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Original Article
Depressive symptoms in adolescence and adult educational and employment outcomes: a structured life course analysis
- José A. López-López, Kate Tilling, Rebecca M. Pearson, Mina S. Fazel, Elizabeth Washbrook, Yiwen Zhu, Brooke J. Smith, Erin C. Dunn, Andrew D. A. C. Smith
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- Published online by Cambridge University Press:
- 31 May 2024, pp. 1-8
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Background
Depression is a common mental health disorder that often starts during adolescence, with potentially important future consequences including ‘Not in Education, Employment or Training’ (NEET) status.
MethodsWe took a structured life course modeling approach to examine how depressive symptoms during adolescence might be associated with later NEET status, using a high-quality longitudinal data resource. We considered four plausible life course models: (1) an early adolescent sensitive period model where depressive symptoms in early adolescence are more associated with later NEET status relative to exposure at other stages; (2) a mid adolescent sensitive period model where depressive symptoms during the transition from compulsory education to adult life might be more deleterious regarding NEET status; (3) a late adolescent sensitive period model, meaning that depressive symptoms around the time when most adults have completed their education and started their careers are the most strongly associated with NEET status; and (4) an accumulation of risk model which highlights the importance of chronicity of symptoms.
ResultsOur analysis sample included participants with full information on NEET status (N = 3951), and the results supported the accumulation of risk model, showing that the odds of NEET increase by 1.015 (95% CI 1.012–1.019) for an increase of 1 unit in depression at any age between 11 and 24 years.
ConclusionsGiven the adverse implications of NEET status, our results emphasize the importance of supporting mental health during adolescence and early adulthood, as well as considering specific needs of young people with re-occurring depressed mood.
Exploring intra-diagnosis heterogeneity and inter-diagnosis commonality in genetic architectures of bipolar disorders: association of polygenic risks of major psychiatric illnesses and lifetime phenotype dimensions
- Ji Hyun Baek, Dongbin Lee, Dongeun Lee, Hyewon Jeong, Eun-Young Cho, Tae Hyon Ha, Kyooseob Ha, Kyung Sue Hong
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- Published online by Cambridge University Press:
- 30 May 2024, pp. 1-7
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Background
Bipolar disorder (BD) shows heterogeneous illness presentation both cross-sectionally and longitudinally. This phenotypic heterogeneity might reflect underlying genetic heterogeneity. At the same time, overlapping characteristics between BD and other psychiatric illnesses are observed at clinical and biomarker levels, which implies a shared biological mechanism between them. Incorporating these two issues in a single study design, this study investigated whether phenotypically heterogeneous subtypes of BD have a distinct polygenic basis shared with other psychiatric illnesses.
MethodsSix lifetime phenotype dimensions of BD identified in our previous study were used as target phenotypes. Associations between these phenotype dimensions and polygenic risk scores (PRSs) of major psychiatric illnesses from East Asian (EA) and other available populations were analyzed.
ResultsEach phenotype dimension showed a different association pattern with PRSs of mental illnesses. PRS for EA schizophrenia showed a significant negative association with the cyclicity dimension (p = 0.044) but a significant positive association with the psychotic/irritable mania dimension (p = 0.001). PRS of EA major depressive disorder demonstrated a significant negative association with the elation dimension (p = 0.003) but a significant positive association with the comorbidity dimension (p = 0.028).
ConclusionThis study demonstrates that well-defined phenotype dimensions of lifetime-basis in BD have distinct genetic risks shared with other major mental illnesses. This finding supports genetic heterogeneity in BD and suggests a pleiotropy among BD subtypes and other psychiatric disorders beyond BD. Further genomic analyses adopting deep phenotyping across mental illnesses in ancestrally diverse populations are warranted to clarify intra-diagnosis heterogeneity and inter-diagnoses commonality issues in psychiatry.
Characterizing the distinct imaging phenotypes, clinical behavior, and genetic vulnerability of brain maturational subtypes in mood disorders
- Junjie Zheng, Xiaofen Zong, Lili Tang, Huiling Guo, Pengfei Zhao, Fay Y. Womer, Xizhe Zhang, Yanqing Tang, Fei Wang
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- Published online by Cambridge University Press:
- 28 May 2024, pp. 1-11
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Background
Mood disorders are characterized by great heterogeneity in clinical manifestation. Uncovering such heterogeneity using neuroimaging-based individual biomarkers, clinical behaviors, and genetic risks, might contribute to elucidating the etiology of these diseases and support precision medicine.
