Original Article
Association between psychomotor disturbance and treatment outcome in psychotic depression: a STOP-PD II report
- Alastair J. Flint, Kathleen S. Bingham, Nicholas H. Neufeld, George S. Alexopoulos, Benoit H. Mulsant, Anthony J. Rothschild, Ellen M. Whyte, Aristotle N. Voineskos, Patricia Marino, Barnett S. Meyers
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- Published online by Cambridge University Press:
- 26 March 2021, pp. 3957-3963
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Background
Little is known about the relationship between psychomotor disturbance (PMD) and treatment outcome of psychotic depression. This study examined the association between PMD and subsequent remission and relapse of treated psychotic depression.
MethodsTwo hundred and sixty-nine men and women aged 18–85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission or near-remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine (n = 64) with sertraline plus placebo (n = 62). PMD was measured with the psychiatrist-rated sign-based CORE at acute phase baseline and at RCT baseline. Spearman's correlations and logistic regression analyses were used to analyze the association between CORE total score at acute phase baseline and remission/near-remission and CORE total score at RCT baseline and relapse.
ResultsHigher CORE total score at acute phase baseline was associated with lower frequency of remission/near-remission. Higher CORE total score at RCT baseline was associated with higher frequency of relapse, in the RCT sample as a whole, as well as in each of the two randomized groups.
ConclusionsPMD is associated with poorer outcome of psychotic depression treated with sertraline plus olanzapine. Future research needs to examine the neurobiology of PMD in psychotic depression in relation to treatment outcome.
Effects of tDCS during inhibitory control training on performance and PTSD, aggression and anxiety symptoms: a randomized-controlled trial in a military sample
- Fenne M. Smits, Elbert Geuze, Dennis J. L. G. Schutter, Jack van Honk, Thomas E. Gladwin
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- Published online by Cambridge University Press:
- 24 March 2021, pp. 3964-3974
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Background
Post-traumatic stress disorder (PTSD), anxiety, and impulsive aggression are linked to transdiagnostic neurocognitive deficits. This includes impaired inhibitory control over inappropriate responses. Prior studies showed that inhibitory control can be improved by modulating the right inferior frontal gyrus (IFG) with transcranial direct current stimulation (tDCS) in combination with inhibitory control training. However, its clinical potential remains unclear. We therefore aimed to replicate a tDCS-enhanced inhibitory control training in a clinical sample and test whether this reduces stress-related mental health symptoms.
MethodsIn a preregistered double-blind randomized-controlled trial, 100 active-duty military personnel and post-active veterans with PTSD, anxiety, or impulsive aggression symptoms underwent a 5-session intervention where a stop-signal response inhibition training was combined with anodal tDCS over the right IFG for 20 min at 1.25 mA. Inhibitory control was evaluated with the emotional go/no-go task and implicit association test. Stress-related symptoms were assessed by self-report at baseline, post-intervention, and after 3-months and 1-year follow-ups.
ResultsActive relative to sham tDCS neither influenced performance during inhibitory control training nor on assessment tasks, and did also not significantly influence self-reported symptoms of PTSD, anxiety, impulsive aggression, or depression at post-assessment or follow-up.
ConclusionsOur results do not support the idea that anodal tDCS over the right IFG at 1.25 mA enhances response inhibition training in a clinical sample, or that this tDCS-training combination can reduce stress-related symptoms. Applying different tDCS parameters or combining tDCS with more challenging tasks might provide better conditions to modulate cognitive functioning and stress-related symptoms.
Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder
- Jessica Mundy, Christopher Hübel, Joel Gelernter, Daniel Levey, Robin M. Murray, Megan Skelton, Murray B. Stein, The Million Veteran Program, Post Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium , Evangelos Vassos, Gerome Breen, Jonathan R. I. Coleman
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- Published online by Cambridge University Press:
- 04 June 2021, pp. 3975-3984
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Background
Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD.
MethodsGenetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals.
ResultsGenetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01–1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ2 > 166, p < 0.001)
ConclusionsOur findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.
Impaired executive function exacerbates neural markers of posttraumatic stress disorder
- Audreyana Jagger-Rickels, Anna Stumps, David Rothlein, Hannah Park, Francesca Fortenbaugh, Agnieszka Zuberer, Jennifer R. Fonda, Catherine B. Fortier, Joseph DeGutis, William Milberg, Regina McGlinchey, Michael Esterman
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- Published online by Cambridge University Press:
- 21 April 2021, pp. 3985-3998
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Background
A major obstacle in understanding and treating posttraumatic stress disorder (PTSD) is its clinical and neurobiological heterogeneity. To address this barrier, the field has become increasingly interested in identifying subtypes of PTSD based on dysfunction in neural networks alongside cognitive impairments that may underlie the development and maintenance of symptoms. The current study aimed to determine if subtypes of PTSD, based on normative-based cognitive dysfunction across multiple domains, have unique neural network signatures.
