Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.

The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

Auditory verbal hallucinations (AVHs) in schizophrenia have been suggested to arise from failure of corollary discharge mechanisms to correctly predict and suppress self-initiated inner speech. However, it is unclear whether such dysfunction is related to motor preparation of inner speech during which sensorimotor predictions are formed. The contingent negative variation (CNV) is a slow-going negative event-related potential that occurs prior to executing an action. A recent meta-analysis has revealed a large effect for CNV blunting in schizophrenia. Given that inner speech, similar to overt speech, has been shown to be preceded by a CNV, the present study tested the notion that AVHs are associated with inner speech-specific motor preparation deficits.

The present study aimed to provide a useful framework for directly testing the long-held idea that AVHs may be related to inner speech-specific CNV blunting in patients with schizophrenia. This may hold promise for a reliable biomarker of AVHs.

Hallucinating (n=52) and non-hallucinating (n=45) patients with schizophrenia, along with matched healthy controls (n=42), participated in a novel electroencephalographic (EEG) paradigm. In the Active condition, they were asked to imagine a single phoneme at a cue moment while, precisely at the same time, being presented with an auditory probe. In the Passive condition, they were asked to passively listen to the auditory probes. The amplitude of the CNV preceding the production of inner speech was examined.

Healthy controls showed a larger CNV amplitude (p = .002, d = .50) in the Active compared to the Passive condition, replicating previous results of a CNV preceding inner speech. However, both patient groups did not show a difference between the two conditions (p > .05). Importantly, a repeated measure ANOVA revealed a significant interaction effect (p = .007, ηp2 = .05). Follow-up contrasts showed that healthy controls exhibited a larger CNV amplitude in the Active condition than both the hallucinating (p = .013, d = .52) and non-hallucinating patients (p < .001, d = .88). No difference was found between the two patient groups (p = .320, d = .20).

The results indicated that motor preparation of inner speech in schizophrenia was disrupted. While the production of inner speech resulted in a larger CNV than passive listening in healthy controls, which was indicative of the involvement of motor planning, patients exhibited markedly blunted motor preparatory activity to inner speech. This may reflect dysfunction in the formation of corollary discharges. Interestingly, the deficits did not differ between hallucinating and non-hallucinating patients. Future work is needed to elucidate the specificity of inner speech-specific motor preparation deficits with AVHs. Overall, this study provides evidence in support of atypical inner speech monitoring in schizophrenia.

None Declared

In recent years, rates of alcohol consumption and alcohol use disorder have steadily increased among adults age 60 and older. Large studies have demonstrated that moderate-to-heavy alcohol consumption (>7 drinks per week) is a risk factor for developing various types of dementias. The effects of alcohol-related problems on cognition are less clear, and are particularly understudied in older adults. Similarly, while there is an established link between worse cognition and financial exploitation vulnerability in older adults, no studies have examined relationships between alcohol-related problems and financial exploitation in this population. The current study therefore explores whether alcohol-related problems are associated with neuropsychological performance and financial exploitation vulnerability in a sample of older adults.

Participants were a community sample of cognitively unimpaired adults over the age of 50 (N = 55, Age M(SD) = 69.1(6.2), 74.5% female, Years of education M(SD) = 16.8(2.3)). Interested individuals were excluded if they reported current or past substance use disorders. Participants completed a laboratory visit that included a neuropsychological assessment. Measures included the NIH Cognition toolbox, CVLT-II, Digit Span, Trails A/B, Benson Complex Figure Recall, and Verbal Fluency: Phonemic and Semantic, from the Alzheimer’s Disease Centers’ Uniform Data Set (UDS) version 3. Participants completed the CAGE Alcohol Abuse Screening Tool and the Short Michigan Alcohol Screener Test - Geriatric Version (SMAST) to assess alcohol-related problems. Both measures are used as clinical screening tools to measure likelihood of a substance use disorder and produce a summary score (0-4 for CAGE, 010 for SMAST) tabulating symptoms of alcohol-related problems. Participants also completed the Perceived Financial Vulnerability Scale (PFVS) to assess financial exploitation vulnerability. As a significant number of participants reported no drinking and therefore no alcohol-related problems, negative binomial regressions were used to test associations between neuropsychological measures, financial exploitation vulnerability, and alcohol-related problems.

