Causal attributions of mental illness and help-seeking recommendations have multiple attitudinal and behavioral consequences; however, these factors have been subject of limited research in our Arab Muslim context.

This study examined causal attributions and help-seeking recommendations for mental illnesses among a large sample of the general population in Arab countries.

We carried out a multinational cross-sectional study using online self-administered surveys in the Arabic language from June to November 2021 across 16 Arab countries.The Community Attitudes toward the Mentally Ill scale,the Mental Health Knowledge Schedule scale and the Attitudes Toward Seeking Professional Psychological Help Scale-Short Form were administered to participants from the general public.

The study sample was predominantly female (77%), married (41%), educated (89% with tertiary education), living in urban areas (85%), with a mean age of 29.6 ± 10.8 years.

Psychosocial causes including lack of parental affection (88.0%) and childhood sexual abuse (85.5%) were the most common causal attributions of mental illnesses endorsed by our participants, with 95.7% of them agreeing with at least any one of the psychosocial causes.

Palestinians were the most inclined to believe that mental illness is caused by Jinn possession and Magic/witchcraft (65.9% and 68.1%, respectively), followed by Algerians (56.2% and 68.6%, respectively), Kuwaitis (52.3%, and 62.7%, respectively), Yemenis (50.2%, and 61.4%, respectively) and Saudi participants (49.7%, and 61.2% respectively); whereas Tunisians were the least inclined to believe in these causes (18.6%, and 21.6%, respectively) (Table S3, supplemental material).

Even though most of the study subjects tended to have a higher preference to seek help from formal sources than informal sources, they showed a high propensity to some informal sources such as family members (80.4%) and confidants (68.6%). Besides, Algerians were the most likely to ask help from a cleric or traditional healers (68.6% and 69.9%), followed by Palestinians (61.8% and 65.3%, respectively), Egyptians (58.4% and 48.8%), Jordanians (57.7% and 64.2%) and Kuwaitis (57.0% and 61.9%).

Interventions aiming at improving help-seeking attitudes and behaviors and promoting early access to care are required to be culturally tailored, and congruent with public beliefs about mental illnesses and their causations.

None Declared

There has been an increasing interest in people’s attitudes toward seeking psychological help. Although recent research has shown a rise in the number of people seeking help from psychological services, there is still a significant number who choose not to see a mental health specialist.

The aim of the current study was to examine the attitudes toward help-seeking psychological help among Arab population and to investigate factors related to these attitudes in the whole sample.

We carried out a multinational cross-sectional study using online self-administered surveys in the Arabic language from June to November 2021 across 16 Arab countries.The Community Attitudes toward the Mentally Ill scale,the Mental Health Knowledge Schedule scale and the Attitudes Toward Seeking Professional Psychological Help Scale-Short Form were administered to participants from the general public.

The study sample was predominantly female (77%), married (41%), educated (89% with tertiary education), living in urban areas (85%), with a mean age of 29.6 ± 10.8 years.

Participants tended to have a higher preference to seek help from a psychologist or a psychiatrist (85.7%) and primary care physicians (80.7%).We also found that family members represented a preferred source of help in 80.4% of the cases.

In bivariate analyses, help-seeking attitudes positively correlated with attitudes (r=.265) and knowledge (r=.121). Besides, multivariate regression analyses revealed that being female, older, having higher knowledge and more positive attitudes toward mental illness, and endorsing biomedical and psychosocial causations were associated with more favorable help-seeking attitudes; whereas having a family psychiatric history and endorsing religious/supernatural causations were associated with more negative help-seeking attitudes.

Attitudes toward seeking professional psychological help are intricate. Determining factors associated with help-seeking attitudes may guide interventions in order to avoid delays in help-seeking.

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Mental disorders are among the most poorly treated illnesses in sub-Saharan Africa. It is estimated that 70-80% of South Africans consult Traditional Health Practitioners (THPs) for the treatment of psychological ailments. Few studies have examined the perceptions of THPs regarding causes of mental illness and whilst we know little about their practices, THPs maintain a strong role in assessing and treating patients with mental illness.

