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

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Structural and functional deviations in schizophrenic patients with formal thought disorder (FTD) point towards a dysfunction within left sided language network.

Independent component analysis (ICA), a new approach to fMRI analysis, enables to target the question of a network dysfunction directly. Using this method in healthy controls it was possible to identify the language networks separately for the left and the right hemispheres In the present study we use ICA analysis to examine changes of the language network separate for each hemisphere in relation to the severity of FTD.

We hypothesize increasing disintegration with increasing severity of FTD only in the left sided language network while the right language network should remain unaffected.

We investigated 16 schizophrenic patients with different severity of FTD and matched healthy controls using ICA decomposition of the BOLD signal. The spatial similarity of the individual language networks was correlated to the severity of FTD.

The integrity of the left language network decrease with increasing severity of FTD (r = -0.79, p < 0.01), while the integrity of the right language network show no significant correlation to the severity of FTD.

For the first time the isolated breakdown of the left sided language network was linked specifically to schizophrenic FTD. This result unites older manly left hemispheric findings of structural and functional abnormalities in schizophrenic FTD.

Motor symptoms are frequent in patients with schizophrenia. Although recent DTI studies point to white matter alterations of the motor system in schizophrenia little is known about specific changes.

To date there is a lack of approaches with hypothesis driven quantification of specific anatomical fibre tracts. Therefore, we aimed to compare structural connectivity between specific parts of the motor system such as the pre-supplementary motor area (SMA), the SMA-proper, the primary motor cortex and the basal ganglia in patients with schizophrenia and in healthy controls in a DTI-fibre-tracking study.

It is the aim of this study to investigate whether fibre tract integrity of the motor system is altered in patients with schizophrenia.

DTI-data were measured in 21 patients with schizophrenia and in 21 healthy controls. Applying a probabilistic fibre tracking approach the most probable anatomical pathways between key regions of the motor system of each participant have been identified. The resulting probabilistic maps were normalized to obtain values between 0 and 1, normalized into the standard MNI-space and smoothed using an isotropic 3-mm Gaussian kernel. Group comparisons have been calculated using two-sample-t-tests.

First results point to altered fibre tract microstructure of loops including cortical motor areas and the basal ganglia. The data analysis is preliminary. Definite results will be presented at the conference.

Altered motor behaviour might be reflected by altered white matter integrity of loops including cortical motor areas and the basal ganglia.