Depressive symptoms are common in mild cognitive impairment (MCI). These may be associated with poorer cognitive function and increased risks of dementia transition.

We aimed to examine the cognitive patterns associated with variations in depressive symptoms in neurodegenerative MCI without a primary mood disorder.

Individuals with MCI (n = 123), including MCI due to Alzheimer’s disease (n = 54) and MCI with Lewy bodies (n = 69), underwent repeated annual assessment of cognitive function and concurrent depressive symptoms using the Addenbrooke’s Cognitive Examination-Revised and the Geriatric Depression Scale-15, respectively.

Between- and within-person differences in depressive symptoms were disaggregated and related to between- and within-person cognitive differences and modification of cognitive performance trajectories over time.

There was strong evidence of a state-based association between depressive symptoms and cognitive function. Intra-individual differences in depressive symptoms were negatively associated with concurrent cognitive performance such that a 2-point increase in depressive score explained a 1-point decrease in cognitive score, on average (point estimate −0.56, 95% credibile interval (CrI) −1.05 to −0.08).

The data did not support a trait-based association between depressive symptoms and cognitive performance (point estimate 0.10, 95% CrI −0.42 to 0.59), nor any between- or within-person trajectory modification associated with depressive symptoms.

Within-person variations in depressive symptom severity are associated with acute cognitive performance differences. Cognitive scores derived during active depressive periods may underestimate longer-term cognitive capabilities. Treating depressive symptoms in MCI may clarify underlying cognitive performance capacity, and help maintain optimal cognitive function for longer.

Previous studies investigating the association between pubertal timing and depression in girls primarily use self-reported age at menarche (AAM). This study examines a range of pubertal timing indicators, including anthropometric and self-reported measures.

Compare associations of multiple indicators of pubertal timing with depressive symptoms and depression in girls and explore whether these associations persist into early adulthood.

The sample comprised 4607 girls from UK-based Avon Longitudinal Study of Parents and Children. Seven measures of pubertal timing were assessed between ages 7 and 17 (age at: peak height velocity (aPHV); peak weight velocity; peak bone mineral content velocity; Tanner pubic hair and breast development stage 3; axillary hair; and AAM). Depressive symptoms were measured at 14, 17, 18 and 24 years using the Short Mood and Feelings Questionnaire. Depression was assessed at 15, 18 and 24 years using the Development and Well-Being Assessment and Clinical Interview Schedule-Revised. Multivariable logistic regression models were adjusted for socioeconomic status and pre-pubertal body mass index.

Later pubertal timing was associated with lower odds of depressive symptoms at age 14 across six measures, including aPHV (adjusted odds ratio (AOR): 0.82; 95% CI 0.72, 0.95) and AAM (AOR: 0.84; 95% CI 0.76, 0.92). Later AAM and Tanner breast stage 3 were associated with lower odds of depression at age 18 (AOR: 0.85; 95% CI 0.75, 0.97 and AOR: 0.83; 95% CI 0.72, 0.95, respectively). Associations attenuated by age 24.

Later pubertal timing was associated with reduced odds of depressive symptoms during mid-adolescence, with associations attenuating by adulthood.

Although workplace mental health screening is often implemented to aid early identification of mental health symptoms and facilitate access to treatment, supporting evidence is limited.

We aimed to evaluate the effect of independently conducted, confidential, online mental health screening, paired with automated tailored feedback recommending referral services, on help-seeking and psychological distress.

We conducted a cluster-randomised controlled trial with firefighters from an Australian fire and rescue service. Randomisation occurred by station (N = 264). Firefighters at stations allocated to the intervention group received tailored information detailing suitable mental health services based on their Kessler-6 psychological distress score (K6). The control group received generic feedback on services irrespective of K6 score. The primary outcome was help-seeking at 3-months post-intervention for those with at least moderate levels of psychological distress at baseline (K6 ≥14). The study was registered with Australian New Zealand Clinical Trials Registry (no. ANZCTR 12621001457831).

Of the 459 firefighters screened, 141 (30.72%) scored ≥14 on K6. Among this subgroup at 3 months, no differences were observed in rates of overall help-seeking between the intervention and control groups (P = 0.31). In contrast, levels of psychological distress remained high in the intervention group but declined in the control group (t[111] = 2.29, 95% CI: 0.24, 3.23, P = 0.024). The difference in psychological distress associated with workplace mental health screening equated to an effect size of −0.42 (95% CI: −0.04, −0.79).

