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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.
Shared and distinct electroencephalogram microstate abnormalities across schizophrenia, bipolar disorder, and depression
- Rui Xue, Xiaojing Li, Wei Deng, Chengqian Liang, Mingxia Chen, Jianning Chen, Sugai Liang, Wei Wei, Yamin Zhang, Hua Yu, Yan Xu, Wanjun Guo, Tao Li
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- Published online by Cambridge University Press:
- 13 May 2024, pp. 1-8
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Background
Microstates of an electroencephalogram (EEG) are canonical voltage topographies that remain quasi-stable for 90 ms, serving as the foundational elements of brain dynamics. Different changes in EEG microstates can be observed in psychiatric disorders like schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). However, the similarities and disparatenesses in whole-brain dynamics on a subsecond timescale among individuals diagnosed with SCZ, BD, and MDD are unclear.
MethodsThis study included 1112 participants (380 individuals diagnosed with SCZ, 330 with BD, 212 with MDD, and 190 demographically matched healthy controls [HCs]). We assembled resting-state EEG data and completed a microstate analysis of all participants using a cross-sectional design.
ResultsOur research indicates that SCZ, BD, and MDD exhibit distinct patterns of transition among the four EEG microstate states (A, B, C, and D). The analysis of transition probabilities showed a higher frequency of switching from microstates A to B and from B to A in each patient group compared to the HC group, and less frequent transitions from microstates A to C and from C to A in the SCZ and MDD groups compared to the HC group. And the probability of the microstate switching from C to D and D to C in the SCZ group significantly increased compared to those in the patient and HC groups.
ConclusionsOur findings provide crucial insights into the abnormalities involved in distributing neural assets and enabling proper transitions between different microstates in patients with major psychiatric disorders.
Invited Commentary
Neuroprogression in bipolar disorder: why right is wrong
- Eduard Vieta
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- 10 May 2024, pp. 1-3
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The controversy on whether bipolar disorder is a neurodevelopmental versus a neuroprogressive illness is still around, despite some reductionistic claims that only one model is right. The current diagnostic classifications are not helpful to address this issue, and there is conflicting evidence in favor and against either model. In practice, though, understanding that many patients may show a progressive cognitive and functional decline which may be correlated with the number and severity of episodes may lead to better outcomes through early intervention strategies.
Original Article
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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- Published online by Cambridge University Press:
- 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.
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.
Cumulative effect of unemployment on suicide mortality in South Korean workers (2018–2019)
- Jaehyuk Jung, Kyeong-Eun Lee, Seri Hong, Jae Bum Park, Inchul Jeong
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- Published online by Cambridge University Press:
- 09 May 2024, pp. 1-7
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Background
While unemployment is known to increase the risk of suicide, its cumulative effect remains underexplored. This study investigates how unemployment affects suicide mortality and whether the effect varies based on the number of unemployment spells using two years of nationwide data.
MethodsUsing the data from the National Statistical Office and Employment Insurance Database for 2018 and 2019, we identified an average of 2365 cases of suicide over two years among 7.76 million workers aged 25–64 years who had been employed within one year before their suicide. The number of unemployment spells was counted using the employment history of the past five years. We calculated crude suicide mortality rates per 100 000 population, age- and sex- standardized mortality rates (SMRs), and proportionate mortality rates (PMRs) for suicide.
ResultsOver the two years, the crude suicide rate was 30.0 per 100 000 among the general population and 30.5 among workers. Workers with no unemployment spells in the past five years had a significantly lower SMR (0.44; 0.42–0.46), while those with four or more unemployment spells had a significantly higher SMR (3.13; 2.92–3.35) than the general population. These findings were consistent across all sex and age groups. Additionally, workers with four or more unemployment spells had a significantly higher PMR than the general population.
ConclusionThe impact of unemployment on suicide mortality intensifies as the number of unemployment spells increases. These results underscore the necessity for additional social and psychological support along with economic assistance for individuals facing recurrent unemployment.
Early-treatment cerebral blood flow change as a predictive biomarker of antidepressant treatment response: evidence from the EMBARC clinical trial
- Yi Dang, Bin Lu, Tamara Vanderwal, Francisco Xavier Castellanos, Chao-Gan Yan
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- 09 May 2024, pp. 1-10
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Background
Major depressive disorder (MDD) is one of the most prevalent and disabling illnesses worldwide. Treatment of MDD typically relies on trial-and-error to find an effective approach. Identifying early response-related biomarkers that predict response to antidepressants would help clinicians to decide, as early as possible, whether a particular treatment might be suitable for a given patient.
