Major depression (MD) is a risk factor for cardiovascular disease. Reduced heart rate variability (HRV) has been observed in MD. Given the predictive value of HRV for cardiovascular health, reduced HRV might be one physiological factor that mediates this association.

The purpose of this study was to provide up-to-date random-effects meta-analyses of studies which compare resting-state measures of HRV between unmedicated adults with MD and controls. Database search considered English and German literature to July 2018.

A total of 21 studies including 2250 patients and 1982 controls were extracted. Significant differences between patients and controls were found for (i) frequency domains such as HF-HRV [Hedges' g = −0.318; 95% CI (−0.388 to −0.247)], LF-HRV (Hedges' g = −0.195; 95% CI (−0.332 to −0.059)], LF/HF-HRV (Hedges' g = 0.195; 95% CI (0.086–0.303)] and VLF-HRV (Hedges' g = −0.096; 95% CI (−0.179 to −0.013)), and for (ii) time-domains such as IBI (Hedges' g = −0.163; 95% CI (−0.304 to −0.022)], RMSSD (Hedges' g = −0.462; 95% CI (−0.612 to −0.312)] and SDNN (Hedges' g = −0.266; 95% CI (−0.431 to −0.100)].

Our findings demonstrate that all HRV-measures were lower in MD than in healthy controls and thus strengthens evidence for lower HRV as a potential cardiovascular risk factor in these patients.

Peripheral low-grade inflammation in depression is increasingly seen as a therapeutic target. We aimed to establish the prevalence of low-grade inflammation in depression, using different C-reactive protein (CRP) levels, through a systematic literature review and meta-analysis.

We searched the PubMed database from its inception to July 2018, and selected studies that assessed depression using a validated tool/scale, and allowed the calculation of the proportion of patients with low-grade inflammation (CRP >3 mg/L) or elevated CRP (>1 mg/L).

After quality assessment, 37 studies comprising 13 541 depressed patients and 155 728 controls were included. Based on the meta-analysis of 30 studies, the prevalence of low-grade inflammation (CRP >3 mg/L) in depression was 27% (95% CI 21–34%); this prevalence was not associated with sample source (inpatient, outpatient or population-based), antidepressant treatment, participant age, BMI or ethnicity. Based on the meta-analysis of 17 studies of depression and matched healthy controls, the odds ratio for low-grade inflammation in depression was 1.46 (95% CI 1.22–1.75). The prevalence of elevated CRP (>1 mg/L) in depression was 58% (95% CI 47–69%), and the meta-analytic odds ratio for elevated CRP in depression compared with controls was 1.47 (95% CI 1.18–1.82).

About a quarter of patients with depression show evidence of low-grade inflammation, and over half of patients show mildly elevated CRP levels. There are significant differences in the prevalence of low-grade inflammation between patients and matched healthy controls. These findings suggest that inflammation could be relevant to a large number of patients with depression.

Schizophrenia is associated with significant cognitive impairment. However, the pathophysiological mechanisms underlying cognitive dysfunction in schizophrenia remain unclear. Brain-derived neurotrophic factor (BDNF) and C-reactive protein (CRP) are among the most commonly investigated peripheral markers of cognition in schizophrenia.

A systematic review in PubMed and Scopus databases was performed until 31 January 2019 to assess the relationship between cognitive impairment, CRP and BDNF levels in schizophrenia. A random-effects meta-analysis was conducted.

Current meta-analysis included 21 studies including 2449 patients with schizophrenia-spectrum disorders. Overall, both BDNF [r = 0.12, confidence interval (CI) 0.04–0.19] and CRP (r = −0.13, CI 0.08–0.18) levels were very modestly but significantly related to cognitive functioning in schizophrenia (r = 0.12, CI 0.04–0.19). In meta-analyses of cognitive domains, BDNF levels were significantly associated with verbal memory (r = 0.16, CI 0.09–0.23), working memory (r = 0.14, CI 0.06–0.22), processing speed (r = 0.18, CI 0.10–0.26) and verbal fluency (r = 0.09, CI 0–0.18) performances. Elevated CRP levels were related to all cognitive domains (r = −0.09 to −0.13) except for fluency. Subgroup analyses suggested that the relationship between cognitive and BDNF levels were more pronounced in chronic samples.

