Centre for Youth Mental Health - Research Publications
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ItemAssociations of depression and regional brain structure across the adult lifespan: Pooled analyses of six population-based and two clinical cohort studies in the European Lifebrain consortium.(Elsevier BV, 2022)OBJECTIVE: Major depressive disorder has been associated with lower prefrontal thickness and hippocampal volume, but it is unknown whether this association also holds for depressive symptoms in the general population. We investigated associations of depressive symptoms and depression status with brain structures across population-based and patient-control cohorts, and explored whether these associations are similar over the lifespan and across sexes. METHODS: We included 3,447 participants aged 18-89 years from six population-based and two clinical patient-control cohorts of the European Lifebrain consortium. Cross-sectional meta-analyses using individual person data were performed for associations of depressive symptoms and depression status with FreeSurfer-derived thickness of bilateral rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC), and hippocampal and total grey matter volume (GMV), separately for population-based and clinical cohorts. RESULTS: Across patient-control cohorts, depressive symptoms and presence of mild-to-severe depression were associated with lower mOFC thickness (rsymptoms = -0.15/ rstatus = -0.22), rACC thickness (rsymptoms = -0.20/ rstatus = -0.25), hippocampal volume (rsymptoms = -0.13/ rstatus = 0.13) and total GMV (rsymptoms = -0.21/ rstatus = -0.25). Effect sizes were slightly larger for presence of moderate-to-severe depression. Associations were similar across age groups and sex. Across population-based cohorts, no associations between depression and brain structures were observed. CONCLUSIONS: Fitting with previous meta-analyses, depressive symptoms and depression status were associated with lower mOFC, rACC thickness, and hippocampal and total grey matter volume in clinical patient-control cohorts, although effect sizes were small. The absence of consistent associations in population-based cohorts with mostly mild depressive symptoms, suggests that significantly lower thickness and volume of the studied brain structures are only detectable in clinical populations with more severe depressive symptoms.
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ItemThe association between clinical and biological characteristics of depression and structural brain alterations.(Elsevier BV, 2022-09-01)BACKGROUND: Structural brain alterations are observed in major depressive disorder (MDD). However, MDD is a highly heterogeneous disorder and specific clinical or biological characteristics of depression might relate to specific structural brain alterations. Clinical symptom subtypes of depression, as well as immuno-metabolic dysregulation associated with subtypes of depression, have been associated with brain alterations. Therefore, we examined if specific clinical and biological characteristics of depression show different brain alterations compared to overall depression. METHOD: Individuals with and without depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA) (328 participants from three timepoints leading to 541 observations) and the Mood Treatment with Antidepressants or Running (MOTAR) study (123 baseline participants) were included. Symptom profiles (atypical energy-related profile, melancholic profile and depression severity) and biological indices (inflammatory, metabolic syndrome, and immuno-metabolic indices) were created. The associations of the clinical and biological profiles with depression-related structural brain measures (anterior cingulate cortex [ACC], orbitofrontal cortex, insula, and nucleus accumbens) were examined dimensionally in both studies and meta-analysed. RESULTS: Depression severity was negatively associated with rostral ACC thickness (B = -0.55, pFDR = 0.03), and melancholic symptoms were negatively associated with caudal ACC thickness (B = -0.42, pFDR = 0.03). The atypical energy-related symptom profile and immuno-metabolic indices did not show a consistent association with structural brain measures across studies. CONCLUSION: Overall depression- and melancholic symptom severity showed a dose-response relationship with reduced ACC thickness. No associations between immuno-metabolic dysregulation and structural brain alterations were found, suggesting that although both are associated with depression, distinct mechanisms may be involved.
