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.

Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Many consultations in primary care involve patients with mental health problems, and primary care is typically the place where many such patients initially seek help. While considerable research has examined the prevalence of mental health disorders in primary care, relatively few papers have examined this issue in recent years. This study aims to address this gap by reviewing contemporary literature from 2014 to 2024 on the prevalence of mental health disorders among general practice patients.

A comprehensive search across PubMed, PsycINFO, and Google Scholar was conducted, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for article selection and assessment, examining the prevalence of mental health disorders in general practice.

Studies varied in methodologies and healthcare settings, with reported prevalence rates of mental health disorders ranging from 2.4% to 56.3%. Demographic characteristics (female gender, older age) were associated with a higher prevalence of mental health disorders in the studies identified. Studies based on patient interviews reported broader prevalence (2.4–56.3%) compared to studies using electronic medical record reviews (12–38%). Prevalence also varied between countries. Notably, there has been a lack of post-COVID-19 studies, especially within Europe, examining the prevalence of mental health prevalence in primary care.

Mental health problems are still common among patients attending general practice; the approach to data collection (i.e., prospective interviews with patients), female gender and older age appear to be correlates of higher estimates. Further research involving a large-scale study with multiple sites is a priority.

Medicare claims are frequently used to study Clostridioides difficile infection (CDI) epidemiology. However, they lack specimen collection and diagnosis dates to assign location of onset. Algorithms to classify CDI onset location using claims data have been published, but the degree of misclassification is unknown.

We linked patients with laboratory-confirmed CDI reported to four Emerging Infections Program (EIP) sites from 2016–2021 to Medicare beneficiaries with fee-for-service Part A/B coverage. We calculated sensitivity of ICD-10-CM codes in claims within ±28 days of EIP specimen collection. CDI was categorized as hospital, long-term care facility, or community-onset using three different Medicare claims-based algorithms based on claim type, ICD-10-CM code position, duration of hospitalization, and ICD-10-CM diagnosis code presence-on-admission indicators. We assessed concordance of EIP case classifications, based on chart review and specimen collection date, with claims case classifications using Cohen’s kappa statistic.

Of 12,671 CDI cases eligible for linkage, 9,032 (71%) were linked to a single, unique Medicare beneficiary. Compared to EIP, sensitivity of CDI ICD-10-CM codes was 81%; codes were more likely to be present for hospitalized patients (93.0%) than those who were not (56.2%). Concordance between EIP and Medicare claims algorithms ranged from 68% to 75%, depending on the algorithm used (κ = 0.56–0.66).

ICD-10-CM codes in Medicare claims data had high sensitivity compared to laboratory-confirmed CDI reported to EIP. Claims-based epidemiologic classification algorithms had moderate concordance with EIP classification of onset location. Misclassification of CDI onset location using Medicare algorithms may bias findings of claims-based CDI studies.

To explore current and potential upcoming legal provisions concerning advance healthcare directives in psychiatry in Ireland, with particular focus on clinical challenges and ethical issues (e.g., self-harm, suicide).

Review and analysis of selected relevant sections of the Assisted Decision-Making (Capacity) Act 2015, Assisted Decision-Making (Capacity) (Amendment) Act 2022, Mental Health Act 2001, Mental Health Bill 2024, and Criminal Law (Suicide) Act 1993, and relevant publications from Ireland’s Medical Council and Decision Support Service.

The Assisted Decision-Making (Capacity) Act 2015 outlined new procedures for advance healthcare directives. The Assisted Decision-Making (Capacity) (Amendment) Act 2022 specified that advance healthcare directives relating to mental health are binding for involuntary patients unless involuntary status is based on Section 3(1)(a) of the Mental Health Act 2001 (i.e., the ‘risk’ criteria). The Mental Health Bill 2024 proposes making advance healthcare directives binding for all involuntary patients. In relation to suicide and self-harm, the Criminal Law (Suicide) Act 1993 states that ‘a person who aids, abets, counsels or procures the suicide of another, or an attempt by another to commit suicide, shall be guilty of an offence’, and the Decision Support Service advises that healthcare professionals are exempted from criminal liability if complying with a valid and applicable advance healthcare directive that refuses life-sustaining treatment, even where the directive-maker has attempted suicide.