This research aims to be among the first studies to identify perceived causes and treatment modalities for mental illness among THPs in Johannesburg, South Africa.

Semi-structured in-depth interviews were conducted with 18 THPs in Johannesburg, South Africa between January and May, 2022. Interviews were transcribed and translated into English. Data was managed using NVivo 12 software and thematically analyzed.

THPs interviewed generally perceived mental illness to be of supernatural causation, either as a result of bewitchment, a calling for the patient to become a THP themselves, due to angry ancestors, or due to natural causes. THPs identified eight primary treatments that they use for treating mental illness. Among these were: throwing of bones (tinhlolo) to start communicating with ancestors, steaming (ukufutha) to start the cleansing process, sneezing (umbhemiso) to forcefully dispel the spirit causing the illness, vomiting (phalaza) and laxatives (mahlabekufeni) to remove the spirits poisoning the body as well as animal sacrifice to purge spirits and communicate with ancestors. This is all followed by cutting (ukucaba) which is the final part of treatment that ensures that the evil spirit cannot return.

This study is among the first to examine the perceived causes and treatments for mental illness used by THPs in Johannesburg, South Africa. As the vast majority of South Africans continue to seek help for mental illness via THPs, it is important to understand what forms of care healers are providing to patients. Future research should continue to document ways in which THPs approach healthcare as well as investigate interventions that can foster collaboration between THPs and biomedical professionals.

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The population in remote areas in Ghana as in other low- and middle- income countries (LMIC’s) are known to suffer from limited access to quality mental health services. The challenges include limited inpatient and outpatient mental health services at the regional and district levels, shortage of well-trained professionals, poor funding by the government and difficulties for the patients to pay for medical costs, poor telecommunication services and the lack of adequate infrastructure.

We present a novel model of professional psychiatric mobile clinic, Gye Nyame Mobile Clinics, in remote areas in Ghana. This comprehensive service package connects the current loose ends of existing structural efforts in the subdistricts, trains regularly district hospital teams and bridges the gap between district hospital, primary health posts down to every patient.

In this retrospective descriptive study we collected demographic data of all the patients who visited the Gye Nyame professional mobile clinic in Psychiatry (GNMC) from November 1, 2008 to October 31, 2019 in the ten health posts of Ghana’s Ashanti Region

Between November 2008 and October 2019, we counted 16.370 visits of patients with psychiatric/ neurological diagnosis. The patients suffered mostly from schizophrenia in 24,1%, general convulsions in 40,8 % and other psychotic disorders in 5,9% of the visits. 78,5% returned to our mobile clinic for follow-up, 100% could be treated on outreach.

This community-based approach delivers psychiatric services to subdistrict and district levels and to patients who have no other access to these professional services. According to the results, a wide spectrum of pathologies and quantity of patients are seen – especially patients with no former treatment- the most common diagnosis in the rural area are schizophrenia, other psychotic disorders and generalized convulsions, followed by intellectual disabilities/autism spectrum disorder and cerebral malaria neuropsychiatric complications.

This is the first study to evaluate the implemented impact of integrated psychiatric services into existing structures in remote areas of LMIC`s.

None Declared

Ghanaian community members with mental health conditions are usually not identified until their families cannot handle their care at home anymore, for example, due to mistrust in medical institutions. From community-based and global mental health research, we know why we should act (for example, early interventions improve the treatment outcomes) and what we should do (for example, task-sharing in community settings). How any of these activities can be implemented on the community level to decrease the delay of access to evidence-based care remains unclear.

The study explored the “how” for a specific identified problem (collaboration between mental health professionals and religious leaders) in the Ketu South Municipality in Ghana; additionally, the study explored the feasibilty and the results of a community-based wellness screening.

