Autoimmune encephalitis (AE) is an important consideration during the diagnostic work-up of secondary mental disorders. Indeed, isolated psychiatric syndromes have been described in case reports of patients with underlying AE. Therefore, the authors performed a systematic literature review of published cases with AE that have predominant psychiatric/neurocognitive manifestations. The aim of this paper is to present the clinical characteristics of these patients.

The authors conducted a systematic Medline search via Ovid, looking for case reports/series of AEs with antineuronal autoantibodies (Abs) against cell surface/intracellular antigens combined with predominant psychiatric/neurocognitive syndromes. The same was done for patients with Hashimoto encephalopathy/SREAT. Only patients with signs of immunological brain involvement or tumors in their diagnostic investigations or improvement under immunomodulatory drugs were included.

We identified 145 patients with AE mimicking predominant psychiatric/neurocognitive syndromes. Of these cases, 64% were female, and the mean age among all patients was 43.9 (±22.1) years. Most of the patients had Abs against neuronal cell surface antigens (55%), most frequently against the NMDA-receptor (N = 46). Amnestic/dementia-like (39%) and schizophreniform (34%) syndromes were the most frequently reported. Cerebrospinal fluid changes were found in 78%, electroencephalography abnormalities in 61%, and magnetic resonance imaging pathologies in 51% of the patients. Immunomodulatory treatment was performed in 87% of the cases, and 94% of the patients responded to treatment.

Our findings indicate that AEs can mimic predominant psychiatric and neurocognitive disorders, such as schizophreniform psychoses or neurodegenerative dementia, and that affected patients can be treated successfully with immunomodulatory drugs.

Changes in autonomic nervous system (ANS) function have been observed in a variety of psychological disorders, including posttraumatic stress disorder (PTSD). Analysis of heart rate variability (HRV) provides insight into the functioning of the ANS. Previous research on PTSD found lower HRV in PTSD patients compared to controls, indicating altered sympathetic and parasympathetic activity, but findings are inconsistent. The purpose of this meta-analysis was to examine differences in HRV indices between individuals with PTSD and healthy controls at baseline and during stress.

The included primary studies present an aggregate of studies analyzing different HRV indices. Examined HRV indices were standard deviation of the normalized NN-intervals (SDNN), root mean square of successive differences (RMSSD), low-frequency (LF) and high-frequency (HF) spectral components, LF/HF ratio, and heart rate (HR). Moderating effects of study design, HRV and PTSD assessment, and sample characteristics were examined via subgroup-analyses and meta-regressions.

Random-effects meta-analyses for HRV parameters at rest revealed significant group differences for RMSSD and HF-HRV, suggesting lower parasympathetic activity in PTSD. The aggregated effect size for SDNN was medium, suggesting diminished total variability in PTSD. A small effect was found for LF-HRV. A higher LF/HF ratio was found in the PTSD sample as compared to controls. Individuals with PTSD showed significantly higher HR. During stress, individuals with PTSD showed higher HR and lower HF-HRV, both indicated by small effect sizes.

Findings suggest that PTSD is associated with ANS dysfunction.

No studies have reported on how to relieve distress or relax in medical health workers while wearing medical protective equipment in coronavirus disease 2019 (COVID-19) pandemic. The study aimed to establish which relaxation technique, among six, is the most feasible in first-line medical health workers wearing medical protective equipment.

This was a two-step study collecting data with online surveys. Step 1: 15 first-line medical health workers were trained to use six different relaxation techniques and reported the two most feasible techniques while wearing medical protective equipment. Step 2: the most two feasible relaxation techniques revealed by step 1 were quantitatively tested in a sample of 65 medical health workers in terms of efficacy, no space limitation, no time limitation, no body position requirement, no environment limitation to be done, easiness to learn, simplicity, convenience, practicality, and acceptance.