Our findings suggest that independent, confidential online mental health screening, paired with tailored online feedback and information on available treatment, does not significantly increase help-seeking and may sustain psychological distress over time compared with receiving generic information. As such, it should not be implemented to promote help-seeking and reduce levels of psychological distress. These findings are relevant for workplaces, mental health researchers and practitioners alike, highlighting the potential risk and potential harm of mental health screening conducted in this way on individuals.

Lurasidone is a second-generation antipsychotic with antidepressant properties, but its effect on depressive symptoms across diagnostic domains is not known.

This systematic review aims to synthesise the evidence for the transdiagnostic efficacy of lurasidone in reducing depressive symptoms.

Electronic databases were searched up to October 2024 to identify randomised controlled trials comparing the effects of lurasidone and placebo on depressive symptoms, as measured by any standardised scale, in populations with different psychiatric diagnoses. Acceptability, tolerability and safety were also measured. The Cochrane risk of bias tool was used to assess study quality, and the GRADE tool to evaluate certainty of evidence. A random-effects meta-analysis was performed to estimate standardised mean differences (SMDs, for continuous outcomes) or relative risks (for dichotomous outcomes) with 95% CI.

Fourteen trials met inclusion criteria. Pooled analysis of 5239 participants found lurasidone to be more efficacious than placebo in improving depression scores (SMD −0.26, 95% CI −0.37, −0.15) across multiple diagnoses (including schizophrenia, bipolar disorder and major depressive disorder). Secondary analyses showed better acceptability (relative risk 0.55, 95% CI 0.43, 0.71) and safety (relative risk 0.73, 95% CI 0.58, 0.91) and comparable tolerability (relative risk 0.74, 95% CI 0.54, 1.02) between lurasidone and placebo. The main limitations were the high risk of bias of several included studies and the high heterogeneity observed in our findings.

Lurasidone is a potentially efficacious and safe strategy for reducing depressive symptomatology across a range of psychiatric diagnoses. Further long-term, robust trials employing precision psychiatry methods are needed to support its broader use to target depressive symptoms transdiagnostically.

Post-traumatic stress disorder (PTSD) and depression are highly comorbid. A comprehensive meta-analysis on the efficacy of PTSD-specific psychotherapies in reducing comorbid depression is lacking.

To examine the short-, mid- and long-term efficacy of PTSD-specific psychotherapies in reducing comorbid depression.

We performed a preregistered (Prospero-ID: CRD42023479224) meta-analysis and followed PRISMA guidelines. PsycINFO, MEDLINE, Web of Science and PTSDpubs were searched. Randomised controlled trials (RCTs) examining psychotherapies for PTSD in samples with ≥70% PTSD diagnosis rate, mean age of sample ≥18 years, ≥10 participants per group and reporting of depression outcome data were included in the meta-analysis.

In total, 136 RCTs (N = 8868) assessed depression. Most data concerned trauma-focused cognitive behaviour therapy (TF-CBT), followed by eye movement desensitisation and reprocessing and non-trauma-focused and other trauma-focused interventions. At post-treatment, TF-CBT was associated with large reductions in depression relative to passive controls (Hedges’ g = 0.97, 95% CI 0.80–1.14, k = 46 trials) and moderate reductions relative to active controls (Hedges’ g = 0.50, 95% CI 0.35–0.65, k = 29). Effects relative to control conditions were similar across the other interventions. Response rates for comorbid depression were three times higher in psychological interventions relative to passive controls (odds ratio 3.07, 95% CI 1.18–7.94, k = 4). In head-to-head comparisons, there was evidence for TF-CBT producing higher short-, mid- and long-term reductions in depression than non-trauma-focused interventions. Results at mid- and long term were generally similar to those at treatment end-point.

PTSD-specific psychotherapies are effective in reducing depression. TF-CBT presented with the highest certainty of results. More long-term data for other interventions are needed. Results are encouraging for clinical practice.

During the perinatal period, women may be more susceptible to depressive symptoms because of fluctuating oestrogen levels. Genetic variations, epigenetic modifications and varying gene expression levels of oestrogen receptor genes may contribute to inter-individual differences in the encoded receptors’ sensitivity to oestrogen, ultimately modulating the susceptibility to depressive symptoms.

The aim of this systematic review was to provide an overview of the literature on the association between oestrogen receptor genes and perinatal depression symptoms by including genetic, epigenetic and gene expression studies.