MethodsIn a sample of 271 veterans (90% male) that completed both neuropsychological testing and resting-state fMRI, two complementary, whole-brain functional connectivity analyses explored the link between brain functioning, PTSD symptoms, and cognition.
ResultsAt the network level, PTSD symptom severity was associated with reduced negative coupling between the limbic network (LN) and frontal-parietal control network (FPCN), driven specifically by the dorsolateral prefrontal cortex and amygdala Hubs of Dysfunction. Further, this relationship was uniquely moderated by executive function (EF). Specifically, those with PTSD and impaired EF had the strongest marker of LN-FPCN dysregulation, while those with above-average EF did not exhibit PTSD-related dysregulation of these networks.
ConclusionThese results suggest that poor executive functioning, alongside LN-FPCN dysregulation, may represent a neurocognitive subtype of PTSD.
Thirty-year outcome of anxiety and depressive disorders and personality status: comprehensive evaluation of mixed symptoms and the general neurotic syndrome in the follow-up of a randomised controlled trial
- Peter Tyrer, Helen Tyrer, Tony Johnson, Min Yang
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- 12 April 2021, pp. 3999-4008
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Background
Cohort studies of the long-term outcome of anxiety, depression and personality status rarely join together.
MethodsTwo hundred and ten patients recruited with anxiety and depression to a randomised controlled trial between 1983 and 1987 (Nottingham Study of Neurotic Disorder) were followed up over 30 years. At trial entry personality status was assessed, together with the general neurotic syndrome, a combined diagnosis of mixed anxiety–depression (cothymia) linked to neurotic personality traits. Personality assessment used a procedure allowing conversion of data to the ICD-11 severity classification of personality disorder. After the original trial, seven further assessments were made. Observer and self-ratings of psychopathology and global outcome were also made. The primary outcome at 30 years was the proportion of those with no Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis.
Data were analysed using multilevel repeated measures models that adjusted for age and gender. Missing data were assumed to be missing at random, and the models allowed all subjects to be included in the analysis with missing data automatically handled in the model estimation.
ResultsAt 30 years, 69% of those with a baseline diagnosis of panic disorder had no DSM diagnosis compared to 37–47% of those with generalised anxiety disorder, dysthymia or mixed symptoms (cothymia) (p = 0.027). Apart from those with no personality dysfunction at entry all patients had worse outcomes after 30 years with regard to total psychopathology, anxiety and depression, social function and global outcome.
ConclusionsThe long-term outcome of disorders formerly called ‘neurotic’ is poor with the exception of panic disorder. Personality dysfunction accentuates poor recovery.
Increased early motivational response to food in adolescent anorexia nervosa revealed by magnetoencephalography
- Hugo Romero Frausto, Kati Roesmann, Isabelle A. G. Klinkenberg, Maimu A. Rehbein, Manuel Föcker, Georg Romer, Markus Junghoefer, Ida Wessing
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- Published online by Cambridge University Press:
- 05 May 2021, pp. 4009-4017
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Background
It remains unclear to what extent reduced nutritional intake in anorexia nervosa (AN) is a consequence of a reduced motivational response to food. Although self-reports typically suggest AN patients have a reduced appetitive response, behavioral and neurophysiological measures have revealed evidence for both increased and reduced attentional biases towards food stimuli. The mechanisms influencing food perception in AN, might be clarified using time-sensitive magnetoencephalography (MEG) to differentiate the early (more automatic processing) stages from the late (more controlled) stages.
MethodsMEG was recorded in 22 partially weight-restored adolescent AN patients and 29 age- and gender-matched healthy control (HC) participants during a rapid serial visual presentation paradigm using 100 high-calorie food, 100 low-calorie food, and 100 non-food pictures. Neural sources of event-related fields were estimated using the L2-Minimum-Norm method and analyzed in early (50–300 ms) and late (350–500 ms) time intervals.
ResultsAN patients rated high-calorie food as less palatable and reported overall less food craving than HC participants. Nevertheless, in response to food pictures AN patients showed relative increased neural activity in the left occipito-temporal and inferior frontal regions in the early time interval. No group differences occurred in the late time interval.
ConclusionsMEG results speak against an overall reduced motivational response to food in AN. Instead, relative increased early food processing in the visual cortex suggests greater motivated attention. A greater appetitive response to food might be an adaptive mechanism in a state of undernourishment. Yet, this relative increased food processing in AN was no longer present later, arguably reflecting rapid downregulation.
