It has been proposed that vascular disease is the mechanism linking depression and cognition, but prospective studies have not supported this hypothesis. This study aims to investigate the inter-relationships between depressive symptoms, cognition and cerebrovascular disease using a well-characterised prospective cohort.

Data came from waves 1 (2005–2007) and 2 (2007–2009) of the Sydney Memory and Ageing Study (n = 462; mean age = 78.3 years).

At wave 1, there was an association between depressive symptoms and white matter hyperintensity (WMH) volume [b = 0.016, t(414) = 2.34, p = 0.020]. Both depressive symptoms [b = −0.058, t(413) = −2.64, p = 0.009] and WMH volume [b = −0.011, t(413) = −3.77, p < 0.001], but not stroke/transient ischaemic attack (TIA) [b = −0.328, t(413) = −1.90, p = 0.058], were independently associated with lower cognition. Prospectively, cerebrovascular disease was not found to predict increasing depressive symptoms [stroke/TIA: b = −0.349, t(374.7) = −0.76, p = 0.448; WMH volume: b = 0.007, t(376.3) = 0.875, p = 0.382]. Depressive symptoms predicted increasing WMH severity [b = 0.012, t(265.9) = −3.291, p = 0.001], but not incident stroke/TIA (odds ratio = 0.995; CI 0.949–1.043; p = 0.820). When examined in separate models, depressive symptoms [b = −0.027, t(373.5) = −2.16, p = 0.032] and a history of stroke/TIA [b = −0.460, t(361.2) = −4.45, p < 0.001], but not WMH volume [b = 0.001, t(362.3) = −0.520, p = 0.603], predicted declines in cognition. When investigated in a combined model, a history of stroke/TIA remained a predictor of cognitive decline [b = −0.443, t(360.6) = −4.28, p < 0.001], whilst depressive symptoms did not [b = −0.012, t(359.7) = −0.96, p = 0.336].

This study is contrasted with previous prospective studies which indicate that depressive symptoms predict cognitive decline independently of vascular disease. Future research should focus on further exploring the vascular mechanisms underpinning the relationship between depressive symptoms and cognition.

Depression is strongly associated with chronic disease; yet, the direction of this relationship is poorly understood. Allostatic load (AL) provides a framework for elucidating depression-disease pathways. We aimed to investigate bidirectional, longitudinal associations of baseline depressive symptoms or AL with 5-year AL or depressive symptoms, respectively.

Data were from baseline, 2-year, and 5-year visits of 620 adults (45–75 years) enrolled in the Boston Puerto Rican Health Study. The Center for Epidemiology Studies Depression (CES-D) scale (0–60) captured depressive symptoms, which were categorized at baseline as low (<8), subthreshold (8–15), or depression-likely (⩾16) symptoms. AL was calculated from 11 parameters of biological functioning, representing five physiological systems. Baseline AL scores were categorized by the number of dysregulated parameters: low (0–2), moderate (3–5), or high (⩾6) AL. Multivariable, multilevel random intercept and slope linear regression models were used to examine associations between 3-category baseline CES-D score and 5-year continuous AL score, and between baseline 3-category AL and 5-year continuous CES-D score.

Baseline subthreshold depressive symptoms [(mean (95% CI)): 4.8 (4.5–5.2)], but not depression-likely symptoms [4.5 (4.2–4.9)], was significantly associated with higher 5-year AL scores, compared to low depressive symptoms [4.3 (3.9–4.7)]. Baseline high AL [19.4 (17.6–21.2)], but not low AL [18.5 (16.5–20.6)], was significantly associated with higher 5-year CES-D score, compared to baseline moderate AL [16.9 (15.3–18.5)].

Depressive symptoms and AL had a bi-directional relationship over time, indicating a nuanced pathway linking depression with chronic diseases among a minority population.

Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness.

A total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects.

Disease state (pFWE < 0.042) and number of hospitalizations (pFWE< 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF.

Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.

Attention deficit hyperactivity disorder (ADHD) is frequently associated with poorer reading ability; however, the specific neuropsychological domains linking this co-occurrence remain unclear. This study evaluates information-processing characteristics as possible neuropsychological links between ADHD symptoms and RA in a community-based sample of children and early adolescents with normal IQ (⩾70).

The participants (n = 1857, aged 6–15 years, 47% female) were evaluated for reading ability (reading single words aloud) and information processing [stimulus discriminability in the two-choice reaction-time task estimated using diffusion models]. ADHD symptoms were ascertained through informant (parent) report using the Development and Well-Being Assessment (DAWBA). Verbal working memory (VWM; digit span backwards), visuospatial working memory (VSWM, Corsi Blocks backwards), sex, socioeconomic status, and IQ were included as covariates.

