Review Article
Effects of psychosis-associated genetic markers on brain volumetry: a systematic review of replicated findings and an independent validation
- Nuno Vouga Ribeiro, Vânia Tavares, Elvira Bramon, Timothea Toulopoulou, Isabel Valli, Sukhi Shergill, Robin Murray, Diana Prata
-
- Published online by Cambridge University Press:
- 28 September 2022, pp. 3753-3768
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Given psychotic illnesses' high heritability and associations with brain structure, numerous neuroimaging-genetics findings have been reported in the last two decades. However, few findings have been replicated. In the present independent sample we aimed to replicate any psychosis-implicated SNPs (single nucleotide polymorphisms), which had previously shown at least two main effects on brain volume.
MethodsA systematic review for SNPs showing a replicated effect on brain volume yielded 25 studies implicating seven SNPs in five genes. Their effect was then tested in 113 subjects with either schizophrenia, bipolar disorder, ‘at risk mental state’ or healthy state, for whole-brain and region-of-interest (ROI) associations with grey and white matter volume changes, using voxel-based morphometry.
ResultsWe found FWER-corrected (Family-wise error rate) (i.e. statistically significant) associations of: (1) CACNA1C-rs769087-A with larger bilateral hippocampus and thalamus white matter, across the whole brain; and (2) CACNA1C-rs769087-A with larger superior frontal gyrus, as ROI. Higher replication concordance with existing literature was found, in decreasing order, for: (1) CACNA1C-rs769087-A, with larger dorsolateral-prefrontal/superior frontal gyrus and hippocampi (both with anatomical and directional concordance); (2) ZNF804A-rs11681373-A, with smaller angular gyrus grey matter and rectus gyri white matter (both with anatomical and directional concordance); and (3) BDNF-rs6265-T with superior frontal and middle cingulate gyri volume change (with anatomical and allelic concordance).
ConclusionsMost literature findings were not herein replicated. Nevertheless, high degree/likelihood of replication was found for two genome-wide association studies- and one candidate-implicated SNPs, supporting their involvement in psychosis and brain structure.
Understanding the development of bipolar disorder and borderline personality disorder in young people: a meta-review of systematic reviews
- Buse Beril Durdurak, Nada Altaweel, Rachel Upthegrove, Steven Marwaha
-
- Published online by Cambridge University Press:
- 30 September 2022, pp. 3769-3782
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
There is ongoing debate on the nosological position of bipolar disorder (BD) and borderline personality disorder (BPD). Identifying the unique and shared risks, developmental pathways, and symptoms in emerging BD and BPD could help the field refine aetiological hypotheses and improve the prediction of the onset of these disorders. This study aimed to: (a) systematically synthesise the available evidence from systematic reviews (SRs) and meta-analyses (MAs) concerning environmental, psychosocial, biological, and clinical factors leading to the emergence of BD and BPD; (b) identify the main differences and common features between the two disorders to characterise their complex interplay and, (c) highlight remaining evidence gaps.
MethodsData sources were; PubMed, PsychINFO, Embase, Cochrane, CINAHL, Medline, ISI Web of Science. Overlap of included SRs/MAs was assessed using the corrected covered area process. The methodological quality of each included SR and MA was assessed using the AMSTAR.
Results22 SRs and MAs involving 249 prospective studies met eligibility criteria. Results demonstrated that family history of psychopathology, affective instability, attention deficit hyperactivity disorder, anxiety disorders, depression, sleep disturbances, substance abuse, psychotic symptoms, suicidality, childhood adversity and temperament were common predisposing factors across both disorders. There are also distinct factors specific to emerging BD or BPD.
ConclusionsProspective studies are required to increase our understanding of the development of BD and BPD onset and their complex interplay by concurrently examining multiple measures in BD and BPD at-risk populations.
Original Article
Weight gain as a risk factor for progressive neurochemical abnormalities in first episode mania patients: a longitudinal magnetic resonance spectroscopy study
- David J. Bond, Leonardo E. Silveira, Ivan J. Torres, Raymond W. Lam, Lakshmi N. Yatham
-
- Published online by Cambridge University Press:
- 12 March 2021, pp. 3783-3791
-
- Article
- Export citation
-
Background
We previously reported that bipolar disorder (BD) patients with clinically significant weight gain (CSWG; ⩾7% of baseline weight) in the 12 months after their first manic episode experienced greater limbic brain volume loss than patients without CSWG. It is unknown whether CSWG is also a risk factor for progressive neurochemical abnormalities.
MethodsWe investigated whether 12-month CSWG predicted greater 12-month decreases in hippocampal N-acetylaspartate (NAA) and greater increases in glutamate + glutamine (Glx) following a first manic episode. In BD patients (n = 58) and healthy comparator subjects (HS; n = 34), we measured baseline and 12-month hippocampal NAA and Glx using bilateral 3-Tesla single-voxel proton magnetic resonance spectroscopy. We used general linear models for repeated measures to investigate whether CSWG predicted neurochemical changes.
