Common mental disorders (CMD) cause large suffering and high societal costs. Cognitive behavioural therapy (CBT) can effectively treat CMD, but access to treatment is insufficient. Guided self-help (GSH) CBT, has shown effects comparable with face-to-face CBT. However, not all patients respond to GSH, and stepping up non-responders to face-to-face CBT, could yield larger response rates. The aim was to test a stepped care model for CMD in primary care by first evaluating the effects of GSH-CBT and secondly, for non-responders, evaluating the additional effect of face-to-face CBT.

Consecutive patients (N = 396) with a principal disorder of depression, anxiety, insomnia, adjustment or exhaustion disorder were included. In Step I, all patients received GSH-CBT. In Step II, non-responders were randomized to face-to-face CBT or continued GSH. The primary outcome was remission status, defined as a score below a pre-established cutoff on a validated disorder-specific scale.

After GSH-CBT in Step I, 40% of patients were in remission. After Step II, 39% of patients following face-to-face CBT were in remission compared with 19% of patients after continued GSH (p = 0.004). Using this stepped care model required less than six therapy sessions per patient and led to an overall remission rate of 63%.

Stepped care can be effective and resource-efficient to treat CMD in primary care, leading to high remission rates with limited therapist resources. Face-to-face CBT speeded up recovery compared with continued GSH. At follow-ups after 6 and 12 months, remission rates were similar in the two groups.

Childhood trauma is a risk factor for psychosis. Deficits in response inhibition are common to psychosis and trauma-exposed populations, and associated brain functions may be affected by trauma exposure in psychotic disorders. We aimed to identify the influence of trauma-exposure on brain activation and functional connectivity during a response inhibition task.

We used functional magnetic resonance imaging to examine brain function within regions-of-interest [left and right inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex, right supplementary motor area, right inferior parietal lobule and dorsal anterior cingulate cortex], during the performance of a Go/No-Go Flanker task, in 112 clinical cases with psychotic disorders and 53 healthy controls (HCs). Among the participants, 71 clinical cases and 21 HCs reported significant levels of childhood trauma exposure, while 41 clinical cases and 32 HCs did not.

In the absence of effects on response inhibition performance, childhood trauma exposure was associated with increased activation in the left IFG, and increased connectivity between the left IFG seed region and the cerebellum and calcarine sulcus, in both cases and healthy individuals. There was no main effect of psychosis, and no trauma-by-psychosis interaction for any other region-of-interest. Within the clinical sample, the effects of trauma-exposure on the left IFG activation were mediated by symptom severity.

Trauma-related increases in activation of the left IFG were not associated with performance differences, or dependent on clinical diagnostic status; increased IFG functionality may represent a compensatory (overactivation) mechanism required to exert adequate inhibitory control of the motor response.

Evidence regarding the association between cannabis use and depression remain conflicting, especially as studies have not typically adopted a longitudinal design with a follow-up period that was long enough to adequately cover the risk period for onset of depression.

Males from the Cambridge Study in Delinquent Development (CSDD) (N = 285) were assessed seven times from age 8 to 48 years to prospectively investigate the association between cannabis use and risk of major depressive disorder (MDD). A combination of multiple analyses (logistic regression, Cox regression, fixed-effects analysis) was employed to explore the strength and direction of effect within different developmental stages.

Multiple regression analyses revealed that early-onset cannabis use (before age 18) but not late-onset cannabis use (after age 27) was associated with a higher risk and shorter time until a subsequent MDD diagnosis. This effect was present in high-frequency [(odds ratio (OR) 8.83, 95% confidence interval (CI) 1.29–70.79]; [hazard ratio (HR) 8.69, 95% CI 2.07–36.52)] and low-frequency early-onset users (OR 2.41, 95% CI 1.22–4.76; HR 2.09, 95% CI 1.16–3.74). Effect of increased frequency of cannabis use on increased risk of subsequent MDD was observed only for use during adolescence (age 14–18) but not at later life stages, while controlling for observed and non-unobserved time-invariant factors. Conversely, MDD in adulthood (age 18–32) was linked to a reduction in subsequent cannabis use (age 32–48).

The present findings provide evidence implicating frequent cannabis use during adolescence as a risk factor for later life depression. Future studies should further examine causality of effects in larger samples.