We used a human-centered design approach to tackle this challenge in the Ketu South Municipality in Ghana. We invited 80 mental health professionals, religious leaders, and service users to participate in this exercise. The participants innovated the so-called Brain Spirit Desk, which builds collaboration between mental health professionals and religious leaders. The participants also designed a 9-question wellness screening tool, including four validated screening scales in Ghana: PHQ-2, GAD-2, one question about suicidality, and CAGE-AID. The participating religious leaders were trained to use this screening tool and administer it by themselves or allow mental health professionals to administer it in their respective institutions. Referral pathways were established for community members who screened positive on the wellness screening tool.

1065 community members (787 females, 278 males, mean age: 32.42 years) were screened using the wellness screening tool over five months (January - May 2022); 215 of these community members were already connected to mental health clinics in hospitals. 60 community members out of 203 who screened positive on the PHQ-2 were not receiving treatment at the time of screening and were referred for further assessment and treatment. Another 52, 53, and 142 community members were referred for further evaluation and treatment based on their answers to the GAD-2, suicidality, and CAGE-AID screening questions, respectively. Completed referrals across conditions averaged around 55%.

Our activities explored, guided through principles of a human-centered design approach, how the delay in access to evidence-based mental health care in the Ketu South Municipality in Ghana can be decreased through a collaborative effort of mental health professionals and religious leaders. A developed screening tool identified potential cases of mental health conditions. Importantly, religious leaders’ involvement and endorsement built trust in the activities.

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Evidence suggests that minorities tend to under-utilize mental health services, and may face specific barriers and facilitators towards recovery. One community which remains particularly under-researched in the Western World are Haredi Jews — a diverse group of individuals characterized by a shared devotion to traditional Talmudic and Halakhah teachings and observances.

The overarching aim of this study is to document and analyze barriers and facilitators towards recovery and mental health service utilization among Haredi Jews with a history of mental distress. Specific objectives include: (i) eliciting and understanding participants’ mental health knowledge, beliefs, behaviours & attitudes; (ii) exploring their pathways and barriers to mental health care, especially examining the role of religiosity, religious community and rabbinical advice; and (iii) investigating their experience within the official mental health care system.

To gain an in-depth understanding, we conducted a qualitative study. This involved semi-structured interviews with 24 participants who (i) identified as Haredi Jews; (ii) had used mental health services; and (iii) were 18+ years of age. It also included interviews with several key stakeholders, for example local Rabbis and other community leaders. Data was analyzed using thematic analysis techniques.

Participants typically had experienced mild to moderate mental distress, and tended to view mental health services in a positive light, mainly expressing satisfaction with services received. The analysis revealed three important facilitators and three important barriers to recovery. Facilitators comprised of (i) high levels of social support within the community, including specific well-being support groups; (ii) a positive relationship and connection with G-d, considered to provide guidance and support during troubled times; and (iii) the presence of many bridges and resources within the local Haredi community, including community-run health services, and Rabbis who encouraged mental health care utilization where appropriate. Barriers comprised of (i) stigma related to marriageability of self and offspring, inhibiting disclosure and mental health care use; (ii) acknowledged lack of awareness and knowledge about mental health, mental illness, treatments, and therapies; and (iii) generic health service issues, including long waitlists, limited availability and lack of appropriate therapists.

Study participants tended to have positive views of psychiatric services, and utilized different health care and community-based resources to help foster recovery. However, ongoing issues of stigma and low levels of mental health literacy may inhibit mental health care use and recovery. This implies a need for religiously-informed and community-grounded mental health literacy campaigns among Haredi Jewish communities.

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First generation immigrants in many European countries have insufficient mastery of the host language to complete self-report questionnaires. To address this problem, we translated and validated Turkish, Moroccan Arabic and Moroccan Berber versions of the Dutch 48-item Symptom Questionnaire (SQ-48), which is a validated and clinical useful measure of psychopathology.