After covarying for age and sex, SMAST was negatively associated with NIH toolbox total cognition (B(SE) = -.14(.07), p<.05) and marginally negatively associated with fluid cognition (B(SE) = -.07(.04), p=.06). Neither SMAST nor CAGE scores were significantly associated with performance on any other neuropsychological test (ps = .13-.99). SMAST was positively associated with financial exploitation vulnerability (B(SE) = .31(.16), p = .05); this effect remained significant after covarying for NIH total composite score in a secondary analysis.

In a community sample of cognitively unimpaired, low-drinking adults over the age of 50, more alcohol-related problems were associated with worse NIH toolbox cognition scores. Similarly, more alcohol-related problems were associated with greater financial exploitation vulnerability, and this relationship was not driven by worse cognition. These results suggest that even low amounts of drinking and alcohol-related problems may be associated with cognition and financial exploitation vulnerability in cognitively unimpaired older adults. This study also corroborates the use of the SMAST over the CAGE in older adult populations that may be more sensitive to cognitive changes.

Prior work suggests financial exploitation vulnerability may be an early behavioral manifestation of Alzheimer’s disease (AD). Brain morphometric measures of the parahippocampal gyrus and entorhinal cortex have been shown to be sensitive to early AD progression. We hypothesized that perceived financial exploitation vulnerability may be associated with morphometric measures of the parahippocampal gyrus and entorhinal cortex in cognitively unimpaired older adults. We secondarily investigated the association of morphometric measures with neuropsychological measures.

The sample consisted of 39 cognitively unimpaired older adults (mean age = 68.74 ± 6.43, mean education = 16.87 ± 2.35, 77% female). Cognitive impairment was screened using the telephone version of the Montreal Cognitive Assessment (MoCA) and the cut-off was 21 for study participation. Perceived financial exploitation vulnerability was characterized using a 6-item self-report measure derived from the contextual items of the Lichtenberg Financial Rating Scale. Neuropsychological measures included the CVLT-II Long Delay Free Recall (verbal memory), Benson Complex Figure Recall (visual memory), and Verbal Fluency: Phonemic Test from the Alzheimer’s Disease Centers’ Uniform Data Set (UDS) version 3. Brain images were collected on a 7 Tesla Siemens Magnetom with the following parameters: TE=2.95ms, TR=2200ms, 240 sagittal slices, acquired voxel size (avs)=0.7mm x 0.7mm x 0.7mm. Structural brain images were processed using FreeSurfer version 7.2.0. Cortical thickness and volume measures were generated using the Killiany/Desikian parcellation atlas. Regions were averaged across hemispheres to obtain a single value for each region. Volume measures were adjusted for intracranial volume. Bivariate analyses were conducted to assess relationships between each outcome variable and potential confounders (age, sex, and education). Linear regression models were adjusted for any covariates significantly associated with the outcome variable (none for perceived financial exploitation vulnerability; sex and age for verbal memory; education for visual memory; sex for verbal fluency).

Smaller entorhinal cortex volume (β = -1275.14, SE = 582.79, p < 0.05) and lower parahippocampal gyrus thickness (β = -3.37, SE = 1.57, p < 0.05) were significantly associated with greater perceived financial exploitation vulnerability. Lower entorhinal cortex thickness was marginally associated with greater perceived financial exploitation vulnerability (β = -2.03, SE = 1.11, p = 0.08). Higher parahippocampal gyrus thickness was associated with better verbal fluency (β = 17.66, SE = 7.01, p < 0.05). Higher entorhinal cortex thickness was associated with better visual memory (β = 4.71, SE = 1.73, p < 0.05). No significant associations were observed between structural brain measures and verbal memory.

These results suggest smaller entorhinal cortex volume and lower parahippocampal gyrus thickness are associated with higher perceived financial exploitation vulnerability in cognitively normal older adults. Additionally, parahippocampal gyrus thickness appears to be associated with verbal fluency abilities while entorhinal cortex thickness appears to be associated with visual memory. Taken together, these findings lend support to the notion that financial exploitation vulnerability may serve as an early behavioral manifestation of preclinical AD. Longitudinal studies are needed to better understand the temporal nature of these relationships.

