Original Article
Effect of managed transition on mental health outcomes for young people at the child–adult mental health service boundary: a randomised clinical trial
- S. P. Singh, H. Tuomainen, G. Bouliotis, A. Canaway, G. De Girolamo, G. C. Dieleman, T. Franić, J. Madan, A. Maras, F. McNicholas, M. Paul, D. Purper-Ouakil, P. Santosh, U. M. E. Schulze, C. Street, S. Tremmery, F. C. Verhulst, P. Wells, D. Wolke, J. Warwick, the MILESTONE Consortium
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- Published online by Cambridge University Press:
- 29 October 2021, pp. 2193-2204
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Background
Poor transition planning contributes to discontinuity of care at the child–adult mental health service boundary (SB), adversely affecting mental health outcomes in young people (YP). The aim of the study was to determine whether managed transition (MT) improves mental health outcomes of YP reaching the child/adolescent mental health service (CAMHS) boundary compared with usual care (UC).
MethodsA two-arm cluster-randomised trial (ISRCTN83240263 and NCT03013595) with clusters allocated 1:2 between MT and UC. Recruitment took place in 40 CAMHS (eight European countries) between October 2015 and December 2016. Eligible participants were CAMHS service users who were receiving treatment or had a diagnosed mental disorder, had an IQ ⩾ 70 and were within 1 year of reaching the SB. MT was a multi-component intervention that included CAMHS training, systematic identification of YP approaching SB, a structured assessment (Transition Readiness and Appropriateness Measure) and sharing of information between CAMHS and adult mental health services. The primary outcome was HoNOSCA (Health of the Nation Outcome Scale for Children and Adolescents) score 15-months post-entry to the trial.
ResultsThe mean difference in HoNOSCA scores between the MT and UC arms at 15 months was −1.11 points (95% confidence interval −2.07 to −0.14, p = 0.03). The cost of delivering the intervention was relatively modest (€17–€65 per service user).
ConclusionsMT led to improved mental health of YP after the SB but the magnitude of the effect was small. The intervention can be implemented at low cost and form part of planned and purposeful transitional care.
Longitudinal associations between interpersonal relationship functioning and posttraumatic stress disorder (PTSD) in recently traumatized individuals: differential findings by assessment method
- Candice M. Monson, Philippe Shnaider, Anne C. Wagner, Rachel E. Liebman, Nicole D. Pukay-Martin, Meredith S. H. Landy, Sonya G. Wanklyn, Michael Suvak, Tae L. Hart, Naomi Koerner
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- Published online by Cambridge University Press:
- 08 October 2021, pp. 2205-2215
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Background
The role of interpersonal relationship functioning in trauma recovery is well-established. However, much of this research has been done with cross-sectional samples, often years after trauma exposure, using self-report methodology only, and is focused on intimate relationship adjustment.
MethodsThe current study investigated the longitudinal associations between interpersonal (intimate and non-intimate) relationship functioning and clinician- and self-reported posttraumatic stress disorder (PTSD) symptoms in 151 recently (within the past 6 months) traumatized individuals. Participants were assessed at four time points over 1 year.
ResultsApproximately 53% of the sample was diagnosed with PTSD at initial assessment, with declining rates of diagnostic status over time to 16%. Latent difference score (LDS) modeling revealed nonlinear declines in both clinician-assessed and self-reported PTSD symptom severity, with faster declines in earlier periods. Likewise, LDS models revealed nonlinear declines in negative (conflict) aspects of interpersonal relationship functioning, but linear declines in positive (support, depth) aspects. The relationship between PTSD and relationship functioning differed for clinician- and self-reported PTSD. Bivariate LDS modeling revealed significant cross-lagged effects from relationship conflict to clinician-assessed PTSD, and significant cross-lagged effects from self-reported PTSD to relationship conflict over time.
ConclusionsThese results highlight that the variability in prior results may be related to the method of assessing PTSD symptomatology and different relational constructs. Implications for theory and early intervention are discussed.
Relapse risk revealed by degree centrality and cluster analysis in heroin addicts undergoing methadone maintenance treatment
- Lei Wang, Feng Hu, Wei Li, Qiang Li, Yongbin Li, Jia Zhu, Xuan Wei, Jian Yang, Jianxin Guo, Yue Qin, Hong Shi, Wei Wang, Yarong Wang
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- Published online by Cambridge University Press:
- 27 October 2021, pp. 2216-2228
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Background
Based on hubs of neural circuits associated with addiction and their degree centrality (DC), this study aimed to construct the addiction-related brain networks for patients diagnosed with heroin dependence undertaking stable methadone maintenance treatment (MMT) and further prospectively identify the ones at high risk for relapse with cluster analysis.
