additionally, the OCD group displayed greater functional connectivity between OST and CON compared to the other two groups, which did not differ significantly from each other.
ConclusionsOur findings indicate that previously noted network connectivity differences in pediatric patients with OCD were likely not attributable to co-morbid anxiety disorders. Moreover, these results suggest that specific patterns of hyperconnectivity within CON and between CON and OST circuitry may characterize OCD relative to non-OCD anxiety disorders in youth. This study improves understanding of network dysfunction underlying pediatric OCD as compared to pediatric anxiety.
Lower circulating neuron-specific enolase concentrations in adults and adolescents with severe mental illness
- Dimitrios Andreou, Nils Eiel Steen, Kjetil Nordbø Jørgensen, Runar Elle Smelror, Kirsten Wedervang-Resell, Stener Nerland, Lars T. Westlye, Terje Nærland, Anne Margrethe Myhre, Inge Joa, Solveig Merete Klæbo Reitan, Arne Vaaler, Gunnar Morken, Erlend Bøen, Torbjørn Elvsåshagen, Birgitte Boye, Ulrik Fredrik Malt, Pål Aukrust, Silje Skrede, Rune Andreas Kroken, Erik Johnsen, Srdjan Djurovic, Ole A. Andreassen, Thor Ueland, Ingrid Agartz
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- Published online by Cambridge University Press:
- 11 August 2021, pp. 1479-1488
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Background
Both neurodegenerative and neurodevelopmental abnormalities have been suggested to be part of the etiopathology of severe mental illness (SMI). Neuron-specific enolase (NSE), mainly located in the neuronal cytoplasm, may indicate the process as it is upregulated after neuronal injury while a switch from non-neuronal enolase to NSE occurs during neuronal maturation.
MethodsWe included 1132 adult patients with SMI [schizophrenia (SZ) or bipolar spectrum disorders], 903 adult healthy controls (HC), 32 adolescent patients with SMI and 67 adolescent HC. Plasma NSE concentrations were measured by enzyme immunoassay. For 842 adults and 85 adolescents, we used total grey matter volume (TGMV) based on T1-weighted magnetic resonance images processed in FreeSurfer v6.0. We explored NSE case-control differences in adults and adolescents separately. To investigate whether putative case-control differences in NSE were TGMV-dependent we controlled for TGMV.
ResultsWe found significantly lower NSE concentrations in both adult (p < 0.001) and adolescent patients with SMI (p = 0.007) compared to HC. The results remained significant after controlling for TGMV. Among adults, both patients with SZ spectrum (p < 0.001) and bipolar spectrum disorders (p = 0.005) had lower NSE than HC. In both patient subgroups, lower NSE levels were associated with increased symptom severity. Among adults (p < 0.001) and adolescents (p = 0.040), females had lower NSE concentrations than males.
ConclusionWe found lower NSE concentrations in adult and adolescent patients with SMI compared to HC. The results suggest the lack of progressive neuronal injury, and may reflect abnormal neuronal maturation. This provides further support of a neurodevelopmental rather than a neurodegenerative mechanism in SMI.
Forecasting prognostic trajectories with mismatch negativity in early psychosis
- Minah Kim, Taekwan Kim, Wu Jeong Hwang, Silvia Kyungjin Lho, Sun-Young Moon, Tae Young Lee, Jun Soo Kwon
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- Published online by Cambridge University Press:
- 02 September 2021, pp. 1489-1499
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Background
Prognostic heterogeneity in early psychosis patients yields significant difficulties in determining the degree and duration of early intervention; this heterogeneity highlights the need for prognostic biomarkers. Although mismatch negativity (MMN) has been widely studied across early phases of psychotic disorders, its potential as a common prognostic biomarker in early periods, such as clinical high risk (CHR) for psychosis and first-episode psychosis (FEP), has not been fully studied.
MethodsA total of 104 FEP patients, 102 CHR individuals, and 107 healthy controls (HCs) participated in baseline MMN recording. Clinical outcomes were assessed; 17 FEP patients were treatment resistant, 73 FEP patients were nonresistant, 56 CHR individuals were nonremitters (15 transitioned to a psychotic disorder), and 22 CHR subjects were remitters. Baseline MMN amplitudes were compared across clinical outcome groups and tested for utility prognostic biomarkers using binary logistic regression.
