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.

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.

Hematological diseases represent a diverse disease group ranging from benign to life-threatening conditions, with hematological malignancies being a major cause of mortality in the population worldwide. Although most hematological diseases require ongoing medical care making these conditions even more difficult for patients to endure. Since these diseases can pose many challenges by causing symptoms and limitations in various aspects of daily life, health-related quality of life (HRQoL) is a crucial aspect of their healthcare. Different dimensions of health-related quality of life are influenced by several psychological factors, including illness perception, stigmatization, and optimism: a more positive illness perception, along with optimism and reduced stigmatization, can contribute to a better HRQoL among hematology patients.

Since hematological diseases often cause serious life changes, the current study aimed to explore the direct and indirect effects of illness perception on health-related quality of life among hematology patients in Hungary, including stigmatization and optimism as possible contributors.

In this cross-sectional study, 96 hematology patients (mean age = 56.45 years; SD = 15.55 years; 43.8% female) completed a self-administered survey including the following instruments: EORTC Quality of Life Scale, Brief Illness Perception Questionnaire, Stigma Scale for Chronic Illness, Revised Life Orientation Test.

By creating two pathway models, illness perception had significant indirect effects on physical functioning (β = -.205, p < .05) through role and cognitive functioning while emotional functioning had significant indirect effects on social functioning (β = .369, p < .01) through illness perception and stigmatization, both effects moderated by optimism. After controlling for other factors, both illness perception and emotional functioning directly influenced physical and social functioning, respectively.

Our study supports previous research on the direct and indirect effects of illness perception on HRQoL. Based on our data, more optimistic illness perceptions and greater emotional functioning improve hematology patients’ health-related quality of life by facilitating an unbiased understanding of the disease. Optimism serves as a potential moderating mechanism by positively altering indirect effects. Healthcare professionals need to optimize patients’ illness perception to improve physical and social functioning.

H. Kiss Grant / Research support from: This work was supported by the New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund, #ÚNKP-22-4-SZTE-301., V. Müller: None Declared, K. Dani: None Declared, B. Pikó: None Declared

The prevalence of mild to moderate cognitive impairment, including episodic memory deficits, in people living with HIV (PLWH) remains high despite the life-extending success of antiretroviral pharmacotherapy. With PLWH now reaching near-normal life expectancy, questions concerning a potential synergy between age- and HIV disease-related effects, including degradation in fronto-limbic circuits, neural systems also compromised in Parkinson’s disease (PD), have emerged.

This cross-sectional study examined the similarities and differences in component processes of verbal episodic memory and their neural correlates in 42 PLWH, 41 individuals with PD, and 37 controls (CTRL) (all participants aged 45-79 years). Learning over five trials, short-delay (SD) and long-delay, (LD), free-recall (FR) and cued-recall (CR) indices were assessed using the California Verbal Learning Test-2. Retention scores for FR and CR were derived adjusting for Trial 5 performance. All memory scores were age- and education-corrected based on the control group and reported as Z-scores. Regional brain volumes were calculated using 3T MRI data and the SRI24 atlas to delineate frontal (precentral, superior, orbital, middle, inferior, supplemental motor, and medial) and limbic (hippocampus, thalamus) regions. Brain volumes were age- and head-sized corrected based on 238 controls (19-86 years old).

Compared with the CTRL group, the HIV and PD groups were impaired on learning across trials and on SD and LD free- and cued-recall, with no group difference between the HIV and PD groups on any score. All three groups benefited similarly from cues compared with free-recall. The HIV and PD groups did not differ from CTRL on retention scores. Regarding brain volumes, the HIV group had smaller middle frontal volumes than the PD or CTRL groups and smaller thalamic volumes than the PD group. Correlational analyses (Bonferroni correction for 8 comparisons, p<.01) indicated that fewer total number of words recalled on Trial 5, learning over Trials 1-5, total words recalled on SD-CR, LD-FR, and LD-CR were associated with smaller orbitofrontal volume in the HIV but not the PD group; the correlations between orbitofrontal volume and memory scores were significantly different between the HIV and PD groups. In PD, but not HIV, lower retention scores on SD-FR and LD-CR correlated to smaller hippocampal volume.

Impairment in learning and cued recall performance indicate that both encoding and retrieval processes are affected in PLWH and PD. Neural correlates of verbal memory differed between groups, with orbitofrontal volume associated with learning and recall in PLWH, whereas hippocampal volume was associated with retention scores in PD. Together, these results suggest that different nodes within the fronto-limbic mnemonic circuitry underlie the mutual verbal episodic memory deficits observed in older PLWH and PD. Support: AA023165, AA005965, AA107347, AA010723, NS07097, MH113406, and the Michael J. Fox Foundation for Parkinson’s Research

The AD8 is a validated screening instrument for functional changes that may be caused by cognitive decline and dementia. It is frequently used in clinics and research studies because it is short and easy to administer, with a cut off score of 2 out of 8 items recommended to maximize sensitivity and specificity. This cutoff assumes that all 8 items provide equivalent “information” about everyday functioning. In this study, we used item response theory (IRT) to test this assumption. To determine the relevance of this measure of everyday functioning in men and women, and across race, ethnicity, and education, we conducted differential item functioning (DIF) analysis to test for item bias.