The high cardiovascular (CV) morbidity and mortality reported for patients with psychiatric disorders may possibly be due to a poorer management of CV risk factors (CVRFs). However, these healthcare disparities remain poorly understood. In this paper, studies comparing the management of smoking, diabetes, hypertension and dyslipidaemia, in patients with and without depression, anxiety, schizophrenia, bipolar or personality disorder, were reviewed.

Prospective studies comparing rates of screening, diagnosis, treatment and control of CVRFs were searched in PubMed, Embase, PsychInfo, Scopus and Web of Science (inception to January 2017). The Meta-analysis of Observational Studies in Epidemiology (MOOSE) criteria were used. Studies were assessed for quality. Wherever possible, meta-analyses were conducted to summarize the findings.

Twenty studies, out of the 18 333 references initially identified, were included. Most studies were heterogeneous in design. Two areas permitted meta-analyses: the pooled odds ratio for quitting smoking for those with depression was 0.64 (0.49–0.80) p < 0.001; the pooled difference of glycated haemoglobin for patients with type 2 diabetes and depression was 0.18 (0.06–0.31) p = 0.005. Individual studies showed associations between: schizophrenia and lower probability of having smoking habit recorded; schizoid personality disorder and higher probability of remaining non-smokers after quitting; anxiety and poorer control of type I diabetes; depression, anxiety or schizophrenia and lower probability of having a diagnosis of hypertension; schizophrenia or bipolar disorder and lower use of antihypertensive and lipid-lowering drugs.

A proactive clinical management, together with further studies, are needed to reduce the CV morbidity and mortality of patients with psychiatric disorders.

Ethnic minority individuals have an increased risk of developing a psychotic disorder, particularly if they live in areas of ethnic segregation, or low own group ethnic density. The neurobiological mechanisms underlying this ethnic minority associated risk are unknown. We used functional MRI to investigate neural responses to faces of different ethnicity, in individuals of black ethnicity, and a control group of white British ethnicity individuals.

In total 20 individuals of black ethnicity, and 22 individuals of white British ethnicity underwent a 3T MRI scan while viewing faces of black and white ethnicity. Own group ethnic density was calculated from the 2011 census. Neighbourhood segregation was quantified using the Index of Dissimilarity method.

At the within-group level, both groups showed greater right amygdala activation to outgroup faces. Between groups, the black ethnicity group showed greater right amygdala activation to white faces, compared to the white ethnicity group. Within the black ethnicity group, individuals living in areas of lower own group ethnic density showed greater right amygdala reactivity to white faces (r = −0.61, p = 0.01).

This is the first time an increased amygdala response to white faces has been demonstrated in individuals of black ethnicity. In the black ethnicity group, correlations were observed between amygdala response and neighbourhood variables associated with increased psychosis risk. These results may have relevance for our understanding of the increased rates of paranoia and psychotic disorders in ethnic minority individuals.

Schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are developmental disorders with shared clinical characteristics such as cognitive impairments and impulsivity. Impulsivity is a core feature of ADHD and an important factor in aggression, violence, and substance use in schizophrenia. Based on the hypothesis that schizophrenia and ADHD represent a continuum of neurodevelopmental impairments, the aim was to identify overlapping and disease specific forms of impulsivity.

Adolescents between 12 and 17 years of age were assessed with the Schedule for Affective Disorders and Schizophrenia for School-aged Children – Present and Lifetime Version. Subjects with early-onset, first-episode schizophrenia spectrum disorders (EOS) (N = 29) or ADHD (N = 29) and healthy controls (N = 45) were compared on two performance measures (Information Sampling Task, Stop Signal Task) and a subjective personality trait measure of impulsivity (Barratt Impulsiveness Scale, Version 11 (BIS-11)).

Significantly increased reflection impulsivity was observed in ADHD but not in the EOS group. No significant response inhibition deficits (stop signal reaction time) were found in the two clinical groups. The ADHD and the EOS group showed significantly increased motor, attentional, and non-planning subtraits of impulsivity.

Impaired pre-decisional information gathering appeared to be specific for ADHD while the information gathering was not significantly reduced in subjects with EOS. Neither the ADHD nor EOS group showed impaired response inhibition but shared increased personality subtraits of attentional, non-planning, and motor impulsivity although the latter was significantly more pronounced in ADHD. These increased subtraits of impulsivity may reflect diagnostic non-specific neurodevelopmental impairments in ADHD and EOS in adolescence.

Cognitive reserve (CR) has been associated with better cognitive function and lower risk of depression in older people, yet it remains unclear whether CR moderates the association between mood and cognition. This study aimed to investigate whether a comprehensive indicator of CR, including education, occupation and engagement in cognitive and social activities, acts as a moderator of this association.

