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A history of self-injurious thoughts and behaviors (SITBs) is consistently cited as one of the strongest predictors of future suicidal behavior. However, stark discrepancies in the literature raise questions about the true magnitude of these associations. The objective of this study is to examine the magnitude and clinical utility of the associations between SITBs and subsequent suicide ideation, attempts, and death.
Method
We searched PubMed, PsycInfo, and Google Scholar for papers published through December 2014. Inclusion required that studies include at least one longitudinal analysis predicting suicide ideation, attempts, or death using any SITB variable. We identified 2179 longitudinal studies; 172 met inclusion criteria.
Results
The most common outcome was suicide attempt (47.80%), followed by death (40.50%) and ideation (11.60%). Median follow-up was 52 months (mean = 82.52, s.d. = 102.29). Overall prediction was weak, with weighted mean odds ratios (ORs) of 2.07 [95% confidence interval (CI) 1.76–2.43] for ideation, 2.14 (95% CI 2.00–2.30) for attempts, and 1.54 (95% CI 1.39–1.71) for death. Adjusting for publication bias further reduced estimates. Diagnostic accuracy analyses indicated acceptable specificity (86–87%) and poor sensitivity (10–26%), with areas under the curve marginally above chance (0.60–0.62). Most risk factors generated OR estimates of <2.0 and no risk factor exceeded 4.5. Effects were consistent regardless of sample severity, sample age groups, or follow-up length.
Conclusions
Prior SITBs confer risk for later suicidal thoughts and behaviors. However, they only provide a marginal improvement in diagnostic accuracy above chance. Addressing gaps in study design, assessment, and underlying mechanisms may prove useful in improving prediction and prevention of suicidal thoughts and behaviors.
Recent studies suggest that psychotic experiences (PE) in the general population are associated with an increased risk of self-injurious behaviour. Both the magnitude of this association and the level of adjustment for confounders vary among studies. A meta-analysis was performed to integrate the available evidence. The influence of possible confounders, including variably defined depression, was assessed.
Method
A systematic review and meta-analysis was conducted including general population studies reporting on the risk of self-injurious behaviour in individuals with PE. Studies were identified by a systematic search strategy in Pubmed, PsycINFO and Embase. Reported effect sizes were extracted and meta-analytically pooled.
Results
The risk of self-injurious behaviour was 3.20 times higher in individuals with PE compared with those without. Subanalyses showed that PE were associated with self-harm, suicidal ideation as well as suicidal attempts. All studies had scope for considerable residual confounding; effect sizes adjusted for depression were significantly smaller than effect sizes unadjusted for depression. In the longitudinal studies, adjustment for psychopathology resulted in a 74% reduction in excess risk.
Conclusions
PE are associated with self-injurious behaviour, suggesting they have potential as passive markers of suicidality. However, the association is confounded and several methodological issues remain, particularly how to separate PE from the full range of connected psychopathology in determining any specific association with self-injurious behaviour. Given evidence that PE represent an indicator of severity of non-psychotic psychopathology, the association between PE and self-injurious behaviour probably reflects a greater likelihood of self-injurious behaviour in more severe states of mental distress.
Theory of mind (ToM) dysfunction is prominent in a number of psychiatric disorders, in particular, autism and schizophrenia, and can play a significant role in poor functioning. There is now emerging evidence suggesting that ToM abilities are also impaired in bipolar disorder (BP); however, the relationship between ToM deficits and mood state is not clear.
Method
We conducted a meta-analysis of ToM studies in BP. Thirty-four studies comparing 1214 patients with BP and 1097 healthy controls were included. BP groups included remitted (18 samples, 545 BP patients), subsyndromal (12 samples, 510 BP patients), and acute (manic and/or depressed) (10 samples, 159 BP patients) patients.
Results
ToM performance was significantly impaired in BP compared to controls. This impairment was evident across different types of ToM tasks (including affective/cognitive and verbal/visual) and was also evident in strictly euthymic patients with BP (d = 0.50). There were no significant differences between remitted and subsyndromal samples. However, ToM deficit was significantly more severe during acute episodes (d = 1.23). ToM impairment was significantly associated with neurocognitive and particularly with manic symptoms.