Therefore, this study describes the translation and cross cultural validation of the Turkish, Moroccan Arabic, and Moroccan Berber versions of the 48-item Symptom Questionnaire.

Four samples were used: 1) psychiatric outpatients with Turkish or Moroccan background (n=150); 2) non-psychiatric subjects with Turkish or Moroccan background (n=103); 3) native Dutch psychiatric outpatients (n=189); 4) native Dutch non-psychiatric subjects (n=463). Data were analysed by confirmatory factor analysis and receiver operating characteristic curves.

The 253 psychiatric non-native patients and controls were on average 38,3 years old (SD 12,4), and 61% were women. Internal consistency of SQ-48 subscales across groups was adequate to high, the seven-factor structure of SQ-48 fitted the data adequately in the total sample and in each separate group, and AUC values showed acceptable to excellent discrimination. However, the mean severity scores for all SQ-48 subscales were significantly higher in the immigrant groups than those of the Dutch native group. We found full configural, metric and partial scalar invariance.

Psychopathology measured by SQ-48 can largely be interpreted in the same way for persons from different immigrant backgrounds. However, cut-off values for Dutch natives should be ascertained using larger samples as these are likely higher than in Dutch psychiatric patients.

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Functional magnetic resonance imaging (fMRI) has been used to identify the neural activity of both youth and adults diagnosed with major depressive disorder (MDD) in comparison to healthy age-matched controls. Previously reported abnormalities in depressed youth appear to mostly align with those found in depressed adults; however, some of the reported aberrant brain activity in youth has not been consistent with what is observed in adults, and to our knowledge there has not yet been a formal, quantitative comparison of these two groups. In addition, it is not known whether these observed differences between youth and adults with depression are attributable to developmental age or length-of-illness.

The aim of this study is to elucidate the similarities and differences in patterns of abnormal neural activity between adults and youth diagnosed with MDD and to then determine whether these observed differences are due to either developmental age or length-of-illness.

We used multilevel kernel density analysis (MKDA) with ensemble thresholding and triple subtraction to separately determine neural abnormalities throughout the whole brain in primary studies of depressed youth and depressed adults and then directly compare the observed abnormalities between each of those age groups. We then conducted further comparisons between multiple subgroups to control for age and length-of-illness and thereby determine the source of the observed differences between youth and adults with depression.

Adults and youth diagnosed with MDD demonstrated reliable, differential patterns of abnormal activation in various brain regions throughout the cerebral cortex that are statistically significant (p < .05; FWE-corrected). In addition, several of these brain regions that exhibited differential patterns of neural activation between the two age groups can be reliably attributed to either developmental age or length-of-illness.

These findings indicate that there are common and disparate patterns of brain activity between youth and adults with MDD, several of which can be reliably attributed to developmental age or length-of-illness. These results expand our understanding of the neural basis of depression across development and course of illness and may be used to inform the development of new, age-specific clinical treatments as well as prevention strategies for this disorder.

None Declared

High stigma has been considered an important cause for the low rates of help-seeking, lack of access to care, undertreatment, material poverty, and social marginalization.Physicians commonly know about depression but are reluctant to seek mental health treatment.

This study aimed to examine the attitude toward depression in Thai physicians compared with the general population.

A cross-sectional descriptive study was conducted on Thai physicians and the general population. We used the Depression Stigma Scale in the Thai version to assess stigma. The Depression stigma scale was distributed via the internet with a google form program.

Two thousand eighty-three participants responded to the questionnaire. Comparing the Depression Stigma Scale of the general population and physicians by using an independent test demonstrated that there was a significant difference between the two groups (p < 0.001) with an average total score of physicians higher than the general population (37.47 and 35.73, respectively). There was a significant difference in the Perceived Stigma Subscale in the general population p < 0.001 and physicians but not in the Personal Stigma Subscale. A significant difference was shown between the Personal Stigma Subscale of male and female physicians (P < 0.05). No significant difference was demonstrated between the Perceived Stigma Subscale of male and female physicians. However, the male and female general population had no significant differences in the Depression Stigma Scale.