In a moderated mediation model, stimulus discriminability mediated the effect of ADHD on reading ability. This indirect effect was moderated by age such that a larger effect was seen among younger children.

The findings support the hypothesis that ADHD and reading ability are linked among young children via a neuropsychological deficit related to stimulus discriminability. Early interventions targeting stimulus discriminability might improve symptoms of inattention/hyperactivity and reading ability.

Cognitive and motor dysfunction are hallmark features of the psychosis continuum, and have been detected during late childhood and adolescence in youth who report psychotic experiences (PE). However, previous investigations have not explored infancy and early childhood development. It remains unclear whether such deficits emerge much earlier in life, and whether they are associated with psychotic, specifically hallucinatory, experiences (HE).

This study included data from Gen2 participants of The Raine Study (n = 1101), a population-based longitudinal cohort study in Western Australia. Five areas of childhood development comprising: communication; fine motor; gross motor; adaptive (problem-solving); and personal-social skills, were assessed serially at ages 1, 2 and 3 years. Information on HE, depression and anxiety at ages 10, 14 and 17 years was obtained. HE were further subdivided into those with transient or recurrent experiences. Mixed effects logistic regression models and cumulative risk analyses based on multiple domain delays were performed.

Early poorer development in multiple areas was noted from ages 1, 2 and 3 years among youth who reported HE. Early developmental delays significantly increased the risk for later HE. This association was particularly marked in the recurrent HE group, with over 40% having early developmental delays in multiple domains. There was no significant association between early childhood development and later anxiety/depression apart from lower gross motor scores at age 3.

The findings suggest that early pan-developmental deficits are associated with later HE, with the effect strongest for young people who report recurrent HE throughout childhood and adolescence.

Major depression (MD) is often characterised as a categorical disorder; however, observational studies comparing sub-threshold and clinical depression suggest MD is continuous. Many of these studies do not explore the full continuum and are yet to consider genetics as a risk factor. This study sought to understand if polygenic risk for MD could provide insight into the continuous nature of depression.

Factor analysis on symptom-level data from the UK Biobank (N = 148 957) was used to derive continuous depression phenotypes which were tested for association with polygenic risk scores (PRS) for a categorical definition of MD (N = 119 692).

Confirmatory factor analysis showed a five-factor hierarchical model, incorporating 15 of the original 18 items taken from the PHQ-9, GAD-7 and subjective well-being questionnaires, produced good fit to the observed covariance matrix (CFI = 0.992, TLI = 0.99, RMSEA = 0.038, SRMR = 0.031). MD PRS associated with each factor score (standardised β range: 0.057–0.064) and the association remained when the sample was stratified into case- and control-only subsets. The case-only subset had an increased association compared to controls for all factors, shown via a significant interaction between lifetime MD diagnosis and MD PRS (p value range: 2.23 × 10−3–3.94 × 10−7).

An association between MD PRS and a continuous phenotype of depressive symptoms in case- and control-only subsets provides support against a purely categorical phenotype; indicating further insights into MD can be obtained when this within-group variation is considered. The stronger association within cases suggests this variation may be of particular importance.

Rapid progression from the first identifiable symptom to the onset of first-episode psychosis (FEP) allows less time for early intervention. The aim of this study was to examine the association between the first identifiable symptom and the subsequent speed of illness progression.

Data were available for 390 patients attending a catchment-based early intervention service for FEP. Exposure to non-psychotic and subthreshold psychotic symptoms was retrospectively recorded using semi-structured interviews. Outcomes following the onset of the first identifiable symptom were (1) time to onset of FEP and (2) symptom incidence rate (i.e. number of symptoms emerging per person-year until FEP onset). These outcomes were respectively analyzed with Cox proportional hazards and negative binomial regressions.

After Bonferroni correction, having a subthreshold psychotic (v. non-psychotic) symptom as the first symptom was not associated with time to FEP onset [hazard ratio (HR) = 1.39; 95% CI 0.94–2.04] but was associated with higher symptom incidence [incidence rate ratio (IRR) = 1.92; 95% CI 1.10–3.48]. A first symptom of suspiciousness was associated with shorter time to FEP onset (HR = 2.37; 95% CI 1.38–4.08) and higher symptom incidence rate (IRR = 3.20; 95% CI 1.55–7.28) compared to other first symptoms. In contrast, a first symptom of self-harm was associated with lower symptom incidence rate (IRR = 0.06; 95% CI 0.01–0.73) compared to other first symptoms. Several associations between symptoms and illness progression were moderated by the age at symptom onset.

