Interpersonal difficulties in borderline personality disorder (BPD) could be related to the disturbed self-views of BPD patients. This study investigates affective and neural responses to positive and negative social feedback (SF) of BPD patients compared with healthy (HC) and low self-esteem (LSE) controls and how this relates to individual self-views.

BPD (N = 26), HC (N = 32), and LSE (N = 22) performed a SF task in a magnetic resonance imaging scanner. Participants received 15 negative, intermediate and positive evaluative feedback words putatively given by another participant and rated their mood and applicability of the words to the self.

BPD had more negative self-views than HC and felt worse after negative feedback. Applicability of feedback was a less strong determinant of mood in BPD than HC. Increased precuneus activation was observed in HC to negative compared with positive feedback, whereas in BPD, this was similarly low for both valences. HC showed increased temporoparietal junction (TPJ) activation to positive v. negative feedback, while BPD showed more TPJ activation to negative feedback. The LSE group showed a different pattern of results suggesting that LSE cannot explain these findings in BPD.

The negative self-views that BPD have, may obstruct critically examining negative feedback, resulting in lower mood. Moreover, where HC focus on the positive feedback (based on TPJ activation), BPD seem to focus more on negative feedback, potentially maintaining negative self-views. Better balanced self-views may make BPD better equipped to deal with potential negative feedback and more open to positive interactions.

Psychosis spectrum disorder is a heterogeneous, multifactorial clinical phenotype, known to have a high heritability, only a minor portion of which can be explained by molecular measures of genetic variation. This study proposes that the identification of genetic variation underlying psychotic disorder may have suffered due to issues in the psychometric conceptualization of the phenotype. Here we aim to open a new line of research into the genetics of mental disorders by explicitly incorporating genes into symptom networks. Specifically, we investigate whether links between a polygenic risk score (PRS) for schizophrenia and measures of psychosis proneness can be identified in a network model.

We analyzed data from n = 2180 subjects (controls, patients diagnosed with a non-affective psychotic disorder, and the first-degree relatives of the patients). A network structure was computed to examine associations between the 42 symptoms of the Community Assessment of Psychic Experiences (CAPE) and the PRS for schizophrenia.

The resulting network shows that the PRS is directly connected to the spectrum of positive and depressive symptoms, with the items conspiracy and no future being more often located on predictive pathways from PRS to other symptoms.

To our knowledge, the current exploratory study provides a first application of the network framework to the field of behavior genetics research. This allows for a novel outlook on the investigation of the relations between genome-wide association study-based PRSs and symptoms of mental disorders, by focusing on the dependencies among variables.

Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences.

A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models.

PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31–1.99), ASD: aHR = 2.02 (95% CI 1.45–2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19–1.57), ASD: aHR = 1.46 (95% CI 1.21–1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys.

Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.

Depression frequently co-occurs with disorders of glucose and insulin homeostasis (DGIH) and obesity. Low-grade systemic inflammation and lifestyle factors in childhood may predispose to DGIH, obesity and depression. We aim to investigate the cross-sectional and longitudinal associations among DGIH, obesity and depression, and to examine the effect of demographics, lifestyle factors and antecedent low-grade inflammation on such associations in young people.

Using the Avon Longitudinal Study of Parents and Children birth cohort, we used regression analyses to examine: (1) cross-sectional and (2) longitudinal associations between measures of DGIH [insulin resistance (IR); impaired glucose tolerance] and body mass index (BMI) at ages 9 and 18 years, and depression (depressive symptoms and depressive episode) at age 18 years and (3) whether sociodemographics, lifestyle factors or inflammation [interleukin-6 (IL-6) at age 9 years] confounded any such associations.

We included 3208 participants. At age 18 years, IR and BMI were positively associated with depression. These associations may be explained by sociodemographic and lifestyle factors. There were no longitudinal associations between DGIH/BMI and depression, and adjustment for IL-6 and C-reactive protein did not attenuate associations between IR/BMI and depression; however, the longitudinal analyses may have been underpowered.

