Euthymic bipolar disorder (BD) is associated with general and domain-specific cognitive impairment, which predicts poor occupational and social functioning.

We searched Embase, Medline, and PsycInfo for articles published between database inception and June 2024, examining cognitive domains in euthymic BD. We conducted meta-analysis, meta-regressions, including premorbid IQ, demographic, and clinical variables. Newcastle Ottawa Scale, I2 statistic, and funnel plots/Egger’s and Begg’s Test were used to assess quality, heterogeneity, and publication bias, respectively. The Benjamini-Hochberg (BH) procedure was utilised for multiple comparisons.

We identified 95 groups from 75 studies (N = 4,404 BD & 4,037 HC). BD showed significant impairment in general cognitive functioning (Hedge’s g = −0.58, 95%CI: −0.79, −0.37, p <.01), verbal memory (Hedge’s g = −0.70, 95%CI: −0.79, −0.60, p <.01), executive function (Hedge’s g = −0.69, 95%CI: −0.78, −0.60, p <.01), visuo-spatial memory (Hedge’s g = −0.68, 95%CI: −0.83, −0.53, p <.01), attention/processing speed (Hedge’s g = −0.64, 95%CI: −0.75, −0.54, p <.01), working memory (Hedge’s g = −0.61, 95%CI: −0.74, −0.49, p <.01), and premorbid IQ (Hedge’s g = −0.24, 95%CI: −0.36, −0.12, p <.01). Demographic and clinical factors were not associated with cognitive performance, except for a statistically significant, but small positive correlation between years of education and lower impairment in verbal memory, β = .066, adjusted p <.05.

Our findings highlight cognitive domains impaired in euthymic BD, indicating targets for interventions. Substantial variance is unexplained, warranting focus on larger samples of individual-level data.

Psychotic symptoms in depression are linked to worse outcomes, and treatment options are limited. Ketamine and esketamine are effective antidepressants, yet most studies have excluded patients with a history of psychotic symptoms.

To evaluate by systematic review the efficacy and safety of ketamine and esketamine in treating patients with unipolar or bipolar depressive episodes with psychotic features.

A comprehensive search of the PubMed, Ovid and Web of Science databases was conducted up to 2 November 2023. We included any study that reported the use of ketamine or esketamine in patients with depressive episodes with psychotic symptoms. The primary outcomes assessed were variations in depressive and psychotic symptoms and the incidence of adverse events. The protocol was preregistered in PROSPERO (CRD42023488524).

Ten studies were included, encompassing 60 patients with unipolar depression with psychotic symptoms and 19 patients with bipolar depression with psychotic symptoms. Treatment with (es)ketamine showed mean score changes on the Montgomery–Åsberg Depression Rating Scale ranging from −13.7 to −18.2 points in open-label studies of patients with unipolar depression with psychotic symptoms. Up to 50% of participants achieved remission. The largest study with patients with bipolar depression with psychotic symptoms reported a mean Montgomery–Åsberg Depression Rating Scale score change of −14.9 points. Adverse events were mostly mild and transient. There were no reports of switches to (hypo)mania or deterioration of psychotic symptoms, and in six studies there was substantial improvement of the latter.

The available evidence suggests that (es)ketamine shows antidepressant effects in patients with depressive episodes with psychotic features and has a reasonable safety profile. However, the heterogeneity of the studies included in this review and the high risk of bias warrant caution in interpreting the findings and underscore the need for further trials to confirm these preliminary results.

Lithium treatment is associated with reduced mortality in bipolar disorder (BD), but the role of treatment continuity remains underexplored. This study investigated the association between patterns of lithium exposure and all-cause mortality in a population-based cohort.

We analyzed electronic health records from 15,384 individuals with BD in Catalonia, Spain (2010–2019). Patients were classified as having sustained, partial/intermittent, or no lithium exposure based on annual defined daily doses (DDDs). All-cause mortality was the primary outcome. Kaplan–Meier and Cox regression analyses (adjusted for sociodemographic, clinical, and treatment-related variables) estimated hazard ratios (HRs) for mortality risk. Interaction and sensitivity analyses were conducted to assess the role of comorbidity burden and dose effects.

Over the study period, 715 deaths were recorded. In fully adjusted models, sustained lithium exposure was associated with a significantly lower mortality risk compared to no exposure (HR = 0.69, 95% confidence interval [CI]: 0.51–0.93, p = 0.016). In the lithium-exposed subgroup, sustained use was also protective compared to partial/intermittent exposure (HR = 0.70, 95% CI: 0.51–0.97, p = 0.03). No significant interaction was observed between sustained lithium use and comorbidity burden. Sensitivity analyses confirmed this effect at lower dose thresholds but not at higher ones.