Conclusion
Significant but modest sized ToM dysfunction is evident in remitted and subsyndromal BP. Acute episodes are associated with more robust ToM deficits. Exacerbation of ToM deficits may contribute to the more significant interpersonal problems observed in patients with acute or subsyndromal manic symptoms. There is a need for longitudinal studies comparing the developmental trajectory of ToM deficits across the course of the illness.
It is well-established that offspring of depressed mothers are at increased risk for suicidal ideation. However, pathways involved in the transmission of risk for suicidal ideation from depressed mothers to offspring are poorly understood. The aim of this study was to examine the contribution of potential mediators of this association, including maternal suicide attempt, offspring psychiatric disorder and the parent–child relationship.
Method
Data were utilized from a population-based birth cohort (ALSPAC). Three distinct classes of maternal depression symptoms across the first 11 years of the child's life had already been identified (minimal, moderate, chronic-severe). Offspring suicidal ideation was assessed at age 16 years. Data were analysed using structural equation modelling.
Results
There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms compared to offspring of mothers with minimal symptoms (odds ratio 3.04, 95% confidence interval 2.19–4.21). The majority of this association was explained through maternal suicide attempt and offspring psychiatric disorder. There was also evidence for an independent indirect effect via the parent–child relationship in middle childhood. There was no longer evidence of a direct effect of maternal depression on offspring suicidal ideation after accounting for all three mediators. The pattern of results was similar when examining mechanisms for maternal moderate depression symptoms.
Conclusions
Findings highlight that suicide prevention efforts in offspring of depressed mothers should be particularly targeted at both offspring with a psychiatric disorder and offspring whose mothers have made a suicide attempt. Interventions aimed at improving the parent–child relationship may also be beneficial.
Neuroimaging traits of either familial or environmental risk for major depressive disorder (MDD) have been interpreted as possibly useful vulnerability markers. However, the simultaneous occurrence of familial and environmental risk might prove to be a major obstacle in the attempt of recent studies to confine the precise impact of each of these conditions on brain structure. Moreover, the exclusive use of group-level analyses does not permit prediction of individual illness risk which would be the basic requirement for the clinical application of imaging vulnerability markers. Hence, we aimed to distinguish between brain structural characteristics of familial predisposition and environmental stress by using both group- and individual-level analyses.
Method
We investigated grey matter alterations between 20 healthy control subjects (HC) and 20 MDD patients; 16 healthy first-degree relatives of MDD patients (FH+) and 20 healthy subjects exposed to former childhood maltreatment (CM+) by using a combined VBM/pattern recognition approach.
Results
We found similar grey matter reductions in the insula and the orbitofrontal cortex in patients and FH+ subjects and in the hippocampus in patients and CM+ subjects. No direct overlap in grey matter alterations was found between FH+ and CM+ subjects. Pattern classification successfully detected subjects at risk for the disease even by strictly focusing on morphological traits of MDD.
Conclusions
Familial and environmental risk factors for MDD are associated with differing morphometric anomalies. Pattern recognition might be a promising instrument in the search for and future application of vulnerability markers for MDD.
Functional remediation is a novel intervention with demonstrated efficacy at improving functional outcome in euthymic bipolar patients. However, in a previous trial no significant changes in neurocognitive measures were detected. The objective of the present analysis was to test the efficacy of this therapy in the enhancement of neuropsychological functions in a subgroup of neurocognitively impaired bipolar patients.
Method
A total of 188 out of 239 DSM-IV euthymic bipolar patients performing below two standard deviations from the mean of normative data in any neurocognitive test were included in this subanalysis. Repeated-measures analyses of variance were conducted to assess the impact of the treatment arms [functional remediation, psychoeducation, or treatment as usual (TAU)] on participants’ neurocognitive and functional outcomes in the subgroup of neurocognitively impaired patients.
