Original Articles
Dimensional analysis of depressive, anxious and somatic symptoms presented by primary care patients and their relationship with ICD-11 PHC proposed diagnoses
- Carolina Ziebold, David P. Goldberg, Geoffrey M. Reed, Fareed Minhas, Bushra Razzaque, Sandra Fortes, Rebeca Robles, Tai Pong Lam, Julio Bobes, Celso Iglesias, Hugo Cogo-Moreira, José Ángel García, Jair J. Mari
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- Published online by Cambridge University Press:
- 04 June 2018, pp. 764-771
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Background
A study conducted as part of the development of the Eleventh International Classification of Mental Disorders for Primary Health Care (ICD-11 PHC) provided an opportunity to test the relationships among depressive, anxious and somatic symptoms in PHC.
MethodPrimary care physicians participating in the ICD-11 PHC field studies in five countries selected patients who presented with somatic symptoms not explained by known physical pathology by applying a 29-item screening on somatic complaints that were under study for bodily stress disorder. Patients were interviewed using the Clinical Interview Schedule-Revised and assessed using two five-item scales that measure depressive and anxious symptoms. Structural models of anxious-depressive symptoms and somatic complaints were tested using a bi-factor approach.
ResultsA total of 797 patients completed the study procedures. Two bi-factor models fit the data well: Model 1 had all symptoms loaded on a general factor, along with one of three specific depression, anxiety and somatic factors [x2 (627) = 741.016, p < 0.0011, RMSEA = 0.015, CFI = 0.911, TLI = 0.9]. Model 2 had a general factor and two specific anxious depression and somatic factors [x2 (627) = 663.065, p = 0.1543, RMSEA = 0.008, CFI = 0.954, TLI = 0.948].
ConclusionsThese data along with those of previous studies suggest that depressive, anxious and somatic symptoms are largely different presentations of a common latent phenomenon. This study provides support for the ICD-11 PHC conceptualization of mood disturbance, especially anxious depression, as central among patients who present multiple somatic symptoms.
Non-suicidal self-injury prevalence, course, and association with suicidal thoughts and behaviors in two large, representative samples of US Army soldiers
- Brianna J. Turner, Evan M. Kleiman, Matthew K. Nock
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- Published online by Cambridge University Press:
- 22 August 2018, pp. 1470-1480
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Background
Non-suicidal self-injury (NSSI) prospectively predicts suicidal thoughts and behaviors in civilian populations. Despite high rates of suicide among US military members, little is known about the prevalence and course of NSSI, or how NSSI relates to suicidal thoughts and behaviors, in military personnel.
MethodsWe conducted secondary analyses of two representative surveys of active-duty soldiers (N = 21 449) and newly enlisted soldiers (N = 38 507) from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).
ResultsThe lifetime prevalence of NSSI is 6.3% (1.2% 12-month prevalence) in active-duty soldiers and 7.9% (1.3% 12-month prevalence) in new soldiers. Demographic risk factors for lifetime NSSI include female sex, younger age, non-Hispanic white ethnicity, never having married, and lower educational attainment. The association of NSSI with temporally primary internalizing and externalizing disorders varies by service history (new v. active-duty soldiers) and gender (men v. women). In both active-duty and new soldiers, NSSI is associated with increased odds of subsequent onset of suicidal ideation [adjusted odds ratio (OR) = 1.66–1.81] and suicide attempts (adjusted OR = 2.02–2.43), although not with the transition from ideation to attempt (adjusted OR = 0.92–1.36). Soldiers with a history of NSSI are more likely to have made multiple suicide attempts, compared with soldiers without NSSI.
ConclusionsNSSI is prevalent among US Army soldiers and is associated with significantly increased odds of later suicidal thoughts and behaviors, even after NSSI has resolved. Suicide risk assessments in military populations should screen for history of NSSI.
Early change in reward and punishment sensitivity as a predictor of response to antidepressant treatment for major depressive disorder: a CAN-BIND-1 report
- Timothy A. Allen, Raymond W. Lam, Roumen Milev, Sakina J. Rizvi, Benicio N. Frey, Glenda M. MacQueen, Daniel J. Müller, Rudolf Uher, Sidney H. Kennedy, Lena C. Quilty
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- Published online by Cambridge University Press:
- 17 September 2018, pp. 1629-1638
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Background
In an effort to optimize patient outcomes, considerable attention is being devoted to identifying patient characteristics associated with major depressive disorder (MDD) and its responsiveness to treatment. In the current study, we extend this work by evaluating whether early change in these sensitivities is associated with response to antidepressant treatment for MDD.