This was a cross-sectional study utilising baseline data from the Cognitive Function and Ageing Study II (CFAS II), a large population-based cohort of people aged 65+ in England. Complete data on the measures of CR, mood and cognition were available for 6565 dementia-free individuals. Linear regression models were used to investigate the potential modifying effect of CR on the association between cognition and mood with adjustment for age, sex and missing data.

Levels of CR did moderate the negative association between mood and cognition; the difference in cognition between those with and without a clinical level mood disorder was significantly smaller in the middle (−2.28; 95% confidence interval (CI) −3.65 to −0.90) and higher (−1.30; 95% CI −2.46 to −0.15) CR groups compared with the lower CR group (−4.01; 95% CI −5.53 to −2.49). The individual components of CR did not significantly moderate the negative association between mood and cognition.

These results demonstrate that CR, indexed by a composite score based on multiple indicators, can moderate the negative association between lowered mood and cognition, emphasising the importance of continuing to build CR across the lifespan in order to maintain cognitive health.

Previous studies have demonstrated that several major psychiatric disorders are influenced by shared genetic factors. This shared liability may influence clinical features of a given disorder (e.g. severity, age at onset). However, findings have largely been limited to European samples; little is known about the consistency of shared genetic liability across ethnicities.

The relationship between polygenic risk for several major psychiatric diagnoses and major depressive disorder (MDD) was examined in a sample of unrelated Han Chinese women. Polygenic risk scores (PRSs) were generated using European discovery samples and tested in the China, Oxford, and VCU Experimental Research on Genetic Epidemiology [CONVERGE (maximum N = 10 502)], a sample ascertained for recurrent MDD. Genetic correlations between discovery phenotypes and MDD were also assessed. In addition, within-case characteristics were examined.

European-based polygenic risk for several major psychiatric disorder phenotypes was significantly associated with the MDD case status in CONVERGE. Risk for clinically significant indicators (neuroticism and subjective well-being) was also associated with case–control status. The variance accounted for by PRS for both psychopathology and for well-being was similar to estimates reported for within-ethnicity comparisons in European samples. However, European-based PRS were largely unassociated with CONVERGE family history, clinical characteristics, or comorbidity.

The shared genetic liability across severe forms of psychopathology is largely consistent across European and Han Chinese ethnicities, with little attenuation of genetic signal relative to within-ethnicity analyses. The overall absence of associations between PRS for other disorders and within-MDD variation suggests that clinical characteristics of MDD may arise due to contributions from ethnicity-specific factors and/or pathoplasticity.

The postpartum period is well-known risk period for the first onset of autoimmune thyroid disorders (AITDs) as well as first onset of psychiatric disorders. These two disorders are some of the most prevalent medical conditions postpartum, often misdiagnosed and disabling if left untreated. Our study was designed to explore the possible bidirectional association between AITDs and psychiatric disorders during the postpartum period.

A population-based cohort study through linkage of Danish national registers, which comprised 312 779 women who gave birth to their first child during 1997–2010. We conducted Poisson regression analysis to estimate the incidence rate ratio (IRR) of psychiatric disorders among women with first-onset AITDs, the IRR of AITDs among women with first-onset psychiatric disorders as well as the overlap between these disorders using a comorbidity index.

Women with first-onset AITDs postpartum were more likely to have first-onset psychiatric disorders than women who did not have postpartum AITDs (IRR = 1.88, 95% confidence interval (CI): 1.25–2.81). Women with first-onset postpartum psychiatric disorders had a higher risk of AITDs than women with no psychiatric disorders (IRR = 2.16, 95% CI: 1.45–3.20). The comorbidity index 2 years after delivery was 2.26 (95% CI: 1.61–2.90), indicating a comorbidity between first-onset AITDs and psychiatric disorders.

First-onset AITDs and psychiatric disorders co-occur in the postpartum period, which has relevance to further studies on the etiologies of these disorders and why childbirth in particular triggers the onset.

The clinical care of psychiatric patients is often guided by perceptions of suicide risk. The aim of this study was to examine the methods and results of studies reporting high-risk models for inpatient suicide.

We conducted a registered meta-analysis according to PRISMA guidelines. We searched for relevant peer-reviewed cohort and controlled studies indexed in Medline, EMBASE and PsychINFO.