MethodsData were from the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial. A whole-brain, voxel-wise, mixed-effects model was applied to identify early-treatment cerebral blood flow (CBF) changes as biomarkers of treatment response. We examined changes in CBF measured with arterial spin labeling 1-week after initiating double-masked sertraline/placebo. We tested whether these early 1-week scans could be used to predict response observed after 8-weeks of treatment.
ResultsResponse to 8-week placebo treatment was associated with increased cerebral perfusion in temporal cortex and reduced cerebral perfusion in postcentral region captured at 1-week of treatment. Additionally, CBF response in these brain regions was significantly correlated with improvement in Hamilton Depression Rating Scale score in the placebo group. No significant associations were found for selective serotonin reuptake inhibitor treatment.
ConclusionsWe conclude that early CBF responses to placebo administration in multiple brain regions represent candidate neural biomarkers of longer-term antidepressant effects.
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
Factors contributing to readmission in patients with psychotic disorders, with a special reference to first follow-up visit in outpatient care
- Kimmo Suokas, Maija Lindgren, Mika Gissler, Emmi Liukko, Laura Schildt, Raimo K. R. Salokangas, Päivi Rissanen, Tapio Gauffin, Petri Näätänen, Minna Holm, Jaana Suvisaari
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- Published online by Cambridge University Press:
- 09 May 2024, pp. 1-10
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Background
Timely outpatient follow-up and readmission after discharge are common quality indicators in psychiatric care, but their association varies in previous research. We aimed to examine whether the impact of outpatient follow-up and other factors on readmission risk evolves over time in people with non-affective psychotic disorder (NAP).
MethodsThe Finnish Quality of Care Register includes all people diagnosed with NAP since January 2010. Here, we followed patients with a hospital discharge between 2017 and 2021 until readmission, death, or up to 365 days. Time of the first outpatient follow-up appointment, length of stay (LOS), number of previous hospitalizations, psychosis diagnosis, substance use disorder (SUD), residential status, economic activity, gender, age, year, and region were included. Follow-up time was divided into five periods: week 1, weeks 2–4, weeks 5–13, weeks 14–25, and weeks 26–52, and each period was analyzed separately with Cox regression.
ResultsOf the 29 858 discharged individuals, 54.1% had an outpatient follow-up within a week. A total of 10 623 (35.6%) individuals were readmitted. Short LOS increased the readmission risk in the first four weeks, whereas lack of outpatient follow-up raised the risk (adjusted HRs between 1.15 (95% CI 1.04–1.26) and 1.53 (1.37–1.71) in weeks 5–52. The number of previous hospitalizations remained a consistent risk factor throughout the follow-up, while SUD increased risk after 4 weeks and living without family after 13 weeks.
ConclusionsRisk factors of readmission vary over time. These temporal patterns must be considered when developing outpatient treatment programs.
Neuroimaging and epigenetic analysis reveal novel epigenetic loci in major depressive disorder
- Hyun-Ho Yang, Kyu-Man Han, Aram Kim, Youbin Kang, Woo-Suk Tae, Mi-Ryung Han, Byung-Joo Ham
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- 09 May 2024, pp. 1-14
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Background
Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD.
MethodsA total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson's partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci.
ResultsIn total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (EML6, ZFP64, CLSTN3, KCNMA1, TAOK2, and NT5E).
ConclusionThrough combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.
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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- Published online by Cambridge University Press:
- 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 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.
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.
A longitudinal network analysis of suicide risk factors among service members and veterans sampled for suicidal ideation or attempt
- April R. Smith, Lauren N. Forrest, Shruti S. Kinkel-Ram, William Grunewald, S. David Tubman, Aaron Esche, Cheri Levinson
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- Published online by Cambridge University Press:
- 23 April 2024, pp. 1-11
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Background
Suicidal thoughts and behaviors are elevated among active-duty service members (ADSM) and veterans compared to the general population. Hence, it is a priority to examine maintenance factors underlying suicidal ideation among ADSM and veterans to develop effective, targeted interventions. In particular, interpersonal risk factors, hopelessness, and overarousal have been robustly connected to suicidal ideation and intent.
MethodsTo identify the suicidal ideation risk factors that are most relevant, we employed network analysis to examine between-subjects (cross-sectional), contemporaneous (within seconds), and temporal (across four hours) group-level networks of suicidal ideation and related risk factors in a sample of ADSM and veterans (participant n = 92, observations n = 10 650). Participants completed ecological momentary assessment (EMA) surveys four times a day for 30 days, where they answered questions related to suicidal ideation, interpersonal risk factors, hopelessness, and overarousal.