Kegel exercise and autogenic relaxation were the most feasible techniques according to step 1. In step 2, Kegel exercise outperformed autogenic relaxation on all the 10 dimensions among the 65 participants while wearing medical protective equipment (efficacy: 24 v. 15, no space limitation: 30 v. 4, no time limitation: 31 v. 4, no body position requirement: 26 v. 4, no environment limitation: 30 v. 11, easiness to learn: 28 v. 5, simplicity: 29 v. 7, convenience: 29 v. 4, practicality: 30 v. 14, acceptance: 32 v. 6).

Kegel exercise seems a promising self-relaxation technique for first-line medical health workers while wearing medical protective equipment among COVID-19 pandemic.

Virus outbreaks such as the current SARS-CoV-2 pandemic are challenging for health care workers (HCWs), affecting their workload and their mental health. Since both, workload and HCW's well-being are related to the quality of care, continuous monitoring of working hours and indicators of mental health in HCWs is of relevance during the current pandemic. The existing investigations, however, have been limited to a single study period. We examined changes in working hours and mental health in Swiss HCWs at the height of the pandemic (T1) and again after its flattening (T2).

We conducted two cross-sectional online studies among Swiss HCWs assessing working hours, depression, anxiety, and burnout. From each study, 812 demographics-matched participants were included into the analysis. Working hours and mental health were compared between the two samples.

Compared to prior to the pandemic, the share of participants working less hours was the same in both samples, whereas the share of those working more hours was lower in the T2 sample. The level of depression did not differ between the samples. In the T2 sample, participants reported more anxiety, however, this difference was below the minimal clinically important difference. Levels of burnout were slightly higher in the T2 sample.

Two weeks after the health care system started to transition back to normal operations, HCWs' working hours still differed from their regular hours in non-pandemic times. Overall anxiety and depression among HCWs did not change substantially over the course of the current SARS-CoV-2 pandemic.

The COVID-19 pandemic has greatly affected public health and wellbeing. In response to the pandemic threat of the coronavirus epidemic, several countries, including China, adopted lockdown and quarantine policies, which may cause psychological distress. This study aimed to explore the psychological impact of province-wide lockdown and personal quarantine during the COVID-19 outbreak in China as well as the corresponding risk factors and protective factors.

We examined the immediate (2-week) and delayed (2-month) impact of province-wide lockdown and personal quarantine on psychological distress in a national sample of 1390 Chinese residents.

No immediate impact of province-wide lockdown on psychological distress was observed, whereas personal quarantine increased individuals’ anxiety, fear, and anger. Despite the lack of initial association, psychological distress increased among those in province-wide lockdown. Self-stigma and personal control both significantly moderated the association between lockdown and psychological distress, but in different directions. Those with higher self-stigma and lower personal control were more impacted by the lockdown. Government support moderated the impact of quarantine on psychological distress, but not that of lockdown.

The delayed effects of lockdown and quarantine on psychological distress were observed, and self-stigma, social support, and perceived control moderate the relationships. This study is the first to demonstrate the psychological costs of province-wide lockdowns on individuals’ mental health, providing evidence of the need for mitigation strategies and timely public mental health preparedness in countries with recent outbreaks of COVID-19.

Cluster analyses have become popular tools for data-driven classification in biological psychiatric research. However, these analyses are known to be sensitive to the chosen methods and/or modelling options, which may hamper generalizability and replicability of findings. To gain more insight into this problem, we used Specification-Curve Analysis (SCA) to investigate the influence of methodological variation on biomarker-based cluster-analysis results.

Proteomics data (31 biomarkers) were used from patients (n = 688) and healthy controls (n = 426) in the Netherlands Study of Depression and Anxiety. In SCAs, consistency of results was evaluated across 1200 k-means and hierarchical clustering analyses, each with a unique combination of the clustering algorithm, fit-index, and distance metric. Next, SCAs were run in simulated datasets with varying cluster numbers and noise/outlier levels to evaluate the effect of data properties on SCA outcomes.

The real data SCA showed no robust patterns of biological clustering in either the MDD or a combined MDD/healthy dataset. The simulation results showed that the correct number of clusters could be identified quite consistently across the 1200 model specifications, but that correct cluster identification became harder when the number of clusters and noise levels increased.