Processing of infant emotion in mothers with mood disorders and implications for infant development
- Anne J. Bjertrup, Mala Moszkowicz, Ida Egmose, Anette Kjærbye-Thygesen, René E. Nielsen, Christine E. Parsons, Lars V. Kessing, Anne Katrine Pagsberg, Mette S. Væver, Kamilla W. Miskowiak
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- Published online by Cambridge University Press:
- 19 April 2021, pp. 4018-4028
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Background
Atypical neurocognitive responses to emotional stimuli are core features of unipolar depression (UD) and bipolar disorder (BD). For mothers with these mood disorders, this may influence interactions with their infants and consequently infant development. The study aimed to investigate psychophysiological and cognitive responses to infant emotional stimuli, and their relation to mother–infant interaction and infant development, in mothers with BD or UD in full or partial remission.
MethodsFour months after birth, mothers' cognitive responses to emotional infant stimuli were assessed with computerized tasks, while their facial expressions, galvanic skin responses (GSR), gazes, and fixations were recorded. Infant development and mother–infant interactions were also assessed.
ResultsWe included 76 mothers: 27 with BD, 13 with UD, and 36 without known psychiatric disorders, and their infants. Mothers with BD and UD were in full or partial remission and showed blunted GSR and spent less time looking at infant stimuli (unadjusted p values < 0.03). Mothers with BD showed subtle positive neurocognitive biases (unadjusted p values<0.04) and mothers with UD showed negative biases (unadjusted p values < 0.02). Across all mothers, some measures of atypical infant emotion processing correlated with some measures of delays in infant development and suboptimal mother–infant interaction (unadjusted p values<0.04).
ConclusionsMothers with mood disorders in full or partial remission showed atypical cognitive and psychophysiological response to emotional infant stimuli, which could be associated with mother–infant interactions and infant development. The study is explorative, hypothesis generating, and should be replicated in a larger sample. Investigation of the long-term implications of reduced maternal sensitivity is warranted.
The long shadow of childhood trauma for depression in midlife: examining daily psychological stress processes as a persistent risk pathway
- Stefanie E. Mayer, Agus Surachman, Aric A. Prather, Eli Puterman, Kevin L. Delucchi, Michael R. Irwin, Andrea Danese, David M. Almeida, Elissa S. Epel
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- Published online by Cambridge University Press:
- 26 March 2021, pp. 4029-4038
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Background
Childhood trauma (CT) increases the risk of adult depression. Buffering effects require an understanding of the underlying persistent risk pathways. This study examined whether daily psychological stress processes – how an individual interprets and affectively responds to minor everyday events – mediate the effect of CT on adult depressive symptoms.
MethodsMiddle-aged women (N = 183) reported CT at baseline and completed daily diaries of threat appraisals and negative evening affect for 7 days at baseline, 9, and 18 months. Depressive symptoms were measured across the 1.5-year period. Mediation was examined using multilevel structural equation modeling.
ResultsReported CT predicted greater depressive symptoms over the 1.5-year time period (estimate = 0.27, s.e. = 0.07, 95% CI 0.15–0.38, p < 0.001). Daily threat appraisals and negative affect mediated the effect of reported CT on depressive symptoms (estimate = 0.34, s.e. = 0.08, 95% CI 0.22–0.46, p < 0.001). Daily threat appraisals explained more than half of this effect (estimate = 0.19, s.e. = 0.07, 95% CI 0.08–0.30, p = 0.004). Post hoc analyses in individuals who reported at least moderate severity of CT showed that lower threat appraisals buffered depressive symptoms. A similar pattern was found in individuals who reported no/low severity of CT.
ConclusionsA reported history of CT acts as a latent vulnerability, exaggerating threat appraisals of everyday events, which trigger greater negative evening affect – processes that have important mental health consequences and may provide malleable intervention targets.
Associations and limited shared genetic aetiology between bipolar disorder and cardiometabolic traits in the UK Biobank
- Anna E. Fürtjes, Jonathan R. I. Coleman, Jess Tyrrell, Cathryn M. Lewis, Saskia P. Hagenaars
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- Published online by Cambridge University Press:
- 26 March 2021, pp. 4039-4048
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Background
People with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. Previous studies report cardiometabolic abnormalities in BPD, but their shared aetiology remains poorly understood. This study examined the phenotypic associations and shared genetic aetiology between BPD and various cardiometabolic traits.