ResultsThirty-three percent of patients and 18% of HS experienced CSWG. After correcting for multiple comparisons, CSWG in patients predicted a greater decrease in left hippocampal NAA (effect size = −0.52, p = 0.005). CSWG also predicted a greater decrease in left hippocampal NAA in HS with a similar effect size (−0.53). A model including patients and HS found an effect of CSWG on Δleft NAA (p = 0.007), but no diagnosis effect and no diagnosis × CSWG interaction, confirming that CSWG had similar effects in patients and HS.
ConclusionCSWG is a risk factor for decreasing hippocampal NAA in BD patients and HS. These results suggest that the well-known finding of reduced NAA in BD may result from higher body mass index in patients rather than BD diagnosis.
Associations between individual antipsychotics and the risk of arrests and convictions of violent and other crime: a nationwide within-individual study of 74 925 persons
- Amir Sariaslan, Stefan Leucht, Johan Zetterqvist, Paul Lichtenstein, Seena Fazel
-
- Published online by Cambridge University Press:
- 11 March 2021, pp. 3792-3800
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Individuals diagnosed with psychiatric disorders who are prescribed antipsychotics have lower rates of violence and crime but the differential effects of specific antipsychotics are not known. We investigated associations between 10 specific antipsychotic medications and subsequent risks for a range of criminal outcomes.
MethodsWe identified 74 925 individuals who were ever prescribed antipsychotics between 2006 and 2013 using nationwide Swedish registries. We tested for five specific first-generation antipsychotics (levomepromazine, perphenazine, haloperidol, flupentixol, and zuclopenthixol) and five second-generation antipsychotics (clozapine, olanzapine, quetiapine, risperidone, and aripiprazole). The outcomes included violent, drug-related, and any criminal arrests and convictions. We conducted within-individual analyses using fixed-effects Poisson regression models that compared rates of outcomes between periods when each individual was either on or off medication to account for time-stable unmeasured confounders. All models were adjusted for age and concurrent mood stabilizer medications.
ResultsThe relative risks of all crime outcomes were substantially reduced [range of adjusted rate ratios (aRRs): 0.50–0.67] during periods when the patients were prescribed antipsychotics v. periods when they were not. We found that clozapine (aRRs: 0.28–0.44), olanzapine (aRRs: 0.46–0.72), and risperidone (aRRs: 0.53–0.64) were associated with lower arrest and conviction risks than other antipsychotics, including quetiapine (aRRs: 0.68–0.84) and haloperidol (aRRs: 0.67–0.77). Long-acting injectables as a combined medication class were associated with lower risks of the outcomes but only risperidone was associated with lower risks of all six outcomes (aRRs: 0.33–0.69).
ConclusionsThere is heterogeneity in the associations between specific antipsychotics and subsequent arrests and convictions for any drug-related and violent crimes.
Intrauterine testosterone exposure and depression risk in opposite-sex and same-sex twins, a Danish register study
- M. Vinberg, M. K. Wium-Andersen, I. K. Wium-Andersen, M. B. Jørgensen, K. Christensen, M. Osler
-
- Published online by Cambridge University Press:
- 16 March 2021, pp. 3801-3806
-
- Article
- Export citation
-
Background
Males have a lower prevalence of depression than females and testosterone may be a contributing factor. A comparison of opposite-sex and same-sex twins can be used indirectly to establish the role of prenatal testosterone exposure and the risk of depression. We therefore aimed to explore differences in depression risk using opposite-sex and same-sex twins.
MethodsWe included 126 087 opposite-sex and same-sex twins from the Danish Twin Registry followed in nationwide Danish registers. We compared sex-specific incidences of depression diagnosis and prescriptions of antidepressants between opposite-sex and same-sex twins using Cox proportional hazard regression.
ResultsDuring follow-up, 2664 (2.1%) twins were diagnosed with depression and 19 514 (15.5%) twins had purchased at least one prescription of antidepressants. First, in male twins, we found that the opposite-sex male twins had the same risk of depression compared to the same-sex male twins {hazard ratio (HR) = 1.01 [95% confidence interval (CI) 0.88–1.17)]}. Revealing the risk of use of antidepressants, the opposite-sex male twins had a slightly higher risk of 4% (HR = 1.04 (95% CI 1.00–1.11)) compared with the same-sex male twins. Second, in the female opposite-sex twins, we revealed a slightly higher, however, not statistically significant risk of depression (HR = 1.08 (95% CI 0.97–1.29)) or purchase of antidepressants (HR = 1.01 (95% CI 0.96–1.05)) when compared to the same-sex female twins.
