Review Article
Reporting of harms in clinical trials of esketamine in depression: a systematic review
- Tanguy Taillefer de Laportalière, Adeline Jullien, Antoine Yrondi, Philippe Cestac, François Montastruc
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- Published online by Cambridge University Press:
- 26 April 2023, pp. 4305-4315
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While previous systematic reviews of trials evaluating conventional antidepressants highlighted inadequacies and inconsistencies in adverse event (AE) reporting, no evaluation is available on esketamine in resistant depression. The objective of this review was to assess quality of reporting AEs in all published clinical trials studying esketamine. It also aimed to compare the proportions of AEs reported in journal articles to those recorded in the ClinicalTrial.gov Registers. Clinical trials evaluating the efficacy and safety of esketamine in depression were searched using Medline and ClinicalTrials.gov. The quality of reporting harms was assessed using a 21-item checklist from the CONSORT Extension of Harms (1 point by item). The total quality score was graded into four categories: high (17–21), moderate (12–16), low (7–11) and very low (0–6). Ten clinical trials were included in the analysis. Nine trials were classified as ‘low quality’ with regard to safety, one trial was classified as ‘moderate quality’. Compared to AEs recorded in ClinicalTrials.gov, we found that 41.5% of serious AEs and 39% of non-serious AEs were not reported in the published articles. Among them, the majority were psychiatric events but also cardiovascular events and 94% concerned patients from esketamine groups. Quality of AEs reporting in published clinical trials of esketamine was poor and harms were reported less frequently in journal publications than in ClinicalTrial.gov Registers. The study suggests that an assessment of the benefits/risks balance of esketamine based on the results reported in trial publications is flawed due to the poor accuracy and completeness of harm data.
Original Article
Sustained specialized and family treatment in first-episode schizophrenia or related disorders: a 5-year randomized controlled trial
- Lieuwe de Haan, Don Linszen, Luuk Wouters, Koos Zwinderman, Peter Dingemans
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- Published online by Cambridge University Press:
- 08 June 2022, pp. 4316-4323
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Background
The long-term outcome of first-episode schizophrenia needs improvement. Here, we evaluate the effectiveness of 5 years sustained specialist treatment (ST), ST including Parent groups (ST + P) or treatment as usual (TAU) on psychotic relapse and social functioning.
MethodsA three condition randomized, parallel assigned, single-blind efficacy trial, in which 198 first-episode psychosis (FEP) patients aged 15–28 years were included. The effect on time to first relapse, first relapse rates, mean number of relapses per patient, and time to the improvement of social functioning were analyzed using Cox regression or ANOVA.
ResultsWe found no significant differences between treatment conditions in the ITT analysis concerning time to first relapse, nor first relapse rate. Mean number of relapses per patient differed at a trend level between ST, ST + P or TAU conditions, respectively: 0.72; 0.62 or 1.02 (p = 0.069). No evidence was found for differential effect of treatment conditions on social functioning.
ConclusionFive years sustained ST of FEP nor addition of parent groups increased time to first relapse or reduced first relapse rate, compared to sustained TAU. Indications for favorable effects of parent groups were found on relapses per patient.
Objective measures of reward sensitivity and motivation in people with high v. low anhedonia
- Chloe Slaney, Adam M. Perkins, Robert Davis, Ian Penton-Voak, Marcus R. Munafò, Conor J. Houghton, Emma S. J. Robinson
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- Published online by Cambridge University Press:
- 12 May 2022, pp. 4324-4332
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Background
Anhedonia – a diminished interest or pleasure in activities – is a core self-reported symptom of depression which is poorly understood and often resistant to conventional antidepressants. This symptom may occur due to dysfunction in one or more sub-components of reward processing: motivation, consummatory experience and/or learning. However, the precise impairments remain elusive. Dissociating these components (ideally, using cross-species measures) and relating them to the subjective experience of anhedonia is critical as it may benefit fundamental biology research and novel drug development.
MethodsUsing a battery of behavioural tasks based on rodent assays, we examined reward motivation (Joystick-Operated Runway Task, JORT; and Effort-Expenditure for Rewards Task, EEfRT) and reward sensitivity (Sweet Taste Test) in a non-clinical population who scored high (N = 32) or low (N = 34) on an anhedonia questionnaire (Snaith–Hamilton Pleasure Scale).
ResultsCompared to the low anhedonia group, the high anhedonia group displayed marginal impairments in effort-based decision-making (EEfRT) and reduced reward sensitivity (Sweet Taste Test). However, we found no evidence of a difference between groups in physical effort exerted for reward (JORT). Interestingly, whilst the EEfRT and Sweet Taste Test correlated with anhedonia measures, they did not correlate with each other. This poses the question of whether there are subgroups within anhedonia; however, further work is required to directly test this hypothesis.