MethodsParticipants included 210 patients with MDD who were treated with 8 weeks of escitalopram and 112 healthy comparison participants. Of the original 210 patients, 90 non-responders received adjunctive aripiprazole for an additional 8 weeks. Symptoms of depression and anhedonia were assessed at the beginning of treatment and 8 weeks later in both samples. Reward and punishment sensitivity were assessed using the BIS/BAS scales measured at the initiation of treatment and 2 weeks later.
ResultsIndividuals with MDD exhibited higher punishment sensitivity and lower reward sensitivity compared with healthy comparison participants. Change in reward sensitivity during the first 2 weeks of treatment was associated with improved depressive symptoms and anhedonia following 8 weeks of treatment with escitalopram. Similarly, improvement in reward responsiveness during the first 2 weeks of adjunctive therapy with aripiprazole was associated with fewer symptoms of depression at post-treatment.
ConclusionsFindings highlight the predictive utility of early change in reward sensitivity during antidepressant treatment for major depression. In a clinical setting, a lack of change in early reward processing may signal a need to modify a patient's treatment plan with alternative or augmented treatment approaches.
Personalized prediction of antidepressant v. placebo response: evidence from the EMBARC study
- Christian A. Webb, Madhukar H. Trivedi, Zachary D. Cohen, Daniel G. Dillon, Jay C. Fournier, Franziska Goer, Maurizio Fava, Patrick J. McGrath, Myrna Weissman, Ramin Parsey, Phil Adams, Joseph M. Trombello, Crystal Cooper, Patricia Deldin, Maria A. Oquendo, Melvin G. McInnis, Quentin Huys, Gerard Bruder, Benji T. Kurian, Manish Jha, Robert J. DeRubeis, Diego A. Pizzagalli
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- Published online by Cambridge University Press:
- 02 July 2018, pp. 1118-1127
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Background
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
MethodsWithin an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
ResultsFive pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
ConclusionsA subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
Short sleep duration and poor sleep quality predict next-day suicidal ideation: an ecological momentary assessment study
- Donna L. Littlewood, Simon D. Kyle, Lesley-Anne Carter, Sarah Peters, Daniel Pratt, Patricia Gooding
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- Published online by Cambridge University Press:
- 26 April 2018, pp. 403-411
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Background
Sleep problems are a modifiable risk factor for suicidal thoughts and behaviors. Yet, sparse research has examined temporal relationships between sleep disturbance, suicidal ideation, and psychological factors implicated in suicide, such as entrapment. This is the first in-the-moment investigation of relationships between suicidal ideation, objective and subjective sleep parameters, and perceptions of entrapment.
MethodsFifty-one participants with current suicidal ideation completed week-long ecological momentary assessments. An actigraph watch was worn for the duration of the study, which monitored total sleep time, sleep efficiency, and sleep latency. Daily sleep diaries captured subjective ratings of the same sleep parameters, with the addition of sleep quality. Suicidal ideation and entrapment were measured at six quasi-random time points each day. Multi-level random intercept models and moderation analyses were conducted to examine the links between sleep, entrapment, and suicidal ideation, adjusting for anxiety and depression severity.
ResultsAnalyses revealed a unidirectional relationship whereby short sleep duration (both objective and subjective measures), and poor sleep quality, predicted the higher severity of next-day suicidal ideation. However, there was no significant association between daytime suicidal ideation and sleep the following night. Sleep quality moderated the relationship between pre-sleep entrapment and awakening levels of suicidal ideation.
ConclusionsThis is the first study to report night-to-day relationships between sleep disturbance, suicidal ideation, and entrapment. Findings suggest that sleep quality may alter the strength of the relationship between pre-sleep entrapment and awakening suicidal ideation. Clinically, results underscore the importance of assessing and treating sleep disturbance when working with those experiencing suicidal ideation.
Alcohol use and personality trait change: pooled analysis of six cohort studies
- Christian Hakulinen, Markus Jokela
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- 15 March 2018, pp. 224-231
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Background
Personality has been associated with alcohol use, but less is known about how alcohol use may influence long-term personality trait change.
MethodsThe present study examines associations between alcohol use and change in the five major personality traits across two measurement occasions (mean follow-up of 5.6 years). A total of 39 722 participants (54% women) were pooled from six cohort studies for an individual-participant meta-analysis. Alcohol use was measured as (1) average alcohol consumption, (2) frequency of binge drinking, (3) symptoms of alcohol use disorder, and (4) a global indicator of risky alcohol use. Changes in the five major personality traits (extraversion, emotional stability, agreeableness, conscientiousness, and openness to experience) were used as outcomes.
