Individuals with physical comorbidities and polypharmacy may be at higher risk of depression relapse, however, they are not included in the ‘high risk of relapse’ group for whom longer antidepressant treatment durations are recommended.

In individuals with comorbid depression and type 2 diabetes (T2DM), we aimed to investigate the association and interaction between depression relapse and (a) polypharmacy, (b) previous duration of antidepressant treatment.

This was a cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) from years 2000 to 2018. We used Cox regression models with penalised B-splines to describe the association between restarting antidepressants and our two exposures.

We identified 48 001 individuals with comorbid depression and T2DM, who started and discontinued antidepressant treatment during follow-up. Within 1 year of antidepressant discontinuation, 35% of participants restarted treatment indicating depression relapse. As polypharmacy increased, the rate of restarting antidepressants increased until a maximum of 18 concurrent medications, where individuals were more than twice as likely to restart antidepressants (hazard ratio (HR) = 2.15, 95% CI 1.32–3.51). As the duration of previous antidepressant treatment increased, the rate of restarting antidepressants increased – individuals with a previous duration of ≥25 months were more than twice as likely to restart antidepressants than those who previously discontinued in <7 months (HR = 2.36, 95% CI 2.25–2.48). We found no interaction between polypharmacy and previous antidepressant duration.

Polypharmacy and longer durations of previous antidepressant treatment may be associated with depression relapse following the discontinuation of antidepressant treatment.

Current neurobiological models of post-traumatic stress disorder (PTSD) assume excessive medial frontal activation and hypoactivation of cortico-limbic regions as neural markers of post-traumatic dissociation. Script-driven imagery is an established experimental paradigm that is used to study acute dissociative reactions during trauma exposure. However, there is a scarcity of experimental research investigating neural markers of dissociation; findings from existing script-driven neuroimaging studies are inconsistent and based on small sample sizes.

The current aim was to identify the neural correlates of acute post-traumatic dissociation by employing the script-driven imagery paradigm in combination with functional magnetic resonance imaging.

Functional neuroimaging data was acquired in 51 female patients with PTSD with a history of interpersonal childhood trauma. Blood-oxygen-level-dependent response during the traumatic (versus neutral) autobiographical memory recall was analysed, and the derived activation clusters were correlated with dissociation measures.

During trauma recall, enhanced activation in the cerebellum, occipital gyri, supramarginal gyrus and amygdala was identified. None of the derived clusters correlated significantly with dissociative symptoms, although patients reported increased levels of acute dissociation following the paradigm.

The present study is one of the largest functional magnetic resonance imaging investigations of dissociative neural biomarkers in patients with PTSD undergoing experimentally induced trauma confrontation to elicit symptom-specific brain reactivity. In light of the current reproducibility crisis prominent in neuroimaging research owing to costly and time-consuming data acquisition, the current (null) findings highlight the difficulty of extracting reliable neurobiological biomarkers for complex subjective experiences such as dissociation.

To evaluate coronavirus disease 2019 (COVID-19) vaccine hesitancy among healthcare personnel (HCP) with significant clinical exposure to COVID-19 at 2 large, academic hospitals in Philadelphia, Pennsylvania.

HCP were surveyed in November–December 2020 about their intention to receive the COVID-19 vaccine.

The survey measured the intent among HCP to receive a COVID-19 vaccine, timing of vaccination, and reasons for or against vaccination. Among patient-facing HCP, multivariate regression evaluated the associations between healthcare positions (medical doctor, nurse practitioner or physician assistant, and registered nurse) and vaccine hesitancy (intending to decline, delay, or were unsure about vaccination), adjusting for demographic characteristics, reasons why or why not to receive the vaccine, and prior receipt of routine vaccines.

Among 5,929 HCP (2,253 medical doctors [MDs] and doctors of osteopathy [DOs], 582 nurse practitioners [NPs], 158 physician assistants [PAs], and 2,936 nurses), a higher proportion of nurses (47.3%) were COVID-vaccine hesitant compared with 30.0% of PAs and NPs and 13.1% of MDs and DOs. The most common reasons for vaccine hesitancy included concerns about side effects, the newness of the vaccines, and lack of vaccine knowledge. Regardless of position, Black HCP were more hesitant than White HCP (odds ratio [OR], ∼5) and females were more hesitant than males (OR, ∼2).

Although most clinical HCP intended to receive a COVID-19 vaccine, intention varied by healthcare position. Consistent with other studies, hesitancy was also significantly associated with race or ethnicity across all positions. These results highlight the importance of understanding and effectively addressing reasons for hesitancy, especially among frontline HCP who are at increased risk of COVID exposure and play a critical role in recommending vaccines to patients.

Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.

We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.

We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).

Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.

Rey’s Auditory Verbal Learning Test (AVLT) is a widely used word list memory test. We update normative data to include adjustment for verbal memory performance differences between men and women and illustrate the effect of this sex adjustment and the importance of excluding participants with mild cognitive impairment (MCI) from normative samples.

