Dysfunction of N-methyl-D-aspartate receptor (NMDAR) is involved in the pathophysiology of schizophrenia. A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the efficacy and safety of memantine, a non-competitive NMDAR antagonist, in the treatment of schizophrenia.

Standardized/weighted mean differences (SMDs/WMDs), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed.

Included in the meta-analysis were eight RCTs (n = 452) of 11.5 ± 2.6 weeks duration, with 229 patients on memantine (20 mg/day) and 223 patients on placebo. Adjunctive memantine outperformed placebo in the measures of Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms [SMD: −0.63 (95% CI −1.10 to −0.16), p = 0.009, I2 = 77%], but not in the total, positive and general symptoms [SMD: −0.46 to −0.08 (95% CI −0.93 to 0.22), p = 0.06–0.60, I2 = 0–74%] or the Clinical Global Impression Severity Scale [WMD: 0.04 (95% CI −0.24 to 0.32), p = 0.78]. The negative symptoms remained significant after excluding one outlying RCT [SMD: −0.41 (95% CI −0.72 to −0.11), p = 0.008, I2 = 47%]. Compared with the placebo group, adjunctive memantine was associated with significant improvement in neurocognitive function using the Mini-Mental State Examination (MMSE) [WMD: 3.09, (95% CI 1.77–4.42), p < 0.00001, I2 = 22%]. There was no significant difference in the discontinuation rate [RR: 1.34 (95% CI 0.76–2.37), p = 0.31, I2 = 0%] and adverse drug reactions between the two groups.

This meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.

Exposure to traumatic events is surprisingly common, yet little is known about its effect on decision making beyond the fact that those with post-traumatic stress disorder are more likely to have substance-abuse problems. We examined the effects of exposure to severe trauma on decision making in low-income, urban African Americans, a group especially likely to have had such traumatic experiences.

Participants completed three decision-making tasks that assessed the subjective value of delayed monetary rewards and payments and of probabilistic rewards. Trauma-exposed cases and controls were propensity-matched on demographic measures, treatment for psychological problems, and substance dependence.

Trauma-exposed cases discounted the value of delayed rewards and delayed payments, but not probabilistic rewards, more steeply than controls. Surprisingly, given previous findings that suggested women are more affected by trauma when female and male participants’ data were analyzed separately, only the male cases showed steeper delay discounting. Compared with nonalcoholic males who were not exposed to trauma, both severe trauma and alcohol-dependence produced significantly steeper discounting of delayed rewards.

The current study shows that exposure to severe trauma selectively affects fundamental decision-making processes. Only males were affected, and effects were observed only on discounting delayed outcomes (i.e. intertemporal choice) and not on discounting probabilistic outcomes (i.e. risky choice). These findings are the first to show significant differences in the effects of trauma on men's and women's decision making, and the selectivity of these effects has potentially important implications for treatment and also provides clues as to underlying mechanisms.

Cognitive–behavioral group therapy (CBGT) is a first-line treatment for social anxiety disorder (SAD). However, since many patients remain symptomatic post-treatment, there is a need for augmenting procedures. This randomized controlled trial (RCT) examined the potential augmentation effect of attention bias modification (ABM) for CBGT.

Fifty patients with SAD from three therapy groups were randomized to receive an 18-week standard CBGT with either ABM designed to shift attention away from threat (CBGT + ABM), or a placebo protocol not designed to modify threat-related attention (CBGT + placebo). Therapy groups took place in a large mental health center. Clinician and self-report measures of social anxiety and depression were acquired pre-treatment, post-treatment, and at 3-month follow-up. Attention bias was assessed at pre- and post-treatment.

Patients randomized to the CBGT + ABM group, relative to those randomized to the CBGT + placebo group, showed greater reductions in clinician-rated SAD symptoms post-treatment, with effects maintained at 3-month follow-up. Group differences were not evident for self-report or attention-bias measures, with similar reductions in both groups. Finally, reduction in attention bias did not mediate the association between group and reduction in Liebowitz Social Anxiety Scale Structured Interview (LSAS) scores.

This is the first RCT to examine the possible augmenting effect of ABM added to group-based cognitive–behavioral therapy for adult SAD. Training patients’ attention away from threat might augment the treatment response to standard CBGT in SAD, a possibility that could be further evaluated in large-scale RCTs.