ResultsRisky alcohol use was associated with increasing extraversion [0.25 T-scores over the mean follow-up of 5.6 years; 95% confidence interval (CI) 0.07–0.44] and decreasing emotional stability (−0.28; 95% CI −0.48 to −0.08), agreeableness (−0.67; 95% CI −0.87 to −0.36), and conscientiousness (−0.58; 95% CI −0.79 to −0.38). Except the association between alcohol use and extraversion, these associations were consistent across cohort studies and across different measures of alcohol use.
ConclusionsThese findings suggest that alcohol use is associated with personality trait changes in adulthood.
A data-driven method for identifying shorter symptom criteria sets: the case for DSM-5 alcohol use disorder
- Cheryl D. Raffo, Deborah S. Hasin, Paul Appelbaum, Melanie M. Wall
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- 27 June 2018, pp. 931-939
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Background
Although the DSM is a widely used diagnostic guide, lengthy criteria sets can be problematic and provide the primary motivation to identify short-forms. Using the 11 diagnostic criteria provided by the DSM-5 for alcohol use disorder (AUD), the present study develops a data-driven method to systematically identify subsets and associated cut-offs that yield diagnoses as similar as possible to use all 11 criteria.
MethodRelying on data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III), our methodology identifies diagnostic short-forms for AUD by: (1) maximizing the association between the sum scores of all 11 criteria with newly constructed subscales from subsets of criteria; (2) optimizing the similarity of AUD prevalence between the current DSM-5 rule and newly constructed diagnostic short-forms; (3) maximizing sensitivity and specificity of the short-forms against the current DSM-5 rule; and (4) minimizing differences in the accuracy of the short-form across chosen covariates. Replication is shown using NESARC-Wave 2.
ResultsMore than 11 000 diagnostic short-forms for DSM-5 AUD can be created and our method narrows down the optimal choices to eight. Results found that ‘Neglecting major roles’ and ‘Activities given up’ could be dropped with practically no change in who is diagnosed (specificity = 100%, sensitivity ⩾ 99.6%) or the severity of those diagnosed (κ = 0.97).
ConclusionsWith a continuous improvement model adopted by the APA for DSM revisions, we offer a data-driven tool (a SAS Macro) that identifies diagnostic short-forms in a systematic and reproducible way to help advance potential improvements in future DSM revisions.
Mindfulness-based cognitive therapy v. treatment as usual in adults with ADHD: a multicentre, single-blind, randomised controlled trial
- Lotte Janssen, Cornelis C. Kan, Pieter J. Carpentier, Bram Sizoo, Sevket Hepark, Melanie P.J. Schellekens, A. Rogier T. Donders, Jan K. Buitelaar, Anne E.M. Speckens
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- 28 February 2018, pp. 55-65
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Background
There is a high need for evidence-based psychosocial treatments for adult attention-deficit hyperactivity disorder (ADHD) to offer alongside treatment as usual (TAU). Mindfulness-based cognitive therapy (MBCT) is a promising psychosocial treatment. This trial investigated the efficacy of MBCT + TAU v. TAU in reducing core symptoms in adults with ADHD.
MethodsA multicentre, single-blind, randomised controlled trial (ClinicalTrials.gov: NCT02463396). Participants were randomly assigned to MBCT + TAU (n = 60), an 8-weekly group therapy including meditation exercises, psychoeducation and group discussions, or TAU only (n = 60), which reflected usual treatment in the Netherlands and included pharmacotherapy and/or psychoeducation. Primary outcome was ADHD symptoms rated by blinded clinicians. Secondary outcomes included self-reported ADHD symptoms, executive functioning, mindfulness skills, self-compassion, positive mental health and general functioning. Outcomes were assessed at baseline, post-treatment, 3- and 6-month follow-up. Post-treatment effects at group and individual level, and follow-up effects were examined.
ResultsIn MBCT + TAU patients, a significant reduction of clinician-rated ADHD symptoms was found at post-treatment [M difference = −3.44 (−5.75, −1.11), p = 0.004, d = 0.41]. This effect was maintained until 6-month follow-up. More MBCT + TAU (27%) than TAU participants (4%) showed a ⩽30% reduction of ADHD symptoms (p = 0.001). MBCT + TAU patients compared with TAU patients also reported significant improvements in ADHD symptoms, mindfulness skills, self-compassion and positive mental health at post-treatment, which were maintained until 6-month follow-up. Although patients in MBCT + TAU compared with TAU reported no improvement in executive functioning at post-treatment, they did report improvement at 6-month follow-up.