MethodsWe recruited 174 drug-naïve and drug-free patients with major depressive disorder and bipolar disorder, as well as 404 healthy controls. T1 MRI imaging data, clinical symptoms, and neurocognitive assessments, and genetics were obtained and analyzed. We applied regional gray matter volumes (GMV) and quantile normative modeling to create maturation curves, and then calculated individual deviations to identify subtypes within the patients using hierarchical clustering. We compared the between-subtype differences in GMV deviations, clinical behaviors, cell-specific transcriptomic associations, and polygenic risk scores. We also validated the GMV deviations based subtyping analysis in a replication cohort.
ResultsTwo subtypes emerged: subtype 1, characterized by increased GMV deviations in the frontal cortex, cognitive impairment, a higher genetic risk for Alzheimer's disease, and transcriptionally associated with Alzheimer's disease pathways, oligodendrocytes, and endothelial cells; and subtype 2, displaying globally decreased GMV deviations, more severe depressive symptoms, increased genetic vulnerability to major depressive disorder and transcriptionally related to microglia and inhibitory neurons. The distinct patterns of GMV deviations in the frontal, cingulate, and primary motor cortices between subtypes were shown to be replicable.
ConclusionsOur current results provide vital links between MRI-derived phenotypes, spatial transcriptome, genetic vulnerability, and clinical manifestation, and uncover the heterogeneity of mood disorders in biological and behavioral terms.
Shared familial risk for type 2 diabetes mellitus and psychiatric disorders: a nationwide multigenerational genetics study
- Theresa Wimberley, Isabell Brikell, Aske Astrup, Janne T. Larsen, Liselotte V. Petersen, Clara Albiñana, Bjarni J. Vilhjálmsson, Cynthia M. Bulik, Zheng Chang, Giuseppe Fanelli, Janita Bralten, Nina R. Mota, Jordi Salas-Salvadó, Fernando Fernandez-Aranda, Monica Bulló, Barbara Franke, Anders Børglum, Preben B. Mortensen, Henriette T. Horsdal, Søren Dalsgaard
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- Published online by Cambridge University Press:
- 27 May 2024, pp. 1-10
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Background
Psychiatric disorders and type 2 diabetes mellitus (T2DM) are heritable, polygenic, and often comorbid conditions, yet knowledge about their potential shared familial risk is lacking. We used family designs and T2DM polygenic risk score (T2DM-PRS) to investigate the genetic associations between psychiatric disorders and T2DM.
MethodsWe linked 659 906 individuals born in Denmark 1990–2000 to their parents, grandparents, and aunts/uncles using population-based registers. We compared rates of T2DM in relatives of children with and without a diagnosis of any or one of 11 specific psychiatric disorders, including neuropsychiatric and neurodevelopmental disorders, using Cox regression. In a genotyped sample (iPSYCH2015) of individuals born 1981–2008 (n = 134 403), we used logistic regression to estimate associations between a T2DM-PRS and these psychiatric disorders.
ResultsAmong 5 235 300 relative pairs, relatives of individuals with a psychiatric disorder had an increased risk for T2DM with stronger associations for closer relatives (parents:hazard ratio = 1.38, 95% confidence interval 1.35–1.42; grandparents: 1.14, 1.13–1.15; and aunts/uncles: 1.19, 1.16–1.22). In the genetic sample, one standard deviation increase in T2DM-PRS was associated with an increased risk for any psychiatric disorder (odds ratio = 1.11, 1.08–1.14). Both familial T2DM and T2DM-PRS were significantly associated with seven of 11 psychiatric disorders, most strongly with attention-deficit/hyperactivity disorder and conduct disorder, and inversely with anorexia nervosa.
ConclusionsOur findings of familial co-aggregation and higher T2DM polygenic liability associated with psychiatric disorders point toward shared familial risk. This suggests that part of the comorbidity is explained by shared familial risks. The underlying mechanisms still remain largely unknown and the contributions of genetics and environment need further investigation.