Results
Patients receiving functional remediation (n = 56) showed an improvement on delayed free recall when compared with the TAU (n = 63) and psychoeducation (n = 69) groups as shown by the group × time interaction at 6-month follow-up [F2,158 = 3.37, degrees of freedom (df) = 2, p = 0.037]. However, Tukey post-hoc analyses revealed that functional remediation was only superior when compared with TAU (p = 0.04), but not with psychoeducation (p = 0.10). Finally, the patients in the functional remediation group also benefited from the treatment in terms of functional outcome (F2,158 = 4.26, df = 2, p = 0.016).
Conclusions
Functional remediation is effective at improving verbal memory and psychosocial functioning in a sample of neurocognitively impaired bipolar patients at 6-month follow-up. Neurocognitive enhancement may be one of the active ingredients of this novel intervention, and, specifically, verbal memory appears to be the most sensitive function that improves with functional remediation.
Although interventions exist to reduce violent crime, optimal implementation requires accurate targeting. We report the results of an attempt to develop an actuarial model using machine learning methods to predict future violent crimes among US Army soldiers.
Method.
A consolidated administrative database for all 975 057 soldiers in the US Army in 2004–2009 was created in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). Of these soldiers, 5771 committed a first founded major physical violent crime (murder-manslaughter, kidnapping, aggravated arson, aggravated assault, robbery) over that time period. Temporally prior administrative records measuring socio-demographic, Army career, criminal justice, medical/pharmacy, and contextual variables were used to build an actuarial model for these crimes separately among men and women using machine learning methods (cross-validated stepwise regression, random forests, penalized regressions). The model was then validated in an independent 2011–2013 sample.
Results.
Key predictors were indicators of disadvantaged social/socioeconomic status, early career stage, prior crime, and mental disorder treatment. Area under the receiver-operating characteristic curve was 0.80–0.82 in 2004–2009 and 0.77 in the 2011–2013 validation sample. Of all administratively recorded crimes, 36.2–33.1% (male-female) were committed by the 5% of soldiers having the highest predicted risk in 2004–2009 and an even higher proportion (50.5%) in the 2011–2013 validation sample.
Conclusions.
Although these results suggest that the models could be used to target soldiers at high risk of violent crime perpetration for preventive interventions, final implementation decisions would require further validation and weighing of predicted effectiveness against intervention costs and competing risks.
The relationship between childhood adversity (CA) and psychotic disorder is well documented. As the adequacy of the current categorical diagnosis of psychosis is being increasingly questioned, we explored independent associations between different types of CA and specific psychotic symptom dimensions in a well-characterized sample of first-episode psychosis (FEP) patients.
Method
This study involved 236 FEP cases aged 18–65 years who presented for the first time to psychiatric services in South London, UK. Psychopathology was assessed with the Positive and Negative Syndrome Scale and confirmatory factor analysis was used to evaluate the statistical fit of the Wallwork/Fortgang five-factor model of psychosis. CA prior to 17 years of age (physical abuse, sexual abuse, parental separation, parental death, and being taken into care) was retrospectively assessed using the Childhood Experience of Care and Abuse Questionnaire.
Results
Childhood sexual abuse [β = 0.96, 95% confidence interval (CI) 0.40–1.52], childhood physical abuse (β = 0.48, 95% CI 0.03–0.93) and parental separation (β = 0.60, 95% CI 0.10–1.11) showed significant associations with the positive dimension; while being taken into care was associated with the excited dimension (β = 0.36, 95% CI 0.08–0.65), independent of the other types of CA. No significant associations were found between parental death and any of the symptom dimensions.
Conclusions
A degree of specificity was found in the relationships between different types of CA and psychosis symptom dimensions in adulthood, suggesting that distinct pathways may be involved in the CA–psychosis association. These potentially different routes to developing psychosis merit further empirical and theoretical exploration.
Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs.
Method
General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure.
Results
Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types – witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury – accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events.
Conclusions
Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization.
Repeated epidemiological surveys show no decline in depression although uptake of treatments has grown. Universal depression prevention interventions are effective in schools but untested rigorously in adulthood. Selective prevention programmes have poor uptake. Universal interventions may be more acceptable during routine healthcare contacts for example antenatally. One study within routine postnatal healthcare suggested risk of postnatal depression could be reduced in non-depressed women from 11% to 8% by giving health visitors psychological intervention training. Feasibility and effectiveness in other settings, most notably antenatally, is unknown.