Physicians had higher depression stigma than the general population, especially in perceived stigma.

None Declared

Major Depressive Disorder (MDD) is one of the most common mental illnesses worldwide and is strongly associated with suicidality. Commonly used treatments for MDD with suicidality include crisis intervention, oral antidepressants (although risk of suicidal behavior is high among non-responders and during the first 10-14 days of the treatment) benzodiazepines and lithium. Although several interventions addressing suicidality exist, only few studies have characterized in detail patients with MDD and suicidality, including treatment, clinical course and outcomes. Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D)-study is an investigator-initiated trial funded by Janssen-Cilag GmbH.

For population 1 out of 3 OASIS-D populations, to assess the sub-population of patients with suicidality and its correlates in hospitalized individuals with MDD.

The ongoing OASIS-D study consecutively examines hospitalized patients at 8 German psychiatric university hospitals treated as part of routine clinical care. A sub-group of patients with persistent suicidality after >48 hours post-hospitalization are assessed in detail and a sub-group of those are followed for 6 months to assess course and treatment of suicidality associated with MDD. The present analysis focuses on a preplanned interim analysis of the overall hospitalized population with MDD.

Of 2,049 inpatients (age=42.5±15.9 years, females=53.2%), 68.0% had severe MDD without psychosis and 21.2% had moderately severe MDD, with 16.7% having treatment-resistant MDD. Most inpatients referred themselves (49.4%), followed by referrals by outpatient care providers (14.6%), inpatient care providers (9.0%), family/friends (8.5%), and ambulance (6.8%). Of these admissions, 43.1% represented a psychiatric emergency, with suicidality being the reason in 35.9%. Altogether, 72.4% had at least current passive suicidal ideation (SI, lifetime=87.2%), including passive SI (25.1%), active SI without plan (15.5%), active SI with plan (14.2%), and active SI with plan+intent (14.1%), while 11.5% had attempted suicide ≤2 weeks before admission (lifetime=28.7%). Drug-induced mental and behavioral disorders (19.6%) were the most frequent comorbid disorders, followed by personality disorders (8.2%). Upon admission, 64.5% were receiving psychiatric medications, including antidepressants (46.7%), second-generation antipsychotics (23.0%), anxiolytics (11.4%) antiepileptics (6.0%), and lithium (2.8%). Altogether, 9.8% reported nonadherence to medications within 6 months of admission.

In adults admitted for MDD, suicidality was common, representing a psychiatric emergency in 35.9% of patients. Usual-care treatments and outcomes of suicidality in hospitalized adults with MDD require further study.

None Declared

Poor adherence to treatment is currently stated to be one of the causes of depression relapse and recurrence.

Aim of the present study was to assess potential differences in terms of clinical and socio-demographic characteristics specifically related to adherence to treatment features, medical comorbidities, and substance abuse in a sample of patients diagnosed with Major Depression in an Italian psychiatric department.

Patients with a DSM-5 diagnosis of Unipolar or Bipolar Major Depressive Episode, of either gender or any age were recruited from the Psychiatry Department of Luigi Sacco University Hospital in Milan. Main clinical and socio-demographic variables were collected reviewing patients’ medical records. Moreover, adherence to psychopharmacological treatment was assessed using the Clinician Rating Scale (CRS; Kemp et al, 1996; 1998). Adherence was defined as ratings of > or =5 on the CRS. Descriptive and association analyzes were performed, setting the significance level at p<.05.