A systematic search of three public databases, PubMed, PsycINFO and Web of Science, was conducted in accordance with the PRISMA guidelines (PROSPERO registration number: CRD42023447446). Two independent reviewers extracted data and assessed study quality.

A total of 29 studies were finally included, of which 16 investigated genetic variants, five investigated epigenetic modifications and eight investigated gene expression levels of oestrogen receptor genes. A limited number of genetic variations were found to be associated with perinatal depression symptoms, most of them in ESR1. Moreover, DNA methylation marks involved in oestrogen signalling, and gene expression levels of ESR1 and ESR2, were found to be associated with perinatal depression symptoms.

Genetic variations, epigenetic modifications and gene expression levels of oestrogen receptor genes are associated with susceptibility to perinatal depression symptoms. The underlying mechanism might be the inter-individual modulation of the encoded receptors’ sensitivity to oestrogen. Future research employing more comprehensive and integrative approaches is needed to better understand the aetiology of perinatal depression symptoms.

Core premenstrual disorders (PMDs), including premenstrual syndrome (PMS) and premenstrual dysphoric disorder, can cause significant impairment. Despite evidence linking stress and premenstrual symptoms, a systematic synthesis is lacking.

To systematically review the literature and meta-analyse evidence on the relationship between premenstrual symptoms and stress.

Four databases (Web of Science, PubMed, PsycINFO, Scopus) and Google Scholar were searched for studies indexed before 27 August 2024 (no language/year restrictions) assessing the relationship between self-reported stress and premenstrual symptoms in regularly menstruating individuals (PROSPERO: CRD42021244503). Three multilevel meta-analyses estimated (a) the correlation between stress and premenstrual symptom severity, (b) stress differences between individuals with and without core PMD across the menstrual cycle and (c) the impact of traumatic experiences on the occurrence of premenstrual symptoms. Study quality and publication bias were assessed.

We synthesised 188 effect sizes from 66 studies (N = 38 344), indicating (a) a positive correlation (r = 0.29, 95% CI 0.23–0.36); (b) higher stress levels in participants with core PMD (d = 0.79, 95% CI 0.32–1.26), particularly during the luteal phase (dlut = 1.01, 95% CI 0.46–1.57); and (c) over twofold higher odds (odds ratio 2.45, 95% CI 1.87–3.23) of PMS in individuals with a history of trauma. Heterogeneity was high (I2 = 84.64–91.38%); one meta-analysis (c) showed evidence of publication bias.

The results indicate an association between stress and premenstrual symptoms, an effect of cycle phase and trauma as a risk factor for PMS. Future research should explore underlying biopsychosocial mechanisms.

The use of community treatment orders (CTOs) has increased in many jurisdictions despite very limited evidence for their efficacy. In this context, it is important to investigate any differences in outcome by subgroup.

To investigate the variables associated with CTO placement and the impact of CTOs on admissions and bed-days over the following 12 months, including differences by diagnosis.

Cases and controls from a complete jurisdiction, the state of Queensland, Australia, were analysed. Administrative health data were matched by age, sex and time of hospital discharge (index date) with two controls per case subject to a CTO. Multivariate analyses were used to examine factors associated with CTOs, as well as the impact on admissions and bed-days over the 12 months after CTO placement. Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12624000152527).

We identified 10 872 cases and 21 710 controls from January 2018 to December 2022 (total n = 32 582). CTO use was more likely in First Nations people (adjusted odds ratio = 1.14; 95% CI: 1.06–1.23), people from culturally diverse backgrounds (adjusted odds ratio = 1.45; 95% CI: 1.33–1.59) and those with a preferred language other than English (adjusted odds ratio = 1.21; 95% CI: 1.02–1.44). When all diagnostic groups were considered, there were no differences in subsequent admissions or bed-days between cases and controls. However, both re-admissions and bed-days were significantly reduced for CTO cases compared with controls in analyses restricted to non-affective psychoses (e.g. adjusted odds ratio = 0.77, 95% CI: 0.71–0.84 for re-admission).

Queenslanders from culturally or linguistically diverse backgrounds and First Nations peoples are more likely to be placed on CTOs. Targeting CTO use to people with non-affective psychosis would both address rising CTO rates and mean that people placed on these orders derive possible benefit. This has implications for both clinical practice and policy.