Considerable public and professional education are needed if advance healthcare directives are to be widely used. The ethical dimensions of certain advance directives require additional thought and, ideally, professional ethical guidance.

Concerns about penicillin-cephalosporin cross-reactivity have historically led to conservative prescribing and avoidance of cephalosporins in patients with penicillin allergy labels, potentially causing suboptimal outcomes. Recent evidence suggests a lower risk of cross-reactivity, prompting a reassessment of alert systems.

To assess the impact of limited penicillin cross-reactivity alerts on outpatient cephalosporin use and the incidence of adverse reactions in a healthcare setting.

This retrospective cohort study compared cephalosporin prescribing and adverse reactions in patients labeled as penicillin-allergic before and after limiting penicillin cross-reactivity alerts in the electronic medical record at a large academic medical center.

Among 17,174 patients (8,131 pre- and 9,043 post-implementation), there was a statistically significant increase in outpatient cephalosporin prescribing by 8% (P < .001). The use of alternative antibiotic classes decreased. There was no statistically significant increase in adverse events pre- and post-implementation (0.036%–0.058%, P = .547), and no severe events were attributable to cross-reactivity. The alert modification reduced alerts by 92% (P < .001).

The reduction of penicillin-cephalosporin cross-reactivity alerts was associated with increased cephalosporin use, without a significant increase in adverse reactions. This demonstrates that the practice is safe and decreases alert burden.

Bathing intensive care unit (ICU) patients with chlorhexidine gluconate (CHG) decreases healthcare-associated infections (HAIs). The optimal method of CHG bathing remains undefined.

Prospective crossover study comparing CHG daily bathing with 2% CHG-impregnated cloths versus 4% CHG solution. In phase 1, from January 2020 through March 2020, 1 ICU utilized 2% cloths, while the other ICU utilized 4% solution. After an interruption caused by the coronavirus disease 2019 pandemic, in phase 2, from July 2020 through September 2020, the unit CHG bathing assignments were reversed. Swabs were performed 3 times weekly from patients’ arms and legs to measure skin microbial colonization and CHG concentration. Other outcomes included HAIs, adverse reactions, and skin tolerability.

411 assessments occurred after baths with 2% cloth, and 425 assessments occurred after baths with 4% solution. Average microbial colonization was 691 (interquartile range 0, 30) colony-forming units per square centimeter (CFU/cm2) for patients bathed with 2% cloths, 1,627 (0, 265) CFUs/cm2 for 4% solution, and 8,519 (10, 1130) CFUs/cm2 for patients who did not have a CHG bath (P < .001). Average CHG skin concentration (parts per million) was 1300.4 (100, 2000) for 2% cloths, 307.2 (30, 200) for 4% solution, and 32.8 (0, 20) for patients without a recorded CHG bath. Both CHG bathing methods were well tolerated. Although underpowered, no difference in HAI was noted between groups.

Either CHG bathing method resulted in a significant decrease in microbial skin colonization with a greater CHG concentration and fewer organisms associated with 2% CHG cloths.

Long-acting injectable antipsychotics (LAIs) reduce relapses in schizophrenia; however, most healthcare professionals (HCPs) reserve LAIs for nonadherence to oral antipsychotics (OAs) or severe disease.

US HCPs were surveyed regarding attitudes and perceptions toward LAIs for schizophrenia and LAI selection preferences. Respondents were grouped by LAI use (high [≥31% of patients using LAIs], low [≤14% using LAIs]; mid not analyzed) and archetype based on response to, “Which of the following best fits the current way you view your use of [LAIs] for your patients with schizophrenia?” (see responses below).

Respondents (106 high, 130 low LAI use) were distributed across early LAI use (n=123), severity-reserved (n=88), adherence-reserved (n=113), and LAI-hesitant (n=56) archetypes.