Larger putamen in individuals at risk and with manifest bipolar disorder
- Florian Thomas-Odenthal, Frederike Stein, Christoph Vogelbacher, Nina Alexander, Andreas Bechdolf, Felix Bermpohl, Kyra Bröckel, Katharina Brosch, Christoph U. Correll, Ulrika Evermann, Irina Falkenberg, Andreas Fallgatter, Kira Flinkenflügel, Dominik Grotegerd, Tim Hahn, Martin Hautzinger, Andreas Jansen, Georg Juckel, Axel Krug, Martin Lambert, Gregor Leicht, Karolina Leopold, Susanne Meinert, Pavol Mikolas, Christoph Mulert, Igor Nenadić, Julia-Katharina Pfarr, Andreas Reif, Kai Ringwald, Philipp Ritter, Thomas Stamm, Benjamin Straube, Lea Teutenberg, Katharina Thiel, Paula Usemann, Alexandra Winter, Adrian Wroblewski, Udo Dannlowski, Michael Bauer, Andrea Pfennig, Tilo Kircher
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- Published online by Cambridge University Press:
- 27 May 2024, pp. 1-11
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Background:
Individuals at risk for bipolar disorder (BD) have a wide range of genetic and non-genetic risk factors, like a positive family history of BD or (sub)threshold affective symptoms. Yet, it is unclear whether these individuals at risk and those diagnosed with BD share similar gray matter brain alterations.
Methods:In 410 male and female participants aged 17–35 years, we compared gray matter volume (3T MRI) between individuals at risk for BD (as assessed using the EPIbipolar scale; n = 208), patients with a DSM-IV-TR diagnosis of BD (n = 87), and healthy controls (n = 115) using voxel-based morphometry in SPM12/CAT12. We applied conjunction analyses to identify similarities in gray matter volume alterations in individuals at risk and BD patients, relative to healthy controls. We also performed exploratory whole-brain analyses to identify differences in gray matter volume among groups. ComBat was used to harmonize imaging data from seven sites.
Results:Both individuals at risk and BD patients showed larger volumes in the right putamen than healthy controls. Furthermore, individuals at risk had smaller volumes in the right inferior occipital gyrus, and BD patients had larger volumes in the left precuneus, compared to healthy controls. These findings were independent of course of illness (number of lifetime manic and depressive episodes, number of hospitalizations), comorbid diagnoses (major depressive disorder, attention-deficit hyperactivity disorder, anxiety disorder, eating disorder), familial risk, current disease severity (global functioning, remission status), and current medication intake.
Conclusions:Our findings indicate that alterations in the right putamen might constitute a vulnerability marker for BD.
Understanding the mechanisms underlying cognitive control in psychosis
- R. Maitra, I. L. J. Lemmers-Jansen, M. Vooren, Lucy Vanes, Timea Szentgyorgyi, Charlotte Crisp, Elias Mouchlianitis, S. S. Shergill
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- Published online by Cambridge University Press:
- 23 May 2024, pp. 1-10
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Background
Cognitive control (CC) involves a top–down mechanism to flexibly respond to complex stimuli and is impaired in schizophrenia.
MethodsThis study investigated the impact of increasing complexity of CC processing in 140 subjects with psychosis and 39 healthy adults, with assessments of behavioral performance, neural regions of interest and symptom severity.
ResultsThe lowest level of CC (Stroop task) was impaired in all patients; the intermediate level of CC (Faces task) with explicit emotional information was most impaired in patients with first episode psychosis. Patients showed activation of distinct neural CC and reward networks, but iterative learning based on the higher-order of CC during the trust game, was most impaired in chronic schizophrenia. Subjects with first episode psychosis, and patients with lower symptom load, demonstrate flexibility of the CC network to facilitate learning, which appeared compromised in the more chronic stages of schizophrenia.
ConclusionThese data suggest optimal windows for opportunities to introduce therapeutic interventions to improve CC.
Lost in translation? Deciphering the role of language differences in the excess risk of psychosis among migrant groups
- Kelly K. Anderson, Jahin Ali Khan, Jordan Edwards, Britney Le, Giuseppe Longobardi, Ivan Witt, María Francisca Alonso-Sánchez, Lena Palaniyappan
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- Published online by Cambridge University Press:
- 22 May 2024, pp. 1-8
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Background
Migration is a well-established risk factor for psychotic disorders, and migrant language has been proposed as a novel factor that may improve our understanding of this relationship. Our objective was to explore the association between indicators of linguistic distance and the risk of psychotic disorders among first-generation migrant groups.
MethodsUsing linked health administrative data, we constructed a retrospective cohort of first-generation migrants to Ontario over a 20-year period (1992–2011). Linguistic distance of the first language was categorized using several approaches, including language family classifications, estimated acquisition time, syntax-based distance scores, and lexical-based distance scores. Incident cases of non-affective psychotic disorder were identified over a 5- to 25-year period. We used Poisson regression to estimate incidence rate ratios (IRR) for each language variable, after adjustment for knowledge of English at arrival and other factors.