MethodsIn a subset of the UK Biobank sample (N = 61 508) we investigated phenotypic associations between BPD (ncases = 4186) and cardiometabolic traits, represented by biomarkers, anthropometric traits and cardiometabolic diseases. To determine shared genetic aetiology in European ancestry, polygenic risk scores (PRS) and genetic correlations were calculated between BPD and cardiometabolic traits.
ResultsSeveral traits were significantly associated with increased risk for BPD, namely low total cholesterol, low high-density lipoprotein cholesterol, high triglycerides, high glycated haemoglobin, low systolic blood pressure, high body mass index, high waist-to-hip ratio; and stroke, coronary artery disease and type 2 diabetes diagnosis. BPD was associated with higher polygenic risk for triglycerides, waist-to-hip ratio, coronary artery disease and type 2 diabetes. Shared genetic aetiology persisted for coronary artery disease, when correcting PRS associations for cardiometabolic base phenotypes. Associations were not replicated using genetic correlations.
ConclusionsThis large study identified increased phenotypic cardiometabolic abnormalities in BPD participants. It is found that the comorbidity of coronary artery disease may be based on shared genetic aetiology. These results motivate hypothesis-driven research to consider individual cardiometabolic traits rather than a composite metabolic syndrome when attempting to disentangle driving mechanisms of cardiometabolic abnormalities in BPD.
Understanding different trajectories of mental health across the general population during the COVID-19 pandemic
- Rob Saunders, Joshua E. J. Buckman, Peter Fonagy, Daisy Fancourt
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- Published online by Cambridge University Press:
- 03 March 2021, pp. 4049-4057
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Background
The COVID-19 pandemic and nationally mandated restrictions to control the virus have been associated with increased mental health issues. However, the differential impact of the pandemic and lockdown on groups of individuals, and the personal characteristics associated with poorer outcomes are unknown.
MethodData from 21 938 adults in England who participated in a stratified cohort study were analysed. Trajectories of depression and anxiety symptoms were identified using growth mixture modelling. Multinomial and logistic regression models were constructed to identify sociodemographic and personality-related risk factors associated with trajectory class membership.
ResultsFour trajectories of depression and five for anxiety were identified. The most common group presented with low symptom severity throughout, other classes were identified that showed: severe levels of symptoms which increased; moderate symptoms throughout; worsening mental health during lockdown but improvements after lockdown ended; and for anxiety only, severe initial anxiety that decreased quickly during lockdown. Age, gender, ethnicity, income, previous diagnoses, living situation, personality factors and sociability were associated with different trajectories.
ConclusionsNearly 30% of participants experienced trajectories with symptoms in the clinical range during lockdown, and did not follow the average curve or majority group, highlighting the importance of differential trajectories. Young, female, outgoing and sociable people and essential workers experienced severe anxiety around the announcement of lockdown which rapidly decreased. Younger individuals with lower incomes and previous mental health diagnoses experienced higher and increasing levels of symptoms. Recognising the likely symptom trajectories for such groups may allow for targeted care or interventions.
Altered activation and functional connectivity in individuals with social anhedonia when envisioning positive future episodes
- Zhuo-ya Yang, Rui-ting Zhang, Yong-ming Wang, Jia Huang, Han-yu Zhou, Eric F. C. Cheung, Raymond C. K. Chan
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- Published online by Cambridge University Press:
- 29 March 2021, pp. 4058-4066
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Background
Anticipatory pleasure deficits are closely correlated with negative symptoms in schizophrenia, and may be found in both clinical and subclinical populations along the psychosis continuum. Prospection, which is an important component of anticipatory pleasure, is impaired in individuals with social anhedonia (SocAnh). In this study, we examined the neural correlates of envisioning positive future events in individuals with SocAnh.
MethodsForty-nine individuals with SocAnh and 33 matched controls were recruited to undergo functional MRI scanning, during which they were instructed to simulate positive or neutral future episodes according to cue words. Two stages of prospection were distinguished: construction and elaboration.
ResultsReduced activation at the caudate and the precuneus when prospecting positive (v. neutral) future events was observed in individuals with SocAnh. Furthermore, compared with controls, increased functional connectivity between the caudate and the inferior occipital gyrus during positive (v. neutral) prospection was found in individuals with SocAnh. Both groups exhibited a similar pattern of brain activation for the construction v. elaboration contrast, regardless of the emotional context.
ConclusionsOur results provide further evidence on the neural mechanism of anticipatory pleasure deficits in subclinical individuals with SocAnh and suggest that altered cortico-striatal circuit may play a role in anticipatory pleasure deficits in these individuals.
