Preclinical evidence suggests that diazepam enhances hippocampal γ-aminobutyric acid (GABA) signalling and normalises a psychosis-relevant cortico-limbic-striatal circuit. Hippocampal network dysconnectivity, particularly from the CA1 subfield, is evident in people at clinical high-risk for psychosis (CHR-P), representing a potential treatment target. This study aimed to forward-translate this preclinical evidence.

In this randomised, double-blind, placebo-controlled study, 18 CHR-P individuals underwent resting-state functional magnetic resonance imaging twice, once following a 5 mg dose of diazepam and once following a placebo. They were compared to 20 healthy controls (HC) who did not receive diazepam/placebo. Functional connectivity (FC) between the hippocampal CA1 subfield and the nucleus accumbens (NAc), amygdala, and ventromedial prefrontal cortex (vmPFC) was calculated. Mixed-effects models investigated the effect of group (CHR-P placebo/diazepam vs. HC) and condition (CHR-P diazepam vs. placebo) on CA1-to-region FC.

In the placebo condition, CHR-P individuals showed significantly lower CA1-vmPFC (Z = 3.17, PFWE = 0.002) and CA1-NAc (Z = 2.94, PFWE = 0.005) FC compared to HC. In the diazepam condition, CA1-vmPFC FC was significantly increased (Z = 4.13, PFWE = 0.008) compared to placebo in CHR-P individuals, and both CA1-vmPFC and CA1-NAc FC were normalised to HC levels. In contrast, compared to HC, CA1-amygdala FC was significantly lower contralaterally and higher ipsilaterally in CHR-P individuals in both the placebo and diazepam conditions (lower: placebo Z = 3.46, PFWE = 0.002, diazepam Z = 3.33, PFWE = 0.003; higher: placebo Z = 4.48, PFWE < 0.001, diazepam Z = 4.22, PFWE < 0.001).

This study demonstrates that diazepam can partially restore hippocampal CA1 dysconnectivity in CHR-P individuals, suggesting that modulation of GABAergic function might be useful in the treatment of this clinical group.

Adults with mood and/or anxiety disorders have increased risks of comorbidities, chronic treatments and polypharmacy, increasing the risk of drug–drug interactions (DDIs) with antidepressants.

To use primary care records from the UK Biobank to assess DDIs with citalopram, the most widely prescribed antidepressant in UK primary care.

We classified drugs with pharmacokinetic or pharmacodynamic DDIs with citalopram, then identified prescription windows for these drugs that overlapped with citalopram prescriptions in UK Biobank participants with primary care records. We tested for associations of DDI status (yes/no) with sociodemographic and clinical characteristics and with cytochrome 2C19 activity, using univariate tests, then fitted multivariable models for variables that reached Bonferroni-corrected significance.

In UK Biobank primary care data, 25 508 participants received citalopram prescription(s), among which 11 941 (46.8%) had at least one DDI, with an average of 1.96 interacting drugs. The drugs most commonly involved were proton pump inhibitors (40% of co-prescription instances). Individuals with DDIs were more often female and older, had more severe and less treatment-responsive depression, and had higher rates of psychiatric and physical disorders. In the multivariable models, treatment resistance and markers of severity (e.g. history of suicidal and self-harm behaviours) were strongly associated with DDIs, as well as comorbidity with cardiovascular disorders. Cytochrome 2C19 activity was not associated with the occurrence of DDIs.

The high frequency of DDIs with citalopram in fragile groups confirms the need for careful consideration before prescribing and periodic re-evaluation.

Cognitive deficits and immune system dysregulation are core features of psychotic disorders. Among inflammatory markers, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) have been linked to both psychosis pathophysiology and related cognitive impairments.

We investigated associations among IL-6, TNF-α, and neurocognitive performance in 107 participants: individuals at clinical high risk for psychosis (CHR-P, n = 35), first-episode psychosis (FEP, n = 39), and healthy controls (HC, n = 33). Assessments included memory, processing speed, executive function, and social cognition. Cytokines were measured from fasting serum samples. Analyses included ANOVA, correlations, and multivariate regressions controlling for age, sex, IQ, group, and symptom severity.

TNF-α levels were significantly elevated in FEP compared to CHR-P (p = 0.0251); IL-6 differences were non-significant. FEP showed poorer performance in multiple cognitive domains, especially social cognition. CHR-P individuals exhibited intermediate profiles between FEP and HC in cognition. In adjusted regression models, IL-6 was significantly associated with undermentalization on the MASC task (β = 0.28, p = 0.0337) and showed a trend-level association with slower processing speed (β = 0.98, p = 0.075). TNF-α levels predicted poorer facial emotion recognition (β = −1.37, p = 0.0022). IQ and group were significant covariates in most models.

Our findings suggest that peripheral inflammation, particularly IL-6 and TNF-α, may selectively impact social cognitive functioning in early psychosis. Though modest, these associations highlight potential inflammatory contributions to functional impairment and support further investigation of immunological targets in early intervention.