Current findings suggest that cognitive impairment in schizophrenia is significantly related to elevated CRP and reduced BDNF levels in schizophrenia, particularly in chronic samples. However, small effect sizes of these correlations suggest that inflammation and decreased BDNF levels do not play a major role in cognitive dysfunction in most patients with schizophrenia. Further studies are needed to investigate the potential intermediating and confounding factors which can influence the level of relationship between inflammation, neurotrophic factors and cognition in schizophrenia.

Few studies have investigated the patterns of posttraumatic stress disorder (PTSD) symptom change in prolonged exposure (PE) therapy. In this study, we aimed to understand the patterns of PTSD symptom change in both PE and present-centered therapy (PCT).

Participants were active duty military personnel (N = 326, 89.3% male, 61.2% white, 32.5 years old) randomized to spaced-PE (S-PE; 10 sessions over 8 weeks), PCT (10 sessions over 8 weeks), or massed-PE (M-PE; 10 sessions over 2 weeks). Using latent profile analysis, we determined the optimal number of PTSD symptom change classes over time and analyzed whether baseline and follow-up variables were associated with class membership.

Five classes, namely rapid responder (7–17%), steep linear responder (14–22%), gradual responder (30–34%), non-responder (27–33%), and symptom exacerbation (7–13%) classes, characterized each treatment. No baseline clinical characteristics predicted class membership for S-PE and M-PE; in PCT, more negative baseline trauma cognitions predicted membership in the non-responder v. gradual responder class. Class membership was robustly associated with PTSD, trauma cognitions, and depression up to 6 months after treatment for both S-PE and M-PE but not for PCT.

Distinct profiles of treatment response emerged that were similar across interventions. By and large, no baseline variables predicted responder class. Responder status was a strong predictor of future symptom severity for PE, whereas response to PCT was not as strongly associated with future symptoms.

This study aim to derive and validate a simple and well-performing risk calculator (RC) for predicting psychosis in individual patients at clinical high risk (CHR).

From the ongoing ShangHai-At-Risk-for-Psychosis (SHARP) program, 417 CHR cases were identified based on the Structured Interview for Prodromal Symptoms (SIPS), of whom 349 had at least 1-year follow-up assessment. Of these 349 cases, 83 converted to psychosis. Logistic regression was used to build a multivariate model to predict conversion. The area under the receiver operating characteristic (ROC) curve (AUC) was used to test the effectiveness of the SIPS-RC. Second, an independent sample of 100 CHR subjects was recruited based on an identical baseline and follow-up procedures to validate the performance of the SIPS-RC.

Four predictors (each based on a subset of SIPS-based items) were used to construct the SIPS-RC: (1) functional decline; (2) positive symptoms (unusual thoughts, suspiciousness); (3) negative symptoms (social anhedonia, expression of emotion, ideational richness); and (4) general symptoms (dysphoric mood). The SIPS-RC showed moderate discrimination of subsequent transition to psychosis with an AUC of 0.744 (p < 0.001). A risk estimate of 25% or higher had around 75% accuracy for predicting psychosis. The personalized risk generated by the SIPS-RC provided a solid estimate of conversion outcomes in the independent validation sample, with an AUC of 0.804 [95% confidence interval (CI) 0.662–0.951].

The SIPS-RC, which is simple and easy to use, can perform in the same manner as the NAPLS-2 RC in the Chinese clinical population. Such a tool may be used by clinicians to counsel appropriately their patients about clinical monitor v. potential treatment options.

Excessive worry is a defining feature of generalized anxiety disorder and is present in a wide range of other psychiatric conditions. Therefore, individualized predictions of worry propensity could be highly relevant in clinical practice, with respect to the assessment of worry symptom severity at the individual level.

We applied a multivariate machine learning approach to predict dispositional worry based on microstructural integrity of white matter (WM) tracts.

We demonstrated that the machine learning model was able to decode individual dispositional worry scores from microstructural properties in widely distributed WM tracts (mean absolute error = 10.46, p < 0.001; root mean squared error = 12.82, p < 0.001; prediction R2 = 0.17, p < 0.001). WM tracts that contributed to worry prediction included the posterior limb of internal capsule, anterior corona radiate, and cerebral peduncle, as well as the corticolimbic pathways (e.g. uncinate fasciculus, cingulum, and fornix) already known to be critical for emotion processing and regulation.