ConclusionsOur findings suggest that anhedonia is a heterogeneous symptom associated with impairments in reward sensitivity and effort-based decision-making.
Multimorbidity clusters among people with serious mental illness: a representative primary and secondary data linkage cohort study
- Ruimin Ma, Eugenia Romano, Mark Ashworth, Mohammad E. Yadegarfar, Alexandru Dregan, Amy Ronaldson, Claire de Oliveira, Rowena Jacobs, Robert Stewart, Brendon Stubbs
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- Published online by Cambridge University Press:
- 29 April 2022, pp. 4333-4344
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Background
People with serious mental illness (SMI) experience higher mortality partially attributable to higher long-term condition (LTC) prevalence. However, little is known about multiple LTCs (MLTCs) clustering in this population.
MethodsPeople from South London with SMI and two or more existing LTCs aged 18+ at diagnosis were included using linked primary and mental healthcare records, 2012–2020. Latent class analysis (LCA) determined MLTC classes and multinominal logistic regression examined associations between demographic/clinical characteristics and latent class membership.
ResultsThe sample included 1924 patients (mean (s.d.) age 48.2 (17.3) years). Five latent classes were identified: ‘substance related’ (24.9%), ‘atopic’ (24.2%), ‘pure affective’ (30.4%), ‘cardiovascular’ (14.1%), and ‘complex multimorbidity’ (6.4%). Patients had on average 7–9 LTCs in each cluster. Males were at increased odds of MLTCs in all four clusters, compared to the ‘pure affective’. Compared to the largest cluster (‘pure affective’), the ‘substance related’ and the ‘atopic’ clusters were younger [odds ratios (OR) per year increase 0.99 (95% CI 0.98–1.00) and 0.96 (0.95–0.97) respectively], and the ‘cardiovascular’ and ‘complex multimorbidity’ clusters were older (ORs 1.09 (1.07–1.10) and 1.16 (1.14–1.18) respectively). The ‘substance related’ cluster was more likely to be White, the ‘cardiovascular’ cluster more likely to be Black (compared to White; OR 1.75, 95% CI 1.10–2.79), and both more likely to have schizophrenia, compared to other clusters.
ConclusionThe current study identified five latent class MLTC clusters among patients with SMI. An integrated care model for treating MLTCs in this population is recommended to improve multimorbidity care.
Reduced anhedonia following internet-based cognitive-behavioral therapy for depression is mediated by enhanced reward circuit activation
- Shir Hanuka, Elizabeth A. Olson, Roee Admon, Christian A. Webb, William D. S. Killgore, Scott L. Rauch, Isabelle M. Rosso, Diego A. Pizzagalli
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- 17 June 2022, pp. 4345-4354
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Background
Major depressive disorder (MDD) is a highly prevalent psychiatric condition, yet many patients do not receive adequate treatment. Novel and highly scalable interventions such as internet-based cognitive-behavioral-therapy (iCBT) may help to address this treatment gap. Anhedonia, a hallmark symptom of MDD that refers to diminished interest and ability to experience pleasure, has been associated with reduced reactivity in a neural reward circuit that includes medial prefrontal and striatal brain regions. Whether iCBT can reduce anhedonia severity in MDD patients, and whether these therapeutic effects are accompanied by enhanced reward circuit reactivity has yet to be examined.
MethodsFifty-two MDD patients were randomly assigned to either 10-week iCBT (n = 26) or monitored attention control (MAC, n = 26) programs. All patients completed pre- and post-treatment assessments of anhedonia (Snaith–Hamilton Pleasure Scale; SHAPS) and reward circuit reactivity [monetary incentive delay (MID) task during functional magnetic resonance imaging (fMRI)]. Healthy control participants (n = 42) also underwent two fMRI scans while completing the MID task 10 weeks apart.
ResultsBoth iCBT and MAC groups exhibited a reduction in anhedonia severity post-treatment. Nevertheless, only the iCBT group exhibited enhanced nucleus accumbens (Nacc) and subgenual anterior cingulate cortex (sgACC) activation and functional connectivity from pre- to post-treatment in response to reward feedback. Enhanced Nacc and sgACC activations were associated with reduced anhedonia severity following iCBT treatment, with enhanced Nacc activation also mediating the reduction in anhedonia severity post-treatment.
ConclusionsThese findings suggest that increased reward circuit reactivity may contribute to a reduction in anhedonia severity following iCBT treatment for depression.