Schizotypal traits are considered a phenotypic-indicator of schizotypy, a latent personality organization reflecting a putative liability for psychosis. To date, no previous study has examined the comparability of factorial structures across samples originating from different countries and cultures. The main goal was to evaluate the factorial structure and reliability of the Schizotypal Personality Questionnaire (SPQ) scores by amalgamating data from studies conducted in 12 countries and across 21 sites.

The overall sample consisted of 27 001 participants (37.5% males, n = 4251 drawn from the general population). The mean age was 22.12 years (s.d. = 6.28, range 16–55 years). The SPQ was used. Confirmatory factor analysis (CFA) and Multilevel CFA (ML-CFA) were used to evaluate the factor structure underlying the SPQ scores.

At the SPQ item level, the nine factor and second-order factor models showed adequate goodness-of-fit. At the SPQ subscale level, three- and four-factor models displayed better goodness-of-fit indices than other CFA models. ML-CFA showed that the intraclass correlation coefficients values were lower than 0.106. The three-factor model showed adequate goodness of fit indices in multilevel analysis. The ordinal α coefficients were high, ranging from 0.73 to 0.94 across individual samples, and from 0.84 to 0.91 for the combined sample.

The results are consistent with the conceptual notion that schizotypal personality is a multifaceted construct and support the validity and utility of SPQ in cross-cultural research. We discuss theoretical and clinical implications of our results for diagnostic systems, psychosis models and cross-national mental health strategies.

Decline in cognitive functioning precedes the first psychotic episode in the course of schizophrenia and is considered a hallmark symptom of the disorder. Given the low incidence of schizophrenia, it remains a challenge to investigate whether cognitive decline coincides with disease-related changes in brain structure, such as white matter abnormalities. The 22q11.2 deletion syndrome (22q11DS) is an appealing model in this context, as 25% of patients develop psychosis. Furthermore, we recently showed that cognitive decline also precedes the onset of psychosis in individuals with 22q11DS. Here, we investigate whether the early cognitive decline in patients with 22q11DS is associated with alterations in white matter microstructure.

We compared the fractional anisotropy (FA) of white matter in 22q11DS patients with cognitive decline [n = 16; −18.34 (15.8) VIQ percentile points over 6.80 (2.39) years] to 22q11DS patients without cognitive decline [n = 18; 17.71 (20.17) VIQ percentile points over 5.27 (2.03) years] by applying an atlas-based approach to diffusion-weighted imaging data.

FA was significantly increased (p < 0.05, FDR) in 22q11DS patients with a cognitive decline in the bilateral superior longitudinal fasciculus, the bilateral cingulum bundle, all subcomponents of the left internal capsule and the left superior frontal-occipital fasciculus as compared with 22q11DS patients without cognitive decline.

Within 22q11DS, the early cognitive decline is associated with microstructural differences in white matter. At the mean age of 17.8 years, these changes are reflected in increased FA in several tracts. We hypothesize that similar brain alterations associated with cognitive decline take place early in the trajectory of schizophrenia.

There has been increasing evidence that chronic low-grade inflammation is associated with mood disorders. However, the findings have been inconsistent because of heterogeneity across studies and methodological limitations. Our aim is to prospectively evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α and high sensitivity C-reactive protein (hsCRP) with mood disorders.

The sample consisted of 3118 participants (53.7% women; mean age: 51.0, s.d. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, s.d. 0.6). Current and remitted mood disorders including bipolar and major depressive disorders (MDD) and its subtypes (atypical, melancholic, combined atypical and melancholic, and unspecified) were based on semi-structured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. Associations were tested by multiple linear and logistic regression models.

Current combined MDD [β = 0.29, 95% confidence interval (CI) 0.03–0.55] and current atypical MDD (β = 0.32, 95% CI 0.10–0.55) at baseline were associated with increased levels of hsCRP at follow-up. There was little evidence for inflammation markers at baseline predicting mood disorders at follow-up.

The prospective unidirectional association between current MDD subtype with atypical features and hsCRP levels at follow-up suggests that inflammation may be a consequence of this condition. The role of inflammation, particularly hsCRP that is critically involved in cardiovascular diseases, warrants further study. Future research that examines potential influences of medications on inflammatory processes is indicated.