The current work thus elucidates potential neuromarkers for clinical assessment of worry symptoms across a wide range of psychiatric disorders. In addition, the identification of widely distributed pathways underlying worry propensity serves to better improve the understanding of the neurobiological mechanisms associated with worry.

Although prior research has shown that cognitive training may improve cognition for schizophrenia patients, it is currently unclear which domains of cognition should be targeted in training. One suggestion is to target low- or mid-level cognitive processes. In particular, working memory (WM) and processing speed (PS) have been named as two key areas of impairment in schizophrenia, and two domains of cognition that are linked to higher-order cognition and daily functioning. This study aimed to investigate the near-transfer (transfer of gains to related contexts), far-transfer (transfer of gains to unrelated contexts), and real-world gains associated with WM and PS training in schizophrenia.

Eighty-three participants with schizophrenia were recruited and randomly assigned to computerized WM training, PS training, or a no-training control group. Outcome measures included WM, PS, fluid intelligence, executive functioning, social cognition, and daily functioning and symptoms.

PS training led to significant gains in untrained PS tasks, as well as gains in far-transfer tasks that required speed of processing. WM training did not lead to gains in untrained WM tasks and showed inconsistent effects on some far-transfer tasks.

These results suggest some benefit of domain-specific cognitive training, specifically PS training, in schizophrenia. Far-transfer of gains to other cognitive domains and to real-world functioning may not occur after targeted WM or PS training, though non-specific effects (e.g. through behavioral activation, increased motivation) may lead to improvements in some tasks. Future studies should continue to investigate the mechanisms by which cognitive training may enhance cognition and functioning in schizophrenia.

Previous studies on reporting bias generally examined whether trials were published in stand-alone publications. In this study, we investigated whether pooled-trials publications constitute a specific form of reporting bias. We assessed whether negative trials were more likely to be exclusively published in pooled-trials publications than positive trials and examined the research questions, individual trial results, and conclusions presented in these articles.

Data from a cohort of 105 randomized controlled trials of 16 antidepressants were extracted from earlier publications and the corresponding Food and Drug Administration (FDA) reviews. A systematic literature search was conducted to identify pooled-trials publications.

We found 107 pooled-trials publications that reported results of 23 (72%) of 32 trials not published in stand-alone publications. Only two (3.8%) of 54 positive trials were published exclusively in pooled-trials publications, compared with 21 (41.1%) of 51 negative trials (p < 0.001). Thirteen (12%) of 107 publications had as primary aim to present data on the trial's primary research question (drug efficacy compared with placebo). Only four of these publications, reporting on five (22%) trials, presented individual efficacy data for the primary research question. Additionally, only five (5%) of 107 pooled-trials publications had a negative conclusion.

Compared with positive trials, negative trials of antidepressants for depression were much more likely to be reported exclusively in pooled-trials publications. Pooled-trials publications flood the evidence base with often-redundant articles that, instead of addressing the original primary research question, present (positive) results on secondary questions. Therefore, pooled-trials publications distort the apparent risk–benefit profile of antidepressants.

Emerging adulthood is a peak period of risk for alcohol and illicit drug use. Recent advances in psychiatric genetics suggest that the co-occurrence of substance use and psychopathology arises, in part, from a shared genetic etiology. We sought to extend this research by investigating the influence of genetic risk for schizophrenia on trajectories of four substance use behaviors as they occurred across emerging adulthood.

Young adult participants of non-Hispanic European descent provided DNA samples and completed daily reports of substance use for 1 month per year across 4 years (N = 30 085 observations of N = 342 participants). A schizophrenia polygenic score was included in two-level hierarchical linear models designed to test associations between genetic risk for schizophrenia, participant age, and four substance use phenotypes.

Participants with a greater schizophrenia polygenic score experienced greater age-related increases in the likelihood of using substances across emerging adulthood (p < 0.005). Additionally, our results suggest that the polygenic score was positively associated with participants’ overall likelihood to engage in illicit drug use but not alcohol-related substance use.

This study used a novel combination of polygenic prediction and intensive longitudinal methods to characterize the influence of genetic risk for schizophrenia on patterns of age-related change in substance use across emerging adulthood. Results suggest that genetic risk for schizophrenia has developmentally specific effects on substance use behaviors in a non-clinical population of young adults.

In a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors.

In a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models.

A lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (β = −0.09, t = −3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (β = 0.09, t = 3.04, p = 0.002).