ConclusionsWe found limited support for the hypothesis that prenatal exposure to testosterone was associated with the risk of depression later in life.
Childhood adversity, pubertal timing and self-harm: a longitudinal cohort study
- Abigail Emma Russell, Carol Joinson, Elystan Roberts, Jon Heron, Tamsin Ford, David Gunnell, Paul Moran, Caroline Relton, Matthew Suderman, Becky Mars
-
- Published online by Cambridge University Press:
- 08 March 2021, pp. 3807-3815
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
The occurrence of early childhood adversity is strongly linked to later self-harm, but there is poor understanding of how this distal risk factor might influence later behaviours. One possible mechanism is through an earlier onset of puberty in children exposed to adversity, since early puberty is associated with an increased risk of adolescent self-harm. We investigated whether early pubertal timing mediates the association between childhood adversity and later self-harm.
MethodsParticipants were 6698 young people from a UK population-based birth cohort (ALSPAC). We measured exposure to nine types of adversity from 0 to 9 years old, and self-harm when participants were aged 16 and 21 years. Pubertal timing measures were age at peak height velocity (aPHV – males and females) and age at menarche (AAM). We used generalised structural equation modelling for analyses.
ResultsFor every additional type of adversity; participants had an average 12–14% increased risk of self-harm by 16. Relative risk (RR) estimates were stronger for direct effects when outcomes were self-harm with suicidal intent. There was no evidence that earlier pubertal timing mediated the association between adversity and self-harm [indirect effect RR 1.00, 95% confidence interval (CI) 1.00–1.00 for aPHV and RR 1.00, 95% CI 1.00–1.01 for AAM].
ConclusionsA cumulative measure of exposure to multiple types of adversity does not confer an increased risk of self-harm via early pubertal timing, however both childhood adversity and early puberty are risk factors for later self-harm. Research identifying mechanisms underlying the link between childhood adversity and later self-harm is needed to inform interventions.
Apolipoprotein E e4 allele status and later-life depression in the Lothian Birth Cohort 1936
- Matthew H. Iveson, Adele Taylor, Sarah E. Harris, Ian J. Deary, Andrew M. McIntosh
-
- Published online by Cambridge University Press:
- 02 March 2021, pp. 3816-3824
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Previous results have been mixed regarding the role of the apolipoprotein E e4 (APOE e4) allele in later-life depression: some studies note that carriers experience greater symptoms and increased risk while others find no such association. However, there are few prospective, population-based studies of the APOE e4-depression association and fewer that examine depressive symptom trajectory and depression risk longitudinally. We examined the association between APOE e4 allele status and longitudinal change in depressive symptoms and depression risk in later-life, over a 12-year follow-up period.
MethodsWe used data from 690 participants of the Lothian Birth Cohort 1936 who took part in the Scottish Mental Survey 1947 (aged 11) and were followed-up in later-life over five waves from 2004 to 2019 (aged 70–82). We used APOE e4 allele status to predict longitudinal change in depressive symptom scores and risk of depression (defined by a symptom score threshold or use of depression-related medication). Models were adjusted for sex, childhood cognitive ability, childhood social class, education, adult social class, smoking status and functional limitations at baseline.
ResultsDepressive symptom scores increased with age. Once adjusted for covariates, APOE e4 allele status did not significantly predict symptom score trajectories or depression risk. Greater functional limitations at baseline significantly predicted poorer symptom score trajectories and increased depression risk (defined by medications). APOE e4 allele status did not significantly moderate the contribution of sex, education or functional limitations.
ConclusionsThere was no evidence that APOE e4 carriers experience an increased risk for later-life depression.
How does the COVID-19 pandemic impact on population mental health? A network analysis of COVID influences on depression, anxiety and traumatic stress in the UK population
- Orestis Zavlis, Sarah Butter, Kate Bennett, Todd K. Hartman, Philip Hyland, Liam Mason, Orla McBride, Jamie Murphy, Jilly Gibson-Miller, Liat Levita, Anton P. Martinez, Mark Shevlin, Thomas V. A. Stocks, Frédérique Vallières, Richard P. Bentall
-
- Published online by Cambridge University Press:
- 16 March 2021, pp. 3825-3833
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
The coronavirus disease 2019 (COVID-19) emergency has led to numerous attempts to assess the impact of the pandemic on population mental health. The findings indicate an increase in depression and anxiety but have been limited by the lack of specificity about which aspects of the pandemic (e.g. viral exposure or economic threats) have led to adverse mental health outcomes.