Negative symptoms significantly contribute to disability and lack of community participation for low functioning individuals with schizophrenia. Cognitive therapy has been shown to improve negative symptoms and functional outcome in this population. Elucidation of the mechanisms of the therapy would lead to a better understanding of negative symptoms and the development of more effective interventions to promote recovery. The objective of this study was to determine (1) whether guided success at a card-sorting task will produce improvement in defeatist beliefs, positive beliefs about the self, mood, and card-sorting performance, and (2) whether these changes in beliefs and mood predict improvements in unguided card-sorting.

Individuals with schizophrenia having prominent negative symptoms and impaired neurocognitive performance (N = 35) were randomized to guided success (n = 19) or a control (n = 16) condition.

Controlling for baseline performance, the experimental group performed significantly better, endorsed defeatist beliefs to a lesser degree, reported greater positive self-concept, and reported better mood than the control condition immediately after the experimental session. A composite index of change in defeatist beliefs, self-concept, and mood was significantly correlated with improvements in card-sorting.

This analogue study supports the rationale of cognitive therapy and provides a general therapeutic model in which experiential interventions that produce success have a significant immediate effect on a behavioral task, mediated by changes in beliefs and mood. The rapid improvement is a promising indicator of the responsiveness of this population, often regarded as recalcitrant, to cognitively-targeted behavioral interventions.

Schizophrenia (SZ) and bipolar disorder (BP) are causes of severe disability worldwide and parents’ severe mental illness (SMI) is associated with childhood adversity, and socio-emotional and cognitive problems in children. Yet, how parental BP and SZ affect educational attainment in offspring is still unclear.

We included all children (N = 684.248) born and living in Denmark between 1986 and 1996 and their parents. Our follow-up lasted from 1986 until children's graduation in 2014. The main outcome variable was their school grades following their primary education. School outcomes were divided into four categories: not graduated, low-grade point average (GPA), medium GPA and high GPA. We then performed a multiple logistic regression with medium GPA as the reference category, with the children of parents without SZ or BP as the reference group.

Children of parents with SZ faced higher odds than their peers of not graduating primary education (OR 2.6), along with low GPA (odds ratios (OR) 1.6) and lower odds for a high GPA (OR 0.7). Moreover, it was the children of mothers rather than fathers with BP who had higher odds of not graduating primary education (OR 1.6). Lastly, child placement was associated with lower grades and lower graduation rates, and outcomes for children of parents with SMI were favorable compared with other children placed in care.

For children, parental SZ is associated with lower grades and lower chances for graduating primary education. In contrast, the children of parents with BP were indistinguishable from the reference group regarding school grades. This signifies that specificity of parental severe mental illness is important in relation to educational achievement of children.

Childhood adversity is associated with cognitive impairments in schizophrenia. However, findings to date are inconsistent and little is known about the relationship between social cognition and childhood trauma. We investigated the relationship between childhood abuse and neglect and cognitive function in patients with a first-episode of schizophrenia or schizophreniform disorder (n = 56) and matched healthy controls (n = 52). To the best of our knowledge, this is the first study assessing this relationship in patients and controls exposed to similarly high levels of trauma.

Pearson correlational coefficients were used to assess correlations between Childhood Trauma Questionnaire abuse and neglect scores and cognition. For the MCCB domains displaying significant (p < 0.05) correlations, within group hierarchical linear regression, was done to assess whether abuse and neglect were significant predictors of cognition after controlling for the effect of education.

Patients and controls reported similarly high levels of abuse and neglect. Cognitive performance was poorer for patients compared with controls for all cognitive domains except working memory and social cognition. After controlling for education, exposure to childhood neglect remained a significant predictor of impairment in social cognition in both patients and controls. Neglect was also a significant predictor of poorer verbal learning in patients and of attention/vigilance in controls. However, childhood abuse did not significantly predict cognitive impairments in either patients or controls.

These findings are cross sectional and do not infer causality. Nonetheless, they indicate that associations between one type of childhood adversity (i.e. neglect) and social cognition are present and are not illness-specific.

Previous cross-lagged studies on depression and memory impairment among the elderly have revealed conflicting findings relating to the direction of influence between depression and memory impairment. The current study aims to clarify this direction of influence by examining the cross-lagged relationships between memory impairment and depression in an Asian sample of elderly community dwellers, as well as synthesizing previous relevant cross-lagged findings via a meta-analysis.