Associations of neuroimaging markers with depressive symptoms over time in middle-aged and elderly persons
- Fatih Özel, Saima Hilal, Maud de Feijter, Isabelle van der Velpen, Nese Direk, M. Arfan Ikram, Meike W. Vernooij, Annemarie I. Luik
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- Published online by Cambridge University Press:
- 10 May 2022, pp. 4355-4363
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Background
Cerebrovascular disease is regarded as a potential cause of late-life depression. Yet, evidence for associations of neuroimaging markers of vascular brain disease with depressive symptoms is inconclusive. We examined the associations of neuroimaging markers and depressive symptoms in a large population-based study of middle-aged and elderly persons over time.
MethodsA total of 4943 participants (mean age = 64.6 ± 11.1 years, 55.7% women) from the Rotterdam Study were included. At baseline, total brain volume, gray matter volume, white matter volume, white matter hyperintensities volume, cortical infarcts, lacunar infarcts, microbleeds, white matter fractional anisotropy, and mean diffusivity (MD) were measured with a brain MRI (1.5T). Depressive symptoms were assessed twice with the Center for Epidemiologic Studies Depression scale (median follow-up time: 5.5 years, IQR = 0.9). To assess temporal associations of neuroimaging markers and depressive symptoms, linear mixed models were used.
ResultsA smaller total brain volume (β = −0.107, 95% CI −0.192 to −0.022), larger white matter hyperintensities volume (β = 0.047, 95% CI 0.010–0.084), presence of cortical infarcts (β = 0.194, 95% CI 0.047–0.341), and higher MD levels (β = 0.060, 95% CI 0.022–0.098) were cross-sectionally associated with more depressive symptoms. Longitudinal analyses showed that small total brain volume (β = −0.091, 95% CI −0.167 to −0.015) and presence of cortical infarcts (β = 0.168, 95% CI 0.022–0.314) were associated with increasing depressive symptoms over time. After stratification on age, effect sizes were more pronounced at older ages.
ConclusionsNeuroimaging markers of white matter microstructural damage were associated with depressive symptoms longitudinally in this study of middle-aged and elderly persons. These associations were more pronounced at older ages, providing evidence for the role of white matter structure in late-life depressive symptomatology.
Trends in suicide attempts and suicide deaths before and during the COVID-19 pandemic in New Taipei City, Taiwan: an interrupted time-series analysis
- Yi-Jen Su, Hsiu-Ting Yu, Ting-Yu Liu, Kuan-Hung Lu, Chung-Chieh Tu, Yu-Ching Lin, Ran-Chou Chen
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- Published online by Cambridge University Press:
- 28 April 2022, pp. 4364-4372
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Background
The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented global health crisis that may cause mental health problems and heighten suicide risk. We investigated the impact of the COVID-19 pandemic on trends in suicide attempts and suicide deaths in New Taipei City, Taiwan.
MethodsThe current study used the official daily data on suicide attempts and deaths in New Taipei City, Taiwan (4 million inhabitants) between 2015 and 2020 from the Taiwan National Suicide Prevention Reporting System. Interrupted time-series (ITS) analyses with parameters corrected by the estimated autocorrelations were applied on weekly aggregated data to examine whether the suicide trends during the early COVID-19 pandemic (late January to July 2020) deviated from previous trends (January 2015 to late January 2020). The impact due to the suicide prevention policy change was also examined (since August 2020).
ResultsITS analyses revealed no significant increases in both mean and trend on weekly suicide deaths during the COVID-19 pandemic and after the policy change. In contrast, there was a significant increasing trend in weekly suicide attempts since the COVID-19 outbreak at the rate of 1.54 attempts per week (95% confidence interval 0.49–2.60; p = 0.004). Sex difference analysis revealed that, however, this increasing trend was observed only in females not in males.
ConclusionsThe COVID-19 pandemic has different impacts on suicides attempts and deaths during the early pandemic in New Taipei City, Taiwan. The COVID-19 outbreak drastically increased the trend of suicide attempts. In contrast, the number of suicide deaths had remained constant in the investigated periods.
Virtual reality (VR) therapy for patients with psychosis: satisfaction and side effects
- Daniel Freeman, Laina Rosebrock, Felicity Waite, Bao Sheng Loe, Thomas Kabir, Ariane Petit, Robert Dudley, Kate Chapman, Anthony Morrison, Eileen O'Regan, Charlotte Aynsworth, Julia Jones, Elizabeth Murphy, Rosie Powling, Heather Peel, Harry Walker, Rory Byrne, Jason Freeman, Aitor Rovira, Ushma Galal, Ly-Mee Yu, David M. Clark, Sinéad Lambe
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- Published online by Cambridge University Press:
- 28 April 2022, pp. 4373-4384
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Background
Automated virtual reality therapies are being developed to increase access to psychological interventions. We assessed the experience with one such therapy of patients diagnosed with psychosis, including satisfaction, side effects, and positive experiences of access to the technology. We tested whether side effects affected therapy.