Young people with depression show evidence of DGIH and raised BMI, which may be related to sociodemographic and lifestyle effects such as deprivation, smoking, ethnicity and gender. In future, studies with larger samples are required to confirm this. Preventative strategies for the poorer physical health outcomes associated with depression should focus on malleable lifestyle factors.

Distinguishing a disorder of persistent and impairing grief from normative grief allows clinicians to identify this often undetected and disabling condition. As four diagnostic criteria sets for a grief disorder have been proposed, their similarities and differences need to be elucidated.

Participants were family members bereaved by US military service death (N = 1732). We conducted analyses to assess the accuracy of each criteria set in identifying threshold cases (participants who endorsed baseline Inventory of Complicated Grief ⩾30 and Work and Social Adjustment Scale ⩾20) and excluding those below this threshold. We also calculated agreement among criteria sets by varying numbers of required associated symptoms.

All four criteria sets accurately excluded participants below our identified clinical threshold (i.e. correctly excluding 86–96% of those subthreshold), but they varied in identification of threshold cases (i.e. correctly identifying 47–82%). When the number of associated symptoms was held constant, criteria sets performed similarly. Accurate case identification was optimized when one or two associated symptoms were required. When employing optimized symptom numbers, pairwise agreements among criteria became correspondingly ‘very good’ (κ = 0.86–0.96).

The four proposed criteria sets describe a similar condition of persistent and impairing grief, but differ primarily in criteria restrictiveness. Diagnostic guidance for prolonged grief disorder in International Classification of Diseases, 11th Edition (ICD-11) functions well, whereas the criteria put forth in Section III of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) are unnecessarily restrictive.

Disturbances in emotion regulation (ER) are characteristic of both patients with bipolar disorder (BD) and schizophrenia (SZ). We investigated the temporal dynamics of brain activation during cognitive ER in BD and SZ to understand the contribution of temporal characteristics of disturbed ER to their unique and shared symptomatology.

Forty-six participants performed an ER-task (BD, n = 15; SZ, n = 16; controls, n = 15) during functional magnetic resonance imaging, in which they were instructed to use cognitive reappraisal techniques to regulate their emotional responses. Finite impulse response modeling was applied to estimate the temporal dynamics of brain responses during cognitive reappraisal (v. passive attending) of negative pictures. Group, time, and group × time effects were tested using multivariate modeling.

We observed a group × time interaction during ER in the ventrolateral prefrontal cortex (VLPFC), supplementary motor area (SMA) and inferior occipital gyrus. Patients with SZ demonstrated initial hyper-activation of the VLPFC and SMA activation that was not sustained in later regulatory phases. Response profiles in the inferior occipital gyrus in SZ showed abnormal activation in the later phases of regulation. BD-patients showed general blunted responsivity in these regions.

These results suggest that ER-disturbances in SZ are characterized by an inefficient initialization and failure to sustain regulatory control, whereas in BD, a failure to recruit regulatory resources may represent initial deficits in formulating adequate representations of the regulatory needs. This may help to further understand how ER-disturbances give rise to symptomatology of BD and SZ.

Given the frequency of natural hazards in Haiti, disaster risk reduction is crucial. However, evidence suggests that many people exposed to prior disasters do not engage in disaster preparedness, even when they receive training and have adequate resources. This may be partially explained by a link between mental health symptoms and preparedness; however, these components are typically not integrated in intervention.

The current study assesses effectiveness of an integrated mental health and disaster preparedness intervention. This group-based model was tested in three earthquake-exposed and flood-prone communities (N = 480), across three time points, using a randomized controlled trial design. The 3-day community-based intervention was culturally-adapted, facilitated by trained Haitian lay mental health workers, and focused on enhancing disaster preparedness, reducing mental health symptoms, and fostering community cohesion.

Consistent with hypotheses, the intervention increased disaster preparedness, reduced symptoms associated with depression, post-traumatic stress disorder, anxiety, and functional impairment, and increased peer-based help-giving and help-seeking. Mediation models indicated support for the underlying theoretical model, such that the effect of the intervention on preparedness was mediated by mental health, and that effects on mental health were likewise mediated by preparedness.