MethodsSixty-two male MMT patients and 30 matched healthy controls (HC) underwent brain resting-state functional MRI data acquisition. The patients received 26-month follow-up for the monthly illegal-drug-use information. Ten addiction-related hubs were chosen to construct a user-defined network for the patients. Then the networks were discriminated with K-means-clustering-algorithm into different groups and followed by comparative analysis to the groups and HC. Regression analysis was used to investigate the brain regions significantly contributed to relapse.
ResultsSixty MMT patients were classified into two groups according to their brain-network patterns calculated by the best clustering-number-K. The two groups had no difference in the demographic, psychological indicators and clinical information except relapse rate and total heroin consumption. The group with high-relapse had a wider range of DC changes in the cortical−striatal−thalamic circuit relative to HC and a reduced DC in the mesocorticolimbic circuit relative to the low-relapse group. DC activity in NAc, vACC, hippocampus and amygdala were closely related with relapse.
ConclusionMMT patients can be identified and classified into two subgroups with significantly different relapse rates by defining distinct brain-network patterns even if we are blind to their relapse outcomes in advance. This may provide a new strategy to optimize MMT.
Condition openness is associated with better mental health in individuals with an intersex/differences of sex development condition: structural equation modeling of European multicenter data
- Tim C. van de Grift
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- Published online by Cambridge University Press:
- 19 October 2021, pp. 2229-2240
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Background
Openness on one's health condition or (stigmatized) identity generally improves mental health. Intersex or differences of sex development (DSD) conditions have long been kept concealed and high levels of (internalizing) mental health problems are reported. This study examines the effects of condition openness on anxiety and depression and the role of mediating concepts in this population.
MethodsCross-sectional data of individuals of 16 years and older with an intersex/DSD condition was collected in 14 specialized European clinics as part of the dsd-LIFE study. Patient-reported measures were taken on openness and shame (Coping with DSD), self-esteem (Rosenberg Self-Esteem Scale), satisfaction with care (CSQ4), anxiety and depression (HADS). Scores were compared per clinical group and data were analyzed via structural equation modeling (SEM) to calculate prediction and mediation models.
ResultsData of 903 individuals were included in this study (Turner syndrome (n = 284), 46, XY DSD (n = 233), CAH (n = 206) and Klinefelter syndrome (n = 180)). Participants were moderately open on their condition. High levels of both anxiety and depression were observed across the sample. In SEM analysis, the tested models predicted 25% of openness, 31% of anxiety and 48% of depression. More condition openness directly predicted lower anxiety and depression symptoms, as well as indirectly through increased self-esteem, self-satisfaction and satisfaction with social support.
ConclusionsCondition openness is associated with lower anxiety and depression in individuals with an intersex/DSD condition. Healthcare may provide the necessary knowledge and skills to employ one's optimal level of self-disclosure in order to improve mental health.
Shared genetic influences on depression and menopause symptoms
- Joeri J. Meijsen, Hanyang Shen, Mytilee Vemuri, Natalie L. Rasgon, Karestan C. Koenen, Laramie E. Duncan
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- Published online by Cambridge University Press:
- 06 December 2021, pp. 2241-2251
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Background
Women experience major depression and post-traumatic stress disorder (PTSD) approximately twice as often as men. Estrogen is thought to contribute to sex differences in these disorders, and reduced estrogen is also known to be a key driver of menopause symptoms such as hot flashes. Moreover, estrogen is used to treat menopause symptoms. In order to test for potential shared genetic influences between menopause symptoms and psychiatric disorders, we conducted a genome-wide association study (GWAS) of estrogen medication use (as a proxy for menopause symptoms) in the UK Biobank.
MethodsThe analysis included 232 993 women aged 39–71 in the UK Biobank. The outcome variable for genetic analyses was estrogen medication use, excluding women using hormonal contraceptives. Trans-ancestry GWAS meta-analyses were conducted along with genetic correlation analyses on the European ancestry GWAS results. Hormone usage was also tested for association with depression and PTSD.
ResultsGWAS of estrogen medication use (compared to non-use) identified a locus in the TACR3 gene, which was previously linked to hot flashes in menopause [top rs77322567, odds ratio (OR) = 0.78, p = 7.7 × 10−15]. Genetic correlation analyses revealed shared genetic influences on menopause symptoms and depression (rg = 0.231, s.e. = 0.055, p = 2.8 × 10−5). Non-genetic analyses revealed higher psychiatric symptoms scores among women using estrogen medications.