An association between second-hand smoke exposure and depressive symptoms has been reported; however, further research is needed for clarity.

This 20-year prospective cohort study aimed to longitudinally explore the relationships of smoking and second-hand smoke exposure with incident depressive symptoms in community-dwelling middle-aged and older adults.

Data of adults aged ≥40 years were collected from the National Institute for Longevity Sciences – Longitudinal Study of Aging database (third to ninth waves). Participants with baseline (third wave) depressive symptoms, missing data or no follow-up participation were excluded. Baseline data on current cigarette smoking and second-hand smoke exposure were collected. Depressive symptoms were defined as a Center for Epidemiologic Studies Depression Scale score ≥16. Generalised estimating equation models evaluated longitudinal relationships of smoking and second-hand smoke exposure with incident depressive symptoms.

The final analysis included 1697 participants (mean (s.d.) age, 58.7 (11.2) years; mean follow-up, 12.9 years). Depressive symptom incidence ranged from 8.0% (wave 4) to 6.5% (wave 9). Compared with non-current smokers, current smokers showed no significantly higher risk of incident depressive symptoms (multivariable-adjusted odds ratio (95% CI): 1.27 (0.96−1.68)). Subgroup analysis revealed higher risks in male current smokers (adjusted odds ratio (95% CI): 1.40 (1.00−1.94)) and current smokers aged ≥65 years (adjusted odds ratio (95% CI): 1.62 (1.00−2.63)). Current smokers exposed to second-hand smoke had a higher depressive symptom risk than unexposed non-smokers (odds ratio (95% CI): 1.50 (1.05−2.14)) and greater risk (odds ratio (95% CI): 1.39 (1.00−1.94)) than unexposed current smokers.

Smoking, combined with second-hand smoke exposure, is associated with future depressive symptoms in community-dwelling middle-aged and older adults.

Targeting the glutamatergic system is posited as a potentially novel therapeutic strategy for psychotic disorders. While studies in subjects indicate that antipsychotic medication reduces brain glutamatergic measures, they were unable to disambiguate clinical changes from drug effects.

To address this, we investigated the effects of a dopamine D2 receptor partial agonist (aripiprazole) and a dopamine D2 receptor antagonist (amisulpride) on glutamatergic metabolites in the anterior cingulate cortex (ACC), striatum and thalamus in healthy controls.

A double-blind, within-subject, cross-over, placebo-controlled study design with two arms (n = 25 per arm) was conducted. Healthy volunteers received either aripiprazole (up to 10 mg/day) for 7 days or amisulpride (up to 400 mg/day) and a corresponding period of placebo treatment in a pseudo-randomised order. Magnetic resonance spectroscopy (1H-MRS) was used to measure glutamatergic metabolite levels and was carried out at three different time points: baseline, after 1 week of drug and after 1 week of placebo. Values were analysed as a combined measure across the ACC, striatum and thalamus.

Aripiprazole significantly increased glutamate + glutamine (Glx) levels compared with placebo (β = 0.55, 95% CI [0.15, 0.95], P = 0.007). At baseline, the mean Glx level was 8.14 institutional units (s.d. = 2.15); following aripiprazole treatment, the mean Glx level was 8.16 institutional units (s.d. = 2.40) compared with 7.61 institutional units (s.d. = 2.36) for placebo. This effect remained significant after adjusting for plasma parent and active metabolite drug levels. There was an observed increase with amisulpride that did not reach statistical significance.

One week of aripiprazole administration in healthy participants altered brain Glx levels as compared with placebo administration. These findings provide novel insights into the relationship between antipsychotic treatment and brain metabolites in a healthy participant cohort.

The Resilience Hub was established to coordinate mental health and psychosocial support for anyone affected by the 2017 Manchester Arena terrorist attack.

To use the Hub’s mental health screening data to examine the variation in symptoms reported by children and young persons (CYP) and their parent/guardian and explore any association with time delay in post-event registration or parental distress.

CYP engaging with Hub services were separated into eight ‘admission’ groups depending on when they registered post-incident. CYP were screened for trauma, depression, and generalised and separation anxiety. Parents/guardians also completed screening measures for their own and their child’s anxiety. Baseline and follow-up scores were compared between admission groups. Parental and CYP assessments of the CYP’s anxiety score was compared with the measure of parental distress.