ResultsOur cohort included 1 863 803 first-generation migrants. Migrants whose first language was in a different language family than English had higher rates of psychotic disorders (IRR = 1.08, 95% CI 1.01–1.16), relative to those whose first language was English. Similarly, migrants in the highest quintile of linguistic distance based on lexical similarity had an elevated risk of psychotic disorder (IRR = 1.15, 95% CI 1.06–1.24). Adjustment for knowledge of English at arrival had minimal effect on observed estimates.
ConclusionWe found some evidence that linguistic factors that impair comprehension may play a role in the excess risk of psychosis among migrant groups; however, the magnitude of effect is small and unlikely to fully explain the elevated rates of psychotic disorder across migrant groups.
Effectiveness of a digital alcohol intervention as an add-on to depression treatment for young adults: results of a pragmatic randomized controlled trial
- Maria J. E. Schouten, Anna E. Goudriaan, Michael P. Schaub, Jack J. M. Dekker, Matthijs Blankers
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- Published online by Cambridge University Press:
- 22 May 2024, pp. 1-12
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Background
Problematic drinking frequently co-occurs with depression among young adults, but often remains unaddressed in depression treatment. Evidence is insufficient on whether digital alcohol interventions can be effective in this young comorbid population. In a randomized controlled trial, we examined the effectiveness of Beating the Booze (BtB), an add-on digital alcohol intervention to complement depression treatment for young adults.
MethodsParticipants were randomized to BtB + depression treatment as usual (BTB + TAU, n = 81) or TAU (n = 82). The primary outcome was treatment response, a combined measure for alcohol and depression after 6-month follow-up. Secondary outcomes were number of weekly drinks (Timeline Follow-back) and depressive symptoms (Center for Epidemiologic Studies Depression scale). Treatment response was analyzed using generalized linear modeling and secondary outcomes using robust linear mixed modeling.
ResultsLow treatment response was found due to lower than expected depression remission rates. No statistically significant between-group effect was found for treatment response after 6-month follow-up (odds ratio 2.86, p = 0.089, 95% confidence interval [CI] 0.85–9.63). For our secondary outcomes, statistically significant larger reductions in weekly drinks were found in the intervention group after 3-month (B = −4.00, p = 0.009, 95% CI −6.97 to −1.02, d = 0.27) and 6-month follow-up (B = −3.20, p = 0.032, 95% CI −6.13 to −0.27, d = 0.23). We found no statistically significant between-group differences on depressive symptoms after 3-month (B = −0.57, p = 0.732, 95% CI −3.83 to 2.69) nor after 6-month follow-up (B = −0.44, p = 0.793, 95% CI −3.69 to 2.82).
ConclusionsThe add-on digital alcohol intervention was effective in reducing alcohol use, but not in reducing depressive symptoms and treatment response among young adults with co-occurring depressive disorders and problematic alcohol use.
Trial registration:Pre-registered on October 29, 2019 in the Overview of Medical Research in the Netherlands (OMON), formerly the Dutch Trial Register(https://onderzoekmetmensen.nl/en/trial/49219).
Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study
- Stephanie Haering, Antonia V. Seligowski, Sarah D. Linnstaedt, Vasiliki Michopoulos, Stacey L. House, Francesca L. Beaudoin, Xinming An, Thomas C. Neylan, Gari D. Clifford, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Jr., Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Robert A. Swor, Nina T. Gentile, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Brian J. O'Neil, Leon D. Sanchez, Steven E. Bruce, Steven E. Harte, Samuel A. McLean, Ronald C. Kessler, Karestan C. Koenen, Jennifer S. Stevens, Abigail Powers
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- 22 May 2024, pp. 1-11
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Background
Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.
MethodsAs part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.
ResultsWomen reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.
ConclusionsOur findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.
Age-dependent association of cannabis use with risk of psychotic disorder
- André J. McDonald, Paul Kurdyak, Jürgen Rehm, Michael Roerecke, Susan J. Bondy
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- Published online by Cambridge University Press:
- 22 May 2024, pp. 1-11
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Background
Epidemiologic research suggests that youth cannabis use is associated with psychotic disorders. However, current evidence is based heavily on 20th-century data when cannabis was substantially less potent than today.