80 patients with a diagnosis of Unipolar Major depressive episode (48.9%) and Bipolar Major Depressive Episode (51.1%) were included. For the purposes of the study, the total sample was divided into two subgroups based on adherence to pharmacological treatment (A+ vs A-). Significantly higher rates of inpatients from psychiatric ward were A- compared to A+ patients (84.6% vs 48.1%, p=.011). A- patients were significantly more unemployed (57.9% vs 23.8%, p=.015), were mostly living in their family of origin (50% vs 21.4%, p=.027), and had fewer years of education compared to A+ subgroup (10.52±3.28 vs 12.2±3.1 years, p=.053). Higher rates of Bipolar Depression diagnosis and a prevalent manic polarity lifetime emerged in A- compared to the A+ group (73.1% vs 42.3%, p=.010; 30.8% vs 3%, p=.011, respectively). Moreover, A+ reported significantly higher rates of depressive prevalent polarity lifetime (72.7% vs 30.8%, p=.011). A- reported significantly higher rates of comorbidity with alcohol or other substance use disorders lifetime (46.2% vs 5.7%, p=.006) and almost one involuntary commitment lifetime (23.1% vs 11.1%, p=.013).

In our sample adherence to treatments showed significant differences in terms of clinical and socio-demographic characteristics. Low levels of adherence have been associated with higher hospitalization rates, involuntary commitments, greater comorbidity with alcohol or drugs. Our data therefore seem to suggest that less adherence leads to a worse disease course and a worse quality of life. It therefore appears useful to include an assessment of adherence in the clinical practice and implement interventions to improve therapeutic adherence and ensure a better quality of life.

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Research indicates that co-morbid diabetes and depression is common; however, the implications for clinical practice remain unclear

The aim of the study was to check the prevalence of depression in patients with T1DM who are provided with optimal conditions of diabetes care and to identify possible risk factors connected with affective traits

Out of the 107 patients, 78 (54 females, 24 males) were included for the analysis (HbA1c [%] 7.11±1.0, BMI [kg/m2] 25.3, ± 5.6; Years of T1DM [N] 13.7±8.3). The patients filled in a set of questionnaires during their regular visit to the outpatient clinic. Three patients from the whole group were on intensive insulin therapy with Multiple Daily Injections (MDI) and Self-Monitoring of Blood Glucose (SMBG), all the rest were on various types of personal insulin pumps (years on insulin pump [N] 9.1±4.5). All the patients were on regular diabetologist care, with regular visits in a Centre for Advanced Technologies in Diabetes (at least every 6 months).

In QIDS-S 26 patients (33.8%) were screened positive for depression, in PHQ 57.7% of the patients (45 patients) had symptoms of depression (age was negatively correlated with PHQ score (r= -0.26; p=0.023)). In CES-D 16 (20%) of the patients assessed their present affect as depressed. Quality of sleep was highly correlated with depressive symptoms CESD (r=0.61, p=0.001), PHQ Score (r=0.62; p=0.001), QISD (r=0.68; p=0.001).

The prevalence of affective disorders and poor sleep quality in the examined T1DM patients was much higher than in the general population. Even if the patients have in general good glycemic control, their mental health condition should not be neglected. Well organized cooperation between patients, diabetologists, psychiatrists and psychotherapists is needed.

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Depressive disorders are known heterogeneous both in their clinical manifestations and etiopathophysiology. Affective temperaments have a strong biological background and heritability, manifest at early age and remain stable throughout the life span, and have a pathoplastic effect in depression. Thus, they have been suggested as intermediate phenotypes for depression.

Our aim was to investigate if polygenic risk scores (PRS) calculated for the five affective temperaments predict depression and to examine their interaction effects of early and recent stressors.

1820 nonrelated participants from a general population were genotyped and provided data on current depression (Brief Symptom Inventory-BSI), early (Childhood Trauma Questionnaire, CHA) and recent stressors (List of Threatening Life Events, RLE), and affective temperaments (Temperament Evaluation of Memphis, Pisa, Paris and San Diego, TEMPS-A). Our previously performed TEMPS-A GWAS analysis was used as discovery sample and the NewMood database as target sample for analysing the effects of affective temperament PRS on depression. Linear regression models were used to calculate the interaction effect of early and recent stressors.