The community-based mental health-integrated disaster preparedness intervention is effective in improving mental health and preparedness among community members in Haiti vulnerable to natural hazards. This brief intervention has the potential to be scaled up for use with other communities vulnerable to earthquakes, seasonal flooding, and other natural hazards.

The present paper presents a fundamentally novel approach to model individual differences of persons with the same biologically heterogeneous mental disorder. Unlike prevalent case-control analyses, that assume a clear distinction between patient and control groups and thereby introducing the concept of an ‘average patient’, we describe each patient's biology individually, gaining insights into the different facets that characterize persistent attention-deficit/hyperactivity disorder (ADHD).

Using a normative modeling approach, we mapped inter-individual differences in reference to normative structural brain changes across the lifespan to examine the degree to which case-control analyses disguise differences between individuals.

At the level of the individual, deviations from the normative model were frequent in persistent ADHD. However, the overlap of more than 2% between participants with ADHD was only observed in few brain loci. On average, participants with ADHD showed significantly reduced gray matter in the cerebellum and hippocampus compared to healthy individuals. While the case-control differences were in line with the literature on ADHD, individuals with ADHD only marginally reflected these group differences.

Case-control comparisons, disguise inter-individual differences in brain biology in individuals with persistent ADHD. The present results show that the ‘average ADHD patient’ has limited informative value, providing the first evidence for the necessity to explore different biological facets of ADHD at the level of the individual and practical means to achieve this end.

We aimed to spatially describe mental illness prevalence in England at small-area geographical level, as measured by prevalence of depression, severe mental illness (SMI) and antidepressant prescription volume in primary care records, and how much of their variation was explained by deprivation, social fragmentation and sociodemographic characteristics.

Information on prevalence of depression and SMI was obtained from the Quality and Outcomes Framework (QOF) administrative dataset for 2015/16 and the national dispensing dataset for 2015/16. Linear regression models were fitted to examine ecological associations between deprivation, social fragmentation, other sociodemographic characteristics and mental illness prevalence.

Mental illness prevalence varied within and between regions, with clusters of high prevalence identified across England. Our models explained 33.4–68.2% of variability in prevalence, but substantial variability between regions remained after adjusting for covariates. People in socially cohesive and socially deprived areas were more likely to be diagnosed with depression, while people in more socially fragmented and more socially deprived areas were more likely to be diagnosed with SMI.

Our findings suggest that to tackle mental health inequalities, attention needs to be targeted at more socially deprived localities. The role of social fragmentation warrants further investigation, and it is possible that depression remains undiagnosed in more socially fragmented areas. The wealth of routinely collected data can provide robust evidence to aid optimal resource allocation. If comparable data are available in other countries, similar methods could be deployed to identify high prevalence clusters and target funding to areas of greater need.

Increased neural error-signals have been observed in obsessive-compulsive disorder (OCD), anxiety disorders, and inconsistently in depression. Reduced neural error-signals have been observed in substance use disorders (SUD). Thus, alterations in error-monitoring are proposed as a transdiagnostic endophenotype. To strengthen this notion, data from unaffected individuals with a family history for the respective disorders are needed.

The error-related negativity (ERN) as a neural indicator of error-monitoring was measured during a flanker task from 117 OCD patients, 50 unaffected first-degree relatives of OCD patients, and 130 healthy comparison participants. Family history information indicated, that 76 healthy controls were free of a family history for psychopathology, whereas the remaining had first-degree relatives with depression (n = 28), anxiety (n = 27), and/or SUD (n = 27).

Increased ERN amplitudes were found in OCD patients and unaffected first-degree relatives of OCD patients. In addition, unaffected first-degree relatives of individuals with anxiety disorders were also characterized by increased ERN amplitudes, whereas relatives of individuals with SUD showed reduced amplitudes.