MethodsWe linked population-based survey data from 2009 to 2012 with records of health services covered under universal healthcare in Ontario, Canada, up to 2018. The cohort included respondents aged 12–24 years at baseline with no prior psychotic disorder (N = 11 363). The primary outcome was days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder according to validated diagnostic codes. Due to non-proportional hazards, we estimated age-specific hazard ratios during adolescence (12–19 years) and young adulthood (20–33 years). Sensitivity analyses explored alternative model conditions including restricting the outcome to hospitalizations and ED visits to increase specificity.
ResultsCompared to no cannabis use, cannabis use was significantly associated with psychotic disorders during adolescence (aHR = 11.2; 95% CI 4.6–27.3), but not during young adulthood (aHR = 1.3; 95% CI 0.6–2.6). When we restricted the outcome to hospitalizations and ED visits only, the strength of association increased markedly during adolescence (aHR = 26.7; 95% CI 7.7–92.8) but did not change meaningfully during young adulthood (aHR = 1.8; 95% CI 0.6–5.4).
ConclusionsThis study provides new evidence of a strong but age-dependent association between cannabis use and risk of psychotic disorder, consistent with the neurodevelopmental theory that adolescence is a vulnerable time to use cannabis. The strength of association during adolescence was notably greater than in previous studies, possibly reflecting the recent rise in cannabis potency.
Person-specific and pooled prediction models for binge eating, alcohol use and binge drinking in bulimia nervosa and alcohol use disorder
- N. Leenaerts, P. Soyster, J. Ceccarini, S. Sunaert, A. Fisher, E. Vrieze
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- Published online by Cambridge University Press:
- 22 May 2024, pp. 1-16
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Background
Machine learning could predict binge behavior and help develop treatments for bulimia nervosa (BN) and alcohol use disorder (AUD). Therefore, this study evaluates person-specific and pooled prediction models for binge eating (BE), alcohol use, and binge drinking (BD) in daily life, and identifies the most important predictors.
MethodsA total of 120 patients (BN: 50; AUD: 51; BN/AUD: 19) participated in an experience sampling study, where over a period of 12 months they reported on their eating and drinking behaviors as well as on several other emotional, behavioral, and contextual factors in daily life. The study had a burst-measurement design, where assessments occurred eight times a day on Thursdays, Fridays, and Saturdays in seven bursts of three weeks. Afterwards, person-specific and pooled models were fit with elastic net regularized regression and evaluated with cross-validation. From these models, the variables with the 10% highest estimates were identified.
ResultsThe person-specific models had a median AUC of 0.61, 0.80, and 0.85 for BE, alcohol use, and BD respectively, while the pooled models had a median AUC of 0.70, 0.90, and 0.93. The most important predictors across the behaviors were craving and time of day. However, predictors concerning social context and affect differed among BE, alcohol use, and BD.
ConclusionsPooled models outperformed person-specific models and the models for alcohol use and BD outperformed those for BE. Future studies should explore how the performance of these models can be improved and how they can be used to deliver interventions in daily life.
Neighborhood social composition and refugee mental health – quasi-experimental evidence of associations from a Danish population register study
- Peter Schofield, Christopher Jamil de Montgomery, Anna Piil Damm, Esben Agerbo
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- Published online by Cambridge University Press:
- 20 May 2024, pp. 1-9
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Background
Refugees are at an elevated risk of some mental disorders with studies highlighting the contributing role of post-migration factors. Studies of migrant groups show neighborhood social composition, such as ethnic density, to be important. This is the first longitudinal study to examine this question for refugees and uses a novel quasi-experimental design.
MethodsWe followed a cohort of 44 033 refugees from being first assigned housing under the Danish dispersal policy, operating from 1986 to 1998, until 2019. This comprised, in effect, a natural experiment whereby the influence of assigned neighborhood could be determined independently of endogenous factors. We examined three aspects of neighborhood social composition: proportion of co-nationals, refugees, and first-generation migrants; and subsequent incidence of different mental disorders.
ResultsRefugees assigned to neighborhoods with fewer co-nationals (lowest v. highest quartile) were more likely to receive a subsequent diagnosis of non-affective psychosis, incident rate ratio (IRR) 1.25 (95% confidence interval (CI) 1.06–1.48), and post-traumatic stress disorder (PTSD), IRR 1.21 (95% CI I.05–1.39). A comparable but smaller effect was observed for mood disorders but none observed for stress disorders overall. Neighborhood proportion of refugees was less clearly associated with subsequent mental disorders other than non-affective psychosis, IRR 1.24 (95% CI 1.03–1.50). We found no statistically significant associations with proportion of migrants.