SCA can provide useful insights into the presence of clusters in biomarker data. However, SCA is likely to show inconsistent results in real-world biomarker datasets that are complex and contain considerable levels of noise. Here, the number and nature of the observed clusters may depend strongly on the chosen model-specification, precluding conclusions about the existence of biological clusters among psychiatric patients.

Uncertainty exists about what causes brain structure alterations associated with schizophrenia (SZ) and bipolar disorder (BD). Whether a history of asphyxia-related obstetric complication (ASP) – a common but harmful condition for neural tissue – contributes to variations in adult brain structure is unclear. We investigated ASP and its relationship to intracranial (ICV), global brain volumes and regional cortical and subcortical structures.

A total of 311 patients on the SZ – BD spectrum and 218 healthy control (HC) participants underwent structural magnetic resonance imaging. They were evaluated for ASP using prospective information obtained from the Medical Birth Registry of Norway.

In all groups, ASP was related to smaller ICV, total brain, white and gray matter volumes and total surface area, but not to cortical thickness. Smaller cortical surface areas were found across frontal, parietal, occipital, temporal and insular regions. Smaller hippocampal, amygdala, thalamus, caudate and putamen volumes were reported for all ASP subgroups. ASP effects did not survive ICV correction, except in the caudate, which remained significantly smaller in both patient ASP subgroups, but not in the HC.

Since ASP was associated with smaller brain volumes in all groups, the genetic risk of developing a severe mental illness, alone, cannot easily explain the smaller ICV. Only the smaller caudate volumes of ASP patients specifically suggest that injury from ASP can be related to disease development. Our findings give support for the ICV as a marker of aberrant neurodevelopment and ASP in the etiology of brain development in BD and SZ.

Evidence suggests the incidence of non-affective psychotic disorders (NAPDs) varies across persons and places, but data from the Global South is scarce. We aimed to estimate the treated incidence of NAPD in Chile, and variance by person, place and time.

We used national register data from Chile including all people, 10–65 years, with the first episode of NAPD (International Classification of Diseases, Tenth Revision: F20–F29) between 1 January 2005 and 29 August 2018. Denominators were estimated from Chilean National Census data. Our main outcome was treated incidence of NAPD and age group, sex, calendar year and regional-level population density, multidimensional poverty and latitude were exposures of interest.

We identified 32 358 NAPD cases [12 136 (39.5%) women; median age-at-first-contact: 24 years (interquartile range 18–39 years)] during 171.1 million person-years [crude incidence: 18.9 per 100 000 person-years; 95% confidence interval (CI) 18.7–19.1]. Multilevel Poisson regression identified a strong age–sex interaction in incidence, with rates peaking in men (57.6 per 100 000 person-years; 95% CI 56.0–59.2) and women (29.5 per 100 000 person-years; 95% CI 28.4–30.7) between 15 and 19 years old. Rates also decreased (non-linearly) over time for women, but not men. We observed a non-linear association with multidimensional poverty and latitude, with the highest rates in the poorest regions and those immediately south of Santiago; no association with regional population density was observed.

Our findings inform the aetiology of NAPDs, replicating typical associations with age, sex and multidimensional poverty in a Global South context. The absence of association with population density suggests this risk may be context-dependent.

Psychosis, and in particular auditory verbal hallucinations (AVHs), are associated with adversity exposure. However, AVHs also occur in populations with no need for care or distress.

This study investigated whether adversity exposure would differentiate clinical and healthy voice-hearers within the context of a ‘three-hit’ model of vulnerability and stress exposure.

Samples of 57 clinical and 45 healthy voice-hearers were compared on the three ‘hits’: familial risk; adversity exposure in childhood and in adolescence/adulthood.