ConclusionsThese results suggest that menopause symptoms have a complex genetic etiology which is partially shared with genetic influences on depression. Moreover, the TACR3 gene identified here has direct clinical relevance; antagonists for the neurokinin 3 receptor (coded for by TACR3) are effective treatments for hot flashes.
Evidence that a novel transdiagnostic eating disorder treatment reduces reward region response to the thin beauty ideal and high-calorie binge foods
- Eric Stice, Sonja Yokum, Paul Rohde, Jeff Gau, Heather Shaw
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- 12 October 2021, pp. 2252-2262
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Background
Findings from brain imaging studies with small samples can show limited reproducibility. Thus, we tested whether the evidence that a transdiagnostic eating disorder treatment reduces responsivity of brain valuation regions to thin models and high-calorie binge foods, the intervention targets, from a smaller earlier trial emerged when we recruited additional participants.
MethodsWomen with DSM-5 eating disorders (N = 138) were randomized to the dissonance-based body project treatment (BPT) or a waitlist control condition and completed functional magnetic resonance imaging (fMRI) scans assessing neural response to thin models and high-calorie foods at pretest and posttest.
ResultsBPT v. control participants showed significantly greater reductions in responsivity of regions implicated in reward valuation (caudate) and attentional motivation (precuneus) to thin v. average-weight models, echoing findings from the smaller sample. Data from this larger sample also provided novel evidence that BPT v. control participants showed greater reductions in responsivity of regions implicated in reward valuation (ventrolateral prefrontal cortex) and food craving (hippocampus) to high-calorie binge foods v. low-calorie foods, as well as significantly greater reductions in eating disorder symptoms, abstinence from binge eating and purging behaviors, palatability ratings for high calorie foods, monetary value for high-calorie binge foods, and significantly greater increases in attractiveness ratings of average weight models.
ConclusionsResults from this larger sample provide evidence that BPT reduces valuation of the thin ideal and high-calorie binge foods, the intervention targets, per objective brain imaging data, and produces clinically meaningful reductions in eating pathology.
Dynamics of diurnal cortisol and alpha-amylase secretion and their associations with PTSD onset in recent interpersonal trauma survivors
- Kerry L. Kinney, Uma Rao, Brooklynn Bailey, Natalie Hellman, Chris Kelly, Nicholas W. McAfee, Matthew C. Morris
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- Published online by Cambridge University Press:
- 12 October 2021, pp. 2263-2273
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Background
Dysfunction in major stress response systems during the acute aftermath of trauma may contribute to risk for developing posttraumatic stress disorder (PTSD). The current study investigated how PTSD diagnosis and symptom severity, depressive symptoms, and childhood trauma uniquely relate to diurnal neuroendocrine secretion (cortisol and alpha-amylase rhythms) in women who recently experienced interpersonal trauma compared to non-traumatized controls (NTCs).
MethodUsing a longitudinal design, we examined diurnal cortisol and alpha-amylase rhythms in 98 young women (n = 57 exposed to recent interpersonal trauma, n = 41 NTCs). Participants provided saliva samples and completed symptom measures at baseline and 1-, 3-, and 6-month follow-up.
ResultsMultilevel models (MLMs) revealed lower waking cortisol predicted the development of PTSD in trauma survivors and distinguished at-risk women from NTCs. Women with greater childhood trauma exposure exhibited flatter diurnal cortisol slopes. Among trauma-exposed individuals, lower waking cortisol levels were associated with higher concurrent PTSD symptom severity. Regarding alpha-amylase, MLMs revealed women with greater childhood trauma exposure exhibited higher waking alpha-amylase and slower diurnal alpha-amylase increase.
ConclusionsResults suggest lower waking cortisol in the acute aftermath of trauma may be implicated in PTSD onset and maintenance. Findings also suggest childhood trauma may predict a different pattern of dysfunction in stress response systems following subsequent trauma exposure than the stress system dynamics associated with PTSD risk; childhood trauma appears to be associated with flattened diurnal cortisol and alpha-amylase slopes, as well as higher waking alpha-amylase.
Iron deficiency and internalizing symptom severity in unmedicated adolescents: a pilot study
- Malak Abbas, Kellen Gandy, Ramiro Salas, Sridevi Devaraj, Chadi A. Calarge
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- Published online by Cambridge University Press:
- 16 December 2021, pp. 2274-2284
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Background
Iron plays a key role in a broad set of metabolic processes. Iron deficiency is the most common nutritional deficiency in the world, but its neuropsychiatric implications in adolescents have not been examined.