ConclusionsFor refugees, living in a neighborhood with a lower proportion of co-nationals is related to subsequent increased risk of diagnosed mental disorders particularly non-affective psychosis and PTSD.
Review Article
Approaches to improving mental health care for autistic children and young people: a systematic review and meta-analysis
- Tamara Pemovska, Sofia Loizou, Rebecca Appleton, Debbie Spain, Theodora Stefanidou, Ariana Kular, Ruth Cooper, Anna Greenburgh, Jessica Griffiths, Phoebe Barnett, Una Foye, Helen Baldwin, Matilda Minchin, Gráinne Brady, Katherine R. K. Saunders, Nafiso Ahmed, Robin Jackson, Rachel Rowan Olive, Jennie Parker, Amanda Timmerman, Suzi Sapiets, Eva Driskell, Beverley Chipp, Bethany Parsons, Vaso Totsika, Will Mandy, Richard Pender, Philippa Clery, Brynmor Lloyd-Evans, Alan Simpson, Sonia Johnson
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- Published online by Cambridge University Press:
- 17 May 2024, pp. 1-31
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Autistic children and young people (CYP) experience mental health difficulties but face many barriers to accessing and benefiting from mental health care. There is a need to explore strategies in mental health care for autistic CYP to guide clinical practice and future research and support their mental health needs. Our aim was to identify strategies used to improve mental health care for autistic CYP and examine evidence on their acceptability, feasibility, and effectiveness. A systematic review and meta-analysis were carried out. All study designs reporting acceptability/feasibility outcomes and empirical quantitative studies reporting effectiveness outcomes for strategies tested within mental health care were eligible. We conducted a narrative synthesis and separate meta-analyses by informant (self, parent, and clinician). Fifty-seven papers were included, with most investigating cognitive behavioral therapy (CBT)-based interventions for anxiety and several exploring service-level strategies, such as autism screening tools, clinician training, and adaptations regarding organization of services. Most papers described caregiver involvement in therapy and reported adaptations to communication and intervention content; a few reported environmental adjustments. In the meta-analyses, parent- and clinician-reported outcomes, but not self-reported outcomes, showed with moderate certainty that CBT for anxiety was an effective treatment compared to any comparison condition in reducing anxiety symptoms in autistic individuals. The certainty of evidence for effectiveness, synthesized narratively, ranged from low to moderate. Evidence for feasibility and acceptability tended to be positive. Many identified strategies are simple, reasonable adjustments that can be implemented in services to enhance mental health care for autistic individuals. Notable research gaps persist, however.
Original Article
Neural responses to facial emotions and subsequent clinical outcomes in difficult-to-treat depression
- Diede Fennema, Gareth J. Barker, Owen O'Daly, Suqian Duan, Beata R. Godlewska, Kimberley Goldsmith, Allan H. Young, Jorge Moll, Roland Zahn
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- Published online by Cambridge University Press:
- 17 May 2024, pp. 1-9
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Background
Amygdala and dorsal anterior cingulate cortex responses to facial emotions have shown promise in predicting treatment response in medication-free major depressive disorder (MDD). Here, we examined their role in the pathophysiology of clinical outcomes in more chronic, difficult-to-treat forms of MDD.
MethodsForty-five people with current MDD who had not responded to ⩾2 serotonergic antidepressants (n = 42, meeting pre-defined fMRI minimum quality thresholds) were enrolled and followed up over four months of standard primary care. Prior to medication review, subliminal facial emotion fMRI was used to extract blood-oxygen level-dependent effects for sad v. happy faces from two pre-registered a priori defined regions: bilateral amygdala and dorsal/pregenual anterior cingulate cortex. Clinical outcome was the percentage change on the self-reported Quick Inventory of Depressive Symptomatology (16-item).
ResultsWe corroborated our pre-registered hypothesis (NCT04342299) that lower bilateral amygdala activation for sad v. happy faces predicted favorable clinical outcomes (rs[38] = 0.40, p = 0.01). In contrast, there was no effect for dorsal/pregenual anterior cingulate cortex activation (rs[38] = 0.18, p = 0.29), nor when using voxel-based whole-brain analyses (voxel-based Family-Wise Error-corrected p < 0.05). Predictive effects were mainly driven by the right amygdala whose response to happy faces was reduced in patients with higher anxiety levels.