MethodsIn a clinical trial 122 patients diagnosed with psychosis completed baseline measures of psychiatric symptoms, received gameChange VR therapy, and then completed a satisfaction questionnaire, the Oxford-VR Side Effects Checklist, and outcome measures.
Results79 (65.8%) patients were very satisfied with VR therapy, 37 (30.8%) were mostly satisfied, 3 (2.5%) were indifferent/mildly dissatisfied, and 1 (0.8%) person was quite dissatisfied. The most common side effects were: difficulties concentrating because of thinking about what might be happening in the room (n = 17, 14.2%); lasting headache (n = 10, 8.3%); and the headset causing feelings of panic (n = 9, 7.4%). Side effects formed three factors: difficulties concentrating when wearing a headset, feelings of panic using VR, and worries following VR. The occurrence of side effects was not associated with number of VR sessions, therapy outcomes, or psychiatric symptoms. Difficulties concentrating in VR were associated with slightly lower satisfaction. VR therapy provision and engagement made patients feel: proud (n = 99, 81.8%); valued (n = 97, 80.2%); and optimistic (n = 96, 79.3%).
ConclusionsPatients with psychosis were generally very positive towards the VR therapy, valued having the opportunity to try the technology, and experienced few adverse effects. Side effects did not significantly impact VR therapy. Patient experience of VR is likely to facilitate widespread adoption.
Multiple serum biomarkers for predicting suicidal behaviours in depressive patients receiving pharmacotherapy
- Jae-Min Kim, Hee-Ju Kang, Ju-Wan Kim, Wonsuk Choi, Ju-Yeon Lee, Sung-Wan Kim, Il-Seon Shin, Min-Gon Kim, Byung Jo Chun, Robert Stewart
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- Published online by Cambridge University Press:
- 17 May 2022, pp. 4385-4394
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Background
Predictive values of multiple serum biomarkers for suicidal behaviours (SBs) have rarely been tested. This study sought to evaluate and develop a panel of multiple serum biomarkers for predicting SBs in outpatients receiving a 12-month pharmacotherapy programme for depressive disorders.
MethodsAt baseline, 14 serum biomarkers and socio-demographic/clinical characteristics including previous suicidal attempt and present suicidal severity were evaluated in 1094 patients with depressive disorders without a bipolar diagnosis. Of these, 884 were followed for increased suicidal severity and fatal/non-fatal suicide attempt outcomes over a 12-month treatment period. Individual and combined effects of serum biomarkers on these two prospective SBs were estimated using logistic regression analysis after adjustment for relevant covariates.
ResultsIncreased suicidal severity and fatal/non-fatal suicide attempt during the 12-month pharmacotherapy were present in 155 (17.5%) and 38 (4.3%) participants, respectively. Combined cortisol, total cholesterol, and folate serum biomarkers predicted fatal/non-fatal suicide attempt, and these with interleukin-1 beta and homocysteine additionally predicted increased suicidal severity, with clear gradients robust to adjustment (p values < 0.001).
ConclusionsApplication of multiple serum biomarkers could considerably improve the predictability of SBs during the outpatient treatment of depressive disorders, potentially highlighting the need for more frequent monitoring and risk appraisal.
Risk of psychosis among migrants to the Netherlands by time since arrival
- Fabian Termorshuizen, Jean-Paul Selten
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- 05 May 2022, pp. 4395-4404
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Background
The high risk of psychosis among migrants is often attributed to social stressors in the host country. We examined whether the relative risk of psychosis among migrants is low on arrival and increases thereafter.
MethodsIn this cohort study, first-generation immigrants to the Netherlands, aged 10 years and older (N = 1 281 678), were matched by birth year and sex to 2 542 313 native-born Dutch controls. The first occurrence of psychosis after arrival was established using data on dispensing of antipsychotic medication (APM) (during 2006–2017) and on insurance claims for treatment of psychosis (2011–2016). The Incidence Rate Ratios (IRRs) for migrants compared to controls were estimated by year since arrival.
ResultsThe IRR of APM was 0.22 (95% CI 0.21–0.24) in the year of arrival (‘year 1’) and increased gradually to 1.39 (1.19–1.62) after 10 or more years. The IRR of an insurance claim increased from 0.57 (0.51–0.62) to 1.87 (1.38–2.55) in year 5. Among migrants from sub-Saharan Africa, the IRR of an insurance claim was already high in year 1 [2.46 (1.95–3.11)], especially when aged 10–20 years at arrival [6.09 (2.93–12.64)]. Among migrants from other non-Western countries, the IRR was already significantly increased in year 2 [1.28 (1.03–1.59)].
ConclusionsThe relative risk of psychosis among migrants was generally low at arrival and increased thereafter. The increased IRRs in the early years after arrival among those from non-Western countries indicate that for these groups certain risk factors are already relevant shortly after arrival.