MethodsTwelve- to 17-year-old unmedicated females with major depressive or anxiety disorders or with no psychopathology underwent a comprehensive psychiatric assessment for this pilot study. A T1-weighted magnetic resonance imaging scan was obtained, segmented using Freesurfer. Serum ferritin concentration (sF) was measured. Correlational analyses examined the association between body iron stores, psychiatric symptom severity, and basal ganglia volumes, accounting for confounding variables.
ResultsForty females were enrolled, 73% having a major depressive and/or anxiety disorder, 35% with sF < 15 ng/mL, and 50% with sF < 20 ng/mL. Serum ferritin was inversely correlated with both anxiety and depressive symptom severity (r = −0.34, p < 0.04 and r = −0.30, p < 0.06, respectively). Participants with sF < 15 ng/mL exhibited more severe depressive and anxiety symptoms as did those with sF < 20 ng/mL. Moreover, after adjusting for age and total intracranial volume, sF was inversely associated with left caudate (Spearman's r = −0.46, p < 0.04), left putamen (r = −0.58, p < 0.005), and right putamen (r = −0.53, p < 0.01) volume.
ConclusionsBrain iron may become depleted at a sF concentration higher than the established threshold to diagnose iron deficiency (i.e. 15 ng/mL), potentially disrupting brain maturation and contributing to the emergence of internalizing disorders in adolescents.
Null results of oxytocin and vasopressin administration on mentalizing in a large fMRI sample: evidence from a randomized controlled trial
- Mark A. Straccia, Adam R. Teed, Perri L. Katzman, Kevin M. Tan, Michael H. Parrish, Michael R. Irwin, Naomi I. Eisenberger, Matthew D. Lieberman, Benjamin A. Tabak
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- Published online by Cambridge University Press:
- 15 October 2021, pp. 2285-2295
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Background
Although potential links between oxytocin (OT), vasopressin (AVP), and social cognition are well-grounded theoretically, most studies have included all male samples, and few have demonstrated consistent effects of either neuropeptide on mentalizing (i.e. understanding the mental states of others). To understand the potential of either neuropeptide as a pharmacological treatment for individuals with impairments in social cognition, it is important to demonstrate the beneficial effects of OT and AVP on mentalizing in healthy individuals.
MethodsIn the present randomized, double-blind, placebo-controlled study (n = 186) of healthy individuals, we examined the effects of OT and AVP administration on behavioral responses and neural activity in response to a mentalizing task.
ResultsRelative to placebo, neither drug showed an effect on task reaction time or accuracy, nor on whole-brain neural activation or functional connectivity observed within brain networks associated with mentalizing. Exploratory analyses included several variables previously shown to moderate OT's effects on social processes (e.g., self-reported empathy, alexithymia) but resulted in no significant interaction effects.
ConclusionsResults add to a growing literature demonstrating that intranasal administration of OT and AVP may have a more limited effect on social cognition, at both the behavioral and neural level, than initially assumed. Randomized controlled trial registrations: ClinicalTrials.gov; NCT02393443; NCT02393456; NCT02394054.
Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study
- Jonathan D. Schaefer, Seon-Kyeong Jang, D. Angus Clark, Joseph D. Deak, Brian M. Hicks, William G. Iacono, Mengzhen Liu, Matt McGue, Scott I. Vrieze, Sylia Wilson
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- Published online by Cambridge University Press:
- 12 October 2021, pp. 2296-2306
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Background
Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation v. demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.
MethodsPGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (N = 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.
ResultsNearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.
ConclusionsPGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.
Plasma acetyl-l-carnitine and l-carnitine in major depressive episodes: a case–control study before and after treatment
- Abd El Kader Ait Tayeb, Romain Colle, Khalil El-Asmar, Kenneth Chappell, Cécile Acquaviva-Bourdain, Denis J. David, Séverine Trabado, Philippe Chanson, Bruno Feve, Laurent Becquemont, Céline Verstuyft, Emmanuelle Corruble
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- Published online by Cambridge University Press:
- 14 October 2021, pp. 2307-2316
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Background
Major depressive disorder (MDD) is the main cause of disability worldwide, its outcome is poor, and its underlying mechanisms deserve a better understanding. Recently, peripheral acetyl-l-carnitine (ALC) has been shown to be lower in patients with major depressive episodes (MDEs) than in controls. l-Carnitine is involved in mitochondrial function and ALC is its short-chain acetyl-ester. Our first aim was to compare the plasma levels of l-carnitine and ALC, and the l-carnitine/ALC ratio in patients with a current MDE and healthy controls (HCs). Our second aim was to assess their changes after antidepressant treatment.
Methodsl-Carnitine and ALC levels and the carnitine/ALC ratio were measured in 460 patients with an MDE in a context of MDD and in 893 HCs. Depressed patients were re-assessed after 3 and 6 months of antidepressant treatment for biology and clinical outcome.