ConclusionsMBCT might be a valuable treatment option alongside TAU for adult ADHD aimed at alleviating symptoms.
Prediction of psychosis in prodrome: development and validation of a simple, personalized risk calculator
- TianHong Zhang, LiHua Xu, YingYing Tang, HuiJun Li, XiaoChen Tang, HuiRu Cui, YanYan Wei, Yan Wang, Qiang Hu, XiaoHua Liu, ChunBo Li, Zheng Lu, Robert W. McCarley, Larry J. Seidman, JiJun Wang, on behalf of the SHARP (ShangHai At Risk for Psychosis) Study Group
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- 14 September 2018, pp. 1990-1998
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Background
This study aim to derive and validate a simple and well-performing risk calculator (RC) for predicting psychosis in individual patients at clinical high risk (CHR).
MethodsFrom the ongoing ShangHai-At-Risk-for-Psychosis (SHARP) program, 417 CHR cases were identified based on the Structured Interview for Prodromal Symptoms (SIPS), of whom 349 had at least 1-year follow-up assessment. Of these 349 cases, 83 converted to psychosis. Logistic regression was used to build a multivariate model to predict conversion. The area under the receiver operating characteristic (ROC) curve (AUC) was used to test the effectiveness of the SIPS-RC. Second, an independent sample of 100 CHR subjects was recruited based on an identical baseline and follow-up procedures to validate the performance of the SIPS-RC.
ResultsFour predictors (each based on a subset of SIPS-based items) were used to construct the SIPS-RC: (1) functional decline; (2) positive symptoms (unusual thoughts, suspiciousness); (3) negative symptoms (social anhedonia, expression of emotion, ideational richness); and (4) general symptoms (dysphoric mood). The SIPS-RC showed moderate discrimination of subsequent transition to psychosis with an AUC of 0.744 (p < 0.001). A risk estimate of 25% or higher had around 75% accuracy for predicting psychosis. The personalized risk generated by the SIPS-RC provided a solid estimate of conversion outcomes in the independent validation sample, with an AUC of 0.804 [95% confidence interval (CI) 0.662–0.951].
ConclusionThe SIPS-RC, which is simple and easy to use, can perform in the same manner as the NAPLS-2 RC in the Chinese clinical population. Such a tool may be used by clinicians to counsel appropriately their patients about clinical monitor v. potential treatment options.
Exploring shared genetic bases and causal relationships of schizophrenia and bipolar disorder with 28 cardiovascular and metabolic traits
- Hon-Cheong So, Kwan-Long Chau, Fu-Kiu Ao, Cheuk-Hei Mo, Pak-Chung Sham
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- 26 July 2018, pp. 1286-1298
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Background
Cardiovascular diseases represent a major health issue in patients with schizophrenia (SCZ) and bipolar disorder (BD), but the exact nature of cardiometabolic (CM) abnormalities involved and the underlying mechanisms remain unclear. Psychiatric medications are known risk factors, but it is unclear whether there is a connection between the disorders (SCZ/BD) themselves and CM abnormalities.
MethodsUsing polygenic risk scores and linkage disequilibrium score regression, we investigated the shared genetic bases of SCZ and BD with 28 CM traits. We performed Mendelian randomization (MR) to elucidate causal relationships between the two groups of disorders. The analysis was based on large-scale meta-analyses of genome-wide association studies. We also identified the potential shared genetic variants and inferred the pathways involved.
ResultsWe found tentative polygenic associations of SCZ with glucose metabolism abnormalities, adverse adipokine profiles, increased waist-to-hip ratio and visceral adiposity (false discovery rate or FDR<0.05). However, there was an inverse association with body mass index. For BD, we observed several polygenic associations with favorable CM profiles at FDR<0.05. MR analysis showed that SCZ may be causally linked to raised triglyceride and that lower fasting glucose may be linked to BD. We also identified numerous single nucleotide polymorphisms and pathways shared between SCZ/BD with CM traits, some of which are related to inflammation or the immune system.
ConclusionsOur findings suggest that SCZ patients may be genetically predisposed to several CM abnormalities independent of medication side effects. On the other hand, CM abnormalities in BD may be more likely to be secondary. However, the findings require further validation.