Gendered experiences of unemployment, suicide and self-harm: a population-level record linkage study
- R. Cunningham, A. Milner, S. Gibb, V. Rijnberg, G. Disney, A. M. Kavanagh
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- Published online by Cambridge University Press:
- 20 April 2021, pp. 4067-4075
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Background
Unemployment and being not in the labour force (NILF) are risk factors for suicide, but their association with self-harm is unclear, and there is continuing debate about the role of confounding by prior mental health conditions. We examine associations between employment status and self-harm and suicide in a prospective cohort, taking into account prior mental-health-related factors.
MethodsWe used linked data from the New Zealand Integrated Data Infrastructure. The outcomes were chosen to be hospital presentation for self-harm and death by suicide. The exposure was employment status, defined as employed, unemployed, or NILF, measured at the 2013 Census. Confounders included demographic factors and mental health history (use of antidepressant medication, use of mental health services, and prior self-harm). Logistic regression was used to model effects. Analyses were stratified by gender.
ResultsFor males, unemployment was associated with an increased risk of suicide [odds ratio (OR): 1.48, 95% confidence interval (CI): 1.20–1.84] and self-harm (OR: 1.55, 95% CI: 1.45–1.68) after full adjustment for confounders. NILF was associated with an increased risk of self-harm (OR: 1.43, 95% CI: 1.32–1.55), but less of an association was seen with suicide (OR: 1.19, 95% CI: 0.94–1.49). For females, unemployment was associated with an increased risk of suicide (OR: 1.30, 95% CI: 0.93–1.80) and of self-harm (OR: 1.52, 95% CI: 1.43–1.62), and NILF was associated with a similar increase in risk for suicide (OR: 1.31, 95% CI: 0.98–1.75) and self-harm (OR: 1.32, 95% CI: 1.26–1.40).
DiscussionExclusion from employment is associated with a considerably heightened risk of suicide and self-harm for both men and women, even among those without prior mental health problems.
Maternal health around pregnancy and autism risk: a diagnosis-wide, population-based study
- Arad Kodesh, Stephen Z. Levine, Vahe Khachadourian, Rayees Rahman, Avner Schlessinger, Paul F. O'Reilly, Jakob Grove, Diana Schendel, Joseph D. Buxbaum, Lisa Croen, Abraham Reichenberg, Sven Sandin, Magdalena Janecka
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- Published online by Cambridge University Press:
- 26 March 2021, pp. 4076-4084
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Background
Many studies have reported an increased risk of autism spectrum disorder (ASD) associated with some maternal diagnoses in pregnancy. However, such associations have not been studied systematically, accounting for comorbidity between maternal disorders. Therefore our aim was to comprehensively test the associations between maternal diagnoses around pregnancy and ASD risk in offspring.
MethodsThis exploratory case–cohort study included children born in Israel from 1997 to 2008, and followed up until 2015. We used information on all ICD-9 codes received by their mothers during pregnancy and the preceding year. ASD risk associated with each of those conditions was calculated using Cox proportional hazards regression, adjusted for the confounders (birth year, maternal age, socioeconomic status and number of ICD-9 diagnoses during the exposure period).
ResultsThe analytic sample consisted of 80 187 individuals (1132 cases, 79 055 controls), with 822 unique ICD-9 codes recorded in their mothers. After extensive quality control, 22 maternal diagnoses were nominally significantly associated with offspring ASD, with 16 of those surviving subsequent filtering steps (permutation testing, multiple testing correction, multiple regression). Among those, we recorded an increased risk of ASD associated with metabolic [e.g. hypertension; HR = 2.74 (1.92–3.90), p = 2.43 × 10−8], genitourinary [e.g. non-inflammatory disorders of cervix; HR = 1.88 (1.38–2.57), p = 7.06 × 10−5] and psychiatric [depressive disorder; HR = 2.11 (1.32–3.35), p = 1.70 × 10−3] diagnoses. Meanwhile, mothers of children with ASD were less likely to attend prenatal care appointment [HR = 0.62 (0.54–0.71), p = 1.80 × 10−11].
ConclusionsSixteen maternal diagnoses were associated with ASD in the offspring, after rigorous filtering of potential false-positive associations. Replication in other cohorts and further research to understand the mechanisms underlying the observed associations with ASD are warranted.
Psychiatric comorbidity as predictor and moderator of binge-eating disorder treatment outcomes: an analysis of aggregated randomized controlled trials
- Janet A. Lydecker, Carlos M. Grilo
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- Published online by Cambridge University Press:
- 14 April 2021, pp. 4085-4093
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Background
Psychiatric comorbidity is common in binge-eating disorder (BED) but effects on treatment outcomes are unknown. The current study aimed to determine whether psychiatric comorbidity predicted or moderated BED treatment outcomes.