Evaluating the role of maladaptive personality traits in schema therapy and cognitive behavioural therapy for depression
- Katharina Rek, Nils Kappelmann, Johannes Zimmermann, Martin Rein, Samy Egli, Johannes Kopf-Beck
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- Published online by Cambridge University Press:
- 10 May 2022, pp. 4405-4414
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Background
Advancements in the treatment of depression are pivotal due to high levels of non-response and relapse. This study evaluated the role of personality pathology in the treatment of depression by testing whether maladaptive personality traits (1) predict changes in depression over treatment or vice versa, (2) change themselves over treatment, (3) change differentially depending on treatment with schema therapy (ST) or cognitive behavioural therapy (CBT), and (4) moderate the effectiveness of these treatments.
MethodsWe included 193 depressed inpatients (53.4% women, Mage = 42.9, SD = 13.4) participating in an assessor-blind randomized clinical trial and receiving a 7-week course of ST or CBT. The research questions were addressed using multiple indicator latent change score models as well as multigroup structural equation models implemented in EffectLiteR.
ResultsMaladaptive traits did not predict changes in depressive symptoms at post-treatment, or vice versa. However, maladaptive trait domains decreased over treatment (standardized Δμ range: −0.38 to −0.89), irrespective of treatment with ST or CBT. Maladaptive traits at baseline did not moderate the effectiveness of these treatments.
ConclusionsSelf-reported maladaptive personality traits can change during treatment of depression, but may have limited prognostic or prescriptive value, at least in the context of ST or CBT. These results need to be replicated using follow-up data, larger and more diverse samples, and informant-rated measures of personality pathology.
A lifespan perspective on depression in the postpartum period in a racially and socioeconomically diverse sample of young mothers
- Alison E. Hipwell, Irene Tung, Robert T. Krafty, Audrey W. Leong, Meredith Spada, Hope Vaccaro, Sarah C. Homitsky, Eydie Moses-Kolko, Kate Keenan
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- Published online by Cambridge University Press:
- 06 May 2022, pp. 4415-4423
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Background
Consistent evidence from retrospective reports and case registry studies indicates that a history of depression is a major risk factor for depression in the peripartum period. However, longitudinal studies with racially and socioeconomically diverse samples of young mothers are lacking, and little is known about developmental patterns of depression across the lifespan that can inform preventive interventions.
MethodsYoung primiparous mothers (n = 399, 13–25 years, 81% Black) were recruited from a population-based prospective study that began in childhood. Women reported on depression symptoms for at least 3 years prior to their pregnancy, during pregnancy, and at 4 months postpartum. Linear regression models were used to estimate change in pre-pregnancy depression severity and to evaluate associations between patterns of lifetime history and postpartum depression symptoms.
ResultsResults revealed high levels of continuity in depression from pregnancy to postpartum, and across multiple years pre-pregnancy to postpartum. Overall, depression severity leading up to pregnancy decreased over time, but patterns of worsening or improving symptoms were not associated with depression severity in the postpartum period. Instead, area under the pre-pregnancy trajectory curve, representing cumulative lifetime depression burden, was uniquely associated with postpartum depression after adjusting for prenatal depression severity.
ConclusionsDepression in the postpartum period should be considered within a lifespan perspective of risk that accumulates before conception. Clinical screening and early interventions are needed in adolescence and young adulthood to prevent the onset and persistence of depressive symptoms that could have long-term implications for peripartum health.
Multi-modal assessment of reward functioning in adolescent anhedonia
- Laura Murray, Elana S. Israel, Emma G. Balkind, Brianna Pastro, Nathaniel Lovell-Smith, Scott E. Lukas, Erika E. Forbes, Diego A. Pizzagalli, Christian A. Webb
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- Published online by Cambridge University Press:
- 17 June 2022, pp. 4424-4433
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Background
Anhedonia is a core symptom of depression that predicts worse treatment outcomes. Dysfunction in neural reward circuits is thought to contribute to anhedonia. However, whether laboratory-based assessments of anhedonia and reward-related neural function translate to adolescents' subjective affective experiences in real-world contexts remains unclear.
MethodsWe recruited a sample of adolescents (n = 82; ages 12–18; mean = 15.83) who varied in anhedonia and measured the relationships among clinician-rated and self-reported anhedonia, behaviorally assessed reward learning ability, neural response to monetary reward and loss (as assessed with functional magnetic resonance imaging), and repeated ecological momentary assessment (EMA) of positive affect (PA) and negative affect (NA) in daily life.
ResultsAnhedonia was associated with lower mean PA and higher mean NA across the 5-day EMA period. Anhedonia was not related to impaired behavioral reward learning, but low PA was associated with reduced nucleus accumbens response during reward anticipation and reduced medial prefrontal cortex (mPFC) response during reward outcome. Greater mean NA was associated with increased mPFC response to loss outcome.