MethodsNetwork analyses were conducted on data from wave 1 (N = 2025, recruited 23 March–28 March 2020) and wave 2 (N = 1406, recontacts 22 April–1 May 2020) of the COVID-19 Psychological Research Consortium Study, an online longitudinal survey of a representative sample of the UK adult population. Our models included depression (PHQ-9), generalized anxiety (GAD-7) and trauma symptoms (ITQ); and measures of COVID-specific anxiety, exposure to the virus in self and close others, as well as economic loss due to the pandemic.
ResultsA mixed graphical model at wave 1 identified a potential pathway from economic adversity to anxiety symptoms via COVID-specific anxiety. There was no association between viral exposure and symptoms. Ising network models using clinical cut-offs for symptom scores at each wave yielded similar findings, with the exception of a modest effect of viral exposure on trauma symptoms at wave 1 only. Anxiety and depression symptoms formed separate clusters at wave 1 but not wave 2.
ConclusionsThe psychological impact of the pandemic evolved in the early phase of lockdown. COVID-related anxiety may represent the mechanism through which economic consequences of the pandemic are associated with psychiatric symptoms.
Latent cause inference during extinction learning in trauma-exposed individuals with and without PTSD
- Agnes Norbury, Hannah Brinkman, Mary Kowalchyk, Elisa Monti, Robert H. Pietrzak, Daniela Schiller, Adriana Feder
-
- Published online by Cambridge University Press:
- 08 March 2021, pp. 3834-3845
-
- Article
- Export citation
-
Background
Problems in learning that sights, sounds, or situations that were once associated with danger have become safe (extinction learning) may explain why some individuals suffer prolonged psychological distress following traumatic experiences. Although simple learning models have been unable to provide a convincing account of why this learning fails, it has recently been proposed that this may be explained by individual differences in beliefs about the causal structure of the environment.
MethodsHere, we tested two competing hypotheses as to how differences in causal inference might be related to trauma-related psychopathology, using extinction learning data collected from clinically well-characterised individuals with varying degrees of post-traumatic stress (N = 56). Model parameters describing individual differences in causal inference were related to multiple post-traumatic stress disorder (PTSD) and depression symptom dimensions via network analysis.
ResultsIndividuals with more severe PTSD were more likely to assign observations from conditioning and extinction stages to a single underlying cause. Specifically, greater re-experiencing symptom severity was associated with a lower likelihood of inferring that multiple causes were active in the environment.
ConclusionsWe interpret these results as providing evidence of a primary deficit in discriminative learning in participants with more severe PTSD. Specifically, a tendency to attribute a greater diversity of stimulus configurations to the same underlying cause resulted in greater uncertainty about stimulus-outcome associations, impeding learning both that certain stimuli were safe, and that certain stimuli were no longer dangerous. In the future, better understanding of the role of causal inference in trauma-related psychopathology may help refine cognitive therapies for these disorders.
The role of characterisation in everyday voice engagement and AVATAR therapy dialogue
- Thomas Ward, Rachel Lister, Miriam Fornells-Ambrojo, Mar Rus-Calafell, Clementine J. Edwards, Conan O'Brien, Tom KJ Craig, Philippa Garety
-
- Published online by Cambridge University Press:
- 08 April 2021, pp. 3846-3853
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Voices are commonly experienced as communication with a personified ‘other’ with ascribed attitudes, intentionality and personality (their own ‘character’). Phenomenological work exploring voice characterisation informs a new wave of relational therapies. To date, no study has investigated the role of characterisation in behavioural engagement with voices or within psychological therapy for distressing voices.
MethodsBaseline characterisation (the degree to which the voice is an identifiable and characterful entity) of the dominant voice was rated (high, medium or low) using a newly developed coding framework, for n = 60 people prior to starting AVATAR therapy. Associations between degree of characterisation and (i) everyday behavioural engagement with voices (The Beliefs about Voices Questionnaire-Revised; n = 60); and (ii) interaction within avatar dialogue [Session 4 Time in Conversation (participant–avatar); n = 45 therapy completers] were explored.
ResultsThirty-three per cent reported high voice characterisation, 42% medium and 25% low. There was a significant association between characterisation and behavioural engagement [H(2) = 7.65, p = 0.022, ɛ2 = 0.130] and duration of participant–avatar conversation [F(2,42) = 6.483, p = 0.004, η2 = 0.236]. High characterisation was associated with increased behavioural engagement compared with medium (p = 0.004, r = 0.34; moderate effect) and low (p = 0.027, r = 0.25; small−moderate effect) with a similar pattern observed for the avatar dialogue [high v. medium: p = 0.008, Hedges’ g = 1.02 (large effect); high v. low: p = 0.023, Hedges' g = 1.03 (large effect)]. No differences were observed between medium and low characterisation.
DiscussionComplex voice characterisation is associated with how individuals interact with their voice(s) in and out of therapy. Clinical implications and future directions for AVATAR therapy and other relational therapies are discussed.