A total of 160 participants (Mage = 68.14, s.d. = 5.34) were assessed across two time points (average of 1.9 years apart) on measures of memory and depressive symptoms. The data were then fitted to a structural equation model to examine two cross-lagged effects (i.e. depressive symptoms→memory; memory→depressive symptoms). A total of 14 effect-sizes for each of the two cross-lagged directions were extracted from six studies (including the present; total N = 8324). These effects were then meta-analyzed using a three-level mixed effects model.

In the current sample, lower memory ability at baseline was associated with worse depressive symptoms levels at follow-up, after controlling for baseline depressive symptoms. However, the reverse effect was not significant; baseline depressive symptoms did not predict subsequent memory ability after controlling for baseline memory. The results of the meta-analysis revealed the same pattern of relationship between memory and depressive symptoms.

These results provide robust evidence that the relationship between memory impairment and depressive symptoms is unidirectional; memory impairment predicts subsequent depressive symptoms but not vice-versa. The implications of these findings are discussed

Multiple studies have found Conscientiousness to be protective against dementia. The purpose of this study is to identify which specific aspects, or facets, of Conscientiousness are most protective against cognitive impairment and whether these associations are moderated by demographic factors and/or genetic risk.

Health and Retirement Study participants were selected for analysis if they completed the facets of Conscientiousness measure, scored in the range of normal cognitive functioning at the baseline personality assessment, and had at least one follow-up assessment of cognition over the up to 6-year follow-up (N = 11 181). Cox regression was used to test for risk of incident dementia and risk of incident cognitive impairment not dementia (CIND).

Over the follow-up, 278 participants developed dementia and 2186 participants developed CIND. The facet of responsibility had the strongest and most consistent association with dementia risk: every standard deviation increase in this facet was associated with a nearly 35% decreased risk of dementia; self-control and industriousness were also protective. Associations were generally similar when controlling for clinical, behavioral, and genetic risk factors. These three facets were also independent predictors of decreased risk of CIND.

The present research indicates that individuals who see themselves as responsible, able to control their behavior, and hard workers are less likely to develop CIND or dementia and that these associations persist after accounting for some common clinical, behavioral, and genetic risk factors.

Although the study of the neuroanatomical correlates of generalized anxiety disorder (GAD) is gaining increasing interest, up to now the cortical anatomy of GAD patients has been poorly investigated and still no data on cortical gyrification are available. The aim of the present study is to quantitatively examine the cortical morphology in patients with GAD compared with healthy controls (HC) using magnetic resonance imaging (MRI). To the best of our knowledge, this is the first study analyzing the gyrification patterns in GAD.

A total of 31 GAD patients and 31 HC underwent 3 T structural MRI. For each subject, cortical surface area (CSA), cortical thickness (CT), gray matter volume (GMV), and local gyrification index (LGI) were estimated in 19 regions of interest using the Freesurfer software. These parameters were then compared between the two groups using General Linear Model designs.

Compared with HC, GAD patients showed: (1) reduced CT in right caudal middle frontal gyrus (p < 0.05, Bonferroni corrected), (2) hyper-gyrification in right fusiform, inferior temporal, superior parietal and supramarginal gyri and in left supramarginal and superior frontal gyri (p < 0.05, Bonferroni corrected). No significant alterations in CSA and GMV were observed.

Our findings support the hypothesis of a neuroanatomical basis for GAD, highlighting a possible key role of the right hemisphere. The alterations of CT and gyrification in GAD suggest a neurodevelopmental origin of the disorder. Further studies on GAD are needed to understand the evolution of the cerebral morphology with age and during the clinical course of the illness.

Distinguishing temporal patterns of depressive symptoms during pregnancy and after childbirth has important clinical implications for diagnosis, treatment, and maternal and child outcomes. The primary aim of the present study was to distinguish patterns of chronically elevated levels of depressive symptoms v. trajectories that are either elevated during pregnancy but then remit after childbirth, v. patterns that increase after childbirth.

The report uses latent growth mixture modeling in a large, population-based cohort (N = 12 121) to investigate temporal patterns of depressive symptoms. We examined theoretically relevant sociodemographic factors, exposure to adversity, and offspring gender as predictors.

Four distinct trajectories emerged, including resilient (74.3%), improving (9.2%), emergent (4.0%), and chronic (11.5%). Lower maternal and paternal education distinguished chronic from resilient depressive trajectories, whereas higher maternal and partner education, and female offspring gender, distinguished the emergent trajectory from the chronic trajectory. Younger maternal age distinguished the improving group from the resilient group. Exposure to medical, interpersonal, financial, and housing adversity predicted membership in the chronic, emergent, and improving trajectories compared with the resilient trajectory. Finally, exposure to medical, interpersonal, and financial adversity was associated with the chronic v. improving group, and inversely related to the emergent class relative to the improving group.