Across all groups, HCPs estimated OA nonadherence in their practice (21%– 32%) to be lower than for patients nationwide (50%– 56%). Overall, 27% were dissatisfied with their LAI:OA use ratio, most thinking their OA use was too high. In all groups, side effects/tolerability was ranked as most important when choosing an LAI and “preference for the molecule” was ranked least important. Overall, 71%– 77% of HCPs were somewhat/much more likely to use a particular LAI based on multiple injection site options, small/on par needle, and price, and 63%– 82% of HCPs were somewhat/much more likely to select an LAI dosed once monthly or less often compared with an LAI dosed once every 2 weeks (8%). HCPs with high LAI use or early LAI use archetype were more likely to disagree that managing patients with schizophrenia increased their stress (64% and 63% vs 27%-45%, P<.05 each) and/or left them feeling “burned out” (77% and 79% vs 50%– 64%, P<.05 each).

Compared with other groups, greater proportions with high LAI use or early LAI use archetype consistently read new LAI publications (18% and 19% vs 0%– 5%, P<.01) and were confident in key aspects of LAI treatment (ie, dosing, managing side effects, access; 67%– 74% and 59%– 70% vs 11%– 57%, P<.05 each).

HCPs with low LAI use estimated the proportion of patients who initially refuse LAIs to be higher (mean, 55%) than those with low LAI use (44%, P<.01); there were no differences among archetypes (49%– 54%). HCPs with high LAI use or early LAI use archetype were more likely to “use any means necessary to ensure that a patient is on an LAI” vs other groups (44% and 51% vs 5%– 22%, P<.01 each) or had used guardianship to assist with treatment (70% and 69% vs 32%– 56%, P<.05 each); greater proportions with high LAI use or early LAI use archetype strongly agreed it was “worth [their] time to resolve issues with the insurance company” (42% and 45% vs 16%– 30%, P<.05 each) and were confident they would be able to do so (23% and 20% vs 2%– 11%, P<.05 each). Greater proportions of HCPs with early LAI use archetype vs the severity-reserved archetype strongly agreed that they attempt to determine the patient’s/caregiver’s preferred role before involving them (43% vs 27%, P<.05) and encourage them to participate (72% vs 57%, P<.05) in shared decision-making.

Comparing HCPs with high LAI use or early LAI use archetype vs other groups, multiple factors (eg, attitudes, preferences, training, knowledge base) combine to influence LAI use. These results highlight considerations for developing educational materials to increase LAI use in this population.

Teva Branded Pharmaceutical Products R&D, Inc.

To outline the life and work of Greek physician Asclepiades of Bithynia (124–40 BC), especially his contributions to thinking about mental illness.

Review and discussion of relevant fragments of Asclepiades’ work that survive and review of secondary literature, supplemented by relevant systematic literature searches (e.g. PubMed).

Asclepiades challenged the long-standing Hippocratic doctrine of the four humours and developed an approach to physical and mental illness that was humane, reasoned, and a forerunner of later developments in psychiatry. Asclepiades argued that the human body, like everything in the universe, comprised tiny, imperceptible particles, which he called önkoi, seamless masses in perpetual motion. In consequence, Yapijakis describes Asclepiades as ‘the father of molecular medicine’. Asclepiades held that good health was maintained by free, balanced motion of önkoi through theoretical pores, while disease resulted from blockage or impaction of önkoi passing through pores in various body parts (e.g. brain). Based on this idea, Asclepiades recommended releasing people with apparent mental illness from confinement and using judicious combinations of diet, exercise, massage, bathing, and music to treat ‘phrenitis’ (delirium) and melancholia. He suggested that the physician act ‘safely, swiftly and pleasantly’ (‘cito, tutu, jucunde’) for both physical and mental illness.

Asclepiades belongs to the historical tradition of progressive medical approaches to mental illness, not least because he applied his principles for the treatment of physical illness to mental illness. His ideas about psychiatry set the scene for further evolution of attitudes to mental illness and its treatment over subsequent centuries.

Paediatric patients with heart failure requiring ventricular assist devices are at heightened risk of neurologic injury and psychosocial adjustment challenges, resulting in a need for neurodevelopmental and psychosocial support following device placement. Through a descriptive survey developed in collaboration by the Advanced Cardiac Therapies Improving Outcomes Network and the Cardiac Neurodevelopmental Outcome Collaborative, the present study aimed to characterise current neurodevelopmental and psychosocial care practices for paediatric patients with ventricular assist devices.