Method
We conducted an external pilot study using a cluster trial design consisting of recruitment and enhanced psychological training of randomly selected clusters of community midwives (CMWs), recruitment of pregnant women of all levels of risk of depression, collection of baseline and outcome data prior to childbirth, allowing time for women ‘at increased risk’ to complete CMW-provided psychological support sessions.
Results
Seventy-nine percent of eligible women approached agreed to take part. Two hundred and ninety-eight women in eight clusters participated and 186 termed ‘at low risk’ for depression, based on an Edinburgh Perinatal Depression Scale (EPDS) score of <12 at 12 weeks gestation, provided baseline and outcome data at 34 weeks gestation. All trial protocol procedures were shown to be feasible. Antenatal effect sizes in women ‘at low risk’ were similar to those previously demonstrated postnatally. Qualitative work confirmed the acceptability of the approach to CMWs and intervention group women.
Conclusion
A fully powered trial testing universal prevention of depression in pregnancy is feasible, acceptable and worth undertaking.
Obsessive-compulsive disorder (OCD) is a chronic, relapsing mental illness. Selective serotonin reuptake inhibitors block serotonin transporters (SERTs) and are the mainstay of treatment for OCD. SERT abnormalities are reported in drug-free patients with OCD, but it is not known what happens to SERT levels during treatment. This is important as alterations in SERT levels in patients under treatment could underlie poor response, or relapse during or after treatment. The aim of the present study was first to validate a novel approach to measuring SERT levels in people taking treatment and then to investigate SERT binding potential (BP) using [11C]DASB PET in patients with OCD currently treated with escitalopram in comparison with healthy controls.
Method
Twelve patients and age- and sex-matched healthy controls were enrolled. The patients and healthy controls underwent serial PET scans after administration of escitalopram and blood samples for drug concentrations were collected simultaneously with the scans. Drug-free BPs were obtained by using an inhibitory Emax model we developed previously.
Results
The inhibitory Emax model was able to accurately predict drug-free SERT BP in people taking drug treatment. The drug-free BP in patients with OCD currently treated with escitalopram was significantly different from those in healthy volunteers [Cohen's d = 0.03 (caudate), 1.16 (putamen), 1.46 (thalamus), −5.67 (dorsal raphe nucleus)].
Conclusions
This result extends previous findings showing SERT abnormalities in drug-free patients with OCD by indicating that altered SERT availability is seen in OCD despite treatment. This could account for poor response and the high risk of relapse in OCD.
Obsessive-compulsive disorder (OCD) is associated with an abnormally large error-related negativity (ERN), an electrophysiological measure of error monitoring in response to performance errors, but it is unclear if hoarding disorder (HD) also shows this abnormality. This study aimed to determine whether the neurophysiological mechanisms underlying error monitoring are similarly compromised in HD and OCD.
Method
We used a visual flanker task to assess ERN in response to performance errors in 14 individuals with HD, 27 with OCD, 10 with HD+OCD, and 45 healthy controls (HC). Age-corrected performance and ERN amplitudes were examined using analyses of variance and planned pairwise group comparisons.
Results
A main effect of hoarding on ERN (p = 0.031) was observed, indicating ERN amplitudes were attenuated in HD relative to non-HD subjects. A group × age interaction effect on ERN was also evident. In HD-positive subjects, ERN amplitude deficits were significantly greater in younger individuals (r = −0.479, p = 0.018), whereas there were no significant ERN changes with increasing age in OCD and HC participants.
Conclusions
The reduced ERN in HD relative to OCD and HC provides evidence that HD is neurobiologically distinct from OCD, and suggests that deficient error monitoring may be a core pathophysiological feature of HD. This effect was particularly prominent in younger HD participants, further suggesting that deficient error monitoring manifests most strongly early in the illness course and/or in individuals with a relatively early illness onset.