ResultsAs compared to HC, depressed patients had lower ALC levels (p < 0.00001), higher l-carnitine levels (p < 0.00001) and higher l-carnitine/ALC ratios (p < 0.00001). ALC levels increased [coefficient: 0.18; 95% confidence interval (CI) 0.12–0.24; p < 0.00001], and l-carnitine levels (coefficient: −0.58; 95% CI −0.75 to −0.41; p < 0.00001) and l-carnitine/ALC ratios (coefficient: −0.41; 95% CI −0.47 to −0.34; p < 0.00001), decreased after treatment. These parameters were completely restored after 6 months of antidepressant. Moreover, the baseline l-carnitine/ALC ratio predicted remission after 3 months of treatment (odds ratio = 1.14; 95% CI 1.03–1.27; p = 0.015).
ConclusionsOur data suggest a decreased mitochondrial metabolism of l-carnitine into ALC during MDE. This decreased mitochondrial metabolism is restored after a 6-month antidepressant treatment. Moreover, the magnitude of mitochondrial dysfunction may predict remission after 3 months of antidepressant treatment. New strategies targeting mitochondria should be explored to improve treatments of MDD.
Longitudinal clinical and functional outcome in distinct cognitive subgroups of first-episode psychosis: a cluster analysis
- Priscilla P. Oomen, Marieke J. H. Begemann, Bodyl A. Brand, Lieuwe de Haan, Wim Veling, Sanne Koops, Jim van Os, Filip Smit, P. Roberto Bakker, Nico van Beveren, Nynke Boonstra, Sinan Gülöksüz, Martijn Kikkert, Joran Lokkerbol, Machteld Marcelis, Bram-Sieben Rosema, Franciska de Beer, Shiral S. Gangadin, Chris N. W. Geraets, Erna van ‘t Hag, Yudith Haveman, Inge van der Heijden, Alban E. Voppel, Elske Willemse, Therese van Amelsvoort, Maarten Bak, Albert Batalla, Agaath Been, Marinte van den Bosch, Truus van den Brink, Gunnar Faber, Koen P. Grootens, Martin de Jonge, Rikus Knegtering, Jörg Kurkamp, Amrita Mahabir, Gerdina H. M. Pijnenborg, Tonnie Staring, Natalie Veen, Selene Veerman, Sybren Wiersma, Ellen Graveland, Joelle Hoornaar, Iris E. C. Sommer
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- Published online by Cambridge University Press:
- 19 October 2021, pp. 2317-2327
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Background
Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes.
Methods204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up.
ResultsThree distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present.
ConclusionsCurrent results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.
Emotional cognition subgroups in unaffected first-degree relatives of patients with mood disorders
- Hanne Lie Kjærstad, Cristina Varo, Iselin Meluken, Eduard Vieta, Maj Vinberg, Lars Vedel Kessing, Kamilla Woznica Miskowiak
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- Published online by Cambridge University Press:
- 21 October 2021, pp. 2328-2338
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Background
Patients with major depressive disorder (MDD) or bipolar disorder (BD) exhibit difficulties with emotional cognition even during remission. There is evidence for aberrant emotional cognition in unaffected relatives of patients with these mood disorders, but studies are conflicting. We aimed to investigate whether emotional cognition in unaffected first-degree relatives of patients with mood disorders is characterised by heterogeneity using a data-driven approach.
MethodsData from 94 unaffected relatives (33 of MDD patients; 61 of BD patients) and 203 healthy controls were pooled from two cohort studies. Emotional cognition was assessed with the Social Scenarios Test, Facial Expression Recognition Test and Faces Dot-Probe Test. Hierarchical cluster analysis was conducted using emotional cognition data from the 94 unaffected relatives. The resulting emotional cognition clusters and controls were compared for emotional and non-emotional cognition, demographic characteristics and functioning.
ResultsTwo distinct clusters of unaffected relatives were identified: a relatively ‘emotionally preserved’ cluster (55%; 40% relatives of MDD probands) and an ‘emotionally blunted’ cluster (45%; 29% relatives of MDD probands). ‘Emotionally blunted’ relatives presented with poorer neurocognitive performance (global cognition p = 0.010), heightened subsyndromal mania symptoms (p = 0.004), lower years of education (p = 0.004) and difficulties with interpersonal functioning (p = 0.005) than controls, whereas ‘emotionally preserved’ relatives were comparable to controls on these measures.