Sustained lithium use is associated with improved survival in BD. Discontinuous exposure does not confer the same benefit. Ensuring treatment continuity may maximize lithium’s protective effect and improve long-term outcomes.

There are limited data to guide treatment continuation decisions for clinicians caring for patients with treatment resistant depression (TRD). Identifying the magnitude of early improvement (at Weeks 4 and 8) as a predictor of long-term outcomes for TRD can guide treatment continuation decisions.

To evaluate the probability of achieving response or remission by Week 32 in patients with TRD after 4 or 8 weeks of esketamine nasal spray (ESK-NS) treatment, flexibly dosed in combination with an ongoing selective serotonin/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI).

ESCAPE‑TRD was a randomised phase IIIb trial comparing the efficacy of ESK-NS versus quetiapine extended release, both in combination with an ongoing SSRI/SNRI, in patients with TRD (Reif et al. NEJM 2023; 389 1298–309). Remission was defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤10, and partial response and response as ≥25% and ≥50% improvements, respectively, in total MADRS score (or remission). Long-term outcomes were based on the best outcome on-treatment across 32 weeks (≥1 instance of response or remission) from earliest outcome endpoint onwards. Non-responder imputation (NRI) was applied after treatment discontinuations.

336 patients were randomised to ESK-NS; 334 received ≥1 dose. Table 1 shows long-term outcomes following at least partial response, response or no partial response at Weeks 4 and 8. For example, among those who had at least a partial response at Week 4, 94.1% and 79.8% had response and remission by Week 32, respectively.

Image 1:

This analysis demonstrated a relationship between short- and long-term outcomes. Presence of at least partial response at Week 4 led to more favourable outcomes by Week 32. Moreover, most patients with response by Week 4 achieved remission by Week 32. Continued symptom improvements were observed beyond the induction phase even in some patients with no partial response at Week 4.

None Declared

Noradrenergic activation in the central and peripheral nervous systems is a putative mechanism explaining the link between hypertension and affective disorders.

We investigated whether these stress-sensitive comorbidities may be dependent on basal noradrenergic activity and whether vascular responses to centrally acting stimuli vary according to noradrenergic activity.

We examined the relation of affective disorders and stress-mediated vascular responses to plasma concentrations of normetanephrine, a measure of noradrenergic activity, in subjects with primary hypertension (n = 100, mean ± s.d. age 43 ± 11 years, 54% male). The questionnaires Patient Health Questionnaire-9 (PHQ-9), 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDSSR-16) and Generalized Anxiety Disorder-7 (GAD-7) were used for evaluation of symptoms of depression and anxiety. Forearm blood flow (strain gauge plethysmography) was used to assess vascular responses to mental stress and to device-guided breathing (DGB), interventions that respectively increase or decrease noradrenergic activity in the prefrontal cortex and locus coeruleus.

Low mood and high anxiety were two- to threefold higher for hypertensive subjects in the highest compared with the lowest normetanephrine tertiles (each P < 0.005). Forearm vasodilator responses to mental stress and vasoconstrictor responses to DGB were attenuated in those with high compared with low normetanephrine (28.3 ± 21% v. 47.1 ± 30% increases for mental stress and 3.7 ± 21% v. 18.6 ± 15% decreases for DGB for highest versus lowest tertiles of normetanephrine, each P ≤ 0.01).

A hyperadrenergic state in hypertension is associated with mood disturbance and impaired stress-modulated vasomotor responses. This association may be mediated by chronic stress impinging on pathways regulating central arousal and peripheral sympathetic nerve activity.

The prevalence of psychiatric disorders in people with epilepsy is as high as 43% and, among them, psychoses represent a severe comorbidity.

This is a narrative review discussing the interplay between epilepsy and psychosis and identifying challenges in diagnosing and managing psychotic symptoms in epilepsy, focusing on the past 10 years.

Articles published between June 2014 and December 2024 were identified through searches in PubMed using the search terms ‘psychosis’, ’seizure, epilepsy and convulsion’, ‘epile*’, ’seizure*’ and ‘convuls*’.

The association between epilepsy and psychosis was shown to be bidirectional, with people with psychosis being at increased risk of epilepsy. In epilepsy, psychotic symptoms may occur in three clinical scenarios, with clinical presentation and management varying in relationship to these: seizure-related (peri-ictal), treatment-related or independent of the former.

There are no guidelines for the management of psychotic symptoms in epilepsy, but it is possible to apply policies for the treatment of psychoses, taking into account the peculiarities and needs of people with epilepsy.