This study advances the Mayo’s Older Americans Normative Studies (MOANS) by using a new population-based sample through the Mayo Clinic Study of Aging, which randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. Regression-based normative T-score formulas were derived from 4428 cognitively unimpaired adults aged 30–91 years. Fully adjusted T-scores correct for age, sex, and education. We also derived T-scores that correct for (1) age or (2) age and sex. Test-retest reliability data are provided.

From raw score analyses, sex explained a significant amount of variance in performance above and beyond age (8–10%). Applying original age-adjusted MOANS norms to the current sample resulted in significantly fewer-than-expected participants with low delayed recall performance, particularly in women. After application of new T-scores adjusted only for age, even in normative data derived from this sample, these age-adjusted T-scores showed scores <40 T occurred more frequently among men and less frequently among women relative to T-scores that also adjusted for sex.

Our findings highlight the importance of using normative data that adjust for sex with measures of verbal memory and provide new normative data that allow for this adjustment for the AVLT.

Pedophilia is a disorder where sexual preferences of adults are directed towards children. This disorder impacts society with 1–2 out of every 10 children being sexually approached by an adult, often resulting in prolonged negative psychological effects. Prior research reported structural and functional amygdala alterations in pedophilia. As the neurophenomenological model of sexual arousal suggests the importance of the amygdala in the emotional component, we focused on amygdala functional connectivity in pedophilia.

To investigate amygdala functional connectivity (FC) modulated by expectancy and salient stimuli in pedophilic patients.

Thirteen pedophilic patients and 13 matched healthy controls underwent a salience expectancy task in a 7T ultra high fMRI study. Subjects perceived pictures of naked adults and children. Half of the pictures were preceded by an expectancy cue. Participants were instructed to actively expect the picture depending on the cue. We conducted psychophysiological analysis (PPI) to examine amygdala FC changes in two amygdala sub-regions for child/adult stimuli during the expectancy period and the visual stimuli consummation period using as seed regions the basolateral (BLA) and central nucleus of the amygdala (CeA).

Healthy controls, relative to patients showed significant stronger left CeA to right post-central gyrus FC during expectancy of adult > child picture. For picture condition (adult > child picture) we found significant stronger left CeA to left dorsolateral prefrontal cortex FC in patients compared to healthy controls.

These findings add to the recent literature by indicating that amygdala dysfunctional connectivity is involved in development of deviant sexual behavior.

The authors have not supplied their declaration of competing interest.

The development and maintenance of an alcohol addiction is a complex interaction between genetic and environmental factors. Genetic effects seem to contribute substantially to the risk of developing an addiction, but also to its course and patients’ responses to different treatments. Recent studies identified associations between polymorphisms in the genes of glutamate and μ-opioid receptors and addiction risk. Those receptors are of special interest, because they are targets of therapeutic agents, such as acamprosate and topiramate.

Several studies were conducted, in order to further determine the effects of genetic polymorphisms in glutamate and opioid receptor genes on addictive behavior, neural response to alcohol cues and relapse risk.

Genetic effects were investigated in samples of alcohol-dependent patients using functional imaging techniques, neuropsychological tests and follow-up investigation after standard clinical treatment. Data on clinical parameters, neuronal response to alcohol cues, functional neuronal connectivity and relapse risk were collected and analyzed.

Results demonstrate effects of genetic polymorphisms in glutamate and opioid receptors on neuronal response to alcohol cues in frontal and mesolimbic brain areas, subjective craving and time to first relapse. Current findings will be discussed in the light of existing evidence on the contribution of genetic effects to treatment outcome and patient stratification.

The investigation of genetic risk factors and mechanisms by which they affect addiction related phenotypes seems to be a promising tool to identify molecular treatment targets and predictors for successful treatment strategies.

The authors have not supplied their declaration of competing interest.

Cardiovascular risk prediction tools are important for cardiovascular disease (CVD) prevention, however, which algorithms are appropriate for people with severe mental illness (SMI) is unclear.

To determine the cost-effectiveness using the net monetary benefit (NMB) approach of two bespoke SMI-specific risk algorithms compared to standard risk algorithms for primary CVD prevention in those with SMI, from an NHS perspective.

A microsimulation model was populated with 1000 individuals with SMI from The Health Improvement Network Database, aged 30–74 years without CVD. Four cardiovascular risk algorithms were assessed; (1) general population lipid, (2) general population BMI, (3) SMI-specific lipid and (4) SMI-specific BMI, compared against no algorithm. At baseline, each cardiovascular risk algorithm was applied and those high-risk (> 10%) were assumed to be prescribed statin therapy, others received usual care. Individuals entered the model in a ‘healthy’ free of CVD health state and with each year could retain their current health state, have cardiovascular events (non-fatal/fatal) or die from other causes according to transition probabilities.

The SMI-specific BMI and general population lipid algorithms had the highest NMB of the four algorithms resulting in 12 additional QALYs and a cost saving of approximately £37,000 (US$ 58,000) per 1000 patients with SMI over 10 years.

The general population lipid and SMI-specific BMI algorithms performed equally well. The ease and acceptability of use of a SMI-specific BMI algorithm (blood tests not required) makes it an attractive algorithm to implement in clinical settings.

The authors have not supplied their declaration of competing interest.