ResultsThe between-subjects and contemporaneous networks identified agitation, not feeling close to others, and ineffectiveness as the most central symptoms. The temporal network revealed that feeling ineffective was most likely to influence other symptoms in the network over time.
ConclusionOur findings suggest that ineffectiveness, low belongingness, and agitation are important drivers of moment-to-moment and longitudinal relations between risk factors for suicidal ideation in ADSM and veterans. Targeting these symptoms may disrupt suicidal ideation.
Review Article
Personality changes related to presence and treatment of substance use (disorders): a systematic review
- Christina M. Juchem, Antonia Bendau, Leonie C. Bandurski, Nico J. Reich, Saskia Baumgardt, Eva Asselmann
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- Published online by Cambridge University Press:
- 22 April 2024, pp. 1-25
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Heavy substance use (SU) and substance use disorders (SUD) have complex etiologies and often severe consequences. Certain personality traits have been associated with an increased risk for SU(D), but far less is known about personality changes related to SU(D). This review aims to synthesize the existing literature on this research question. A systematic literature search was conducted from November 2022 to February 2023 in PubMed, EbscoHost, and Web of Science. Peer-reviewed original papers on SU(D)-related personality changes were included. Of 55 included studies, 38 were observational population-based studies and 17 were intervention studies. Overall, personality and SU measures, samples, study designs, and statistical approaches were highly heterogenous. In observational studies, higher SU was most consistently related to increases in impulsivity-related traits and (less so) neuroticism, while interventions in the context of SU(D) were mostly associated with increases in conscientiousness and self-efficacy and lasting decreases in neuroticism. Findings for traits related to extraversion, openness, conscientiousness, and agreeableness were mixed and depended on SU measure and age. Studies on bidirectional associations suggest that personality and SU(D) both influence each other over time. Due to their strong association with SU(D), impulsivity-related traits may be important target points for interventions. Future work may investigate the mechanisms underlying personality changes related to SU(D), distinguishing substance-specific effects from general SU(D)-related processes like withdrawal, craving, and loss of control. Furthermore, more research is needed to examine whether SU(D)-related personality changes vary by developmental stage and clinical features (e.g. initial use, onset, remission, and relapse).
Original Article
How much or how often? Examining the screening properties of the DSM cross-cutting symptom measure in a youth population-based sample
- João Pedro Gonçalves Pacheco, Christian Kieling, Pedro H. Manfro, Ana M. B. Menezes, Helen Gonçalves, Isabel O. Oliveira, Fernando C. Wehrmeister, Luis Augusto Rohde, Maurício Scopel Hoffmann
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- 19 April 2024, pp. 1-12
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Background
The DSM Level 1 Cross-Cutting Symptom Measure (DSM-XC) allows for assessing multiple psychopathological domains. However, its capability to screen for mental disorders in a population-based sample and the impact of adverbial framings (intensity and frequency) on its performance are unknown.
MethodsThe study was based on cross-sectional data from the 1993 Pelotas birth cohort in Brazil. Participants with completed DSM-XC and structured diagnostic interviews (n = 3578, aged 22, 53.6% females) were included. Sensitivity, specificity, positive (LR+), and negative (LR−) likelihood ratios for each of the 13 DSM-XC domains were estimated for detecting five internalizing disorders (bipolar, generalized anxiety, major depressive, post-traumatic stress, and social anxiety disorders) and three externalizing disorders (antisocial personality, attention-deficit/hyperactivity, and alcohol use disorders). Sensitivities and specificities >0.75, LR+ > 2 and LR− < 0.5 were considered meaningful. Values were calculated for the DSM-XC's original scoring and for adverbial framings.
ResultsSeveral DSM-XC domains demonstrated meaningful screening properties. The anxiety domain exhibited acceptable sensitivity and LR− values for all internalizing disorders. The suicidal ideation, psychosis, memory, repetitive thoughts and behaviors, and dissociation domains displayed acceptable specificity for all disorders. Domains also yielded small but meaningful LR+ values for internalizing disorders. However, LR+ and LR− values were not generally meaningful for externalizing disorders. Frequency-framed questions improved screening properties.
ConclusionsThe DSM-XC domains showed transdiagnostic screening properties, providing small but meaningful changes in the likelihood of internalizing disorders in the community, which can be improved by asking frequency of symptoms compared to intensity. The DSM-XC is currently lacking meaningful domains for externalizing disorders.