Alterations in neural error-signals in unaffected first-degree relatives with a family history of OCD, anxiety, or SUD support the utility of the ERN as a transdiagnostic endophenotype. Reduced neural error-signals may indicate vulnerability for under-controlled behavior and risk for substance use, whereas a harm- or error-avoidant response style and vulnerability for OCD and anxiety appears to be associated with increased ERN. This adds to findings suggesting a common neurobiological substrate across psychiatric disorders involving the anterior cingulate cortex and deficits in cognitive control.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced somatic symptom and related disorders (SSD) to improve the diagnosis of somatoform disorders. It is unclear whether existing questionnaires are useful to identify patients with SSD. Our study investigates the diagnostic accuracy of the Patient Health Questionnaire-15 (PHQ-15) and the Somatic Symptom Scale-8 (SSS-8) in combination with the Somatic Symptom Disorder – B Criteria Scale (SSD-12).

For this cross-sectional study, participants were recruited from a psychosomatic outpatient clinic. PHQ-15, SSS-8, and SSD-12 were administered and compared with SSD criteria from a diagnostic interview. Sensitivity and specificity were calculated for optimal individual and combined cutpoints. Receiver operator curves were created and area under the curve (AUC) analyses assessed.

Data of n = 372 patients [31.2% male, mean age: 39.3 years (s.d. = 13.6)] were analyzed. A total of 56.2% fulfilled the SSD criteria. Diagnostic accuracy was moderate for each questionnaire (PHQ-15: AUC = 0.70; 95% CI = 0.65–0.76; SSS-8: AUC = 0.71; 95% CI = 0.66–0.77; SSD-12: AUC = 0.74; 95% CI = 0.69–0.80). Combining questionnaires improved diagnostic accuracy (PHQ-15 + SSD-12: AUC = 0.77; 95% CI = 0.72–0.82; SSS-8 + SSD-12: AUC = 0.79; 95% CI = 0.74–0.84). Optimal combined cutpoints were ⩾9 for the PHQ-15 or SSS-8, and ⩾23 for the SSD-12 (sensitivity and specificity = 69% and 70%).

The combination of the PHQ-15 or SSS-8 with the SSD-12 provides an easy-to-use and time- and cost-efficient opportunity to identify persons at risk for SSD. If systematically applied in routine care, effective screening and subsequent treatment might help to improve quality of life and reduce health care excess costs.

The aims of this meta-analysis are (i) to estimate the pooled relative risk (RR) of developing non-affective psychotic disorder (NAPD) and affective psychotic disorder (APD) among migrants and their children; (ii) to adjust these results for socioeconomic status (SES); (iii) to examine the sources of heterogeneity that underlie the risk of NAPD.

We included population-based incidence studies that reported an age-adjusted RR with 95% confidence interval (CI) published 1 January 1977–12 October 2017 and used a random-effects model.

We retrieved studies performed in Europe (n = 43), Israel (n = 3), Canada (n = 2) and Australia (n = 1). The meta-analysis yielded a RR, adjusted for age and sex, of 2.13 (95% CI 1.99–2.27) for NAPD and 2.94 (95% CI 2.28–3.79) for APD. The RRs diminished, but persisted after adjustment for SES. With reference to NAPD: a personal or parental history of migration to Europe from countries outside Europe was associated with a higher RR (RR = 2.94, 95% CI 2.63–3.29) than migration within Europe (RR = 1.88, 95% 1.62–2.18). The corresponding RR was lower in Israel (RR = 1.22; 0.99–1.50) and Canada (RR = 1.21; 0.85–1.74). The RR was highest among individuals with a black skin colour (RR = 4.19, 95% CI 3.42–5.14). The evidence of a difference in risk between first and second generation was insufficient.

Positive selection may explain the low risk in Canada, while the change from exclusion to inclusion may do the same in Israel. Given the high risks among migrants from developing countries in Europe, social exclusion may have a pathogenic role.

Improving quality of life (QOL) for people with dementia is a priority. In care homes, we often rely on proxy ratings from staff and family but we do not know if, or how, they differ in care homes.

We compared 1056 pairs of staff and family DEMQOL-Proxy ratings from 86 care homes across England. We explored factors associated with ratings quantitatively using multilevel modelling and, qualitatively, through thematic analysis of 12 staff and 12 relative interviews.