To investigate the association between parity and the risk of incident dementia in women.

We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).

Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.

Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.

The coronavirus disease 2019 (COVID-19) pandemic has led to significant strain on front-line healthcare workers.

In this multicentre study, we compared the psychological outcomes during the COVID-19 pandemic in various countries in the Asia-Pacific region and identified factors associated with adverse psychological outcomes.

From 29 April to 4 June 2020, the study recruited healthcare workers from major healthcare institutions in five countries in the Asia-Pacific region. A self-administrated survey that collected information on prior medical conditions, presence of symptoms, and scores on the Depression Anxiety Stress Scales and the Impact of Events Scale-Revised were used. The prevalence of depression, anxiety, stress and post-traumatic stress disorder (PTSD) relating to COVID-19 was compared, and multivariable logistic regression identified independent factors associated with adverse psychological outcomes within each country.

A total of 1146 participants from India, Indonesia, Singapore, Malaysia and Vietnam were studied. Despite having the lowest volume of cases, Vietnam displayed the highest prevalence of PTSD. In contrast, Singapore reported the highest case volume, but had a lower prevalence of depression and anxiety. In the multivariable analysis, we found that non-medically trained personnel, the presence of physical symptoms and presence of prior medical conditions were independent predictors across the participating countries.

This study highlights that the varied prevalence of psychological adversity among healthcare workers is independent of the burden of COVID-19 cases within each country. Early psychological interventions may be beneficial for the vulnerable groups of healthcare workers with presence of physical symptoms, prior medical conditions and those who are not medically trained.

To quantify and compare the resource consumption and direct costs of medical mental health care of patients suffering from schizophrenia in France, Germany and the United Kingdom.

In the European Cohort Study of Schizophrenia, a naturalistic two-year follow-up study, patients were recruited in France (N = 288), Germany (N = 618), and the United Kingdom (N = 302). Data about the use of services and medication were collected. Unit cost data were obtained and transformed into United States Dollar Purchasing Power Parities (USD-PPP). Mean service use and costs were estimated using between-effects regression models.

In the French/German/UK sample estimated means for a six-month period were respectively 5.7, 7.5 and 6.4 inpatient days, and 11.0, 1.3, and 0.7 day-clinic days. After controlling for age, sex, number of former hospitalizations and psychopathology (CGI score), mean costs were 3700/2815/3352 USD-PPP.

Service use and estimated costs varied considerably between countries. The greatest differences were related to day-clinic use. The use of services was not consistently higher in one country than in the others. Estimated costs did not necessarily reflect the quantity of service use, since unit costs for individual types of service varied considerably between countries.

To identify predominant dietary patterns in four African populations and examine their association with obesity.

Cross-sectional study.

We used data from the Africa/Harvard School of Public Health Partnership for Cohort Research and Training (PaCT) pilot study established to investigate the feasibility of a multi-country longitudinal study of non-communicable chronic disease in sub-Saharan Africa. We applied principal component analysis to dietary intake data collected from an FFQ developed for PaCT to ascertain dietary patterns in Tanzania, South Africa, and peri-urban and rural Uganda. The sample consisted of 444 women and 294 men.

We identified two dietary patterns: the Mixed Diet pattern characterized by high intakes of unprocessed foods such as vegetables and fresh fish, but also cold cuts and refined grains; and the Processed Diet pattern characterized by high intakes of salad dressing, cold cuts and sweets. Women in the highest tertile of the Processed Diet pattern score were 3·00 times more likely to be overweight (95 % CI 1·66, 5·45; prevalence=74 %) and 4·24 times more likely to be obese (95 % CI 2·23, 8·05; prevalence=44 %) than women in this pattern’s lowest tertile (both P<0·0001; prevalence=47 and 14 %, respectively). We found similarly strong associations in men. There was no association between the Mixed Diet pattern and overweight or obesity.

We identified two major dietary patterns in several African populations, a Mixed Diet pattern and a Processed Diet pattern. The Processed Diet pattern was associated with obesity.