Data came from the 2021 follow up of the High School & Beyond cohort (N=8,690; mean age 57.5 ± 1.2; 55% women), a nationally representative, longitudinal study of Americans who were first surveyed in 1980 when they were in the 10th or 12th grade. Participants were asked AD8 questions about their own functioning via phone or internet survey. First, we estimated a one-parameter (i.e., differing difficulty, equal discrimination across items) and two-parameter IRT model (i.e., differing difficulty and differing discrimination across items). We compared model fit using a likelihood-ratio test. Second, we tested for uniform and non-uniform DIF on AD8 items by sex, race and ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic), education level (high school or less, some college, BA degree or more), and survey mode (phone or internet). We examined DIF salience by comparing the difference between original and DIF-adjusted AD8 scores to the standard error of measurement of the original score.

The two-parameter IRT model fit the data significantly better than the one-parameter model, indicating that some items were more strongly related to underlying everyday functional ability than others. For example, the “problems with judgment” item had higher discrimination (more information) than the “less interest in hobbies/activities” item. There were significant differences in item endorsement by race/ethnicity, education, and survey mode. We found significant uniform and non-uniform DIF on several items across each of these groups. For example, for a given level of functional decline (theta) White participants were more likely to endorse “Daily problems with thinking/memory” than Black and Hispanic participants. The DIF was salient (i.e., caused AD8 scores to change by greater than the standard error of measurement for a large portion of respondents) for those with a college degree and phone respondents.

In a population representative sample of Americans ∼age 57, the items on the AD8 contributed differing levels of discrimination along the range of everyday functioning that is impacted by later life cognitive impairment. This suggests that a simple cut-off or summed score may not be appropriate since some items yield more information about the underlying construct than others. Furthermore, we observed significant and salient DIF on several items by education and survey mode, AD8 scores should not be compared across education groups and assessment modes without adjustment for this measurement bias.

Cancer patients often present with psychological symptoms that affect their quality of life, physical health outcomes and survival. Two of the most frequent psychiatric comorbidities are anxiety and depression. However, the prevalence of these disorders among cancer patients remains unclear, as studies frequently report varying rates. In the present study, we aimed to provide robust point estimates for the prevalence of anxiety and depression for both a mixed cancer sample and for 13 cancer types separately, considering confounding variables.

In a sample of 7509 cancer outpatients (51.4% female), we used the Hospital Anxiety and Depression Scale to assess rates of anxiety and depression. Applying ordinal logistic regression models, we compared the prevalence of anxiety and depression between different cancer types, controlling for age and gender.

About one third of our sample showed symptoms of anxiety (35.2%) or depression (27.9%), and every sixth patient had a very likely psychiatric condition, with women being more frequently affected. Elderly patients more often showed signs of depression. The prevalence of anxiety and depression was significantly higher in lung and brain cancer patients, than in other cancer patients. Lowest depression rates were found in breast cancer patients.

The prevalence of anxiety and depression is high in cancer patients. Type of cancer is an important predictor for anxiety and depressive symptoms, with lung and brain cancer patients being highly burdened. Considering a personalised medicine approach, physicians should take into account the high prevalence of psychiatric comorbidities and include psychiatric consultations in the treatment plan.

Exposure to early life stress (ELS) strongly predicts prevalent, impairing, and costly psychiatric illness throughout life including mental disorders. The reason, some individuals are more vulnerable to ELS whereas others remain resilient, is poorly understood. There is a need for better understanding of early biological changes triggered by ELS with responsibility to negative outcomes in health.

We stratify animals after ELS according to corticosterone levels. [1] Re-challenging the animals to a second stressor, chronic social defeat (CSD) [2], in adulthood was performed to understand individual trajectories depending on corticosterone exposure during early adverse conditions.

We performed ELS as previously reported [1]. Behavior of mothers was observed during ELS. Correlation between level of corticosterone and behavior observed in dams. ELS animals were exposed to a second stress in adulthood. A battery of tests for different behavioral domains was performed. Behavioral analyses was combined with assessment of litter HPA system reactivity and observed behavior in dams.

Stress dams where significantly higher in number of sorties over whole observation period, time dams spent outside the nest differed. We could correlate the number of sorties on p3 with corticosterone plasma level at p9. Control dams spent significantly more time outside in 9pm recordings than stress animals. We could show reduced interaction with social juvenile targets in sociability test for CSD mice. Light dark transition was significantly higher for control mice compared to CSD but lower for control vs ELS animals.

Behavior in dams during ELS correlates with chronic stress coping mechanisms in offspring’s adulthood.

No significant relationships.

Although integrated community care programs specifically tailored to patients with severe mental illness (SMI) are available, recent studies show that these programs are not always provided to the population which would benefit the most from it.

Aims of this study were the selection of clinical and psychosocial characteristics and the development of a screening algorithm indicating the need for integrated community care services in people with mental disorders.

Data of an observational longitudinal study including N=511 participants has been used to examine the hypothesized determinants. At baseline, self-reported empowerment has been assessed via the EPAS and psychosocial impairment and perceived needs have been rated by research workers via the HoNOS and the CAN, respectively. Use of integrated community care services was defined as at least four appointments with service providers over six months and has been recorded via the CSSRI twelve to 18 months after baseline. Mixed-effects regression analyses have been performed to test the predictive value of the hypothesized determinants and marginal predictions were used to define cut-offs for the assessment tool.

EPAS, HoNOS and CAN scores each proved to be significant predictors for using integrated community care services. Cut-off scores for each predictor are presented, forming practical assessment guidelines for future studies.

A screening tool and an algorithm for the identification of mentally ill patients who can be expected to benefit from integrated community mental health care programs is available for the German health care system.

No significant relationships.