There are distinct temporal patterns of depressive symptoms during pregnancy, after childbirth, and beyond. Most women show stable low levels of depressive symptoms, while emergent and chronic depression patterns are separable with distinct correlates, most notably maternal age, education levels, adversity exposure, and child gender.

The neuropsychological origins of negative syndrome of schizophrenia remain elusive. Evidence from behavioural studies, which utilised emotion-inducing pictures to elicit motivated behaviour generally reported that that schizophrenia patients experienced similar affective experience as healthy individuals but failed to translate emotional salience to motivated behaviour, a phenomenon called emotion–behaviour decoupling. However, a few studies have examined emotion–behaviour decoupling in non-psychotic high-risk populations, who are relatively unaffected by medication effects.

In this study, we examined the nature and extent of emotion–behaviour decoupling in in three independent samples (65 schizophrenia patients v. 63 controls; 40 unaffected relatives v. 45 controls; and 32 individuals with social anhedonia v. 32 controls). We administered an experimental task to examine their affective experience and its coupling with behaviour, using emotion-inducing slides, and allowed participants to alter stimulus exposure using button-pressing to seek pleasure or avoid aversion.

Schizophrenia patients reported similar affective experiences as their controls, while their unaffected relatives and individuals with high levels of social anhedonia exhibited attenuated affective experiences, in particular in the arousal aspect. Compared with their respective control groups, all of the three groups showed emotion–behaviour decoupling.

Our findings support that both genetically and behaviourally high-risk groups exhibit emotion–behaviour decoupling. The familial association apparently supports its role as a putative trait marker for schizophrenia.

Can core genetic liabilities for suicidal behavior be indexed using psychological and neural indicators combined? The current work addressed this question by examining phenotypic and genetic associations of two biobehavioral traits, threat sensitivity (THT) and disinhibition (DIS) – operationalized as psychoneurometric variables (i.e., composites of psychological-scale and neurophysiological measures) – with suicidal behaviors in a sample of adult twins.

Participants were 444 identical and fraternal twins recruited from an urban community. THT was assessed using a psychological-scale measure of fear/fearlessness combined with physiological indicators of reactivity to aversive pictures, and DIS was assessed using scale measures of disinhibitory tendencies combined with indicators of brain response from lab performance tasks. Suicidality was assessed using items from structured interview and questionnaire protocols.

THT and DIS each contributed uniquely to prediction of suicidality when assessed psychoneurometrically (i.e., as composites of scale and neurophysiological indicators). In addition, these traits predicted suicidality interactively, with participants high on both reporting the greatest degree of suicidal behaviors. Biometric (twin-modeling) analyses revealed that a high percentage of the predictive association for each psychoneurometric trait (83% for THT, 68% for DIS) was attributable to genetic variance in common with suicidality.

Findings indicate that psychoneurometric assessments of biobehavioral traits index genetic liability for suicidal behavior, and as such, can serve as innovative targets for research on core biological processes contributing to severe psychopathology, including suicidal proclivities and actions.

The experience of childhood maltreatment is a significant risk factor for the development of depression. This risk is particularly heightened after exposure to additional, more contemporaneous stress. While behavioral evidence exists for this relation, little is known about biological correlates of these stress interactions. Identifying such correlates may provide biomarkers of risk for later depression.

Here, we leverage behavioral, experiential, and neuroimaging data from the Duke Neurogenetics Study to identify potential biomarkers of stress exposure. Based on the past research, we were specifically interested in reward-related connectivity and the interaction of early and more recent stress. We examined psychophysiological interactions between the ventral striatum and other brain regions in relation to these stress variables, as well as measures of internalizing symptomatology (n = 926, participant age range = 18–22 years of age).

We found relatively increased reward-related functional connectivity between the left ventral striatum and the medial prefrontal cortex in individuals exposed to greater levels of childhood maltreatment who also experienced greater levels of recent life stress (β = 0.199, p < 0.005). This pattern of functional connectivity was further associated with elevated symptoms of depression (β = 0.089, p = 0.006). Furthermore, using a moderated mediation framework, we demonstrate that this functional connectivity provides a biological link between cumulative stress exposure and internalizing symptomatology.