PRSs derived from anxious, cyclothymic, depressive, and irritable temperaments had a significant effect on current depression, explaining 2.6-7.1% of variance. PRSs calculated from the anxious, depressive and hyperthymic temperaments significantly predicted current depression in interaction with CHA, explaining 10% of variance. In case of interaction models including both early and recent stressors, a significant effect of depressive PRS was found. Detailed results are shown in Table 1.

Our results confirm the genetic association between affective temperaments and depressive symptoms, which highlight their role as possible clinically relevant intermediate phenotypes for depression.

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Psychopathic personality traits (PPT) are known to deteriorate emotional and cognitive functions, however, little is known about their role in depression. Nevertheless, depressive symptoms have also shown to be associated with emotional problems and worse cognitive functions and could thus also interact with PPT.

This study aimed to set up an integrative model by examining the correlative relationships and moderating role of PPT in the association between emotional competence and cognitive functioning in individuals with depression.

Data from 373 individuals diagnosed with depression (158 males, 215 females) were investigated. Subjects filled out questionnaires surveying PPT and emotional competences. Furthermore, a comprehensive neuropsychological test battery investigating the cognitive domains Attention/Psychomotor Speed, Executive Functions and Verbal Learning/Memory was administered.

Correlation analyses revealed a significant positive association between emotional competence and overall cognitive functioning. Further, negative associations between emotional competence and the PPT “Blame Externalisation” and “Careless Nonplanfulness”, as well as positive associations with psychopathic “Social Potency” and “Stress Immunity” were found. Moderation analyses indicated a significant positive influence of psychopathic “Stress Immunity” and “Social Influence” on the relationship between emotional competence and cognitive parameters.

The findings highlight the importance of considering PPT in further research on depression and reflect their impact in therapeutic settings.

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The human body carries large and diverse communities of symbiotic microbes that are important for human health and development. While the impact of the bacterial microbiota, which are mostly found in the human gut, on host physiology is relatively well described, much less is known about the interactions between the mycobiota and the host and the resulting effects on human health. At the level of the nervous system, there is increasing evidence implicating the gut microbiota in a variety of neurological disorders. Similar demonstrations of a causal or supportive role of the mycobioma in neurological disorders are still rare, but several studies linking fungal dysbiosis to disease in humans suggest a contribution of symbiotic fungi to neurocognitive and behavioral disorders.

We aim through this review to show the role of mycobiota in neurocognitive and behavioral disorders.

We comprehensively review the scientific literature using Pubmed database and other search platforms such as Google scholar to state the role of mycobiota in neurocognitive and behavioral disorders.

Our bibliographic review revealed that, according to recent studies, Candida species are overrepresented in the stool of individuals with autism spectrum disorders and Rett syndrome compared to healthy controls. Other studies revealed mycobiome signatures specific to cognitive impairment and demonstrated that different diets modulate the mycobiome in association with Alzheimer’s disease markers and fungal-bacterial co-regulatory networks in patients with cognitive impairment.

Our understanding of the role of the mycobiota in the biology of neurocognitive disorders-whether causal, consequential, or predisposing-could open up new hypotheses in this area and inspire further research on potential mycobiotic signatures, associated dysbiosis and dysfunction in the neurocognitive developmental-homeostasis spectrum that may contribute to neurocognitive and behavioral developmental disorders and predisposition to cognitive decline, dementia, and progression of neurodegenerative diseases including Parkinson’s and Alzheimer’s disease in high-risk subjects.

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Chromatin modifications and epigenetics are important pathogenesis mechanisms leading to various neurologic and psychiatric disorders including epilepsy, drug addictions, depression, autistic spectrum, learning disabilities and schizophrenia. Recently, the disruption of the chromatin remodeling BAF complex has been linked to several neurodevelopmental syndromes, commonly referred to as PBAFopathies.

Here, we review the implication of PBAF complex genes in schizophrenia and we outline syndromes caused by mutations in these chromatin-modifying enzymes labelled as PBAFopathies to discuss the functional consequences of reported mutations in the literature.