Prefrontal glutamate levels predict altered amygdala–prefrontal connectivity in traumatized youths
- Olga Therese Ousdal, Anne Marita Milde, Alexander R. Craven, Lars Ersland, Tor Endestad, Annika Melinder, Quentin J. Huys, Kenneth Hugdahl
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- Published online by Cambridge University Press:
- 18 September 2018, pp. 1822-1830
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Background
Neurobiological models of stress and stress-related mental illness, including post-traumatic stress disorder, converge on the amygdala and the prefrontal cortex (PFC). While a surge of research has reported altered structural and functional connectivity between amygdala and the medial PFC following severe stress, few have addressed the underlying neurochemistry.
MethodsWe combined resting-state functional magnetic resonance imaging measures of amygdala connectivity with in vivo MR-spectroscopy (1H-MRS) measurements of glutamate in 26 survivors from the 2011 Norwegian terror attack and 34 control subjects.
ResultsTraumatized youths showed altered amygdala–anterior midcingulate cortex (aMCC) and amygdala–ventromedial prefrontal cortex (vmPFC) connectivity. Moreover, the trauma survivors exhibited reduced levels of glutamate in the vmPFC which fits with the previous findings of reduced levels of Glx (glutamate + glutamine) in the aMCC (Ousdal et al., 2017) and together suggest long-term impact of a traumatic experience on glutamatergic pathways. Importantly, local glutamatergic metabolite levels predicted the individual amygdala–aMCC and amygdala–vmPFC functional connectivity, and also mediated the observed group difference in amygdala–aMCC connectivity.
ConclusionsOur findings suggest that traumatic stress may influence amygdala–prefrontal neuronal connectivity through an effect on prefrontal glutamate and its compounds. Understanding the neurochemical underpinning of altered amygdala connectivity after trauma may ultimately lead to the discovery of new pharmacological agents which can prevent or treat stress-related mental illness.
Joint factorial structure of psychopathology and personality
- Tom Rosenström, Line C. Gjerde, Robert F. Krueger, Steven H. Aggen, Nikolai Olavi Czajkowski, Nathan A. Gillespie, Kenneth S. Kendler, Ted Reichborn-Kjennerud, Fartein Ask Torvik, Eivind Ystrom
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- Published online by Cambridge University Press:
- 05 November 2018, pp. 2158-2167
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Background
Normative and pathological personality traits have rarely been integrated into a joint large-scale structural analysis with psychiatric disorders, although a recent study suggested they entail a common individual differences continuum.
MethodsWe explored the joint factor structure of 11 psychiatric disorders, five personality-disorder trait domains (DSM-5 Section III), and five normative personality trait domains (the ‘Big Five’) in a population-based sample of 2796 Norwegian twins, aged 19‒46.
ResultsThree factors could be interpreted: (i) a general risk factor for all psychopathology, (ii) a risk factor specific to internalizing disorders and traits, and (iii) a risk factor specific to externalizing disorders and traits. Heritability estimates for the three risk factor scores were 48% (95% CI 41‒54%), 35% (CI 28‒42%), and 37% (CI 31‒44%), respectively. All 11 disorders had uniform loadings on the general factor (congruence coefficient of 0.991 with uniformity). Ignoring sign and excluding the openness trait, this uniformity of factor loadings held for all the personality trait domains and all disorders (congruence 0.983).
ConclusionsBased on our findings, future research should investigate joint etiologic and transdiagnostic models for normative and pathological personality and other psychopathology.
No sex differences in the origins of covariation between social and physical aggression
- Brooke L. Slawinski, Kelly L. Klump, S. Alexandra Burt
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- Published online by Cambridge University Press:
- 11 December 2018, pp. 2515-2523
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Background
Prior work has indicated both theoretical and empirical overlap between social and physical aggression. The extent to which their covariance can be explained by the same underlying genetic or environmental factors, however, remains unclear. It is also uncertain whether or how the origins of their covariance might vary across sex. The current study sought to fill these gaps in the literature.
MethodsWe examined maternal and teacher reports of youth physical and social aggression in over 1000 6–10 years old (mean age = 8.02 years) twin pairs from the Michigan State University Twin Registry. We made use of the bivariate correlated factors model to clarify the origins of their association. We further tested both sex difference and no-sex difference versions of that model to determine whether there are sex differences in the association between social and physical aggression, as often assumed.
ResultsThe covariation between social and physical aggression was due to overlapping genetic factors and common environmental conditions. Specifically, 50–57% of the genetic factors, 74–100% of the shared environmental factors, and 28–40% of the unique environmental factors influencing physical aggression also influenced social aggression according to both mother and teacher reports. These shared etiological factors did not differ across sex.