ConclusionsWe confirmed the prediction that a lower amygdala response to negative v. positive facial expressions might be an adaptive neural signature, which predicts subsequent symptom improvement also in difficult-to-treat MDD. Anxiety reduced adaptive amygdala responses.
Review Article
Exploring decision-making performance in young adults with mental health disorders: a comparative study using the Cambridge gambling task
- R. Effah, K. Ioannidis, J.E. Grant, S.R. Chamberlain
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- Published online by Cambridge University Press:
- 09 May 2024, pp. 1-7
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Decision-making deficits, assessed cognitively, are often associated with mental health symptoms, however, this relationship is not fully understood. This paper explores the relationship between mental health disorders and decision-making, using the Cambridge Gambling Task (CGT). Our study investigated how decision-making varied across 20 different mental health conditions compared to controls in a sample of 572 young adults from the Minneapolis and Chicago metropolitan areas, using a computerized laboratory-based task. Almost all mental health conditions were associated with at least mild (i.e. at least small effect size) impairment in all three studied parameters of the CGT (risk adjustment, quality of decision-making and overall proportion of bet). Notably, binge eating disorder had the largest cognitive impairment and gambling disorder had moderate impairment. Post-traumatic stress disorder (PTSD) was associated with impaired decision-making while obsessive–compulsive disorder (OCD) and depression showed moderate impairment. Additionally, half of the disorders assessed had moderate to large impairment in risk adjustment.These findings suggest that mental health conditions may have a more complex cognitive profile than previously thought, and a better understanding of these impairments may aid in risk assessment and targeted clinical interventions. This study underscores the need for further research to determine the causal pathways between mental health conditions and cognition, as well as to better understand the day-to-day impact of such deficits.
Original Article
The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe
- J. P. Selten, M. Di Forti, D. Quattrone, P. B. Jones, H. E. Jongsma, C. Gayer-Anderson, A. Szöke, P. M. Llorca, C. Arango, M. Bernardo, J. Sanjuan, J. L. Santos, M. Arrojo, I. Tarricone, D. Berardi, A. Lasalvia, S. Tosato, C. la Cascia, E. Velthorst, E. M. A. van der Ven, L. de Haan, B. P. Rutten, J. van Os, J. B. Kirkbride, C. M. Morgan, R. M. Murray, F. Termorshuizen
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- Published online by Cambridge University Press:
- 09 May 2024, pp. 1-10
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Background
We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.
MethodsWe used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.
ResultsThe OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39–2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38–2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25–4.79) to 1.61 (95% CI 0.74–3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07–6.15) to 1.67 (95% CI 0.62–4.53).
ConclusionsThe contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.
Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score associations
- Sarah E. Paul, David A.A. Baranger, Emma C. Johnson, Joshua J. Jackson, Aaron J. Gorelik, Alex P. Miller, Alexander S. Hatoum, Wesley K. Thompson, Michael Strube, Danielle M. Dick, Chella Kamarajan, John R. Kramer, Martin H. Plawecki, Grace Chan, Andrey P. Anokhin, David B. Chorlian, Sivan Kinreich, Jacquelyn L. Meyers, Bernice Porjesz, Howard J. Edenberg, Arpana Agrawal, Kathleen K. Bucholz, Ryan Bogdan
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- 09 May 2024, pp. 1-14
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Background
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
MethodsData came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
ResultsExternalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
ConclusionsBehavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
Uncovering novel drug targets for bipolar disorder: a Mendelian randomization analysis of brain, cerebrospinal fluid, and plasma proteomes
- Tingting Jia, Tiancheng Liu, Shiyi Hu, Yongjun Li, Peixi Chen, Fengqin Qin, Yongji He, Feng Han, Chengcheng Zhang
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- 09 May 2024, pp. 1-11
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Background
There is a clear demand for innovative therapeutics for bipolar disorder (BD).
MethodsWe integrated the largest BD genome-wide association study (GWAS) dataset (NCase = 41 917, NControl = 371 549) with protein quantitative trait loci from brain, cerebrospinal fluid, and plasma. Using a range of integrative analyses, including Mendelian randomization (MR), Steiger filter analysis, Bayesian colocalization, and phenome-wide MR analysis, we prioritized novel drug targets for BD. Additionally, we incorporated data from the UK Biobank (NCase = 1064, NControl = 365 476) and the FinnGen study (NCase = 7006, NControl = 329 192) for robust biological validation.