Appreciating the content and timing of early symptoms can identify windows and treatment targets for early interventions in psychosis.

Mental disorders, including depression, obsessive compulsive disorder (OCD), and schizophrenia, share a common neuropathy of disturbed large-scale coordinated brain maturation. However, high-interindividual heterogeneity hinders the identification of shared and distinct patterns of brain network abnormalities across mental disorders. This study aimed to identify shared and distinct patterns of altered structural covariance across mental disorders.

Subject-level structural covariance aberrance in patients with mental disorders was investigated using individualized differential structural covariance network. This method inferred structural covariance aberrance at the individual level by measuring the degree of structural covariance in patients deviating from matched healthy controls (HCs). T1-weighted anatomical images of 513 participants (105, 98, 190 participants with depression, OCD and schizophrenia, respectively, and 130 age- and sex-matched HCs) were acquired and analyzed.

Patients with mental disorders exhibited notable heterogeneity in terms of altered edges, which were otherwise obscured by group-level analysis. The three disorders shared high difference variability in edges attached to the frontal network and the subcortical-cerebellum network, and they also exhibited disease-specific variability distributions. Despite notable variability, patients with the same disorder shared disease-specific groups of altered edges. Specifically, depression was characterized by altered edges attached to the subcortical-cerebellum network; OCD, by altered edges linking the subcortical-cerebellum and motor networks; and schizophrenia, by altered edges related to the frontal network.

These results have potential implications for understanding heterogeneity and facilitating personalized diagnosis and interventions for mental disorders.

Alcohol, cannabis, and nicotine use are highly comorbid and alarmingly prevalent in young adults. The hippocampus may be particularly sensitive to substance exposure. This remains largely untested in humans and familial risk may confound exposure effects. We extend prior work on alcohol and hippocampal volume in women by testing common and unique substance use effects and the potential moderating role of sex on hippocampal volume during emerging adulthood. A quasi-experimental cotwin control (CTC) design was used to separate familial risk from exposure consequences.

In a population-based sample of 435 24-year-old same-sex twins (58% women), dimensional measures (e.g. frequency, amount) of alcohol, cannabis, and nicotine use across emerging adulthood were assessed. Hippocampal volume was assessed using MRI.

Greater substance use was significantly associated with lower hippocampal volume for women but not men. The same pattern was observed for alcohol, cannabis, and nicotine. CTC analyses provided evidence that hippocampal effects likely reflected familial risk and the consequence of substance use in general and alcohol and nicotine in particular; cannabis effects were in the expected direction but not significant. Within-pair mediation analyses suggested that the effect of alcohol use on the hippocampus may reflect, in part, comorbid nicotine use.

The observed hippocampal volume deviations in women likely reflected substance-related premorbid familial risk and the consequences of smoking and, to a lesser degree, drinking. Findings contribute to a growing body of work suggesting heightened risk among women toward experiencing deleterious effects of substance exposure on the still-developing young adult hippocampus.

Deficits in event-related potential (ERP) including duration mismatch negativity (MMN) and P3a have been demonstrated widely in chronic schizophrenia (SZ) but inconsistent findings were reported in first-episode patients. Psychotropic medications and diagnosis might contribute to different findings on MMN/P3a ERP in first-episode patients. The present study examined MMN and P3a in first episode drug naïve SZ and bipolar disorder (BPD) patients and explored the relationships among ERPs, neurocognition and global functioning.

Twenty SZ, 24 BPD and 49 age and sex-matched healthy controls were enrolled in this study. Data of clinical symptoms [Positive and Negative Symptoms Scale (PANSS), Young Manic Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD)], neurocognition [Wechsler Adult Intelligence Scale (WAIS), Cattell's Culture Fair Intelligence Test (CCFT), Delay Matching to Sample (DMS), Rapid Visual Information Processing (RVP)], and functioning [Functioning Assessment Short Test (FAST)] were collected. P3a and MMN were elicited using a passive auditory oddball paradigm.

Significant MMN and P3a deficits and impaired neurocognition were found in both SZ and BPD patients. In SZ, MMN was significantly correlated with FAST (r = 0.48) and CCFT (r = −0.31). In BPD, MMN was significantly correlated with DMS (r = −0.54). For P3a, RVP and FAST scores were significant predictors in SZ, whereas RVP, WAIS and FAST were significant predictors in BPD.

The present study found deficits in MMN, P3a, neurocognition in drug naïve SZ and BPD patients. These deficits appeared to link with levels of higher-order cognition and functioning.