ConclusionsOur findings show discrete emotional cognition profiles that occur across healthy first-degree relatives of patients with MDD and BD. These emotional cognition clusters may provide insight into emotional cognitive markers of genetically distinct subgroups of individuals at familial risk of mood disorders.
Effectiveness and optimal duration of early intervention treatment in adult-onset psychosis: a randomized clinical trial
- Christy Lai Ming Hui, Andreas Kar Hin Wong, Elise Chun Ning Ho, Bertha Sze Ting Lam, Priscilla Wing Man Hui, Tiffany Junchen Tao, Wing Chung Chang, Sherry Kit Wa Chan, Edwin Ho Ming Lee, Yi Nam Suen, May Mei Ling Lam, Cindy Pui Yu Chiu, Frendi Wing Sai Li, Kwok Fai Leung, Sarah M. McGhee, Chi Wing Law, Dicky Wai Sau Chung, Wai Song Yeung, Michael Gar Chung Yiu, Edwin Pui Fai Pang, Steve Tso, Simon Sai Yu Lui, Se Fong Hung, Wing King Lee, Ka Chee Yip, Ka Lik Kwan, Roger Man Kin Ng, Pak Chung Sham, William G. Honer, Eric Yu Hai Chen
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- Published online by Cambridge University Press:
- 11 February 2022, pp. 2339-2351
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Background
Contrasting the well-described effects of early intervention (EI) services for youth-onset psychosis, the potential benefits of the intervention for adult-onset psychosis are uncertain. This paper aims to examine the effectiveness of EI on functioning and symptomatic improvement in adult-onset psychosis, and the optimal duration of the intervention.
Methods360 psychosis patients aged 26–55 years were randomized to receive either standard care (SC, n = 120), or case management for two (2-year EI, n = 120) or 4 years (4-year EI, n = 120) in a 4-year rater-masked, parallel-group, superiority, randomized controlled trial of treatment effectiveness (Clinicaltrials.gov: NCT00919620). Primary (i.e. social and occupational functioning) and secondary outcomes (i.e. positive and negative symptoms, and quality of life) were assessed at baseline, 6-month, and yearly for 4 years.
ResultsCompared with SC, patients with 4-year EI had better Role Functioning Scale (RFS) immediate [interaction estimate = 0.008, 95% confidence interval (CI) = 0.001–0.014, p = 0.02] and extended social network (interaction estimate = 0.011, 95% CI = 0.004–0.018, p = 0.003) scores. Specifically, these improvements were observed in the first 2 years. Compared with the 2-year EI group, the 4-year EI group had better RFS total (p = 0.01), immediate (p = 0.01), and extended social network (p = 0.05) scores at the fourth year. Meanwhile, the 4-year (p = 0.02) and 2-year EI (p = 0.004) group had less severe symptoms than the SC group at the first year.
ConclusionsSpecialized EI treatment for psychosis patients aged 26–55 should be provided for at least the initial 2 years of illness. Further treatment up to 4 years confers little benefits in this age range over the course of the study.
Dynamic risk for first onset of depressive disorders in adolescence: does change matter?
- Wenting Mu, Kaiqiao Li, Yuan Tian, Greg Perlman, Giorgia Michelini, David Watson, Hans Ormel, Daniel N. Klein, Roman Kotov
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- Published online by Cambridge University Press:
- 22 November 2021, pp. 2352-2360
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Background
Risk factors for depressive disorders (DD) change substantially over time, but the prognostic value of these changes remains unclear. Two basic types of dynamic effects are possible. The ‘Risk Escalation hypothesis’ posits that worsening of risk levels predicts DD onset above average level of risk factors. Alternatively, the ‘Chronic Risk hypothesis’ posits that the average level rather than change predicts first-onset DD.
MethodsWe utilized data from the ADEPT project, a cohort of 496 girls (baseline age 13.5–15.5 years) from the community followed for 3 years. Participants underwent five waves of assessments for risk factors and diagnostic interviews for DD. For illustration purposes, we selected 16 well-established dynamic risk factors for adolescent depression, such as depressive and anxiety symptoms, personality traits, clinical traits, and social risk factors. We conducted Cox regression analyses with time-varying covariates to predict first DD onset.
ResultsConsistently elevated risk factors (i.e. the mean of multiple waves), but not recent escalation, predicted first-onset DD, consistent with the Chronic Risk hypothesis. This hypothesis was supported across all 16 risk factors.
ConclusionsAcross a range of risk factors, girls who had first-onset DD generally did not experience a sharp increase in risk level shortly before the onset of disorder; rather, for years before onset, they exhibited elevated levels of risk. Our findings suggest that chronicity of risk should be a particular focus in screening high-risk populations to prevent the onset of DDs. In particular, regular monitoring of risk factors in school settings is highly informative.