The pooled odds ratio (OR) among 18 studies reporting high-risk models for inpatient suicide was 7.1 [95% confidence interval (CI) 4.2–12.2]. Between-study heterogeneity in ORs was very high (range 0–94.8, first quartile 3.4, median 8.8, third quartile 26.1, prediction interval 0.80–63.1, I2 = 88.1%). The meta-analytically derived sensitivity was 53.1% (95% CI 38.2–67.5%, I2 = 95.9%) and specificity was 84.2% (95% CI 71.6–91.9%, I2 = 99.9%) with an associated meta-analytic area under the curve of 0.83. The positive predictive value of risk categorization among six cohort studies was 0.43% (95% CI 0.014–1.3%, I2 = 95.9%). A history of suicidal behavior and depressive symptoms or affective disorder was included in the majority of high-risk models.

Despite the strength of the pooled association between high-risk categorization and suicide, the very high degree of observed heterogeneity indicates uncertainty about our ability to meaningfully distinguish inpatients according to suicide risk. The limited sensitivity and low positive predictive value of risk categorization suggest that suicide risk models are not a suitable basis for clinical decisions in inpatient settings.

The pathophysiology of cognitive impairment in patients with the major depressive disorder (MDD) may involve neuroinflammation mediated by cytokines.

The aim of this study was to examine the serum interleukin-6 (IL-6) levels, sustained attention, and their association in patients with MDD.

Thirty patients with MDD and 30 healthy controls were enrolled in this case-control study. Sustained attention was measured using the Rapid Visual Information Processing (RVP) task in the Cambridge Neuropsychological Tests Automated Battery. The serum IL-6 levels of all subjects were assessed by sandwich enzyme-linked immunosorbent assays.

There were significant differences in the log10RVP total hits, log10RVP total misses, and log10RVP mean latency between patients with MDD and healthy controls (F = 6.04, p = 0.017; F = 19.77, p < 0.0001; F = 14.42, p < 0.0001, respectively). The serum levels of Log10IL-6 were significantly higher in patients with MDD than in healthy controls (F = 192.27, p < 0.0001). The log10IL-6 levels were also positively correlated with the log10RVP mean latency in patients with MDD (r = 0.45, p = 0.013). A further stepwise multivariate regression analysis indicated that the log10IL-6 levels were significantly associated with the log10RVP mean latency in patients with MDD (β = 0.31, t = 2.41, p = 0.025).

Our data suggested that increased IL-6 levels were associated with the psychopathology of MDD, and that abnormal IL-6 levels were implicated in the impairment of sustained attention in patients with MDD.

Research on post-traumatic stress disorder (PTSD) course finds a substantial proportion of cases remit within 6 months, a majority within 2 years, and a substantial minority persists for many years. Results are inconsistent about pre-trauma predictors.

The WHO World Mental Health surveys assessed lifetime DSM-IV PTSD presence-course after one randomly-selected trauma, allowing retrospective estimates of PTSD duration. Prior traumas, childhood adversities (CAs), and other lifetime DSM-IV mental disorders were examined as predictors using discrete-time person-month survival analysis among the 1575 respondents with lifetime PTSD.

20%, 27%, and 50% of cases recovered within 3, 6, and 24 months and 77% within 10 years (the longest duration allowing stable estimates). Time-related recall bias was found largely for recoveries after 24 months. Recovery was weakly related to most trauma types other than very low [odds-ratio (OR) 0.2–0.3] early-recovery (within 24 months) associated with purposefully injuring/torturing/killing and witnessing atrocities and very low later-recovery (25+ months) associated with being kidnapped. The significant ORs for prior traumas, CAs, and mental disorders were generally inconsistent between early- and later-recovery models. Cross-validated versions of final models nonetheless discriminated significantly between the 50% of respondents with highest and lowest predicted probabilities of both early-recovery (66–55% v. 43%) and later-recovery (75–68% v. 39%).

We found PTSD recovery trajectories similar to those in previous studies. The weak associations of pre-trauma factors with recovery, also consistent with previous studies, presumably are due to stronger influences of post-trauma factors.

Cognitive models postulate that negative-self-schemas (NSS) cause and maintain positive symptoms and that negative affect mediates this link. However, only few studies have tested the temporal mediation claim systematically using an appropriate design.

A longitudinal cohort design in an online community sample (N = 962) from Germany, Indonesia, and the USA was used. NSS, negative affect and positive symptoms were measured at four time-points (T0–T3) over a 1-year period. Cross-lagged panel and longitudinal mediation analyses with structural equation modeling were used to test the temporal mediation.