Self-reported and mother-rated personality traits at age 16 are associated with cognitive function measured concurrently and 30 years later
- Angelina R. Sutin, Yannick Stephan, Martina Luchetti, Damaris Aschwanden, Amanda A. Sesker, Páraic S. O'Súilleabháin, Antonio Terracciano
-
- Published online by Cambridge University Press:
- 12 March 2021, pp. 3854-3864
-
- Article
- Export citation
-
Background
Models of personality and health suggest that personality contributes to health outcomes across adulthood. Personality traits, such as neuroticism and conscientiousness, have long-term predictive power for cognitive impairment in older adulthood, a critical health outcome. Less is known about whether personality measured earlier in life is also associated with cognition across adulthood prior to dementia.
MethodsUsing data from the British Cohort Study 1970 (N = 4218; 58% female), the current research examined the relation between self-reported and mother-rated personality at age 16 and cognitive function concurrently at age 16 and cognitive function measured 30 years later at age 46, and whether these traits mediate the relation between childhood social class and midlife cognition.
ResultsSelf-reported and mother-rated conscientiousness at age 16 were each associated with every cognitive measure at age 16 and most measures at age 46. Self-reported openness was likewise associated with better cognitive performance on all tasks at age 16 and prospectively predicted age 46 performance (mothers did not rate openness). Mother-rated agreeableness, but not self-reported, was associated with better cognitive performance at both time points. Adolescent personality mediated the relation between childhood social class and midlife cognitive function.
ConclusionsThe current study advances personality and cognition by showing that (1) adolescent personality predicts midlife cognition 30 years later, (2) both self-reports and mother-ratings are important sources of information on personality associated with midlife cognition, and (3) adolescent personality may be one pathway through which the early life socioeconomic environment is associated with midlife cognition.
Efficacy of attention bias modification training for depressed adults: a randomized clinical trial
- Kean J. Hsu, Jason Shumake, Kayla Caffey, Semeon Risom, Jocelyn Labrada, Jasper A. J. Smits, David M. Schnyer, Christopher G. Beevers
-
- Published online by Cambridge University Press:
- 26 March 2021, pp. 3865-3873
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
This study examined the efficacy of attention bias modification training (ABMT) for the treatment of depression.
MethodsIn this randomized clinical trial, 145 adults (77% female, 62% white) with at least moderate depression severity [i.e. self-reported Quick Inventory of Depressive Symptomatology (QIDS-SR) ⩾13] and a negative attention bias were randomized to active ABMT, sham ABMT, or assessments only. The training consisted of two in-clinic and three (brief) at-home ABMT sessions per week for 4 weeks (2224 training trials total). The pre-registered primary outcome was change in QIDS-SR. Secondary outcomes were the 17-item Hamilton Depression Rating Scale (HRSD) and anhedonic depression and anxious arousal from the Mood and Anxiety Symptom Questionnaire (MASQ). Primary and secondary outcomes were administered at baseline and four weekly assessments during ABMT.
ResultsIntent-to-treat analyses indicated that, relative to assessment-only, active ABMT significantly reduced QIDS-SR and HRSD scores by an additional 0.62 ± 0.23 (p = 0.008, d = −0.57) and 0.74 ± 0.31 (p = 0.021, d = −0.49) points per week. Similar results were observed for active v. sham ABMT: a greater symptom reduction of 0.44 ± 0.24 QIDS-SR (p = 0.067, d = −0.41) and 0.69 ± 0.32 HRSD (p = 0.033, d = −0.42) points per week. Sham ABMT did not significantly differ from the assessment-only condition. No significant differences were observed for the MASQ scales.
ConclusionDepressed individuals with at least modest negative attentional bias benefitted from active ABMT.
The independent and combined effects of cannabis use and systemic inflammation during the early stages of psychosis: exploring the two-hit hypothesis
- Fabiana Corsi-Zuelli, Leonardo Marques, Daiane Leite da Roza, Camila Marcelino Loureiro, Rosana Shuhama, Marta Di Forti, Paulo Rossi Menezes, Paulo Louzada-Junior, Cristina Marta Del-Ben
-
- Published online by Cambridge University Press:
- 19 March 2021, pp. 3874-3884
-
- Article
- Export citation
-
Background
Cannabis consumption is a modifiable risk factor associated with psychosis, but not all cannabis users develop psychosis. Animal studies suggest that an antecedent active immune system interacts with subsequent cannabis exposure and moderates the cannabis–psychosis association, supporting the two-hit hypothesis. The clinical investigations are few, and it is unclear if the immune system is a biological candidate moderating the cannabis–psychosis association or whether cannabis increases inflammation, which in turn, augments psychosis likelihood.