ConclusionsThese findings argue against the common assumption that social aggression is the ‘female version’ of male physical aggression, and instead suggest that social aggression may be best conceptualized as a form of antisocial behavior that shares developmental pathways with other manifestations of externalizing pathology.
Risk of schizophrenia, schizoaffective, and bipolar disorders by migrant status, region of origin, and age-at-migration: a national cohort study of 1.8 million people
- Jennifer Dykxhoorn, Anna-Clara Hollander, Glyn Lewis, Cecelia Magnusson, Christina Dalman, James B Kirkbride
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- Published online by Cambridge University Press:
- 05 December 2018, pp. 2354-2363
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Background
We assessed whether the risk of various psychotic disorders and non-psychotic bipolar disorder (including mania) varied by migrant status, a region of origin, or age-at-migration, hypothesizing that risk would only be elevated for psychotic disorders.
MethodsWe established a prospective cohort of 1 796 257 Swedish residents born between 1982 and 1996, followed from their 15th birthday, or immigration to Sweden after age 15, until diagnosis, emigration, death, or end of 2011. Cox proportional hazards models were used to model hazard ratios by migration-related factors, adjusted for covariates.
ResultsAll psychotic disorders were elevated among migrants and their children compared with Swedish-born individuals, including schizophrenia and schizoaffective disorder (adjusted hazard ratio [aHR]migrants: 2.20, 95% CI 1.96–2.47; aHRchildren : 2.00, 95% CI 1.79–2.25), affective psychotic disorders (aHRmigrant1.42, 95% CI 1.25–1.63; aHRchildren: 1.22 95% CI 1.07–1.40), and other non-affective psychotic disorders (aHRmigrant: 1.97, 95% CI 1.81–2.14; aHRchildren: 1.68, 95% CI 1.54–1.83). For all psychotic disorders, risks were generally highest in migrants from Africa (i.e. aHRschizophrenia: 5.24, 95% CI 4.26–6.45) and elevated at most ages-of-migration. By contrast, risk of non-psychotic bipolar disorders was lower for migrants (aHR: 0.58, 95% CI 0.52–0.64) overall, and across all ages-of-migration except infancy (aHR: 1.20; 95% CI 1.01–1.42), while risk for their children was similar to the Swedish-born population (aHR: 1.00, 95% CI 0.93–1.08).
ConclusionsIncreased risk of psychiatric disorders associated with migration and minority status may be specific to psychotic disorders, with exact risk dependent on the region of origin.
Translating GWAS findings into therapies for depression and anxiety disorders: gene-set analyses reveal enrichment of psychiatric drug classes and implications for drug repositioning
- Hon-Cheong So, Carlos Kwan-Long Chau, Alexandria Lau, Sze-Yung Wong, Kai Zhao
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- Published online by Cambridge University Press:
- 20 December 2018, pp. 2692-2708
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Background
Depression and anxiety disorders (AD) are the first and sixth leading causes of disability worldwide. Despite their high prevalence and significant disability resulted, there are limited advances in new drug development. Recently, genome-wide association studies (GWAS) have greatly advanced our understanding of the genetic basis underlying psychiatric disorders.
MethodsHere we employed gene-set analyses of GWAS summary statistics for drug repositioning. We explored five related GWAS datasets, including two on major depressive disorder (MDD2018 and MDD-CONVERGE, with the latter focusing on severe melancholic depression), one on AD, and two on depressive symptoms and neuroticism in the population. We extracted gene-sets associated with each drug from DSigDB and examined their association with each GWAS phenotype. We also performed repositioning analyses on meta-analyzed GWAS data, integrating evidence from all related phenotypes.
ResultsImportantly, we showed that the repositioning hits are generally enriched for known psychiatric medications or those considered in clinical trials. Enrichment was seen for antidepressants and anxiolytics but also for antipsychotics. We also revealed new candidates or drug classes for repositioning, some of which were supported by experimental or clinical studies. For example, the top repositioning hit using meta-analyzed p values was fendiline, which was shown to produce antidepressant-like effects in mouse models by inhibition of acid sphingomyelinase.
ConclusionTaken together, our findings suggest that human genomic data such as GWAS are useful in guiding drug discoveries for depression and AD.