Independent cross-lagged panel models showed a significant unidirectional longitudinal path from NSS to positive symptoms (T2–T3, β = 0.18, p < 0.01) and bidirectional longitudinal associations from NSS to negative affect (T0–T1, γ = 0.14, p < 0.01) and vice versa (T0–T1, γ = 0.19, p < 0.01). There was also a significant indirect pathway from NSS at baseline via negative affect at T1 and T2 to positive symptoms at T3 (unstandardized indirect effect coefficient = 0.020, p < 0.05, BCa CI 0.004–0.035), indicating mediation.

Our findings support the postulated affective pathway from NSS to positive symptoms via negative affect. Specifically, our data indicate that NSS and negative affect influence each other and build up over the course of several months before leading on to positive symptoms. We conclude that interrupting this process by targeting NSS and negative affect early in the process could be a promising strategy to prevent the exacerbation of positive symptoms.

Previous studies have highlighted the role of the brain reward and cognitive control systems in the etiology of anorexia nervosa (AN). In an attempt to disentangle the relative contribution of these systems to the disorder, we used functional magnetic resonance imaging (fMRI) to investigate hemodynamic responses to reward-related stimuli presented both subliminally and supraliminally in acutely underweight AN patients and age-matched healthy controls (HC).

fMRI data were collected from a total of 35 AN patients and 35 HC, while they passively viewed subliminally and supraliminally presented streams of food, positive social, and neutral stimuli. Activation patterns of the group×stimulation condition×stimulus type interaction were interrogated to investigate potential group differences in processing different stimulus types under the two stimulation conditions. Moreover, changes in functional connectivity were investigated using generalized psychophysiological interaction analysis.

AN patients showed a generally increased response to supraliminally presented stimuli in the inferior frontal junction (IFJ), but no alterations within the reward system. Increased activation during supraliminal stimulation with food stimuli was observed in the AN group in visual regions including superior occipital gyrus and the fusiform gyrus/parahippocampal gyrus. No group difference was found with respect to the subliminal stimulation condition and functional connectivity.

Increased IFJ activation in AN during supraliminal stimulation may indicate hyperactive cognitive control, which resonates with clinical presentation of excessive self-control in AN patients. Increased activation to food stimuli in visual regions may be interpreted in light of an attentional food bias in AN.

Attenuated inhibitory control is one of the most robust findings in the neuropsychology of attention-deficit/hyperactivity disorder (ADHD). However, it is unclear whether this represents a deficit in outright stopping (reactive inhibition), whether it relates to a deficit in anticipatory response slowing (proactive inhibition), or both. In addition, children with other development disorders, such as autism spectrum disorder (ASD), often have symptoms of inattention, impulsivity, and hyperactivity similar to children with ADHD. These may relate to similar underlying changes in inhibitory processing.

In this study, we used a modified stop-signal task to dissociate reactive and proactive inhibition. We included not only children with ADHD, but also children primarily diagnosed with an ASD and high parent-rated levels of ADHD symptoms.

We replicated the well-documented finding of attenuated reactive inhibition in children with ADHD. In addition, we found a similar deficit in children with ASD and a similar level of ADHD symptoms. In contrast, we found no evidence for deficits in proactive inhibition in either clinical group.

These findings re-emphasize the role of reactive inhibition in children with ADHD and ADHD symptoms. Moreover, our findings stress the importance of a trans-diagnostic approach to the relationship between behavior and neuropsychology.

Studying secular trends in the exposure to risk and protective factors of depression and whether these trends are associated with secular trends in the prevalence of depression is important to estimate future healthcare demands and to identify targets for prevention.

Three birth cohorts of 55–64-year olds from the population-based Longitudinal Aging Study Amsterdam were examined using identical methods in 1992 (n = 944), 2002 (n = 964) and 2012 (n = 957). A two-stage screening design was used to identify subthreshold depression (SUBD) and major depressive disorder (MDD). Multinomial logistic regression analyses were used to identify secular trends in depression prevalence and to identify factors from the biopsychosocial domains of functioning that were associated with these trends.