MethodsIn total, 636 adults with BED in randomized-controlled trials (RCTs) were assessed prior, throughout, and posttreatment by doctoral research-clinicians using reliably-administered semi-structured interviews, self-report measures, and measured weight. Data were aggregated from RCTs testing cognitive-behavioral therapy, behavioral weight loss, multi-modal (combined pharmacological plus cognitive-behavioral/behavioral), and/or control conditions. Intent-to-treat analyses (all available data) tested comorbidity (mood, anxiety, ‘any disorder’ separately) as predictors and moderators of outcomes. Mixed-effects models tested comorbidity effects on binge-eating frequency, global eating-disorder psychopathology, and weight. Generalized estimating equation models tested binge-eating remission (zero binge-eating episodes during the past month; missing data imputed as failure).
ResultsOverall, 41% of patients had current psychiatric comorbidity; 22% had mood and 23% had anxiety disorders. Psychiatric comorbidity did not significantly moderate the outcomes of specific treatments. Psychiatric comorbidity predicted worse eating-disorder psychopathology and higher binge-eating frequency across all treatments and timepoints. Patients with mood comorbidity were significantly less likely to remit than those without mood disorders (30% v. 41%). Psychiatric comorbidity neither predicted nor moderated weight loss.
ConclusionsPsychiatric comorbidity was associated with more severe BED psychopathology throughout treatment but did not moderate outcomes. Findings highlight the need to improve treatments for BED with psychiatric comorbidities but challenge perspectives that combining existing psychological and pharmacological interventions is warranted. Treatment research must identify more effective interventions for BED overall and for patients with comorbidities.
Efficacy of an integrative approach for bipolar disorder: preliminary results from a randomized controlled trial
- Èlia Valls, C. Mar Bonnín, Imma Torres, Mercè Brat, Mireia Prime-Tous, Ivette Morilla, Xavier Segú, Brisa Solé, Carla Torrent, Eduard Vieta, Anabel Martínez-Arán, María Reinares, José Sánchez-Moreno
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- Published online by Cambridge University Press:
- 16 April 2021, pp. 4094-4105
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Background
Bipolar disorder (BD) represents one of the most therapeutically complex psychiatric disorders. The development of a feasible comprehensive psychological approach to complement pharmacotherapy to improve its clinical management is required. The main objective of the present randomized controlled trial (RCT) was to test the efficacy of a novel adjunctive treatment entitled integrative approach in patients with BD, including: psychoeducation, mindfulness training, and functional remediation.
MethodsThis is a parallel two-armed, rater-blind RCT of an integrative approach plus treatment as usual (TAU), v. TAU alone. Participants were recruited at the Hospital Clinic of Barcelona and randomized to one of the two conditions. They were assessed at baseline and after finishing the intervention. The main outcome variable included changes in psychosocial functioning assessed through the Functioning Assessment Short Test (FAST).
ResultsAfter finishing the treatment, the repeated-measures analyses revealed a significant group × time interaction in favor of the patients who received the integrative approach (n = 28) compared to the TAU group (n = 37) (Pillai's trace = 0.10; F(1,57) = 6.9; p = 0.01), improving the functional outcome. Significant effects were also found in two out of the six domains of the FAST, including the cognitive domain (Pillai's trace = 0.25; F(1,57) = 19.1; p < 0.001) and leisure time (Pillai's trace = 0.11; F(1,57) = 7.15; p = 0.01). Regarding the secondary outcomes, a significant group × time interaction in Hamilton Depression Rating Scale changes was detected (Pillai's trace = 0.08; F(1,62) = 5.6; p = 0.02).
ConclusionThis preliminary study suggests that the integrative approach represents a promising cost-effective therapy to improve psychosocial functioning and residual depressive symptoms in patients suffering from BD.
Vitamin D sufficiency attenuates the effect of early social adversity on child antisocial behavior
- Olivia Choy, Adrian Raine
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- Published online by Cambridge University Press:
- 25 March 2021, pp. 4106-4115
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Background
Vitamin D insufficiency and child antisocial behavior are public health concerns. It is unknown whether vitamin D plays a role in antisocial outcomes. This study examines whether higher levels of vitamin D can act as a protective factor against antisocial behavior for children who are exposed to early social adversity.
MethodsIn a community sample of 300 children aged 11–12 years (151 females, 149 males), serum concentrations of 25-hydroxyvitamin D [25(OH)D] were assessed alongside early social adversity, and both parent and child-reported antisocial behavior.