These findings suggest a novel biomarker linking cumulative stress exposure with the later experience of depressive symptoms. Our results are discussed in the context of past research examining stress exposure in relation to depression.

Children with poor mental health often struggle at school. The relationship between childhood psychiatric disorder and exclusion from school has not been frequently studied, but both are associated with poor adult outcomes. We undertook a secondary analysis of the British Child and Adolescent Mental Health Surveys from 2004 and its follow-up in 2007 to explore the relationship between exclusion from school and psychopathology. We predicted poorer mental health among those excluded.

Psychopathology was measured using the Strengths and Difficulties Questionnaire, while psychiatric disorder was assessed using the Development and Well-Being Assessment and applying Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM IV) criteria. Exclusion from school and socio-demographic characteristics were reported by parents. Multi-variable regression models were used to examine the impact of individual factors on exclusion from school or psychological distress.

Exclusion from school was commoner among boys, secondary school pupils and those living in socio-economically deprived circumstances. Poor general health and learning disability among children and poor parental mental health were also associated with exclusion. There were consistently high levels of psychological distress among those who had experienced exclusion at baseline and follow-up.

We detected a bi-directional association between psychological distress and exclusion. Efforts to identify and support children who struggle with school may therefore prevent both future exclusion and future psychiatric disorder.

Previous studies have linked maternal obesity with depressive symptoms during and after pregnancy. It remains unknown whether obesity associates with consistently elevated depressive symptoms throughout pregnancy, predicts symptoms postpartum when accounting for antenatal symptoms, and if co-morbid hypertensive and diabetic disorders add to these associations. We addressed these questions in a sample of Finnish women whom we followed during and after pregnancy.

Early pregnancy body mass index, derived from the Finnish Medical Birth Register and hospital records in 3234 PREDO study participants, was categorized into underweight (<18.5 kg/m2), normal weight (18.5–24.99 kg/m2), overweight (25–29.99 kg/m2), and obese (⩾30 kg/m2) groups. The women completed the Center for Epidemiological Studies Depression Scale biweekly during pregnancy, and at 2.4 (s.d. = 1.2) and/or 28.2 (s.d. = 4.2) weeks after pregnancy.

In comparison to normal weight women, overweight, and obese women reported higher levels of depressive symptoms and had higher odds of clinically significant depressive symptoms during (23% and 43%, respectively) and after pregnancy (22% and 36%, respectively). Underweight women had 68% higher odds of clinically significant depressive symptoms after pregnancy. Overweight and obesity also predicted higher depressive symptoms after pregnancy in women not reporting clinically relevant symptomatology during pregnancy. Hypertensive and diabetic disorders did not explain or add to these associations.

Maternal early pregnancy overweight and obesity and depressive symptoms during and after pregnancy are associated. Mental health promotion should be included as an integral part of lifestyle interventions in early pregnancy obesity and extended to benefit also overweight and underweight women.

Day hospital mentalization-based treatment (MBT-DH) is a promising treatment for borderline personality disorder (BPD) but its evidence base is still limited. This multi-site randomized trial compared the efficacy of MBT-DH delivered by a newly set-up service v. specialist treatment as usual (S-TAU) tailored to the individual needs of patients, and offered by a well-established treatment service.

Two mental healthcare institutes in The Netherlands participated in the study. Patients who met DSM-IV criteria for BPD and had a score of ⩾20 on the borderline personality disorder severity index (BPDSI) were randomly allocated to MBT-DH (N = 54) or S-TAU (N = 41). The primary outcome variable was the total score on the BPDSI. Secondary outcome variables included symptom severity, quality of life, and interpersonal functioning. Data were collected at baseline and every 6 months until 18-month follow-up, and were analyzed using multilevel analyses based on intention-to-treat principles.

Both treatments were associated with significant improvements in all outcome variables. MBT-DH was not superior to S-TAU on any outcome variable. MBT-DH was associated with higher acceptability in BPD patients compared v. S-TAU, reflected in significantly higher early drop-out rates in S-TAU (34%) v. MBT-DH (9%).

MBT-DH delivered by a newly set-up service is as effective as specialist TAU in The Netherlands in the treatment of BPD at 18-month follow-up. Further research is needed to investigate treatment outcomes in the longer term and the cost-effectiveness of these treatments.

Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.

This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).

Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.

Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.