ConclusionsTraditional laboratory-based measures of anhedonia were associated with lower subjective PA and higher subjective NA in youths' daily lives. Lower subjective PA and higher subjective NA were associated with decreased reward-related striatal functioning. Higher NA was also related to increased mPFC activity to loss. Collectively, these findings demonstrate that laboratory-based measures of anhedonia translate to real-world contexts and that subjective ratings of PA and NA may be associated with neural response to reward and loss.
Online harms? Suicide-related online experience: a UK-wide case series study of young people who die by suicide
- C. Rodway, S. G. Tham, N. Richards, S. Ibrahim, P. Turnbull, N. Kapur, L. Appleby
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- Published online by Cambridge University Press:
- 19 May 2022, pp. 4434-4445
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Background
Few studies have examined online experience by young people who die by suicide.
MethodsA 3-year UK-wide consecutive case series of all young people aged 10–19 who died by suicide, based on national mortality data. We extracted information on the antecedents of suicide of 544 of these 595 deaths (91%) from official investigations, mainly inquests.
ResultsSuicide-related online experience was reported in 24% (n = 128/544) of suicide deaths in young people between 2014 and 2016, equivalent to 43 deaths per year, and was more common in girls than boys (OR 1.87, 95% CI 1.23–2.85, p = 0.003) and those identifying as LGBT (OR 2.35, 95% CI 1.10–5.05, p = 0.028). Searching for information about method was most common (n = 68, 13%), followed by posting suicidal ideas online (n = 57, 10%). Self-harm, bereavement (especially by suicide), social isolation, and mental and physical ill-health were more likely in those known to have suicide-related online experience compared to those who did not. 29 (5%) were bullied online, more often girls (OR 2.84, 1.34–6.04, p = 0.007). Online bullying often accompanied face-to-face bullying (n = 16/29, 67%).
ConclusionsSuicide-related online experience is a common, but likely underestimated, antecedent to suicide in young people. Although its causal role is unclear, it may influence suicidality in this population. Mental health professionals should be aware that suicide-related online experience – not limited to social media – is a potential risk for young patients, and may be linked to experiences offline. For public health, wider action is required on internet regulation and support for children and their families.
Effects of religion on the course of suicidality among geriatric patients with mood disorders
- David H. Rosmarin, Steven Pirutinsky, Soohyun Park, Mia Drury, David Harper, Brent P. Forester
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- 12 May 2022, pp. 4446-4453
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Background
A growing volume of research suggests that religion protects against late-life suicide, but it remains unclear whether effects are relevant to clinical samples, which facets of religion are most relevant, and variations over the course of mood disorders (e.g. during periods of euthymia, depression, and/or heightened suicidality).
MethodEighty adults aged 55–85 years with mood disorders completed assessments of religion (affiliation, service attendance, importance of religion, belief and faith in God), depression, and suicidality over time (M = 7.31 measurements over M = 727 days). We computed metrics to identify mean and maximum levels of depression and suicidality, and the number of episodes of significant depression and suicidality experienced by each participant.
ResultsReligious affiliation and importance of religion, but not service attendance, belief, or faith in God, were associated with lower mean and maximum depression. Conversely, all facets of religion predicted significantly lower mean and maximum levels of suicidality (rs ranging from −0.24 to −0.39), and substantially less likelihood of experiencing significant suicidality during the study (ORs ranging from 0.19 to 0.33). Service attendance, belief, and faith in God predicted less suicidality even among individuals who did not affiliate with a religious group.
ConclusionsReligious factors, particularly faith in God, are associated with substantially less suicidality over time among older adults with mood disorders, irrespective of religious affiliation.
Cognitive performances across individuals at high genetic risk for schizophrenia, high genetic risk for bipolar disorder, and low genetic risks: a combined polygenic risk score approach
- Kazutaka Ohi, Daisuke Nishizawa, Shunsuke Sugiyama, Kentaro Takai, Daisuke Fujikane, Ayumi Kuramitsu, Junko Hasegawa, Midori Soda, Kiyoyuki Kitaichi, Ryota Hashimoto, Kazutaka Ikeda, Toshiki Shioiri
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- Published online by Cambridge University Press:
- 16 August 2022, pp. 4454-4463
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Background
Individuals with schizophrenia (SCZ) and bipolar disorder (BD) display cognitive impairments, but the impairments in those with SCZ are more prominent, supported by genetic overlap between SCZ and cognitive impairments. However, it remains unclear whether cognitive performances differ between individuals at high and low genetic risks for SCZ or BD.