ResultsVitamin D moderated the association between early social adversity and multiple antisocial outcomes. Higher social adversity was associated with greater antisocial behavior among vitamin D-insufficient [25(OH)D < 30 ng/mL], but not vitamin D-sufficient children [25(OH)D ⩾ 30 ng/mL], after adjusting for other variables. Results from child reports of antisocial behavior were replicated with parent reports, providing support for the robustness of the findings. At serum 25(OH)D concentrations above 27.16–30.69 ng/mL (close to 30 ng/mL, the recommended optimal vitamin D level for pediatric populations), the effect of social adversity on antisocial behavior outcomes was nullified.
ConclusionsTo our knowledge, this study is the first to document that a nutritional factor, vitamin D, can potentially confer resilience to antisocial behavior. Our findings in a pediatric population suggest a possible role of vitamin D supplementation in interventions to reduce antisocial behavior, which may be further investigated in future randomized controlled trials.
Global cognitive dysfunction and β-amyloid neuropathology in late-life and treatment-resistant major depression
- Cheng-Ta Li, Jong-Ling Fuh, Bang-Hung Yang, Chen-Ji Hong, Chi-Wei Chang, Pei-Chi Tu, Jia-Shyun Jeng, Mu-Hong Chen, Shih-Jen Tsai, Ya-Mei Bai, Tung-Ping Su, Hsuan Lee, Wen-Sheng Huang
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- Published online by Cambridge University Press:
- 26 October 2021, pp. 4116-4126
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Background
Cognitive impairment is common in late-life depression, which may increase Alzheimer disease (AD) risk. Therefore, we aimed to investigate whether late-life major depressive disorder (MDD) has worse cognition and increases the characteristic AD neuropathology. Furthermore, we carried out a comparison between treatment-resistant depression (TRD) and non-TRD. We hypothesized that patients with late-life depression and TRD may have increased β-amyloid (Aβ) deposits in brain regions responsible for global cognition.
MethodsWe recruited 81 subjects, including 54 MDD patients (27 TRD and 27 non-TRD) and 27 matched healthy controls (HCs). Neurocognitive tasks were examined, including Mini-Mental State Examination and Montreal Cognitive Assessment to detect global cognitive functions. PET with Pittsburgh compound-B and fluorodeoxyglucose were used to capture brain Aβ pathology and glucose use, respectively, in some patients.
ResultsMDD patients performed worse in Montreal Cognitive Assessment (p = 0.003) and had more Aβ deposits than HCs across the brain (family-wise error-corrected p < 0.001), with the most significant finding in the left middle frontal gyrus. Significant negative correlations between global cognition and prefrontal Aβ deposits existed in MDD patients, whereas positive correlations were noted in HCs. TRD patients had significantly more deposits in the left-sided brain regions (corrected p < 0.001). The findings were not explained by APOE genotypes. No between-group fluorodeoxyglucose difference was detected.
ConclusionsLate-life depression, particularly TRD, had increased brain Aβ deposits and showed vulnerability to Aβ deposits. A detrimental role of Aβ deposits in global cognition in patients with late-onset or non-late-onset MDD supported the theory that late-life MDD could be a risk factor for AD.
Effects of polygenic risk for major mental disorders and cross-disorder on cortical complexity
- Simon Schmitt, Tina Meller, Frederike Stein, Katharina Brosch, Kai Ringwald, Julia-Katharina Pfarr, Clemens Bordin, Nina Peusch, Olaf Steinsträter, Dominik Grotegerd, Katharina Dohm, Susanne Meinert, Katharina Förster, Ronny Redlich, Nils Opel, Tim Hahn, Andreas Jansen, Andreas J. Forstner, Fabian Streit, Stephanie H. Witt, Marcella Rietschel, Bertram Müller-Myhsok, Markus M. Nöthen, Udo Dannlowski, Axel Krug, Tilo Kircher, Igor Nenadić
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- Published online by Cambridge University Press:
- 08 April 2021, pp. 4127-4138
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Background
MRI-derived cortical folding measures are an indicator of largely genetically driven early developmental processes. However, the effects of genetic risk for major mental disorders on early brain development are not well understood.
MethodsWe extracted cortical complexity values from structural MRI data of 580 healthy participants using the CAT12 toolbox. Polygenic risk scores (PRS) for schizophrenia, bipolar disorder, major depression, and cross-disorder (incorporating cumulative genetic risk for depression, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit hyperactivity disorder) were computed and used in separate general linear models with cortical complexity as the regressand. In brain regions that showed a significant association between polygenic risk for mental disorders and cortical complexity, volume of interest (VOI)/region of interest (ROI) analyses were conducted to investigate additional changes in their volume and cortical thickness.