Almost half of CYP registered in the first 3 months of service launch, with numbers of new registrations falling during each subsequent screening cycle. Generally, there was an increase in baseline screening scores as Hub registration time increased. The Children’s Impact of Event scale score decreased by 0.11 (95% CI: −0.17, −0.05) per month, but the score for depression increased by 0.06 (95% CI: 0.03, 0.10). Longitudinal patterns in anxiety and separation were difficult to discern. Screening scores of CYP registering later reduced at a faster rate than those of the first registrants. Higher levels of parental mental distress were correlated with increased anxiety scores assigned to the CYP in relation to the anxiety score reported by the CYP themselves.

CYP who registered earlier were less symptomatic, although those registering later did show increased improvement in their symptoms, indicating that the Hub was beneficial. Parental well-being was associated with child mental distress, indicating that shared family trauma should be considered when planning care.

Mood disorders are among the leading causes of disease burden worldwide, with 20–70% of affected individuals experiencing comorbid premenstrual disorders. This systematic review and meta-analysis investigated the comorbidity of premenstrual dysphoric disorder (PMDD) or premenstrual syndrome (PMS) with non-reproductive mood disorders.

We aimed to determine the pooled prevalence of PMDD/PMS with adult mood disorders, assess the impact of comorbidity on clinical course and summarise the associated neurobiological findings.

Eligible studies were identified through Embase, MEDLINE and APA PsycINFO from inception to 22 January 2024 (PROSPERO, no. CRD42021246796). Studies on women (‘females‘) with diagnoses of PMDD/PMS and mood disorders were included. Risk of bias was assessed using National Institutes of Health quality assessment tools. A random-effects, pooled-prevalence meta-analysis was conducted using the Comprehensive Meta-Analysis software, categorising diagnostic sampling strategies as follows: mood disorders diagnosed first, PMDD/PMS diagnosed first or concurrent diagnoses. A narrative synthesis explored secondary outcomes, including illness course and biomarkers.

A total of 39 studies were included, with 36 of these (n = 3646) contributing to the meta-analysis. Seven studies focused on bipolar disorders, 18 on unipolar depressive disorders and 14 on mixed samples of bipolar and unipolar disorders. Random-effects pooled-prevalence meta-analyses showed consistently high comorbidity rates between PMDD/PMS and mood disorders, ranging from 42% (95% CI: 30%, 55%) to 49% (95% CI: 38%, 60%) across sampling strategies. Risk of bias varied, with methodological heterogeneity noted.

This review underscores high comorbidity rates between PMDD/PMS and mood disorders, regardless of sampling strategy, and highlights the need for research into clinical and neurobiological characteristics specific to this comorbidity. Limitations include study heterogeneity, reliance on cross-sectional designs and provisional PMDD/PMS diagnoses. Future research should address these gaps to inform diagnostic and therapeutic advancements tailored to this population.

3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy (MDMA-AT) has shown promising safety and efficacy in phase 3 studies of post-traumatic stress disorder, but has not been investigated for a primary diagnosis of major depressive disorder (MDD).

We aimed to explore the proof of principle and safety as a first study with MDMA-AT for MDD, and to provide preliminary efficacy data.

Twelve participants (7 women, 5 men) with moderate to severe MDD received MDMA in 2 open-label sessions 1 month apart, along with psychotherapy before, during and after the MDMA sessions, between January 2023 and May 2024. The primary outcome measure was mean change in Montgomery–Asberg Depression Rating Scale (MADRS), and the secondary outcome measure was mean change in functional impairment as measured with the Sheehan Disability Scale (SDS), both from baseline to 8 weeks following the second MDMA session. We used descriptive statistics and the two-tailed Wilcoxon signed-rank test to compare baseline and outcome scores. Repeated measures were analysed by a mixed-effects model.

Baseline MADRS was 29.6 (s.d. 4.9). Feasibility was demonstrated with sufficient recruitment and retention. MADRS scores were significantly reduced post treatment compared with baseline (mean difference –19.3, s.e. 2.4, CI –14.8 to –23.8, P < 0.001). SDS scores significantly decreased from baseline (mean difference –11.7, s.e. 2.2, CI –7.5 to –15.9, P = 0.001). There were no adverse events of special interest, and no unexpected or serious adverse events.

The study met the primary objectives of safety and feasibility, and provided indications of efficacy for MDMA-AT for MDD. Further studies with a randomised design are required to confirm these findings.

EudraCT no. 2021-000805-26.

Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.

The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.

This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.

Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.

Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.