Multivariate classification provides a neural signature of Tourette disorder
- Giuseppe A. Zito, Andreas Hartmann, Benoît Béranger, Samantha Weber, Selma Aybek, Johann Faouzi, Emmanuel Roze, Marie Vidailhet, Yulia Worbe
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- Published online by Cambridge University Press:
- 03 November 2021, pp. 2361-2369
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Background
Tourette disorder (TD), hallmarks of which are motor and vocal tics, has been related to functional abnormalities in large-scale brain networks. Using a fully data driven approach in a prospective, case–control study, we tested the hypothesis that functional connectivity of these networks carries a neural signature of TD. Our aim was to investigate (i) the brain networks that distinguish adult patients with TD from controls, and (ii) the effects of antipsychotic medication on these networks.
MethodsUsing a multivariate analysis based on support vector machine (SVM), we developed a predictive model of resting state functional connectivity in 48 patients and 51 controls, and identified brain networks that were most affected by disease and pharmacological treatments. We also performed standard univariate analyses to identify differences in specific connections across groups.
ResultsSVM was able to identify TD with 67% accuracy (p = 0.004), based on the connectivity in widespread networks involving the striatum, fronto-parietal cortical areas and the cerebellum. Medicated and unmedicated patients were discriminated with 69% accuracy (p = 0.019), based on the connectivity among striatum, insular and cerebellar networks. Univariate approaches revealed differences in functional connectivity within the striatum in patients v. controls, and between the caudate and insular cortex in medicated v. unmedicated TD.
ConclusionsSVM was able to identify a neuronal network that distinguishes patients with TD from control, as well as medicated and unmedicated patients with TD, holding a promise to identify imaging-based biomarkers of TD for clinical use and evaluation of the effects of treatment.
White matter, cognition and psychotic-like experiences in UK Biobank
- M. J. Bosma, S. R. Cox, T. Ziermans, C. R. Buchanan, X. Shen, E. M. Tucker-Drob, M. J. Adams, H. C. Whalley, S. M. Lawrie
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- Published online by Cambridge University Press:
- 17 November 2021, pp. 2370-2379
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Background
Psychotic-like experiences (PLEs) are risk factors for the development of psychiatric conditions like schizophrenia, particularly if associated with distress. As PLEs have been related to alterations in both white matter and cognition, we investigated whether cognition (g-factor and processing speed) mediates the relationship between white matter and PLEs.
MethodsWe investigated two independent samples (6170 and 19 891) from the UK Biobank, through path analysis. For both samples, measures of whole-brain fractional anisotropy (gFA) and mean diffusivity (gMD), as indications of white matter microstructure, were derived from probabilistic tractography. For the smaller sample, variables whole-brain white matter network efficiency and microstructure were also derived from structural connectome data.
ResultsThe mediation of cognition on the relationships between white matter properties and PLEs was non-significant. However, lower gFA was associated with having PLEs in combination with distress in the full available sample (standardized β = −0.053, p = 0.011). Additionally, lower gFA/higher gMD was associated with lower g-factor (standardized β = 0.049, p < 0.001; standardized β = −0.027, p = 0.003), and partially mediated by processing speed with a proportion mediated of 7% (p = < 0.001) for gFA and 11% (p < 0.001) for gMD.
ConclusionsWe show that lower global white matter microstructure is associated with having PLEs in combination with distress, which suggests a direction of future research that could help clarify how and why individuals progress from subclinical to clinical psychotic symptoms. Furthermore, we replicated that processing speed mediates the relationship between white matter microstructure and g-factor.
Shared genetic and environmental etiology between substance use disorders and suicidal behavior
- Alexis C. Edwards, Henrik Ohlsson, Séverine Lannoy, Mallory Stephenson, Casey Crump, Jan Sundquist, Kristina Sundquist, Kenneth S. Kendler
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- Published online by Cambridge University Press:
- 12 November 2021, pp. 2380-2388
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Background
Previous studies have demonstrated substantial associations between substance use disorders (SUD) and suicidal behavior. The current study empirically assesses the extent to which shared genetic and/or environmental factors contribute to associations between alcohol use disorders (AUD) or drug use disorders (DUD) and suicidal behavior, including attempts and death.
MethodsThe authors used Swedish national registry data, including medical, pharmacy, criminal, and death registrations, for a large cohort of twins, full siblings, and half siblings (N = 1 314 990) born 1960–1980 and followed through 2017. They conducted twin-sibling modeling of suicide attempt (SA) or suicide death (SD) with AUD and DUD to estimate genetic and environmental correlations between outcomes. Analyses were stratified by sex.