MethodsWe explored the mediating and moderating role of blood inflammation using PROCESS macro. We used data from a cross-sectional study, including 153 first-episode psychosis patients and 256 community-based controls. Participants answered the Cannabis Experience Questionnaire (cannabis frequency, age of onset, and duration), and plasma cytokines were measured [interleukin (IL)-1β, IL-6, IL-4, IL-10, tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), transforming growth factor-β (TGF-β); multiplex]. We computed an inflammatory composite score (ICS) to represent the systemic inflammatory state. Confounders included sex, age, ethnicity, educational level, body mass index, tobacco smoking, lifetime use of other drugs, and antipsychotic treatment.
ResultsMediation: Cannabis consumption was not associated with increased inflammation, thus not supporting a mediating effect of inflammation. Moderation: Daily use and age of onset <17 interacted significantly with the ICS to increase the odds of psychosis beyond their individual effects and were only associated with psychosis among those scoring medium–high in the ICS.
ConclusionsImmune dysregulation might be part of the pathophysiology of psychosis, not explained by cannabis use or other confounders. We provide the first and initial evidence that immune dysregulation modifies the cannabis–psychosis association, in line with a two-hit hypothesis.
Cognitive heterogeneity in first-episode psychosis and its relationship with premorbid developmental adjustment
- Eric J. Tan, Susan L. Rossell, Kenneth L. Subotnik, Joseph Ventura, Keith H. Nuechterlein
-
- Published online by Cambridge University Press:
- 12 March 2021, pp. 3885-3894
-
- Article
- Export citation
-
Background
Patients with schizophrenia spectrum disorders have been increasingly recognised to form cognitive subgroups with differential levels of impairment. Using cluster analytical techniques, this study sought to identify cognitive clusters in a sample of first-episode psychosis (FEP) patients and examine clinical and developmental differences across the resultant groups.
MethodsIn total, 105 FEP patients in the University of California Los Angeles Aftercare Research Program were assessed for cognition, symptoms and premorbid developmental adjustment. Hierarchical cluster analysis with Ward's method and squared Euclidean distance was conducted, confirmed by discriminant function analysis and optimised with k-means clustering. The stability of the solution was evaluated through split-sample (random, 80 and 70% samples) and alternate method (average linkage method) replication via Cohen's κ analysis. Controlling for multiple comparisons, one-way analysis of variances examined group differences in symptom severity and premorbid adjustment.
ResultsThree groups were identified: severely impaired (n = 27), moderately impaired (n = 41) and relatively intact (n = 37). There were no significant differences in symptom severity across the groups. Significant differences were observed for scholastic performance at three different developmental stages: childhood, early adolescence and late adolescence, with the relatively intact group demonstrating significantly better scholastic performance at all three stages than both the moderately impaired and severely impaired groups (who did not significantly differ from each other).
ConclusionsThe findings add to growing evidence that cognitive clusters in FEP mirror that of later-stage schizophrenia. They also suggest that premorbid scholastic performance may not just be a risk factor for developing schizophrenia, but is also related to cognitive impairment severity and potentially to prognosis.
Unexpected effects of expressive writing on post-disaster distress in the Hurricane Harvey Study: a randomized controlled trial in perinatal women
- Vincent Paquin, Johanna Bick, Rebecca Lipschutz, Guillaume Elgbeili, David P. Laplante, Brian Biekman, Alain Brunet, Suzanne King, David Olson
-
- Published online by Cambridge University Press:
- 12 March 2021, pp. 3895-3903
-
- Article
- Export citation
-
Background
Expressive writing requires journaling stressor-related thoughts and feelings over four daily sessions of 15 min. Thirty years of research have popularized expressive writing as a brief intervention for fostering trauma-related resilience; however, its ability to surpass placebo remains unclear. This study aimed to determine the efficacy of expressive writing for improving post-traumatic stress symptoms in perinatal women who were living in the Houston area during major flooding caused by Hurricane Harvey.
MethodsA total of 1090 women were randomly allocated (1:1:1) to expressive writing, neutral writing or no writing. Interventions were internet-based. Online questionnaires were completed before randomization and at 2 months post-intervention. The primary outcome was post-traumatic stress symptoms, measured with the Impact of Event Scale-Revised; secondary outcomes were affective symptoms, measured with the 40-item Inventory of Depression and Anxiety Scales. Feelings throughout the intervention were reported daily using tailored questionnaires.
ResultsIn intention-to-treat analyses, no post-treatment between-group differences were found on the primary and secondary outcomes. Per-protocol analyses yielded similar results. A number of putative moderators were tested, but none interacted with expressive writing. Expressive writing produced greater feelings of anxiety and sadness during the intervention compared to neutral writing; further, overall experiences from the intervention mediated associations between expressive writing and greater post-traumatic stress at 2 months post-intervention.
ConclusionsAmong disaster-stricken perinatal women, expressive writing was ineffective in reducing levels of post-traumatic stress, and may have exacerbated these symptoms in some.