Electroconvulsive therapy (ECT) is the most effective intervention for patients with treatment resistant depression. A clinical decision support tool could guide patient selection to improve the overall response rate and avoid ineffective treatments with adverse effects. Initial small-scale, monocenter studies indicate that both structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) biomarkers may predict ECT outcome, but it is not known whether those results can generalize to data from other centers. The objective of this study was to develop and validate neuroimaging biomarkers for ECT outcome in a multicenter setting.

Multimodal data (i.e. clinical, sMRI and resting-state fMRI) were collected from seven centers of the Global ECT-MRI Research Collaboration (GEMRIC). We used data from 189 depressed patients to evaluate which data modalities or combinations thereof could provide the best predictions for treatment remission (HAM-D score ⩽7) using a support vector machine classifier.

Remission classification using a combination of gray matter volume and functional connectivity led to good performing models with average 0.82–0.83 area under the curve (AUC) when trained and tested on samples coming from the three largest centers (N = 109), and remained acceptable when validated using leave-one-site-out cross-validation (0.70–0.73 AUC).

These results show that multimodal neuroimaging data can be used to predict remission with ECT for individual patients across different treatment centers, despite significant variability in clinical characteristics across centers. Future development of a clinical decision support tool applying these biomarkers may be feasible.

The efficacy of the unified protocol of the transdiagnostic treatment for emotional disorders (UP) has been poorly studied in patients with depressive disorders. This study aimed to examine the efficacy of UP for improving depressive symptoms in patients with depressive and/or anxiety-related disorders.

This assessor-blinded, randomized, 20-week, parallel-group, superiority study compared the efficacy of the UP with treatment-as-usual (UP-TAU) v. wait-list with treatment-as-usual (WL-TAU). Patients diagnosed with depressive and/or anxiety disorders and with depressive symptoms participated. The primary outcome was depressive symptoms assessed by GRID-Hamilton depression rating scale (GRID-HAMD) at 21 weeks. The secondary outcomes included assessor-rated anxiety symptoms, severity and improvement of clinical global impression, responder and remission status, and loss of principal diagnosis.

In total, 104 patients participated and were subjected to intention-to-treat analysis [mean age = 37.4, s.d. = 11.5, 63 female (61%), 54 (51.9%) with a principal diagnosis of depressive disorders]. The mean GRID-HAMD scores in the UP-TAU and WL-TAU groups were 16.15 (s.d. = 4.90) and 17.06 (s.d. = 6.46) at baseline and 12.14 (s.d. = 5.47) and 17.34 (s.d. = 5.78) at 21 weeks, with a significant adjusted mean change difference of −3.99 (95% CI −6.10 to −1.87). Patients in the UP-TAU group showed significant superiority in anxiety and clinical global impressions. The improvement in the UP-TAU group was maintained in all outcomes at 43 weeks. No serious adverse events were observed in the UP-TAU group.

The UP is an effective approach for patients with depressive and/or anxiety disorders.

Developing, elaborating, and consolidating positive views of the self is a plausible route to increased psychological well-being. We set out to provide an assessment of positive self-beliefs that could be used in research and clinical practice.

A non-probability online survey was conducted with 2500 UK adults, quota sampled to match the population for age, gender, ethnicity, income, and region. Exploratory factor analysis of a 94-item pool – generated with guidance from people with lived experience of mental health difficulties – was conducted to develop the Oxford Positive Self Scale (OxPos). The item pool was further reduced using regularised structural equation modelling (SEM) before confirmatory factor analysis. Optimal cut-off scores were developed using receiver operating characteristic curves. Additional validations were carried out with two further general population cohorts (n = 1399; n = 1693).

A 24-item scale was developed with an excellent model fit [robust χ2 = 995.676; df = 246; CFI = 0.956; TLI = 0.951; RMSEA = 0.049 (0.047, 0.052); SRMR = 0.031]. The scale comprises four factors: mastery; strength; enjoyment; and character. SEM indicated that the scale explains 68.6% of variance in psychological well-being. The OxPos score was negatively correlated with depression (r = −0.49), anxious avoidance (r = −0.34), paranoia (r = −0.23), hallucinations (r = −0.20), and negative self-beliefs (r = −0.50), and positively correlated with psychological well-being (r = 0.79), self-esteem (r = 0.67), and positive social comparison (r = 0.72). Internal reliability and test–retest reliability were excellent. Cut-offs by age and gender were generated. A short-form was developed, explaining 96% of the full-scale variance.

The new open access scale provides a psychometrically robust assessment of positive cognitions that are strongly connected to psychological well-being.