Clinical voice-hearers showed greater familial risk than healthy voice-hearers, with more family members with a history of psychosis, but not with other mental disorders. The two groups did not differ in their exposure to adversity in childhood [sexual and non-sexual, victimisation; discrimination and socio-economic status (SES)]. Contrary to expectations, clinical voice-hearers did not differ from healthy voice-hearers in their exposure to victimisation (sexual/non-sexual) and discrimination in adolescence/adulthood, but reported more cannabis and substance misuse, and lower SES.

The current study found no evidence that clinical and healthy voice-hearers differ in lifetime victimisation exposure, suggesting victimisation may be linked to the emergence of AVHs generally, rather than need-for-care. Familial risk, substance misuse and lower SES may be additional risk factors involved in the emergence of need-for-care and distress.

A number of genomic conditions caused by copy number variants (CNVs) are associated with a high risk of neurodevelopmental and psychiatric disorders (ND-CNVs). Although these patients also tend to have cognitive impairments, few studies have investigated the range of emotion and behaviour problems in young people with ND-CNVs using measures that are suitable for those with learning difficulties.

A total of 322 young people with 13 ND-CNVs across eight loci (mean age: 9.79 years, range: 6.02–17.91, 66.5% male) took part in the study. Primary carers completed the Developmental Behaviour Checklist (DBC).

Of the total, 69% of individuals with an ND-CNV screened positive for clinically significant difficulties. Young people from families with higher incomes (OR = 0.71, CI = 0.55–0.91, p = .008) were less likely to screen positive. The rate of difficulties differed depending on ND-CNV genotype (χ2 = 39.99, p < 0.001), with the lowest rate in young people with 22q11.2 deletion (45.7%) and the highest in those with 1q21.1 deletion (93.8%). Specific patterns of strengths and weaknesses were found for different ND-CNV genotypes. However, ND-CNV genotype explained no more than 9–16% of the variance, depending on DBC subdomain.

Emotion and behaviour problems are common in young people with ND-CNVs. The ND-CNV specific patterns we find can provide a basis for more tailored support. More research is needed to better understand the variation in emotion and behaviour problems not accounted for by genotype.

During previous pandemic outbreaks, medical staff have reported high levels of psychological distress. The aim of the current study was to report a snapshot of the psychological impact of the coronavirus disease 2019 (COVID-19) pandemic and its correlated factors on medical staff in Guangdong, China.

On the 2nd and 3rd February 2020, soon after the start of the COVID-19 pandemic, we surveyed medical staff at four hospitals in Guangdong, China, to collect demographic characteristics, Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS-14), and Insomnia Severity Index (ISI) scores.

Complete responses were received from 1045 medical staff. Respondents were divided into high- and low-risk groups according to their working environment of contacting with potential or confirmed COVID-19 cases. The proportion of staff with anxiety (55.4% v. 43.0%, p < 0.001) or depression (43.6% v. 36.8%, p = 0.028) was significantly higher in the high-risk group than the low-risk group. The percentage of staff with severe anxiety was similar in the two groups. Doctors were more susceptible to moderate-to-severe depressive symptoms. The high-risk group had higher levels of clinical insomnia (13.5% v. 8.5%, p = 0.011) and were more likely to be in the upper quartile for stress symptoms (24.7% v. 19.3%, p = 0.037) than the low-risk group. Additionally, work experience negatively correlated with insomnia symptoms.

It is important for hospitals and authorities to protect both the physical and psychological health of medical staff during times of pandemic, even those with a low exposure risk.

Depression is a highly prevalent and heterogeneous disorder. This study aims to determine whether depression with atypical features shows different heritability and different degree of overlap with polygenic risk for psychiatric and immuno-metabolic traits than other depression subgroups.

Data included 30 069 European ancestry individuals from the UK Biobank who met criteria for lifetime major depression. Participants reporting both weight gain and hypersomnia were classified as ↑WS depression (N = 1854) and the others as non-↑WS depression (N = 28 215). Cases with non-↑WS depression were further classified as ↓WS depression (i.e. weight loss and insomnia; N = 10 142). Polygenic risk scores (PRS) for 22 traits were generated using genome-wide summary statistics (Bonferroni corrected p = 2.1 × 10−4). Single-nucleotide polymorphism (SNP)-based heritability of depression subgroups was estimated.