Staff and family ratings were weakly correlated (ρs = 0.35). Median staff scores were higher than family's (104 v. 101; p < 0.001). Family were more likely than staff to rate resident QOL as ‘Poor’ (χ2 = 55.91, p < 0.001). Staff and family rated QOL higher when residents had fewer neuropsychiatric symptoms and severe dementia. Staff rated QOL higher in homes with lower staff:resident ratios and when staff were native English speakers. Family rated QOL higher when the resident had spent longer living in the care home and was a native English. Spouses rated residents’ QOL higher than other relatives. Qualitative results suggest differences arise because staff felt good care provided high QOL but families compared the present to the past. Family judgements centre on loss and are complicated by decisions about care home placement and their understandings of dementia.

Proxy reports differ systematically between staff and family. Reports are influenced by the rater:staff and family may conceptualise QOL differently.

Mood and anxiety disorders are ubiquitous but current treatment options are ineffective for many sufferers. Moreover, a number of promising pre-clinical interventions have failed to translate into clinical efficacy in humans. Improved treatments are unlikely without better animal–human translational pipelines. Here, we translate a rodent measure of negative affective bias into humans, exploring its relationship with (1) pathological mood and anxiety symptoms and (2) transient induced anxiety.

Adult participants (age = 29 ± 11) who met criteria for mood or anxiety disorder symptomatology according to a face-to-face neuropsychiatric interview were included in the symptomatic group. Study 1 included N = 77 (47 = asymptomatic [female = 21]; 30 = symptomatic [female = 25]), study 2 included N = 47 asymptomatic participants (25 = female). Outcome measures were choice ratios, reaction times and parameters recovered from a computational model of reaction time – the drift diffusion model (DDM) – from a two-alternative-forced-choice task in which ambiguous and unambiguous auditory stimuli were paired with high and low rewards.

Both groups showed over 93% accuracy on unambiguous tones indicating intact discrimination, but symptomatic individuals demonstrated increased negative affective bias on ambiguous tones [proportion high reward = 0.42 (s.d. = 0.14)] relative to asymptomatic individuals [0.53 (s.d. = 0.17)] as well as a significantly reduced DDM drift rate. No significant effects were observed for the within-subjects anxiety-induction.

Humans with pathological anxiety symptoms directly mimic rodents undergoing anxiogenic manipulation. The lack of sensitivity to transient anxiety suggests the paradigm might be more sensitive to clinically relevant symptoms. Our results establish a direct translational pipeline (and candidate therapeutics screen) from negative affective bias in rodents to pathological mood and anxiety symptoms in humans.

Few studies focused on the relationship between psychological measures, major depressive disorder (MDD) and repetitive transcranial magnetic stimulation (rTMS) response. This study investigated several psychological measures as potential predictors for rTMS treatment response. Additionally, this study employed two approaches to evaluate the robustness of our findings by implementing immediate replication and full-sample exploration with strict p-thresholding.

This study is an open-label, multi-site study with a total of 196 MDD patients. The sample was subdivided in a Discovery (60% of total sample, n = 119) and Replication sample (40% of total sample, n = 77). Patients were treated with right low frequency (1 Hz) or left high frequency (10 Hz) rTMS at the dorsolateral prefrontal cortex. Clinical variables [Beck Depression Inventory (BDI), Neuroticism, Extraversion, Openness Five-Factor Inventory, and Depression, Anxiety, and Stress Scale, and BDI subscales] were obtained at baseline, post-treatment, and at follow-up. Predictors were analyzed in terms of statistical association, robustness (independent replication), as well as for their clinical relevance [positive predictive value (PPV) and negative predictive value (NPV)].

Univariate analyses revealed that non-responders had higher baseline anhedonia scores. Anhedonia scores at baseline correlated negatively with total BDI percentage change over time. This finding was replicated. However, anhedonia scores showed to be marginally predictive of rTMS response, and neither PPV nor NPV reached the levels of clinical relevance.

This study suggests that non-responders to rTMS treatment have higher baseline anhedonia scores. However, anhedonia was only marginally predictive of rTMS response. Since all other psychological measures did not show predictive value, it is concluded that psychological measures cannot be used as clinically relevant predictors to rTMS response in MDD.

The current study explored the temporal pathways of change within two treatments, the Healthy Activity Program (HAP) for depression and the Counselling for Alcohol Problems (CAP) Program for harmful drinking.