Late-life affective disorders (LLADs) are common and are projected to increase by 2050. There have been several studies linking late-life depression to an increased risk of dementia, but it is unclear if bipolar affective disorder or anxiety disorders pose a similar risk.

We aimed to compare the risk of LLADs progressing to all-cause dementia, and the demographic and clinical variables mediating the risk.

We used the South London and Maudsley National Health Service Foundation Trust Clinical Records Interactive Search system to identify patients aged 60 years or older with a diagnosis of any affective disorder. Cox proportional hazard models were used to determine differences in dementia risk between late-life anxiety disorders versus late-life depression, and late-life bipolar disorder versus late-life depression. Demographic and clinical characteristics associated with the risk of dementia were investigated.

Some 5695 patients were identified and included in the final analysis. Of these, 388 had a diagnosis of bipolar affective disorder, 1365 had a diagnosis of an anxiety disorder and 3942 had a diagnosis of a depressive disorder. Bipolar affective disorder was associated with a lower hazard of developing dementia compared to depression (adjusted model including demographics and baseline cognition, hazard ratio: 0.60; 95% CI: 0.41–0.87). Anxiety disorders had a similar hazard of developing dementia (adjusted hazard ratio: 1.05; 95% CI: 0.90–1.22). A prior history of a depressive disorder reduced the risk of late-life depression progressing to dementia – suggesting the new onset of a depressive disorder in later life is associated with higher risk – but a prior history of anxiety disorders or bipolar affective disorder did not alter risk.

LLADs have a differential risk of developing all-cause dementia, with demographic- and illness-related factors influencing the risk. Further prospective cohort studies are needed to explore the link between LLADs and dementia development, and mediators of the lower risk of dementia associated with late-life bipolar disorder compared to late-life depression.

Evaluate Department of Defense (DoD) antimicrobial stewardship programs (ASPs) by assessing the relationship between key clinical outcome metrics (antibiotic use, incidence of resistant pathogens, and incidence of Clostridioides difficile infections) and CDC Core Element (CE) adherence.

Retrospective, cross-sectional study of DoD hospitals in 2018 and 2021

National Healthcare Safety Network Standardized Antimicrobial Administration Ratios (SAARs) were used to measure antibiotic use and microbiology results to evaluate four types of pathogen incidence. A novel CE scoring approach used scores to quantitatively assess relationships with CE adherence and outcome metrics using correlation and regression models. Assessments were repeated with 2021 data for Priority CE adherence and to conduct adjusted regressions for CEs and Priority CEs controlling for categorical bed size.

Compared to 2022 national data, DoD hospitals in 2021 had a similar proportion of facilities with a SAAR statistically significantly > 1.0. Leadership, Action, and Tracking CEs followed a more normal score distribution, while Reporting and Education were somewhat left-skewed. Unadjusted models often showed a positive relationship with higher CE scores associated with worse outcomes for the SAAR and pathogen incidence. Adjusted models indicated that procedural CEs, particularly Priority Reporting, were associated with better ASP-related outcomes.

CEs should be more quantitatively assessed. Results provide initial evidence to prioritize procedural CE implementation within the DoD; however, additional investigation for structural CEs is needed. Patient outcome data should be collected as an important indicator of ASP performance.

Sustained attention is integral to goal-directed tasks in everyday life. It is a demanding and effortful process prone to failure. Deficits are particularly prevalent in mood disorders. However, conventional methods of assessment, rooted in overall measures of performance, neglect the nuanced temporal dimensions inherent in sustained attention, necessitating alternative analytical approaches.

This study investigated sustained attention deficits and temporal patterns of attentional fluctuation in a large clinical cohort of patients with bipolar depression (BPd, n = 33), bipolar euthymia (BPe, n = 84), major depression (MDd, n = 38) and controls (HC, n = 138) using a continuous performance task (CPT). Longitudinal and spectral analyses were employed to examine trial-level reaction time (RT) data.

Longitudinal analysis revealed a significant worsening of performance over time (vigilance decrement) in BPd, whilst spectral analysis unveiled attentional fluctuations concentrated in the frequency range of 0.077 Hz (1/12.90 s)–0.049 Hz (1/20.24 s), with BPd and MDd demonstrating greater spectral power compared to BPe and controls.

Although speculative, the increased variability in this frequency range may have an association with the dysfunctional activity of the Default Mode Network, which has been shown to oscillate at a similar timescale. These findings underscore the importance of considering the temporal dimensions of sustained attention and show the potential of spectral analysis of RT in future clinical research.