ResultsMMN amplitudes were greatest in HCs, intermediate in CHR subjects, and smallest in FEP patients. In the clinical outcome groups, MMN amplitudes were reduced from the baseline in both FEP and CHR patients with poor prognostic trajectories. Reduced baseline MMN amplitudes were a significant predictor of later treatment resistance in FEP patients [Exp(β) = 2.100, 95% confidence interval (CI) 1.104–3.993, p = 0.024] and nonremission in CHR individuals [Exp(β) = 1.898, 95% CI 1.065–3.374, p = 0.030].
ConclusionsThese findings suggest that MMN could be used as a common prognostic biomarker across early psychosis periods, which will aid clinical decisions for early intervention.
Sex-specific risk profiles for suicide mortality in bipolar disorder: incidence, healthcare utilization and comorbidity
- Pao-Huan Chen, Shang-Ying Tsai, Chun-Hung Pan, Yi-Lung Chen, Hu-Ming Chang, Sheng-Siang Su, Chiao-Chicy Chen, Chian-Jue Kuo
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- Published online by Cambridge University Press:
- 11 August 2021, pp. 1500-1509
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Background
Evidence on sex-specific incidence and comorbidity risk factors of suicide among patients with bipolar disorder is scarce. This study investigated the sex-specific risk profiles for suicide among the bipolar disorder population in terms of incidence, healthcare utilization and comorbidity.
MethodsUsing data from the Taiwan National Health Insurance Research Database between 1 January 2000 and 31 December 2016, this nationwide cohort study included patients with bipolar disorder (N = 46 490) and individuals representative of the general population (N = 185 960) matched by age and sex at a 1:4 ratio. Mortality rate ratios (MRRs) of suicide were calculated between suicide rates of bipolar disorder cohort and general population. In addition, a nested case–control study (1428 cases died by suicide and 5710 living controls) was conducted in the bipolar disorder cohort to examine the sex-specific risk of healthcare utilization and comorbidities.
ResultsSuicide risk was considerably higher in the cohort (MRR = 21.9) than in the general population, especially among women (MRR = 35.6). Sex-stratified analyses revealed distinct healthcare utilization patterns and physical comorbidity risk profiles between the sexes. Although female patients who died by suicide had higher risks of nonhypertensive cardiovascular disease, pneumonia, chronic kidney disease, peptic ulcer, irritable bowel syndrome, and sepsis compared to their living counterparts, male patients who died by suicide had higher risks of chronic kidney disease and sepsis compared to the living controls.
ConclusionsPatients with bipolar disorder who died by suicide had sex-specific risk profiles in incidence and physical comorbidities. Identifying these modifiable risk factors may guide interventions for suicide risk reduction.
Neurodevelopmental disorders and subsequent risk of violent victimization: exploring sex differences and mechanisms
- Laura Ghirardi, Ralf Kuja-Halkola, Erik Pettersson, Amir Sariaslan, Louise Arseneault, Seena Fazel, Brian M. D'Onofrio, Paul Lichtenstein, Henrik Larsson
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- Published online by Cambridge University Press:
- 01 September 2021, pp. 1510-1517
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Background
Neurodevelopmental disorders (NDs) are associated with experiences of victimization, but mechanisms remain unclear. We explored sex differences and the role of familial factors and externalizing problems in the association between several NDs and violent victimization in adolescence and young adulthood.
MethodsIndividuals born in Sweden 1985–1997, residing in Sweden at their 15th birthday, were followed until date of violent victimization causing a hospital visit or death, death due to other causes, emigration, or December 31, 2013, whichever came first. The exposures were diagnoses of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID) and other NDs. We used three different Cox regression models: a crude model, a model adjusted for familial confounding using sibling-comparisons, and a model additionally adjusted for externalizing problems.