The study took place in the context of two parallel randomized controlled trials in Goa, India. N = 50 random participants who met a priori criteria were selected from each treatment trial and examined for potential direct and mediational pathways. In HAP, we examined the predictive roles of therapy quality and patient-reported activation, assessing whether activation mediated the effects of therapy quality on depression (Patient Health Questionnaire-9) outcomes. In CAP, we examined the predictive roles of therapy quality and patient change- and counter-change-talk, assessing whether change- or counter-change-talk mediated the effects of therapy quality on daily alcohol consumption.

In HAP, therapy quality (both general and treatment-specific skills) was associated with patient activation; patient activation but not therapy quality significantly predicted depression outcomes, and patient activation mediated the effects of higher general skills on subsequent clinical outcomes [a × b = −2.555, 95% confidence interval (CI) −5.811 to −0.142]. In CAP, higher treatment-specific skills, but not general skills, were directly associated with drinking outcomes, and reduced levels of counter-change talk both independently predicted, and mediated the effects of higher general skills on, reduced alcohol consumption (a × b = −24.515, 95% CI −41.190 to −11.060). Change talk did not predict alcohol consumption and was not correlated with counter-change talk.

These findings suggest that therapy quality in early sessions operated through increased patient activation and reduced counter-change talk to reduce depression and harmful drinking respectively.

Studies investigating the underlying mechanisms of hallucinations in patients with schizophrenia suggest that an imbalance in top-down expectations v. bottom-up processing underlies these errors in perception. This study evaluates this hypothesis by testing if individuals drawn from the general population who have had auditory hallucinations (AH) have more misperceptions in auditory language perception than those who have never hallucinated.

We used an online survey to determine the presence of hallucinations. Participants filled out the Questionnaire for Psychotic Experiences and participated in an auditory verbal recognition task to assess both correct perceptions (hits) and misperceptions (false alarms). A hearing test was performed to screen for hearing problems.

A total of 5115 individuals from the general Dutch population participated in this study. Participants who reported AH in the week preceding the test had a higher false alarm rate in their auditory perception compared with those without such (recent) experiences. The more recent the AH were experienced, the more mistakes participants made. While the presence of verbal AH (AVH) was predictive for false alarm rate in auditory language perception, the presence of non-verbal or visual hallucinations were not.

The presence of AVH predicted false alarm rate in auditory language perception, whereas the presence of non-verbal auditory or visual hallucinations was not, suggesting that enhanced top-down processing does not transfer across modalities. More false alarms were observed in participants who reported more recent AVHs. This is in line with models of enhanced influence of top-down expectations in persons who hallucinate.

Aberrations in reward and penalty processing are implicated in depression and putatively reflect altered dopamine signalling. This study exploits the advantages of a placebo-controlled design to examine how a novel D2 antagonist with adjunctive antidepressant properties modifies activity in the brain's reward network in depression.

We recruited 43 medication-naïve subjects across the range of depression severity (Beck's Depression Inventory-II score range: 0–43), including healthy volunteers, as well as people meeting full-criteria for major depressive disorder. In a double-blind placebo-controlled cross-over design, all subjects received either placebo or lurasidone (20 mg) across two visits separated by 1 week. Functional magnetic resonance imaging with the Monetary Incentive Delay (MID) task assessed reward functions via neural responses during anticipation and receipt of gains and losses. Arterial spin labelling measured cerebral blood flow (CBF) at rest.

Lurasidone altered fronto-striatal activity during anticipation and outcome phases of the MID task. A significant three-way Medication-by-Depression severity-by-Outcome interaction emerged in the anterior cingulate cortex (ACC) after correction for multiple comparisons. Follow-up analyses revealed significantly higher ACC activation to losses in high- v. low depression participants in the placebo condition, with a normalisation by lurasidone. This effect could not be accounted for by shifts in resting CBF.

Lurasidone acutely normalises reward processing signals in individuals with depressive symptoms. Lurasidone's antidepressant effects may arise from reducing responses to penalty outcomes in individuals with depressive symptoms.