Review Article
Mendelian randomization: causal inference leveraging genetic data
- Lane G. Chen, Justin D. Tubbs, Zipeng Liu, Thuan-Quoc Thach, Pak C. Sham
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- Published online by Cambridge University Press:
- 19 April 2024, pp. 1-14
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Mendelian randomization (MR) leverages genetic information to examine the causal relationship between phenotypes allowing for the presence of unmeasured confounders. MR has been widely applied to unresolved questions in epidemiology, making use of summary statistics from genome-wide association studies on an increasing number of human traits. However, an understanding of essential concepts is necessary for the appropriate application and interpretation of MR. This review aims to provide a non-technical overview of MR and demonstrate its relevance to psychiatric research. We begin with the origins of MR and the reasons for its recent expansion, followed by an overview of its statistical methodology. We then describe the limitations of MR, and how these are being addressed by recent methodological advances. We showcase the practical use of MR in psychiatry through three illustrative examples – the connection between cannabis use and psychosis, the link between intelligence and schizophrenia, and the search for modifiable risk factors for depression. The review concludes with a discussion of the prospects of MR, focusing on the integration of multi-omics data and its extension to delineating complex causal networks.
Original Article
Longitudinal changes in resting-state functional connectivity as markers of vulnerability or resilience in first-degree relatives of patients with bipolar disorder
- Julian Macoveanu, Lydia Fortea, Hanne Lie Kjærstad, Klara Coello, Maria Faurholt-Jepsen, Patrick M. Fisher, Gitte Moos Knudsen, Joaquim Radua, Eduard Vieta, Sophia Frangou, Maj Vinberg, Lars Vedel Kessing, Kamilla Woznica Miskowiak
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- Published online by Cambridge University Press:
- 18 April 2024, pp. 1-9
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Background
There is a significant contribution of genetic factors to the etiology of bipolar disorder (BD). Unaffected first-degree relatives of patients (UR) with BD are at increased risk of developing mental disorders and may manifest cognitive impairments and alterations in brain functional and connective dynamics, akin to their affected relatives.
MethodsIn this prospective longitudinal study, resting-state functional connectivity was used to explore stable and progressive markers of vulnerability i.e. abnormalities shared between UR and BD compared to healthy controls (HC) and resilience i.e. features unique to UR compared to HC and BD in full or partial remission (UR n = 72, mean age = 28.0 ± 7.2 years; HC n = 64, mean age = 30.0 ± 9.7 years; BD patients n = 91, mean age = 30.6 ± 7.7 years). Out of these, 34 UR, 48 BD, and 38 HC were investigated again following a mean time of 1.3 ± 0.4 years.
ResultsAt baseline, the UR showed lower connectivity values within the default mode network (DMN), frontoparietal network, and the salience network (SN) compared to HC. This connectivity pattern in UR remained stable over the follow-up period and was not present in BD, suggesting a resilience trait. The UR further demonstrated less negative connectivity between the DMN and SN compared to HC, abnormality that remained stable over time and was also present in BD, suggesting a vulnerability marker.
ConclusionOur findings indicate the coexistence of both vulnerability-related abnormalities in resting-state connectivity, as well as adaptive changes possibly promoting resilience to psychopathology in individual at familial risk.
Seasonality in regional brain glucose metabolism
- Rui Zhang, Dardo Tomasi, Ehsan Shokri-Kojori, Peter Manza, Sukru Baris Demiral, Gene-Jack Wang, Nora D. Volkow
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- Published online by Cambridge University Press:
- 18 April 2024, pp. 1-9
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Background
Daylength and the rates of changes in daylength have been associated with seasonal fluctuations in psychiatric symptoms and in cognition and mood in healthy adults. However, variations in human brain glucose metabolism in concordance with seasonal changes remain under explored.
MethodsIn this cross-sectional study, we examined seasonal effects on brain glucose metabolism, which we measured using 18F-fluorodeoxyglucose-PET in 97 healthy participants. To maximize the sensitivity of regional effects, we computed relative metabolic measures by normalizing the regional measures to white matter metabolism. Additionally, we explored the role of rest–activity rhythms/sleep–wake activity measured with actigraphy in the seasonal variations of regional brain metabolic activity.
ResultsWe found that seasonal variations of cerebral glucose metabolism differed across brain regions. Glucose metabolism in prefrontal regions increased with longer daylength and with greater day-to-day increases in daylength. The cuneus and olfactory bulb had the maximum and minimum metabolic values around the summer and winter solstice respectively (positively associated with daylength), whereas the temporal lobe, brainstem, and postcentral cortex showed maximum and minimum metabolic values around the spring and autumn equinoxes, respectively (positively associated with faster daylength gain). Longer daylength was associated with greater amplitude and robustness of diurnal activity rhythms suggesting circadian involvement.
ConclusionsThe current findings advance our knowledge of seasonal patterns in a key indicator of brain function relevant for mood and cognition. These data could inform treatment interventions for psychiatric symptoms that peak at specific times of the year.