ResultsAmong 1 344 944 individuals followed, on average, for 5 years, 74 487 were diagnosed with NDs and 37 765 had a hospital visit or died due to violence. ADHD was associated with an increased risk of violent victimization in males [hazard ratio (HR) 2.56; 95% confidence interval (CI) 2.43–2.70) and females (HR 5.39; 95% CI 4.97–5.85). ASD and ID were associated with an increased risk of violent victimization in females only. After adjusting for familial factors and externalizing problems, only ADHD was associated with violent victimization among males (HR 1.27; 95% CI 1.06–1.51) and females (HR 1.69; 95% CI 1.21–2.36).
ConclusionsFemales with NDs and males with ADHD are at greater risk of being victim of severe violence during adolescence and young adulthood. Relevant mechanisms include shared familial liability and externalizing problems. ADHD may be independently associated with violent victimization.
Unsound sleep, wound-up mind: a longitudinal examination of acute suicidal affective disturbance features among an eating disorder sample
- Shruti S. Kinkel-Ram, William Grunewald, Lindsay P. Bodell, April R. Smith
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- Published online by Cambridge University Press:
- 05 August 2021, pp. 1518-1526
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Background
Suicide is one of the most commonly reported causes of death in individuals with eating disorders. However, the mechanisms underlying the suicide and disordered eating link are largely unknown, and current assessments are still unable to accurately predict future suicidal thoughts and behaviors. The purpose of this study is to test the utility of two promising proximal risk factors, sleep quality and agitation, in predicting suicidal ideation in a sample of individuals with elevated suicidal thoughts and behaviors, namely those with eating disorders.
MethodsWomen (N = 97) receiving treatment at an eating disorder treatment center completed weekly questionnaires assessing suicidal ideation, agitation, and sleep. General linear mixed models examined whether agitation and/or sleep quality were concurrently or prospectively associated with suicidal ideation across 12 weeks of treatment.
ResultsThere was a significant interaction between within-person agitation and sleep quality on suicidal ideation [B(s.e.) = −0.02(0.01), p < 0.05], such that on weeks when an individual experienced both higher than their average agitation and lower than their average sleep quality, they also experienced their highest levels of suicidal ideation. However, neither agitation nor sleep quality prospectively predicted suicidal ideation.
ConclusionsThis study was the first to examine dynamic associations between interpersonal constructs and suicidal ideation in individuals with eating disorders. Results suggest that ongoing assessment for overarousal symptoms, such as agitation and poor sleep quality, in individuals with eating disorders may be warranted in order to manage suicidal ideation among this vulnerable population.
Can emotional expressivity and writing content predict beneficial effects of expressive writing among breast cancer patients receiving chemotherapy? A secondary analysis of randomized controlled trial data from China
- Yanni Wu, Dongliang Yang, Biao Jian, Chaixiu Li, Liping Liu, Wenji Li, Xiaojin Li, Chunlan Zhou
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- Published online by Cambridge University Press:
- 24 August 2021, pp. 1527-1541
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Background
To explore whether emotional expressivity and the patterns of language use could predict benefits from expressive writing (EW) of breast cancer (BC) patients in a culture that strongly discourages emotional disclosure.
MethodsData were obtained from a recent trial in which we compared the health outcomes between a prolonged EW group (12 sessions) and a standard EW group (four sessions) (n = 56 per group) of BC patients receiving chemotherapy. The Chinese texts were tokenized using the THU Lexical Analyser for Chinese. Then, LIWC2015 was used to quantify positive and negative affect word use.
ResultsOur first hypothesis that BC patients with higher levels of emotional expressivity tended to use higher levels of positive and negative affect words in texts was not supported (r = 0.067, p = 0.549 and r = 0.065, p = 0.559, respectively). The level of emotional expressivity has a significant effect on the quality of life (QOL), and those who used more positive or fewer negative affective words in texts had a better QOL (all p < 0.05). However, no significant difference was identified in physical and psychological well-being (all p > 0.05). Furthermore, the patterns of affective word use during EW did not mediate the effects of emotional expressivity on health outcomes (all p > 0.05).
ConclusionsOur findings suggest that the level of emotional expressivity and the pattern of affective word use could be factors that may moderate the effects of EW on QOL, which may help clinicians identify the individuals most likely to benefit from such writing exercises in China.