MethodsUsing the latest Psychiatric Genomics Consortium (PGC) data, we calculated PGC3 SCZ-, PGC3 BD-, and SCZ v. BD polygenic risk scores (PRSs) in 173 SCZ patients, 70 unaffected first-degree relatives (FRs) and 196 healthy controls (HCs). Based on combinations of three PRS deciles, individuals in the genetic SCZ, genetic BD and low genetic risk groups were extracted. Cognitive performance was assessed by the Brief Assessment of Cognition in Schizophrenia.
ResultsSCZ-, BD-, SCZ v. BD-PRSs were associated with case–control status (R2 = 0.020–0.061), and SCZ-PRS was associated with relative–control status (R2 = 0.023). Furthermore, individuals in the highest decile for SCZ PRSs had elevated BD-PRSs [odds ratio (OR) = 6.33] and SCZ v. BD-PRSs (OR = 1.86) compared with those in the lowest decile. Of the three genetic risk groups, the low genetic risk group contained more HCs, whereas the genetic BD and SCZ groups contained more SCZ patients (p < 0.05). SCZ patients had widespread cognitive impairments, and FRs had cognitive impairments that were between those of SCZ patients and HCs (p < 0.05). Cognitive differences between HCs in the low genetic risk group and SCZ patients in the genetic BD or genetic SCZ groups were more prominent (Cohen's d > −0.20) than those between HCs and SCZ patients in the no genetic risk group. Furthermore, SCZ patients in the genetic SCZ group displayed lower scores in verbal fluency and attention than those in the genetic BD group (d > −0.20).
ConclusionsOur findings suggest that cognitive impairments in SCZ are partially mediated through genetic loadings for SCZ but not BD.
Volume of hippocampus-amygdala transition area predicts outcomes of electroconvulsive therapy in major depressive disorder: high accuracy validated in two independent cohorts
- Jinping Xu, Wenfei Li, Tongjian Bai, Jiaying Li, Jinhuan Zhang, Qingmao Hu, Jiaojian Wang, Yanghua Tian, Kai Wang
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- Published online by Cambridge University Press:
- 23 May 2022, pp. 4464-4473
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Background
Although many previous studies reported structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy (ECT) in major depressive disorder (MDD), yet the exact roles of both areas for antidepressant effects are still controversial.
MethodsIn the current study, segmentation of amygdala and hippocampal sub-regions was used to investigate the longitudinal changes of volume, the relationship between volume and antidepressant effects, and prediction performances for ECT in MDD patients before and after ECT using two independent datasets.
ResultsAs a result, MDD patients showed selectively and consistently increased volume in the left lateral nucleus, right accessory basal nucleus, bilateral basal nucleus, bilateral corticoamygdaloid transition (CAT), bilateral paralaminar nucleus of the amygdala, and bilateral hippocampus-amygdala transition area (HATA) after ECT in both datasets, whereas marginally significant increase of volume in bilateral granule cell molecular layer of the head of dentate gyrus, the bilateral head of cornu ammonis (CA) 4, and left head of CA 3. Correlation analyses revealed that increased volume of left HATA was significantly associated with antidepressant effects after ECT. Moreover, volumes of HATA in the MDD patients before ECT could be served as potential biomarkers to predict ECT remission with the highest accuracy of 86.95% and 82.92% in two datasets (The predictive models were trained on Dataset 2 and the sensitivity, specificity and accuracy of Dataset 2 were obtained from leave-one-out-cross-validation. Thus, they were not independent and very likely to be inflated).
ConclusionsThese results not only suggested that ECT could selectively induce structural plasticity of the amygdala and hippocampal sub-regions associated with antidepressant effects of ECT in MDD patients, but also provided potential biomarkers (especially HATA) for effectively and timely interventions for ECT in clinical applications.
Is an elevated family-genetic risk for major psychiatric disorders specific to creative occupations?
- Kenneth S. Kendler, Henrik Ohlsson, Jan Sundquist, Kristina Sundquist
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- 08 June 2022, pp. 4474-4486
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Background
Despite a large descriptive literature linking creativity and risk for psychiatric illness, the magnitude and specificity of this relationship remain controversial.
MethodsWe examined, in 1 137 354 native Swedes with one of 59 3-digit official and objective occupational codes in managerial and educated classes, their familial genetic risk score (FGRS) for ten major disorders, calculated from 1st through 5th degree relatives. Mean FGRS across disorders were calculated, in 3- and 4-digit occupational groups, and then controlled for those whose disorder onset preceded occupational choice. Using sequential analyses, p values were evaluated using Bonferroni correction.