ResultsThe PRS for depression was associated with cortical complexity in the right orbitofrontal cortex (right hemisphere: p = 0.006). A subsequent VOI/ROI analysis showed no association between polygenic risk for depression and either grey matter volume or cortical thickness. We found no associations between cortical complexity and polygenic risk for either schizophrenia, bipolar disorder or psychiatric cross-disorder when correcting for multiple testing.
ConclusionsChanges in cortical complexity associated with polygenic risk for depression might facilitate well-established volume changes in orbitofrontal cortices in depression. Despite the absence of psychopathology, changed cortical complexity that parallels polygenic risk for depression might also change reward systems, which are also structurally affected in patients with depressive syndrome.
DLPFC volume is a neural correlate of resilience in healthy high-risk individuals with both childhood maltreatment and familial risk for depression
- Katharina Brosch, Frederike Stein, Tina Meller, Simon Schmitt, Dilara Yuksel, Kai Gustav Ringwald, Julia-Katharina Pfarr, Lena Waltemate, Hannah Lemke, Nils Opel, Susanne Meinert, Katharina Dohm, Dominik Grotegerd, Janik Goltermann, Jonathan Repple, Alexandra Winter, Andreas Jansen, Udo Dannlowski, Igor Nenadić, Tilo Kircher, Axel Krug
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- Published online by Cambridge University Press:
- 16 April 2021, pp. 4139-4145
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Background
Two prominent risk factors for major depressive disorder (MDD) are childhood maltreatment (CM) and familial risk for MDD. Despite having these risk factors, there are individuals who maintain mental health, i.e. are resilient, whereas others develop MDD. It is unclear which brain morphological alterations are associated with this kind of resilience. Interaction analyses of risk and diagnosis status are needed that can account for complex adaptation processes, to identify neural correlates of resilience.
MethodsWe analyzed brain structural data (3T magnetic resonance imaging) by means of voxel-based morphometry (CAT12 toolbox), using a 2 × 2 design, comparing four groups (N = 804) that differed in diagnosis (healthy v. MDD) and risk profiles (low-risk, i.e. absence of CM and familial risk v. high-risk, i.e. presence of both CM and familial risk). Using regions of interest (ROIs) from the literature, we conducted an interaction analysis of risk and diagnosis status.
ResultsVolume in the left middle frontal gyrus (MFG), part of the dorsolateral prefrontal cortex (DLPFC), was significantly higher in healthy high-risk individuals. There were no significant results for the bilateral superior frontal gyri, frontal poles, pars orbitalis of the inferior frontal gyri, and the right MFG.
ConclusionsThe healthy high-risk group had significantly higher volumes in the left DLPFC compared to all other groups. The DLPFC is implicated in cognitive and emotional processes, and higher volume in this area might aid high-risk individuals in adaptive coping in order to maintain mental health. This increased volume might therefore constitute a neural correlate of resilience to MDD in high risk.
Effectiveness of cognitive remediation in depression: a meta-analysis
- Amanda M. Legemaat, Maria Semkovska, Marlies Brouwer, Gert J. Geurtsen, Huibert Burger, Damiaan Denys, Claudi L. Bockting
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- Published online by Cambridge University Press:
- 14 April 2021, pp. 4146-4161
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Background
Preliminary evidence suggests beneficial effects of cognitive remediation in depression. An update of the current evidence is needed. The aim was to systematically assess the effectiveness of cognitive remediation in depression on three outcomes.
MethodsThe meta-analysis was pre-registered on PROSPERO (CRD42019124316). PubMed, PsycINFO, Embase and Cochrane Library were searched on 2 February 2019 and 8 November 2020 for peer-reviewed published articles. We included randomized and non-randomized clinical trials comparing cognitive remediation to control conditions in adults with primary depression. Random-effects models were used to calculate Hedges' g, and moderators were assessed using mixed-effects subgroup analyses and meta-regression. Main outcome categories were post-treatment depressive symptomatology (DS), cognitive functioning (CF) and daily functioning (DF).
ResultsWe identified 5221 records and included 21 studies reporting on 24 comparisons, with 438 depressed patients receiving cognitive remediation and 540 patients in a control condition. We found a small effect on DS (g = 0.28, 95% CI 0.09–0.46, I2 40%), a medium effect on CF (g = 0.60, 95% CI 0.37–0.83, I2 44%) and a small effect on DF (g = 0.22, 95% CI 0.06–0.39, I2 3%). There were no significant effects at follow-up. Confounding bias analyses indicated possible overestimation of the DS and DF effects in the original studies.
ConclusionsCognitive remediation in depression improves CF in the short term. The effects on DS and DF may have been overestimated. Baseline depressive symptom severity should be considered when administering cognitive remediation.