Startle habituation, sensory, and sensorimotor gating in trauma-affected refugees with posttraumatic stress disorder
- Hanieh Meteran, Erik Vindbjerg, Sigurd Wiingaard Uldall, Birte Glenthøj, Jessica Carlsson, Bob Oranje
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- Published online by Cambridge University Press:
- 17 May 2018, pp. 581-589
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Background
Impairments in mechanisms underlying early information processing have been reported in posttraumatic stress disorder (PTSD); however, findings in the existing literature are inconsistent. This current study capitalizes on technological advancements of research on electroencephalographic event-related potential and applies it to a novel PTSD population consisting of trauma-affected refugees.
MethodsA total of 25 trauma-affected refugees with PTSD and 20 healthy refugee controls matched on age, gender, and country of origin completed the study. In two distinct auditory paradigms sensory gating, indexed as P50 suppression, and sensorimotor gating, indexed as prepulse inhibition (PPI), startle reactivity, and habituation of the eye-blink startle response were examined. Within the P50 paradigm, N100 and P200 amplitudes were also assessed. In addition, correlations between psychophysiological and clinical measures were investigated.
ResultsPTSD patients demonstrated significantly elevated stimuli responses across the two paradigms, reflected in both increased amplitude of the eye-blink startle response, and increased N100 and P200 amplitudes relative to healthy refugee controls. We found a trend toward reduced habituation in the patients, while the groups did not differ in PPI and P50 suppression. Among correlations, we found that eye-blink startle responses were associated with higher overall illness severity and lower levels of functioning.
ConclusionsFundamental gating mechanisms appeared intact, while the pattern of deficits in trauma-affected refugees with PTSD point toward a different form of sensory overload, an overall neural hypersensitivity and disrupted the ability to down-regulate stimuli responses. This study represents an initial step toward elucidating sensory processing deficits in a PTSD subgroup.
Structural covariance and cortical reorganisation in schizophrenia: a MRI-based morphometric study
- Lena Palaniyappan, Olha Hodgson, Vijender Balain, Sarina Iwabuchi, Penny Gowland, Peter Liddle
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- Published online by Cambridge University Press:
- 06 May 2018, pp. 412-420
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Background
In patients with schizophrenia, distributed abnormalities are observed in grey matter volume. A recent hypothesis posits that these distributed changes are indicative of a plastic reorganisation process occurring in response to a functional defect in neuronal information transmission. We investigated the structural covariance across various brain regions in early-stage schizophrenia to determine if indeed the observed patterns of volumetric loss conform to a coordinated pattern of structural reorganisation.
MethodsStructural magnetic resonance imaging scans were obtained from 40 healthy adults and 41 age, gender and parental socioeconomic status matched patients with schizophrenia. Volumes of grey matter tissue were estimated at the regional level across 90 atlas-based parcellations. Group-level structural covariance was studied using a graph theoretical framework.
ResultsPatients had distributed reduction in grey matter volume, with high degree of localised covariance (clustering) compared with controls. Patients with schizophrenia had reduced centrality of anterior cingulate and insula but increased centrality of the fusiform cortex, compared with controls. Simulating targeted removal of highly central nodes resulted in significant loss of the overall covariance patterns in patients compared with controls.
ConclusionRegional volumetric deficits in schizophrenia are not a result of random, mutually independent processes. Our observations support the occurrence of a spatially interconnected reorganisation with the systematic de-escalation of conventional ‘hub’ regions. This raises the question of whether the morphological architecture in schizophrenia is primed for compensatory functions, albeit with a high risk of inefficiency.
Developmental changes of neuropsychological functioning in individuals with and without childhood ADHD from early adolescence to young adulthood: a 7-year follow-up study
- Yu-Ju Lin, Susan Shur-Fen Gau
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- Published online by Cambridge University Press:
- 26 June 2018, pp. 940-951
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Background
Our knowledge about the developmental change of neuropsychological functioning in attention-deficit/hyperactivity disorder (ADHD) is limited. This prospective longitudinal study examined the changes in neuropsychological functions and their associations with the changes of ADHD symptoms across the developmental stages from early adolescence to young adulthood.
MethodsWe followed up 53 individuals diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) ADHD during childhood (mean age 12.77 years at time 1, 19.81 years at time 2) and 50 non-ADHD controls (mean age 12.80 years at time 1, 19.36 years at time 2) with repeated psychiatric interviews at two time points to confirm ADHD and other psychiatric diagnoses. Neuropsychological functions with high- and low-executive demands, measured by the Cambridge Neuropsychological Testing Automated Battery (CANTAB) at two time points, were compared.