ResultsThrough MR analysis, we found that in the brain, downregulation of DNM3, MCTP1, ABCB8 and elevation of DFNA5 and PDF were risk factors for BD. In cerebrospinal fluid, increased BD risk was associated with increased levels of FRZB, AGRP, and IL36A and decreased CTSF and LRP8. Plasma analysis revealed that decreased LMAN2L, CX3CL1, PI3, NCAM1, and TIMP4 correlated with increased BD risk, but ITIH1 did not. All these proteins passed Steiger filtering, and Bayesian colocalization confirmed that 12 proteins were colocalized with BD. Phenome-wide MR analysis revealed no significant side effects for potential drug targets, except for LRP8. External validation further underscored the concordance between the primary and validation cohorts, confirming MCTP1, DNM3, PDF, CTSF, AGRP, FRZB, LMAN2L, NCAM1, and TIMP4 are intriguing targets for BD.
ConclusionsOur study identified druggable proteins for BD, including MCTP1, DNM3, and PDF in the brain; CTSF, AGRP, and FRZB in cerebrospinal fluid; and LMAN2L, NCAM1, and TIMP4 in plasma, delineating promising avenues to development of novel therapies.
The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis
- Kuan-Yu Pan, Lonneke van Tuijl, Maartje Basten, Judith J. M. Rijnhart, Alexander de Graeff, Joost Dekker, Mirjam I. Geerlings, Adriaan Hoogendoorn, Adelita V. Ranchor, Roel Vermeulen, Lützen Portengen, Adri C. Voogd, Jessica Abell, Philip Awadalla, Aartjan T. F. Beekman, Ottar Bjerkeset, Andy Boyd, Yunsong Cui, Philipp Frank, Henrike Galenkamp, Bert Garssen, Sean Hellingman, Monika Hollander, Martijn Huisman, Anke Huss, Melanie R. Keats, Almar A. L. Kok, Steinar Krokstad, Flora E. van Leeuwen, Annemarie I. Luik, Nolwenn Noisel, Yves Payette, Brenda W. J. H. Penninx, Susan Picavet, Ina Rissanen, Annelieke M. Roest, Judith G. M. Rosmalen, Rikje Ruiter, Robert A. Schoevers, David Soave, Mandy Spaan, Andrew Steptoe, Karien Stronks, Erik R. Sund, Ellen Sweeney, Alison Teyhan, Emma L. Twait, Kimberly D. van der Willik, Femke Lamers
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- Published online by Cambridge University Press:
- 29 April 2024, pp. 1-14
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Background
Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers).
MethodsTwo-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs).
ResultsSmoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01).
ConclusionsSmoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.
The long-term effectiveness of a personality-targeted substance use prevention program on aggression from adolescence to early adulthood
- Siobhan Lawler, Emma L. Barrett, Maree Teesson, Erin Kelly, Katrina E. Champion, Jennifer Debenham, Anna Smout, Cath Chapman, Tim Slade, Patricia J. Conrod, Nicola C. Newton, Lexine Stapinski
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- Published online by Cambridge University Press:
- 29 April 2024, pp. 1-9
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Background
Addressing aggressive behavior in adolescence is a key step toward preventing violence and associated social and economic costs in adulthood. This study examined the secondary effects of the personality-targeted substance use preventive program Preventure on aggressive behavior from ages 13 to 20.
MethodsIn total, 339 young people from nine independent schools (M age = 13.03 years, s.d. = 0.47, range = 12–15) who rated highly on one of the four personality traits associated with increased substance use and other emotional/behavioral symptoms (i.e. impulsivity, anxiety sensitivity, sensation seeking, and negative thinking) were included in the analyses (n = 145 in Preventure, n = 194 in control). Self-report assessments were administered at baseline and follow-up (6 months, 1, 2, 3, 5.5, and 7 years). Overall aggression and subtypes of aggressive behaviors (proactive, reactive) were examined using multilevel mixed-effects analysis accounting for school-level clustering.
ResultsAcross the 7-year follow-up period, the average yearly reduction in the frequency of aggressive behaviors (b = −0.42; 95% confidence interval [CI] −0.64 to −0.20; p < 0.001), reactive aggression (b = −0.22; 95% CI 0.35 to −0.10; p = 0.001), and proactive aggression (b = −0.14; 95% CI −0.23 to −0.05; p = 0.002) was greater for the Preventure group compared to the control group.
ConclusionsThe study suggests a brief personality-targeted intervention may have long-term impacts on aggression among young people; however, this interpretation is limited by imbalance of sex ratios between study groups.