Columbia-Suicide Severity Rating Scale Screen Version: initial screening for suicide risk in a psychiatric emergency department
- Johan Bjureberg, Marie Dahlin, Andreas Carlborg, Hanna Edberg, Axel Haglund, Bo Runeson
-
- Published online by Cambridge University Press:
- 26 March 2021, pp. 3904-3912
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Suicide screening is routine practice in psychiatric emergency (PE) departments, but evidence for screening instruments is sparse. Improved identification of nascent suicide risk is important for suicide prevention. The aim of the current study was to evaluate the association between the novel Colombia Suicide Severity Rating Scale Screen Version (C-SSRS Screen) and subsequent clinical management and suicide within 1 week, 1 month and 1 year from screening.
MethodsConsecutive patients (N = 18 684) attending a PE department in Stockholm, Sweden between 1 May 2016 and 31 December 2017 were assessed with the C-SSRS Screen. All patients (52.1% women; mean age = 39.7, s.d. = 16.9) were followed-up in the National Cause of Death Register. Logistic regression and receiver operating characteristic curves analyses were conducted. Optimal cut-offs and accuracy statistics were calculated.
ResultsBoth suicidal ideation and behaviour were prevalent at screening. In total, 107 patients died by suicide during follow-up. Both C-SSRS Screen Ideation Severity and Behaviour Scales were associated with death by suicide within 1-week, 1-month and 1-year follow-up. The optimal cut-off for the ideation severity scale was associated with at least four times the odds of dying by suicide within 1 week (adjusted OR 4.7, 95% confidence interval 1.5–14.8). Both scales were also associated with short-term clinical management.
ConclusionsThe C-SSRS Screen may be feasible to use in the actual management setting as an initial step before the clinical assessment of suicide risk. Future research may investigate the utility of combining the C-SSRS Screen with a more thorough assessment.
Using multivariate endophenotypes to identify psychophysiological mechanisms associated with polygenic scores for substance use, schizophrenia, and education attainment
- Jeremy Harper, Mengzhen Liu, Stephen M. Malone, Matt McGue, William G. Iacono, Scott I. Vrieze
-
- Published online by Cambridge University Press:
- 18 March 2021, pp. 3913-3923
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
To better characterize brain-based mechanisms of polygenic liability for psychopathology and psychological traits, we extended our previous report (Liu et al. Psychophysiological endophenotypes to characterize mechanisms of known schizophrenia genetic loci. Psychological Medicine, 2017), focused solely on schizophrenia, to test the association between multivariate psychophysiological candidate endophenotypes (including novel measures of θ/δ oscillatory activity) and a range of polygenic scores (PGSs), namely alcohol/cannabis/nicotine use, an updated schizophrenia PGS (containing 52 more genome-wide significant loci than the PGS used in our previous report) and educational attainment.
MethodA large community-based twin/family sample (N = 4893) was genome-wide genotyped and imputed. PGSs were constructed for alcohol use, regular smoking initiation, lifetime cannabis use, schizophrenia, and educational attainment. Eleven endophenotypes were assessed: visual oddball task event-related electroencephalogram (EEG) measures (target-related parietal P3 amplitude, frontal θ, and parietal δ energy/inter-trial phase clustering), band-limited resting-state EEG power, antisaccade error rate. Principal component analysis exploited covariation among endophenotypes to extract a smaller number of meaningful dimensions/components for statistical analysis.
ResultsEndophenotypes were heritable. PGSs showed expected intercorrelations (e.g. schizophrenia PGS correlated positively with alcohol/nicotine/cannabis PGSs). Schizophrenia PGS was negatively associated with an event-related P3/δ component [β = −0.032, nonparametric bootstrap 95% confidence interval (CI) −0.059 to −0.003]. A prefrontal control component (event-related θ/antisaccade errors) was negatively associated with alcohol (β = −0.034, 95% CI −0.063 to −0.006) and regular smoking PGSs (β = −0.032, 95% CI −0.061 to −0.005) and positively associated with educational attainment PGS (β = 0.031, 95% CI 0.003–0.058).
ConclusionsEvidence suggests that multivariate endophenotypes of decision-making (P3/δ) and cognitive/attentional control (θ/antisaccade error) relate to alcohol/nicotine, schizophrenia, and educational attainment PGSs and represent promising targets for future research.
The economic cost of bulimia nervosa and binge eating disorder: a population-based study
- Wadad Kathy Tannous, Phillipa Hay, Federico Girosi, Andreea I. Heriseanu, Moin Uddin Ahmed, Stephen Touyz
-
- Published online by Cambridge University Press:
- 17 May 2021, pp. 3924-3938
-
- Article
- Export citation
-
Background
The most common eating disorders (EDs) are bulimia nervosa (BN) and binge eating disorder (BED), serious psychiatric illnesses that have devastating effects on the physical and psychological wellbeing of sufferers. EDs range in complexity and severity but can be life-threatening without appropriate treatment. Although it is well-known that quality of life impacts is high for ED sufferers, research regarding fiscal and related costs is severely limited. The aim of this study was to understand economic and other costs of EDs at the community level.