ResultsBoth groups showed improvements in all neuropsychological tasks except reaction time in the ADHD group. Despite having a greater improvement in spatial working memory (SWM) than controls, individuals with ADHD still performed worse in various neuropsychological tasks than controls at follow-up. Better baseline intra-dimension/extra-dimension shift and parental occupation predicted fewer ADHD symptoms at follow-up independent of baseline ADHD symptoms. The degree of ADHD symptom reduction was not significantly linearly correlated to the magnitude of neuropsychological function improvement.
ConclusionIndividuals with ADHD and controls had parallel developments in neuropsychological functioning, except a catch-up in SWM in ADHD. Almost all neuropsychological functions herein were still impaired in ADHD at late adolescence/young adulthood. There may be a threshold (i.e. non-linear) relationship between neuropsychological functioning and ADHD symptoms.
Progress of negative symptoms over the initial 5 years of a first episode of psychosis
- Danyael Lutgens, Ridha Joober, Srividya Iyer, Martin Lepage, Ross Norman, Norbert Schmitz, Sally Mustafa, Sherezad Abadi, Ashok Malla
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- Published online by Cambridge University Press:
- 14 March 2018, pp. 66-74
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Background
Specialized early intervention (EI) following a first episode of psychosis (FEP) are effective at reducing negative symptoms, although its trajectory warrants systematic assessment. However, findings are equivocal as to whether extended gains are made post 2 years of EI and whether there is additional benefit of extending EI for an additional 3 years.
MethodsData on 178 FEP patients, from a randomized controlled trial of a 3-year extension of EI service v. transfer to regular care following 2 years of EI service, were used for this report. Repeated measures analysis of variance were conducted separately for the initial 2 years of treatment in an EI service, and for the 3-year post-randomization to examine trajectories of negative symptoms over the two periods in the two arms of the study.
ResultsThere were significant improvements in total negative symptoms over the first 2 years of EI F(4.612, 797.905) = 25.263, p < 0.001 and in domains of ‘expressivity’ and ‘motivation’. In the following 3 years, there were further significant improvements in negative symptoms F(4.318, 759.908) = 4.182, p = 0.002 with no difference between groups F(4.318, 759.908) = 1.073, p = 0.371. Changes in negative symptoms over the extension period were driven by expressivity F(4.01, 674.73) = 7.19, p < 0.01, but not motivation F(6.58, 1112.18) = 0.95, p = 0.46.
ConclusionNegative symptoms improve significantly over the first 2 years of EI. Subsequent amelioration was largely the result of expressivity. Motivation deficits remained stable. Extended EI offered no advantage over regular care post-randomization.
Effect of discontinuation v. maintenance of antipsychotic medication on relapse rates in patients with remitted/stable first-episode psychosis: a meta-analysis
- Taro Kishi, Toshikazu Ikuta, Yuki Matsui, Ken Inada, Yuki Matsuda, Kazuo Mishima, Nakao Iwata
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- Published online by Cambridge University Press:
- 18 June 2018, pp. 772-779
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Background
Discontinuation of antipsychotics predisposes patients with remitted/stable first-episode psychosis (FEP) to a higher risk of relapse, but it remains unclear how long discontinuation increases the relapse rate in these patients compared with maintenance.
MethodsThis meta-analysis of randomized controlled trials (RCTs) compared relapse rates in FEP patients between antipsychotic treatment discontinuation and maintenance groups at 1, 2, 3, 6, 9, 12 (primary), and 18–24 months. The risk ratio (RR) and numbers needed to treat/harm (NNT/NNH) were calculated using a random-effects model.
ResultsTen RCTs were identified (n = 776; mean study duration, 18.6 ± 6.0 months). The antipsychotics were discontinued abruptly in four RCTs (which reported data only at 12 months) and after tapering off gradually over several months (mean length, 3 months) in six RCTs. Compared with the discontinuation group, the maintenance group experienced significantly fewer relapses at all time points except 1 month [RR (NNT): 2 months, 0.49 (13); 3 months, 0.46 (9); 6 months, 0.55 (6); 9 months, 0.48 (3); 12 months, 0.47 (3); and 18–24 months, 0.57 (4)]. The maintenance group was associated with higher discontinuation due to adverse events (RR, 2.61; NNH, not significant).
ConclusionsMaintaining antipsychotic treatment prevented relapse for up to 24 months in FEP patients. Discontinuation of antipsychotics for ⩾2 months significantly increased the risk of relapse. However, 45.7% of patients who discontinued antipsychotics for 12 months (39.4% after 18–24 months) did not experience a relapse.