In this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD.

The field of psychiatry would benefit significantly from developing objective biomarkers that could facilitate the early identification of heterogeneous subtypes of illness. Critically, although machine learning pattern recognition methods have been applied recently to predict many psychiatric disorders, these techniques have not been utilized to predict subtypes of posttraumatic stress disorder (PTSD), including the dissociative subtype of PTSD (PTSD + DS).

Using Multiclass Gaussian Process Classification within PRoNTo, we examined the classification accuracy of: (i) the mean amplitude of low-frequency fluctuations (mALFF; reflecting spontaneous neural activity during rest); and (ii) seed-based amygdala complex functional connectivity within 181 participants [PTSD (n = 81); PTSD + DS (n = 49); and age-matched healthy trauma-unexposed controls (n = 51)]. We also computed mass-univariate analyses in order to observe regional group differences [false-discovery-rate (FDR)-cluster corrected p < 0.05, k = 20].

We found that extracted features could predict accurately the classification of PTSD, PTSD + DS, and healthy controls, using both resting-state mALFF (91.63% balanced accuracy, p < 0.001) and amygdala complex connectivity maps (85.00% balanced accuracy, p < 0.001). These results were replicated using independent machine learning algorithms/cross-validation procedures. Moreover, areas weighted as being most important for group classification also displayed significant group differences at the univariate level. Here, whereas the PTSD + DS group displayed increased activation within emotion regulation regions, the PTSD group showed increased activation within the amygdala, globus pallidus, and motor/somatosensory regions.

The current study has significant implications for advancing machine learning applications within the field of psychiatry, as well as for developing objective biomarkers indicative of diagnostic heterogeneity.

Dialectical behaviour therapy (DBT) and mentalisation-based therapy (MBT) are both widely used evidence-based treatments for borderline personality disorder (BPD), yet a head-to-head comparison of outcomes has never been conducted. The present study therefore aimed to compare the clinical outcomes of DBT v. MBT in patients with BPD.

A non-randomised comparison of clinical outcomes in N = 90 patients with BPD receiving either DBT or MBT over a 12-month period.

After adjusting for potentially confounding differences between participants, participants receiving DBT reported a significantly steeper decline over time in incidents of self-harm (adjusted IRR = 0.93, 95% CI 0.87–0.99, p = 0.02) and in emotional dysregulation (adjusted β = −1.94, 95% CI −3.37 to −0.51, p < 0.01) than participants receiving MBT. Differences in treatment dropout and use of crisis services were no longer significant after adjusting for confounding, and there were no significant differences in BPD symptoms or interpersonal problems.

Within this sample of people using specialist personality disorder treatment services, reductions in self-harm and improvements in emotional regulation at 12 months were greater amongst those receiving DBT than amongst those receiving MBT. Experimental studies assessing outcomes beyond 12 months are needed to examine whether these findings represent differences in the clinical effectiveness of these therapies.

Borderline personality disorder (BPD) is characterized by a heterogeneous clinical phenotype that emerges from interactions among genetic, biological, neurodevelopmental, and psychosocial factors. In the present family study, we evaluated the familial aggregation of key clinical, personality, and neurodevelopmental phenotypes in probands with BPD (n = 103), first-degree biological relatives (n = 74; 43% without a history of psychiatric disorder), and non-psychiatric controls (n = 99).

Participants were assessed on DSM-IV psychiatric diagnoses, symptom dimensions of emotion dysregulation and impulsivity, ‘big five’ personality traits, and neurodevelopmental characteristics, as part of a larger family study on neurocognitive, biological, and genetic markers in BPD.

The most common psychiatric diagnoses in probands and relatives were major depression, substance use disorders, post-traumatic stress disorder, anxiety disorders, and avoidant personality disorder. There was evidence of familial aggregation for specific dimensions of impulsivity and emotion dysregulation, and the big five traits neuroticism and conscientiousness. Both probands and relatives reported an elevated neurodevelopmental history of attentional and behavioral difficulties.

These results support the validity of negative affectivity- and impulse-spectrum phenotypes associated with BPD and its familial risk. Further research is needed to investigate the aggregation of neurocognitive, neural and genetic factors in families with BPD and their associations with core phenotypes underlying the disorder.