↑WS depression had a higher polygenic risk for BMI [OR = 1.20 (1.15–1.26), p = 2.37 × 10−14] and C-reactive protein [OR = 1.11 (1.06–1.17), p = 8.86 × 10−06] v. non-↑WS depression and ↓WS depression. Leptin PRS was close to the significance threshold (p = 2.99 × 10−04), but the effect disappeared when considering GWAS summary statistics of leptin adjusted for BMI. PRS for daily alcohol use was inversely associated with ↑WS depression [OR = 0.88 (0.83–0.93), p = 1.04 × 10−05] v. non-↑WS depression. SNP-based heritability was not significantly different between ↑WS depression and ↓WS depression (14.3% and 12.2%, respectively).

↑WS depression shows evidence of distinct genetic predisposition to immune-metabolic traits and alcohol consumption. These genetic signals suggest that biological targets including immune-cardio-metabolic pathways may be relevant to therapies in individuals with ↑WS depression.

In research and clinical practice, familial risk for depression and anxiety is often constructed as a simple Yes/No dichotomous family history (FH) indicator. However, this measure may not fully capture the liability to these conditions. This study investigated whether a continuous familial loading score (FLS), incorporating family- and disorder-specific characteristics (e.g. family size, prevalence of depression/anxiety), (i) is associated with a polygenic risk score (PRS) for major depression and with clinical/psychosocial vulnerabilities and (ii) still captures variation in clinical/psychosocial vulnerabilities after information on FH has been taken into account.

Data came from 1425 participants with lifetime depression and/or anxiety from the Netherlands Study of Depression and Anxiety. The Family Tree Inventory was used to determine FLS/FH indicators for depression and/or anxiety.

Persons with higher FLS had higher PRS for major depression, more severe depression and anxiety symptoms, higher disease burden, younger age of onset, and more neuroticism, rumination, and childhood trauma. Among these variables, FH was not associated with PRS, severity of symptoms, and neuroticism. After regression out the effect of FH from the FLS, the resulting residualized measure of FLS was still associated with severity of symptoms of depression and anxiety, rumination, and childhood trauma.

Familial risk for depression and anxiety deserves clinical attention due to its associated genetic vulnerability and more unfavorable disease profile, and seems to be better captured by a continuous score that incorporates family- and disorder-specific characteristics than by a dichotomous FH measure.

Inflammation and metabolic dysregulation are age-related physiological changes and are associated with depressive disorder. We tried to identify subgroups of depressed older patients based on their metabolic-inflammatory profile and examined the course of depression for these subgroups.

This clinical cohort study was conducted in a sample of 364 depressed older (⩾60 years) patients according to DSM-IV criteria. Severity of depressive symptoms was monitored every 6 months and a formal diagnostic interview repeated at 2-year follow-up. Latent class analyses based on baseline metabolic and inflammatory biomarkers were performed. Adjusted for confounders, we compared remission of depression at 2-year follow-up between the metabolic-inflammatory subgroups with logistic regression and the course of depression severity over 2-years by linear mixed models.

We identified a ‘healthy’ subgroup (n = 181, 49.7%) and five subgroups characterized by different profiles of metabolic-inflammatory dysregulation. Compared to the healthy subgroup, patients in the subgroup with mild ‘metabolic and inflammatory dysregulation’ (n = 137, 37.6%) had higher depressive symptom scores, a lower rate of improvement in the first year, and were less likely to be remitted after 2-years [OR 0.49 (95% CI 0.26–0.91)]. The four smaller subgroups characterized by a more specific immune-inflammatory dysregulation profile did not differ from the two main subgroups regarding the course of depression.

Nearly half of the patients with late-life depressions suffer from metabolic-inflammatory dysregulation, which is also associated with more severe depression and a worse prognosis. Future studies should examine whether these depressed older patients benefit from a metabolic-inflammatory targeted treatment.