Alongside impulsive suicide attempts, clinicians encounter highly premeditated suicidal acts, particularly in older adults. We have previously found that in contrast to the more impulsive suicide attempters’ inability to delay gratification, serious and highly planned suicide attempts were associated with greater willingness to wait for larger rewards. This study examined neural underpinnings of intertemporal preference in suicide attempters. We expected that impulsivity and suicide attempts, particularly poorly planned ones, would predict altered paralimbic subjective value representations. We also examined lateral prefrontal and paralimbic correlates of premeditation in suicidal behavior.
Method
A total of 48 participants aged 46–90 years underwent extensive clinical and cognitive characterization and completed the delay discounting task in the scanner: 26 individuals with major depression (13 with and 13 without history of suicide attempts) and 22 healthy controls.
Results
More impulsive individuals displayed greater activation in the precuneus/posterior cingulate cortex (PCC) to value difference favoring the delayed option. Suicide attempts, particularly better-planned ones, were associated with deactivation of the lateral prefrontal cortex (lPFC) in response to value difference favoring the immediate option. Findings were robust to medication exposure, depression severity and possible brain damage from suicide attempts, among other confounders. Finally, in suicide attempters longer reward delays were associated with diminished parahippocampal responses.
Conclusions
Impulsivity was associated with an altered paralimbic (precuneus/PCC) encoding of value difference during intertemporal choice. By contrast, better-planned suicidal acts were associated with altered lPFC representations of value difference. The study provides preliminary evidence of impaired decision processes in both impulsive and premeditated suicidal behavior.
Impaired neuropsychological functioning is a feature of major depression. Previous studies have suggested that at least some aspects of neuropsychological functioning improve with successful treatment of major depression. The extent to which medications may affect the degree of normalization of these functions is unclear. The aim of the current study was to examine the course of neuropsychological functioning during treatment of major depression with cognitive–behaviour therapy (CBT) or schema therapy (ST).
Method
A total of 69 out-patients with a primary diagnosis of major depression and 58 healthy controls completed mood ratings, neuropsychological measures, and measures of emotional processing at baseline and after 16 weeks. Participants were randomized after baseline assessment to a year-long course of CBT or ST. Patients reassessed at 16 weeks were medication-free throughout the study.
Results
Significant neuropsychological impairment was evident at baseline in depressed participants compared with healthy controls. After 16 weeks of psychotherapy, mean depression rating scores fell more than 50%. However, no neuropsychological measures showed convincing evidence of significant improvement and emotional processing did not change.
Conclusions
Persisting impairment in neuropsychological functioning after the first 16 weeks of CBT or ST suggests a need to modify psychological treatments to include components targeting cognitive functioning.
A Callous-Unemotional trait specifier (termed ‘Limited Prosocial Emotions’) was added to the diagnosis of conduct disorder in DSM-5. The Inventory of Callous-Unemotional Traits (ICU) is a comprehensive measure of these traits assessing three distinct, yet correlated dimensions – Callousness, Uncaring, and Unemotional – all thought to reflect the general Callous-Unemotional construct. The present study was the first to examine the degree to which the aetiology of these dimensions is shared v. independent.
Method
Parent-reported ICU data from 5092 16-year-old twin pairs from the Twins Early Development Study were subjected to confirmatory factor analysis. Multivariate genetic modelling was applied to the best-fitting structure.
Results
A general-specific structure, retaining a general factor and two uncorrelated specific factors (Callousness-Uncaring, Unemotional), provided the best fit to the data. The general factor was substantially heritable (h2 = 0.58, 95% CI 0.51–0.65). Unusually, shared environmental influences were also important in accounting for this general factor (c2 = 0.26, 95% CI 0.22–0.31), in addition to non-shared environmental influences. The Unemotional dimension appeared phenotypically and genetically distinct as shown by the substantial loadings of unemotional items on a separate dimension and a low genetic correlation between Unemotional and Callousness-Uncaring.
Conclusions
A general factor, indicative of a shared phenotypic structure across the dimensions of the ICU was under substantial common genetic and more modest shared environment influences. Our findings also suggest that the relevance of the Unemotional dimension as part of a comprehensive assessment of CU traits should be investigated further.