The prevalence of sleep problems among pregnant women is over 50%, and daytime sleepiness is among the most common sleep problems. Previous studies have associated antenatal sleep problems with adverse maternal health and neonatal outcomes, but the consequences of antenatal sleep problems and particularly daytime sleepiness on child psychological development have not been assessed prospectively.

In this prospective cohort study including 111 mother-child dyads, we examined the associations of maternal daytime sleepiness during pregnancy, assessed at 17 and 28 weeks of gestation using the Epworth Sleepiness Scale, with child neuropsychiatric problems and neuropsychological development, assessed with mother-rated questionnaires and individually administered neuropsychological tests, at child age 2.6–5.7 years (mean = 4.3 years).

Independently of sociodemographic and perinatal covariates and maternal depressive and anxiety symptoms during and/or after pregnancy, maternal antenatal daytime sleepiness was associated with increased total [unstandardized regression coefficient (B) = 0.25 standard deviation (s.d.) units; 95% confidence interval (CI) 0.01–0.48] and internalizing (B = 0.25 s.d.s: 95% CI 0.01–0.49) psychiatric problems and ADHD symptoms (B = 0.27 s.d.s: 95% CI 0.04–0.50) in children, and with poorer executive function, particularly in the areas of attention, working memory and inhibitory control (B = −0.39 s.d.s: 95% CI −0.69 to −0.10).

Maternal antenatal daytime sleepiness carries adverse consequences for offspring psychological development. The assessment of sleep problems may be an important addition to standard antenatal care.

Discrepancies between population-based estimates of the incidence of psychotic disorder and the treated incidence reported by early psychosis intervention (EPI) programs suggest additional cases may be receiving services elsewhere in the health system. Our objective was to estimate the incidence of non-affective psychotic disorder in the catchment area of an EPI program, and compare this to EPI-treated incidence estimates.

We constructed a retrospective cohort (1997–2015) of incident cases of non-affective psychosis aged 16–50 years in an EPI program catchment using population-based linked health administrative data. Cases were identified by either one hospitalization or two outpatient physician billings within a 12-month period with a diagnosis of non-affective psychosis. We estimated the cumulative incidence and EPI-treated incidence of non-affective psychosis using denominator data from the census. We also estimated the incidence of first-episode psychosis (people who would meet the case definition for an EPI program) using a novel approach.

Our case definition identified 3245 cases of incident non-affective psychosis over the 17-year period. We estimate that the incidence of first-episode non-affective psychosis in the program catchment area is 33.3 per 100 000 per year (95% CI 31.4–35.1), which is more than twice as high as the EPI-treated incidence of 18.8 per 100 000 per year (95% CI 17.4–20.3).

Case ascertainment strategies limited to specialized psychiatric services may substantially underestimate the incidence of non-affective psychotic disorders, relative to population-based estimates. Accurate information on the epidemiology of first-episode psychosis will enable us to more effectively resource EPI services and evaluate their coverage.

Neuropsychological investigations can help untangle the aetiological and phenomenological heterogeneity of schizophrenia but have scarcely been employed in the context of treatment-resistant (TR) schizophrenia. No population-based study has examined neuropsychological function in the first-episode of TR psychosis.

We report baseline neuropsychological findings from a longitudinal, population-based study of first-episode psychosis, which followed up cases from index admission to 10 years. At the 10-year follow up patients were classified as treatment responsive or TR after reconstructing their entire case histories. Of 145 cases with neuropsychological data at baseline, 113 were classified as treatment responsive, and 32 as TR at the 10-year follow-up.

Compared with 257 community controls, both case groups showed baseline deficits in three composite neuropsychological scores, derived from principal component analysis: verbal intelligence and fluency, visuospatial ability and executive function, and verbal memory and learning (p values⩽0.001). Compared with treatment responders, TR cases showed deficits in verbal intelligence and fluency, both in the extended psychosis sample (t = −2.32; p = 0.022) and in the schizophrenia diagnostic subgroup (t = −2.49; p = 0.017). Similar relative deficits in the TR cases emerged in sub-/sensitivity analyses excluding patients with delayed-onset treatment resistance (p values<0.01–0.001) and those born outside the UK (p values<0.05).

Verbal intelligence and fluency are impaired in patients with TR psychosis compared with those who respond to treatment. This differential is already detectable – at a group level – at the first illness episode, supporting the conceptualisation of TR psychosis as a severe, pathogenically distinct variant, embedded in aberrant neurodevelopmental processes.