Compared with 1992, MDD became more prevalent in 2002 (OR 1.90, 95% CI 1.10–3.28, p = 0.022) and 2012 (OR 1.80, 95% CI 1.03–3.14, p = 0.039). This was largely attributable to an increase in the prevalence of chronic diseases and functional limitations. Socioeconomic and psychosocial improvements, including an increase in labor market participation, social support and mastery, hampered MDD rates to rise more and were also associated with a 32% decline of SUBD-rates in 2012 as compared with 2002 (OR 0.68, 95% CI 0.48–0.96, p = 0.03).

Among late middle-aged adults, there is a substantial net increase of MDD, which is associated with deteriorating physical health. If morbidity and disability continue to increase, a further expansion of MDD rates may be expected. Improving socioeconomic and psychosocial conditions may benefit public health, as these factors were protective against a higher prevalence of both MDD and SUBD.

Previous research has shown relatively diminished medial prefrontal cortex activation and heightened psychophysiological responses during the recollection of personal events in post-traumatic stress disorder (PTSD), but the origin of these abnormalities is unknown. Twin studies provide the opportunity to determine whether such abnormalities reflect familial vulnerabilities, result from trauma exposure, or are acquired characteristics of PTSD.

In this case–control twin study, 26 male identical twin pairs (12 PTSD; 14 non-PTSD) discordant for PTSD and combat exposure recalled and imagined trauma-unrelated stressful and neutral life events using a standard script-driven imagery paradigm during functional magnetic resonance imaging and concurrent skin conductance measurement.

Diminished activation in the medial prefrontal cortex during Stressful v. Neutral script-driven imagery was observed in the individuals with PTSD, relative to other groups.

Diminished medial prefrontal cortex activation during Stressful v. Neutral script-driven imagery may be an acquired characteristic of PTSD. If replicated, this finding could be used prospectively to inform diagnosis and the assessment of treatment response.

The number of people entering specialist drug treatment for cannabis problems has increased considerably in recent years. The reasons for this are unclear, but rising cannabis potency could be a contributing factor.

Cannabis potency data were obtained from an ongoing monitoring programme in the Netherlands. We analysed concentrations of δ-9-tetrahydrocannabinol (THC) from the most popular variety of domestic herbal cannabis sold in each retail outlet (2000–2015). Mixed effects linear regression models examined time-dependent associations between THC and first-time cannabis admissions to specialist drug treatment. Candidate time lags were 0–10 years, based on normative European drug treatment data.

THC increased from a mean (95% CI) of 8.62 (7.97–9.27) to 20.38 (19.09–21.67) from 2000 to 2004 and then decreased to 15.31 (14.24–16.38) in 2015. First-time cannabis admissions (per 100 000 inhabitants) rose from 7.08 to 26.36 from 2000 to 2010, and then decreased to 19.82 in 2015. THC was positively associated with treatment entry at lags of 0–9 years, with the strongest association at 5 years, b = 0.370 (0.317–0.424), p < 0.0001. After adjusting for age, sex and non-cannabis drug treatment admissions, these positive associations were attenuated but remained statistically significant at lags of 5–7 years and were again strongest at 5 years, b = 0.082 (0.052–0.111), p < 0.0001.

In this 16-year observational study, we found positive time-dependent associations between changes in cannabis potency and first-time cannabis admissions to drug treatment. These associations are biologically plausible, but their strength after adjustment suggests that other factors are also important.

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.

Worrying has been suggested to prevent emotional and elaborative processing of fears. In cognitive-behavioral therapy (CBT), generalized anxiety disorder (GAD) patients are exposed to their fears during the method of directed threat imagery by inducing emotional reactivity. However, studies investigating neural correlates of directed threat imagery and emotional reactivity in GAD patients are lacking. The present functional magnetic resonance imaging (fMRI) study aimed at delineating neural correlates of directed threat imagery in GAD patients.

Nineteen GAD patients and 19 healthy controls (HC) were exposed to narrative scripts of either disorder-related or neutral content and were encouraged to imagine it as vividly as possible.

Rating results showed that GAD patients experienced disorder-related scripts as more anxiety inducing and arousing than HC. These results were also reflected in fMRI data: Disorder-related v. neutral scripts elicited elevated activity in the amygdala, dorsomedial prefrontal cortex, ventrolateral prefrontal cortex and the thalamus as well as reduced activity in the ventromedial prefrontal cortex/subgenual anterior cingulate cortex in GAD patients relative to HC.

The present study presents the first behavioral and neural evidence for emotional reactivity during directed threat imagery in GAD. The brain activity pattern suggests an involvement of a fear processing network as a neural correlate of initial exposure during directed imagery in CBT in GAD.