ResultsGenetic correlations between SA and SUD ranged from rA = 0.60–0.88; corresponding shared environmental correlations were rC = 0.42–0.89 but accounted for little overall variance; and unique environmental correlations were rE = 0.42–0.57. When replacing attempt with SD, genetic and shared environmental correlations with AUD and DUD were comparable (rA = 0.48–0.72, rC = 0.92–1.00), but were attenuated for unique environmental factors (rE = −0.01 to 0.31).
ConclusionsThese findings indicate that shared genetic and unique environmental factors contribute to comorbidity of suicidal behavior and SUD, in conjunction with previously reported causal associations. Thus, each outcome should be considered an indicator of risk for the others. Opportunities for joint prevention and intervention, while limited by the polygenic nature of these outcomes, may be feasible considering moderate environmental correlations between SA and SUD.
Impact of comorbidity on family genetic risk profiles for psychiatric and substance use disorders: a descriptive analysis
- Kenneth S. Kendler, Henrik Ohlsson, Jan Sundquist, Kristina Sundquist
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- 22 November 2021, pp. 2389-2398
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Background
– Comorbidity between psychiatric disorders is extensive but, from a genetic perspective, still poorly understood. Modern molecular genetic approaches to this problem are limited by a reliance on case–control designs.
Methods– In 5 828 760 individuals born in Sweden from 1932–1995 with a mean (s.d.) age at follow-up of 54.4 (18.1), we examined family genetic risk score (FGRS) profiles including internalizing, psychotic, substance use and developmental disorders in 10 pairs of psychiatric and substance use disorders diagnosed from population registries. We examined these profiles in three groups of patients: disorder A only, disorder B only and comorbid cases with both disorders.
Results– The most common pattern of findings, seen in five pairings, was simple and quantitative. Comorbid cases had higher FGRS than both non-comorbid cases for all (or nearly all) disorders. However, the pattern was more complex in the remaining five pairings and included qualitative changes where the comorbid cases showed no increases in FGRS for certain disorders and in a few cases significant decreases. Several comparisons showed an asymmetric pattern of findings with increases, in comorbidity compared to single disorder cases, of the FGRS for only one of the two disorders.
Conclusions– The examination of FGRS profiles in general population samples where all disorders are assessed in all subjects provides a fruitful line of inquiry to understand the origins of psychiatric comorbidity. Further work will be needed, with an expansion of analytic approaches, to gain deeper insights into the complex mechanisms likely involved.
Childhood trauma, antipsychotic medication, and symptom remission in first-episode psychosis
- Akiah Ottesen, W. T. V. Hegelstad, Inge Joa, Stein E. Opjordsmoen, Bjørn Rishovd Rund, Jan Ivar Røssberg, Erik Simonsen, Jan Olav Johannessen, Tor K. Larsen, Ulrik Helt Haahr, Thomas H. McGlashan, Svein Friis, Ingrid Melle
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- Published online by Cambridge University Press:
- 15 November 2021, pp. 2399-2408
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Background
To what extent psychotic symptoms in first-episode psychosis (FEP) with a history of childhood interpersonal trauma (CIT) are less responsive to antipsychotic medication is not known. In this longitudinal study, we compare symptom trajectories and remission over the first 2 years of treatment in FEP with and without CIT and examine if differences are linked to the use of antipsychotics.
MethodsFEP (N = 191) were recruited from in- and outpatient services 1997–2000, and assessed at baseline, 3 months, 1 and 2 years. Inclusion criteria were 15–65 years, actively psychotic with a DSM-IV diagnosis of psychotic disorder and no previous adequate treatment for psychosis. Antipsychotic medication is reported as defined daily dosage (DDD). CIT (<18) was assessed with the Brief Betrayal Trauma Survey, and symptomatic remission based on scores from the Positive and Negative Syndrome Scale.
ResultsCIT (n = 63, 33%) was not associated with symptomatic remission at 2 years follow-up (71% in remission, 14% in relapse), or time to first remission (CIT 12/ no-CIT 9 weeks, p = 0.51). Those with CIT had significantly more severe positive, depressive, and excited symptoms. FEP with physical (N = 39, 20%) or emotional abuse (N = 22, 14, 7%) had higher DDD at 1 year (p < 0.05). Mean DDD did not excerpt a significant between-group effect on symptom trajectories of positive symptoms.
ConclusionResults indicate that antipsychotic medication is equally beneficial in the achievement of symptomatic remission in FEP after 2 years independent of CIT. Still, FEP patients with CIT had more severe positive, depressive, and excited symptoms throughout.