Results3-digit professions considered to reflect creativity (e.g. ‘artists’ and ‘authors’) were among those with statistically significant elevations of FGRS. Among more specific 4-digit codes, visual artists, actors, and authors stood out with elevated genetic risks, highest for major depression (MD), anxiety disorders (AD) and OCD, more modest for bipolar disorders (BD) and schizophrenia and, for authors, for drug and alcohol use disorders. However, equal or greater elevations in FGRS across disorders were seen for religious (e.g. ministers), helping (e.g. psychologists, social workers), and teaching/academic occupations (e.g. professors). The potential pathway from FGRS → Disorder → Occupation accounts for a modest proportion of the signal, largely for MD and AD risk.
ConclusionsWhile traditional creative occupations were associated with elevated genetic risk for a range of psychiatric disorders, this association was not unique, as similar, or greater elevations were seen for religious, helping and teaching professions and was stronger for internalizing than psychotic disorders.
Continuity of psychopathology v. resilience across the transition to adolescence: role of hair cortisol and sensitive caregiving
- Karen Yirmiya, Shai Motsan, Orna Zagoory-Sharon, Anat Schonblum, Lee Koren, Ruth Feldman
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- Published online by Cambridge University Press:
- 30 May 2022, pp. 4487-4498
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Background
The transition to adolescence implicates heightened vulnerability alongside increased opportunities for resilience. Contexts of early life stress (ELS) exacerbate risk; still, little research addressed biobehavioral mediators of risk and resilience across the adolescent transition following ELS. Utilizing a unique cohort, we tested biosocial moderators of chronicity in adolescents’ internalizing disorders v. resilience.
MethodFamilies exposed to chronic war-related trauma, v. controls, were followed. We utilized data from three time-points framing the adolescent transition: late childhood (N = 177, Mage = 9.3 years ± 1.41), early adolescence (N = 111, Mage = 11 0.66 years ± 1.23), and late adolescence (N = 138, Mage = 15.65 years ± 1.31). In late childhood and late adolescence children's internalizing disorders were diagnosed. At early adolescence maternal and child's hair cortisol concentrations (HCC), maternal sensitivity, and mothers’ post-traumatic symptoms evaluated.
ResultsWar-exposed children exhibited more internalizing disorders of chronic trajectory and mothers were less sensitive and more symptomatic. Three pathways elucidated the continuity of psychopathology: (a) maternal sensitivity moderated the risk of chronic psychopathology, (b) maternal post-traumatic symptoms mediated continuity of risk, (c) trauma exposure moderated the association between child internalizing disorders at late childhood and maternal HCC, which linked with child HCC. Child HCC linked with maternal post-traumatic symptoms, which were associated with child disorders in late adolescence.
ConclusionResults demonstrate the complex interplay of maternal and child's biosocial factors as mediators and moderators of risk chronicity across the adolescent transition following trauma. Findings are first to utilize maternal and child's HCC as biomarkers of chronic stress v. resilience during adolescence, a period of neural reorganization and personal growth that shapes the individual's lifetime adaptation.
Statistical power in clinical trials of interventions for mood, anxiety, and psychotic disorders
- Ymkje Anna de Vries, Robert A. Schoevers, Julian P. T. Higgins, Marcus R. Munafò, Jojanneke A. Bastiaansen
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- 19 May 2022, pp. 4499-4506
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Background
Previous research has suggested that statistical power is suboptimal in many biomedical disciplines, but it is unclear whether power is better in trials for particular interventions, disorders, or outcome types. We therefore performed a detailed examination of power in trials of psychotherapy, pharmacotherapy, and complementary and alternative medicine (CAM) for mood, anxiety, and psychotic disorders.
MethodsWe extracted data from the Cochrane Database of Systematic Reviews (Mental Health). We focused on continuous efficacy outcomes and estimated power to detect predetermined effect sizes (standardized mean difference [SMD] = 0.20–0.80, primary SMD = 0.40) and meta-analytic effect sizes (ESMA). We performed meta-regression to estimate the influence of including underpowered studies in meta-analyses.
ResultsWe included 256 reviews with 10 686 meta-analyses and 47 384 studies. Statistical power for continuous efficacy outcomes was very low across intervention and disorder types (overall median [IQR] power for SMD = 0.40: 0.32 [0.19–0.54]; for ESMA: 0.23 [0.09–0.58]), only reaching conventionally acceptable levels (80%) for SMD = 0.80. Median power to detect the ESMA was higher in treatment-as-usual (TAU)/waitlist-controlled (0.49–0.63) or placebo-controlled (0.12–0.38) trials than in trials comparing active treatments (0.07–0.13). Adequately-powered studies produced smaller effect sizes than underpowered studies (B = −0.06, p ⩽ 0.001).
ConclusionsPower to detect both predetermined and meta-analytic effect sizes in psychiatric trials was low across all interventions and disorders examined. Consistent with the presence of reporting bias, underpowered studies produced larger effect sizes than adequately-powered studies. These results emphasize the need to increase sample sizes and to reduce reporting bias against studies reporting null results to improve the reliability of the published literature.