Episodes of depression and anxiety (D&A) during the transition from late adolescence to adulthood, particularly when persistent, are predictive of long-term disorders and associated public health burden. Understanding risk factors at this time is important to guide intervention. The current objective was to investigate the associations between maternal symptoms of D&A with offspring symptoms during their transition to adulthood.
Method
Data from a large population-based birth cohort study, in South Brazil, were used. Prospective associations between maternal D&A and offspring risk of these symptoms during the transition to adulthood (18/19, 24 and 30 years) were estimated.
Results
Maternal D&A in adolescence was associated with offspring symptoms across the transition to adulthood, associations were consistently stronger for females than for males. Daughters whose mothers reported D&A were 4.6 times (95% confidence interval 2.71–7.84) as likely to report D&A at all three time-points, than daughters of symptom-free mothers.
Conclusions
Maternal D&A is associated with persistent D&A during the daughter's transition to adulthood. Intervention strategies should consider the mother's mental health.
The aim of this study was to analyse a possible synergistic effect between back pain and common mental disorders (CMDs) in relation to future disability pension (DP).
Method
All 4 823 069 individuals aged 16–64 years, living in Sweden in December 2004, not pensioned in 2005 and without ongoing sickness absence at the turn of 2004/2005 formed the cohort of this register-based study. Hazard ratios (HRs) and 95% confidence intervals (CIs) for DP (2006–2010) were estimated. Exposure variables were back pain (M54) (sickness absence or inpatient or specialized outpatient care in 2005) and CMD (F40-F48) [sickness absence or inpatient or specialized outpatient care or antidepressants (N06a) in 2005].
Results
HRs for DP were 4.03 (95% CI 3.87–4.21) and 3.86 (95% CI 3.68–4.04) in women and men with back pain. HRs for DP in women and men with CMD were 4.98 (95% CI 4.88–5.08) and 6.05 (95% CI 5.90–6.21). In women and men with both conditions, HRs for DP were 15.62 (95% CI 14.40–16.94) and 19.84 (95% CI 17.94–21.94). In women, synergy index, relative excess risk due to interaction, and attributable proportion were 1.24 (95% CI 1.13–1.36), 0.18 (95% CI 0.11–0.25), and 2.08 (95% CI 1.09–3.06). The corresponding figures for men were 1.45 (95% CI 1.29–1.62), 0.29 (95% CI 0.22–0.36), and 4.21 (95% CI 2.71–5.70).
Conclusions
Co-morbidity of back pain and CMD is associated with a higher risk of DP than either individual condition, when added up, which has possible clinical implications to prevent further disability and exclusion from the labour market.
Patients with schizophrenia have intact ability to experience emotion, but empirical evidence suggests that they fail to translate emotional salience into effortful behaviour. Previous research in patients with chronic schizophrenia suggests that working memory is important in integrating emotion and behaviour. This study aimed to examine avolition and anhedonia in patients with first-episode schizophrenia and clarify the role of working memory in emotion–behaviour coupling.
Method
We recruited 72 participants with first-episode schizophrenia and 61 healthy controls, and used a validated emotion-inducing behavioural paradigm to measure participants' affective experiences and how experienced emotion coupled with behaviour. Participants were given the opportunity to expend effort to increase or decrease their exposure to emotion-inducing photographs. Participants with schizophrenia having poor working memory were compared with those with intact working memory in their liking and emotion–behaviour coupling.
Results
Patients with first-episode schizophrenia experienced intact ‘in-the-moment’ emotion, but their emotion was less predictive of the effort expended, compared with controls. The emotion–behaviour coupling was significantly weaker in patients with schizophrenia with poor working memory than in those with intact working memory. However, compared with controls, patients with intact working also showed substantial emotion–behaviour decoupling.
Conclusions
Our findings provide strong evidence for emotion–behaviour decoupling in first-episode schizophrenia. Although working memory deficits contribute to defective translation of liking into effortful behaviour, schizophrenia alone affects emotion–behaviour coupling.