It has been reported that abnormal experiences could be common in the general “healthy” population, with the vast majority of individuals never proceeding to manifest a frank mental disorder.

This study aimed to quantify subthreshold psychiatric symptoms in the general population.

The protocol included clinicodemographic data and a mental symptoms questionnaire, and additionally, the CES-D, STAI-S, RASS, and the GloDiS to assess depression, anxiety, suicidality, and functional impairment, respectively. The data were collected online and anonymously from 1504 persons (75.66% females; 23.73% males). Descriptive statistics, risk ratios, and factor analysis were utilized.

Clinical depression was present in approximately 10%, any somatic disorder in 20.21% (9.90% both), and a history of any mental disorder was present in 42.75%. The healthy individuals (46.94% of the study sample) were experiencing distress (8.6%) and subthreshold mental symptoms (attenuated psychotic, schizotypal distrust, emotional lability, conformity, and interpersonal and social functioning). Attenuated psychotic symptoms are present in almost 10%, and the conversion rate to any kind of psychosis was probably 0.5% per year until the age of 40, with one-third of these persons eventually converting. Beyond the age of 40, no conversion to psychosis seems to occur. All aspects of symptoms correlated weakly but significantly with aspects of functional impairment.

The results of the current study are in accord with the literature and suggest that a significant number of persons in the general population experience attenuated psychiatric symptoms and mild functional impairment without ever manifesting an overt mental disorder. There is a need for further research on this matter to confirm these findings and to explore their implications both for mental and somatic health and the provision of health care.

Estimating the risk of developing bipolar disorder (BD) in children and adolescents (C&A) with depressive disorders is important to optimize prevention and early intervention efforts. We aimed to quantitatively examine the risk of developing BD from depressive disorders and identify factors which moderate this development.

In this systematic review and meta-analysis (PROSPERO:CRD42023431301), PubMed and Web-of-Science databases were searched for longitudinal studies reporting the percentage of C&A with ICD/DSM-defined depressive disorders who developed BD during follow-up. Data extraction, random-effects meta-analysis, between-study heterogeneity analysis, quality assessment, sub-group analyses, and meta-regressions were conducted.

Thirty-nine studies were included, including 72,371 individuals (mean age=13.9 years, 57.1% females); 14.7% of C&A with a depressive disorder developed BD after 20.4–288 months: 9.5% developed BD-I (95% CI=4.7 to 18.1); 7.7% developed BD-II (95% CI=3.2% to 17.3%); 19.8% (95% CI=9.9% to 35.6%) of C&A admitted into the hospital with a depressive disorder developed BD. Studies using the DSM (21.6%, 95% CI=20.2% to 23.1%) and studies evaluating C&A with a major depressive disorder only (19.8%, 95% CI=16.8% to 23.1%) found higher rates of development of BD. Younger age at baseline, a history of hospitalization and recruitment from specialized clinics were associated with an increased risk of developing BD at follow-up. Quality of included studies was good in 76.9% of studies.

There is a substantial risk of developing BD in C&A with depressive disorders. This is particularly the case for C&A with MDD, DSM-diagnosed depressive disorders, and C&A admitted into the hospital. Research exploring additional predictors and preventive interventions is crucial.

Sexually transmitted infections (STIs), along with sexual health and behaviour, have received little attention in schizophrenia patients.

To systematically review and meta-analytically characterise the prevalence of STIs and sexual risk behaviours among schizophrenia patients.

Web of Science, PubMed, BIOSIS, KCI-Korean Journal Database, MEDLINE, Russian Science Citation Index, SciELO and Cochrane Central Register were systematically searched from inception to 6 July 2023. Studies reporting on the prevalence or odds ratio of any STI or any outcome related to sexual risk behaviours among schizophrenia samples were included. PRISMA/MOOSE-compliant (CRD42023443602) random-effects meta-analyses were used for the selected outcomes. Q-statistics, I2 index, sensitivity analyses and meta-regressions were used. Study quality and publication bias were assessed.

Forty-eight studies (N = 2 459 456) reporting on STI prevalence (including 15 allowing for calculation of an odds ratio) and 33 studies (N = 4255) reporting on sexual risk behaviours were included. Schizophrenia samples showed a high prevalence of STIs and higher risks of HIV (odds ratio = 2.11; 95% CI 1.23–3.63), hepatitis C virus (HCV, odds ratio = 4.54; 95% CI 2.15–961) and hepatitis B virus (HBV; odds ratio = 2.42; 95% CI 1.95–3.01) infections than healthy controls. HIV prevalence was higher in Africa compared with other continents and in in-patient (rather than out-patient) settings. Finally, 37.7% (95% CI 31.5–44.4%) of patients were sexually active; 35.0% (95% CI 6.6–59.3%) reported consistent condom use, and 55.3% (95% CI 25.0–82.4%) maintained unprotected sexual relationships.

Schizophrenia patients have high prevalence of STIs, with several-fold increased risks of HIV, HBV and HCV infection compared with the general population. Sexual health must be considered as an integral component of care.