Members of both learning networks developed a 25-item electronic survey assessing neurodevelopmental and psychosocial care practices specific to paediatric ventricular assist device patients. The survey was sent to Advanced Cardiac Therapies Improving Outcomes Network site primary investigators and co-primary investigators via email.

Of the 63 eligible sites contacted, responses were received from 24 unique North and South American cardiology centres. Access to neurodevelopmental providers, referral practices, and family neurodevelopmental education varied across sites. Inpatient neurodevelopmental care consults were available at many centres, as were inpatient family support services. Over half of heart centres had outpatient neurodevelopmental testing and individual psychotherapy services available to patients with ventricular assist devices, though few centres had outpatient group psychotherapy (12.5%) or parent support groups (16.7%) available. Barriers to inpatient and outpatient neurodevelopmental care included limited access to neurodevelopmental providers and parent/provider focus on the child’s medical status.

Paediatric patients with ventricular assist devices often have access to neurodevelopmental providers in the inpatient setting, though supports vary by centre. Strengthening family neurodevelopmental education, referral processes, and family-centred psychosocial services may improve current neurodevelopmental/psychosocial care for paediatric ventricular assist device patients.

To measure SARS-CoV-2 anti-nucleocapsid (anti-N) antibody seropositivity among healthcare personnel (HCP) without a history of COVID-19 and to identify HCP characteristics associated with seropositivity.

Prospective cohort study from September 22, 2020, to March 3, 2022.

A tertiary care academic medical center.

727 HCP without prior positive SARS-CoV-2 PCR testing were enrolled; 559 HCP successfully completed follow-up.

At enrollment and follow-up 1–6 months later, HCP underwent SARS-CoV-2 anti-N testing and were surveyed on demographics, employment information, vaccination status, and COVID-19 symptoms and exposures.

Of 727 HCP enrolled, 27 (3.7%) had a positive SARS-CoV-2 anti-N test at enrollment. Seropositive HCPs were more likely to have a household exposure to COVID-19 in the past 30 days (OR 7.92, 95% CI 2.44–25.73), to have had an illness thought to be COVID-19 (4.31, 1.94–9.57), or to work with COVID-19 patients more than half the time (2.09, 0.94–4.77). Among 559 HCP who followed-up, 52 (9.3%) had a positive SARS-CoV-2 anti-N antibody test result. Seropositivity at follow-up was associated with community/household exposures to COVID-19 within the past 30 days (9.50, 5.02–17.96; 2.90, 1.31–6.44), having an illness thought to be COVID-19 (8.24, 4.44–15.29), and working with COVID-19 patients more than half the time (1.50, 0.80–2.78).

Among HCP without prior positive SARS-CoV-2 testing, SARS-CoV-2 anti-N seropositivity was comparable to that of the general population and was associated with COVID-19 symptomatology and both occupational and non-occupational exposures to COVID-19.

Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.

We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.

The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).

The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.

Imagery-focused therapies within cognitive behavioural therapy are growing in interest and use for people with delusions.

This review aimed to examine the outcomes of imagery-focused interventions in people with delusions.

PsycINFO, PubMed, MEDLINE, Web of Science, EMBASE and CINAHL were systematically searched for studies that included a clinical population with psychosis and delusions who experienced mental imagery. The review was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and quality appraisal of all included papers was completed using the Crowe Critical Appraisal Tool. Information from included texts was extracted and collated in Excel, which informed the narrative synthesis of results.

Of 2,736 studies identified, eight were eligible for inclusion and rated for quality with an average score of 70.63%. These studies largely supported their aims in reducing levels of distress and intrusiveness of imagery. Four of the eight studies used case series designs, two were randomised controlled trials, and two reported single case studies. It appears that interventions targeting mental imagery were acceptable and well tolerated within a population of people experiencing psychosis and delusions.

Some therapeutic improvement was reported, although the studies consisted of mainly small sample sizes. Clinical implications include that people with a diagnosis of psychosis can engage with imagery-focused therapeutic interventions with limited adverse events. Future research is needed to tackle existing weaknesses of design and explore the outcomes of imagery interventions within this population in larger samples, under more rigorous methodologies.