MethodData were derived from 2017 household community representative structured interview of 2977 people aged ⩾ 15 years in South Australia. ED diagnoses, health systems, productivity, transaction, out-of-pocket expenses and other related costs of BN and BED were used to estimate the economic burden of EDs in South Australia.
ResultsThe annual total economic cost of EDs in 2018 was estimated at $84 billion for South Australia. This included $81 billion from the burden of disease as the result of years lived with disability (YLD) ($62 billion) and years of life lost ($19 billion). The health system costs, productivity and tax revenue loss to the Australian economy were estimated at $1 billion, $1.6 billion and $0.6 billion, respectively.
ConclusionsThe YLD average cost in 2018 in South Australia was $296 649 per person. This is two-thirds of the costs borne by individuals and the wider economy. Prevention and management initiatives for EDs need to take into account these costs when assessing their potential benefits.
Experimentally imposed circadian misalignment alters the neural response to monetary rewards and response inhibition in healthy adolescents
- Brant P. Hasler, Adriane M. Soehner, Meredith L. Wallace, Ryan W. Logan, Wambui Ngari, Erika E. Forbes, Daniel J. Buysse, Duncan B. Clark
-
- Published online by Cambridge University Press:
- 17 March 2021, pp. 3939-3947
-
- Article
- Export citation
-
Background
Sleep and circadian timing shifts later during adolescence, conflicting with early school start times, and resulting in circadian misalignment. Although circadian misalignment has been linked to depression, substance use, and altered reward function, a paucity of experimental studies precludes the determination of causality. Here we tested, for the first time, whether experimentally-imposed circadian misalignment alters the neural response to monetary reward and/or response inhibition.
MethodsHealthy adolescents (n = 25, ages 13–17) completed two in-lab sleep schedules in counterbalanced order: An ‘aligned’ condition based on typical summer sleep-wake times (0000–0930) and a ‘misaligned’ condition mimicking earlier school year sleep-wake times (2000–0530). Participants completed morning and afternoon functional magnetic resonance imaging scans during each condition, including monetary reward (morning only) and response inhibition (morning and afternoon) tasks. Total sleep time and circadian phase were assessed via actigraphy and salivary melatonin, respectively.
ResultsBilateral ventral striatal (VS) activation during reward outcome was lower during the Misaligned condition after accounting for the prior night's total sleep time. Bilateral VS activation during reward anticipation was lower during the Misaligned condition, including after accounting for covariates, but did not survive correction for multiple comparisons. Right inferior frontal gyrus activation during response inhibition was lower during the Misaligned condition, before and after accounting for total sleep time and vigilant attention, but only during the morning scan.
ConclusionsOur findings provide novel experimental evidence that circadian misalignment analogous to that resulting from school schedules may have measurable impacts on healthy adolescents' reward processing and inhibition of prepotent responses.
A comparison of ‘pruning’ during multi-step planning in depressed and healthy individuals
- Paul Faulkner, Quentin J. M. Huys, Daniel Renz, Neir Eshel, Stephen Pilling, Peter Dayan, Jonathan P. Roiser
-
- Published online by Cambridge University Press:
- 12 March 2021, pp. 3948-3956
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
Background
Real-life decisions are often complex because they involve making sequential choices that constrain future options. We have previously shown that to render such multi-step decisions manageable, people ‘prune’ (i.e. selectively disregard) branches of decision trees that contain negative outcomes. We have theorized that sub-optimal pruning contributes to depression by promoting an oversampling of branches that result in unsavoury outcomes, which results in a negatively-biased valuation of the world. However, no study has tested this theory in depressed individuals.
MethodsThirty unmedicated depressed and 31 healthy participants were administered a sequential reinforcement-based decision-making task to determine pruning behaviours, and completed measures of depression and anxiety. Computational, Bayesian and frequentist analyses examined group differences in task performance and relationships between pruning and depressive symptoms.
ResultsConsistent with prior findings, participants robustly pruned branches of decision trees that began with large losses, regardless of the potential utility of those branches. However, there was no group difference in pruning behaviours. Further, there was no relationship between pruning and levels of depression/anxiety.
ConclusionsWe found no evidence that sub-optimal pruning is evident in depression. Future research could determine whether maladaptive pruning behaviours are observable in specific sub-groups of depressed patients (e.g. in treatment-resistant individuals), or whether misuse of other heuristics may contribute to depression.