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ItemA large-scale ENIGMA multisite replication study of brain age in depression(Elsevier BV, 2022-12)Background: Several studies have evaluated whether depressed persons have older appearing brains than their nondepressed peers. However, the estimated neuroimaging-derived “brain age gap” has varied from study to study, likely driven by differences in training and testing sample (size), age range, and used modality/features. To validate our previously developed ENIGMA brain age model and the identified brain age gap, we aim to replicate the presence and effect size estimate previously found in the largest study in depression to date (N = 2126 controls & N = 2675 cases; +1.08 years [SE 0.22], Cohen’s d = 0.14, 95% CI: 0.08–0.20), in independent cohorts that were not part of the original study. Methods: A previously trained brain age model (www.photon-ai.com/enigma_brainage) based on 77 FreeSurfer brain regions of interest was used to obtain unbiased brain age predictions in 751 controls and 766 persons with depression (18–75 years) from 13 new cohorts collected from 20 different scanners. Meta-regressions were used to examine potential moderating effects of basic cohort characteristics (e.g., clinical and scan technical) on the brain age gap. Results: Our ENIGMA MDD brain age model generalized reasonably well to controls from the new cohorts (predicted age vs. age: r = 0.73, R2 = 0.47, MAE = 7.50 years), although the performance varied from cohort to cohort. In these new cohorts, on average, depressed persons showed a significantly higher brain age gap of +1 year (SE 0.35) (Cohen’s d = 0.15, 95% CI: 0.05–0.25) compared with controls, highly similar to our previous finding. Significant moderating effects of FreeSurfer version 6.0 (d = 0.41, p = 0.007) and Philips scanner vendor (d = 0.50, p < 0.0001) were found, leading to more positive effect size estimates. Conclusions: This study further validates our previously developed ENIGMA brain age algorithm. Importantly, we replicated the brain age gap in depression with a comparable effect size. Thus, two large-scale independent mega-analyses across in total 32 cohorts and >3400 patients and >2800 controls worldwide show reliable but subtle effects of brain aging in adult depression. Future studies are needed to identify factors that may further explain the brain age gap variance between cohorts.
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ItemBrain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.(Springer Science and Business Media LLC, 2022-12-09)Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.
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ItemAdvanced brain age correlates with greater rumination and less mindfulness in schizophrenia.(Elsevier BV, 2023)BACKGROUND: Individual variation in brain aging trajectories is linked with several physical and mental health outcomes. Greater stress levels, worry, and rumination correspond with advanced brain age, while other individual characteristics, like mindfulness, may be protective of brain health. Multiple lines of evidence point to advanced brain aging in schizophrenia (i.e., neural age estimate > chronological age). Whether psychological dimensions such as mindfulness, rumination, and perceived stress contribute to brain aging in schizophrenia is unknown. METHODS: We estimated brain age from high-resolution anatomical scans in 54 healthy controls (HC) and 52 individuals with schizophrenia (SZ) and computed the brain predicted age difference (BrainAGE-diff), i.e., the delta between estimated brain age and chronological age. Emotional well-being summary scores were empirically derived to reflect individual differences in trait mindfulness, rumination, and perceived stress. Core analyses evaluated relationships between BrainAGE-diff and emotional well-being, testing for slopes differences across groups. RESULTS: HC showed higher emotional well-being (greater mindfulness and less rumination/stress), relative to SZ. We observed a significant group difference in the relationship between BrainAge-diff and emotional well-being, explained by BrainAGE-diff negatively correlating with emotional well-being scores in SZ, and not in HC. That is, SZ with younger appearing brains (predicted age < chronological age) had emotional summary scores that were more like HC, a relationship that endured after accounting for several demographic and clinical variables. CONCLUSIONS: These data reveal clinically relevant aspects of brain age heterogeneity among SZ and point to case-control differences in the relationship between advanced brain aging and emotional well-being.
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ItemeLife's new model and its impact on science communication(eLIFE SCIENCES PUBL LTD, 2022-12-08)The eLife Early-Career Advisory Group discusses eLife's new peer review and publishing model, and how the whole process of scientific communication could be improved for the benefit of early-career researchers and the entire scientific community.
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ItemFurther Considerations on Early Intervention for Borderline Personality Disorder-Reply(AMER MEDICAL ASSOC, 2022-04-06)
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ItemNo Preview AvailableIntersections of paranoia and the body in the general population.(SAGE Publications, 2022-10-29)Negative body image may be associated with heightened feelings of paranoia. The current study aimed to conduct multidimensional assessments of body image and psychosis facets in the general population. Respondents were 407 individuals, who provided basic sociodemographic information, and completed online questionnaires evaluating dysmorphic concerns, body consciousness, paranoia, persecutory and magical ideation and perceptual aberration. Correlation analysis and a series of regressions onto various body image facets (i.e. dysmorphic concerns, private body consciousness, public body consciousness and body competence) were conducted. Distinct patterns of significant associations were uncovered across the range of body image and psychosis facets examined. Paranoia significantly contributed to the severity of dysmorphic concerns, and magical ideation significantly contributed to private and public body consciousness, though effect sizes were modest. Our findings corroborate the relationship between paranoia and dysmorphic concerns, and tentatively suggest that challenging paranoid beliefs could be a useful strategy for managing negative body image.
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ItemThe Safety and Efficacy of Psychosocial Adherence Interventions in Young People with Early Psychosis: A Systematic Review.(MDPI AG, 2022-09-09)BACKGROUND: The role of antipsychotic medication in supporting young people in their recovery from early psychosis is complex and controversial. It is common for young people, often given antipsychotic medication for the first time, to express a choice to stop treatment, potentially increasing the risk of relapse and admission to hospital. Our systematic review aimed to evaluate the safety and effectiveness of psychosocial interventions to enhance antipsychotic medication adherence in young people with early psychosis. METHODS: We reviewed studies using any experimental design of psychosocial interventions specifically focused on enhancing adherence with antipsychotic medication in young people with early psychosis. Cochrane CENTRAL Register, Medline, Embase, PsychINFO and CINAHL were searched on 19 November 2021 without time restriction. Studies were assessed for quality using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. RESULTS: Our initial search identified 3469 documents. Following title, abstract and full-text screening, we included three published studies and one unpublished experimental study that met our inclusion criteria. Outcome data were available for three studies that tested adherence-coping-education, adherence therapy, and a health dialogue intervention, all having a positive effect on medication adherence. None of the trials reported data on the safety of the experimental interventions. CONCLUSION: There is a paucity of evidence from high-quality randomized controlled trials that establish the safety and effectiveness of any type of psychosocial intervention to enhance medication adherence in young people with early psychosis. Further high-quality trials are warranted. This review was registered on the Open Science Framework prior to undertaking out initial searches.
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ItemMale-Type Depression Mediates the Relationship between Avoidant Coping and Suicidal Ideation in Men(MDPI, 2022-09-01)Despite known links between men's avoidant coping behaviours (e.g., distraction, denial, substance use) and suicide risk, little research has explored the mechanisms underpinning this relationship. This study sought to examine whether male-type depression symptoms (e.g., anger, aggression, emotion suppression), assessed by the Male Depression Risk Scale, mediate the association between avoidant coping and suicide/self-harm ideation in men. Data were drawn from an online survey of a community sample of 606 Australian men (M age = 50.11 years; SD = 15.00), conducted during the COVID-19 pandemic. Mediation analyses were applied to examine the effect of male-type depression on the association between avoidant coping and suicidal/self-harm ideation, controlling for age, resilience and the experience of two psychosocial stressors during the COVID-19 pandemic (financial stress and government restrictions). Avoidant coping was associated with suicidal/self-harm ideation, r = 0.45, p < 0.001. Results supported a mediating role of male-type depression symptoms in this relationship, R2= 0.29, PM = 0.36, p < 0.001, underscoring the importance of screening for male-type depression symptoms to better identify men at risk of suicidal/self-harm ideation. Results also suggest a need to support men to develop effective coping strategies, particularly in the context of common psychosocial stressors experienced during the COVID-19 pandemic and beyond.