We comprehensively review the scientific literature using Pubmed database and other search platforms such as Google scholar to state the role of PBAF complex genes in schizophrenia and to reveal the most frequent genes mutations reported in literature.

Our review revealed that the human analogs of the subfamily of ATP-dependent chromatin remodeling complexes, which are known in eukaryotes as the mammalian SWI/SNF complex (counting a group of proteins that associate and possess a DNA-stimulated ATPase activity that can destabilize histone-DNA interactions in reconstituted nucleosomes providing crucial nucleosome rearrangement and allowing the activation/repression of genes) are crucial for the regulation of genes expression and cells differentiation. They involve two well-known complexes which are SWI/SNF-A (known as BAF complex) and SWI/SNF-B (known as Polybromo-associated BAF or PBAF complex). SWI/SNF is a multisubunit chromatin-remodeling complex that performs fundamental roles in gene regulation, cell lineage specification, and organismal development and mutations that inactivate SWI/SNF subunits are found in nearly 20% of human cancers and in various developmental disorders, forming a continuum or spectrum of diseases. Since the first description of BRG1/BRM mutations in schizophrenia, other mutations of the SWI/SNF subunits have been reported: SMARCA1, SMARCA2, SMARCA4/BRG1, etc. Single nucleotide polymorphisms (SNPs) in these and other genes of PBAF have been also associated with schizophrenia.

This review focuses on the PBAF SWI/SNF subunits to find out if schizophrenia may be considered as a member of the spectrum of PBAFopathies.

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There are currently no diagnostic or treatment-guiding biomarkers for major depressive disorder (MDD). Microribonucleic acids (miRNA) may facilitate understanding the reorganisation of gene expression networks in MDD. Identifying miRNA and target mRNA pathways that contribute to MDD may open new therapeutic avenues, such as inhibiting endogenous miRNA or administering exogenous miRNA.

This study investigates how miRNAs can clarify the molecular mechanisms of MDD by comparing the miRNA levels in the blood serum of patients with MDD and healthy individuals. The study also investigates the discriminative ability of miRNAs to distinguish between depressed patients and healthy controls.

Sixty depressed patients were matched with 60 healthy controls based on age, gender, ethnicity, and years of education. The severity of depression was measured using the Hamilton Depression Rating Scale, and venous blood was collected for miRNA profiling. Using the QIAGEN Ingenuity Pathway Analysis, networks were constructed to identify the biological pathways associated with MDD influenced by the differentially expressed miRNAs. Analyses of the receiver operating characteristic (ROC) were performed to examine the capacity of miRNAs to distinguish between depressed and healthy individuals.

Six miRNAs (miR-542-3p, miR-181b-3p, miR190a-5p, miR-33a-3p, miR-3690, and miR-6895-3p) were significantly down-regulated in untreated depressed patients compared to healthy controls. miR-542-3p has experimentally validated mRNA targets predicted to be associated with MDD. ROC analyses determined that a panel containing miR-542-3p, miR181b-3p, and miR-3690 distinguished between depressed and healthy individuals with an area under the curve value of 0.67.

Specific miRNAs, including miR-542-3p, miR181b-3p, and miR-3690, may be biomarkers with targets implicated in the pathophysiology of depression. They could also be used to distinguish accurately between depressed and healthy individuals.

None Declared

The glutamatergic system plays an important role in the neurobiology of schizophrenia. A lot of number of variants in the GRIN genes have been found in patients with various neuropsychiatric disorders (Myers et al. F1000Res 2019; 8(F1000 Faculty Rev) 1940). GluN2A, encoded by the GRIN2A gene, is the most abundant of the GluN2 NMDA receptor subunits in the mammalian CNS. Clinical symptoms of schizophrenia vary among individuals. The GRIN2A gene has previously been shown to be associated with early onset schizophrenia (Poltavskaya et al. Life (Basel) 2021; 11(10) 997).

The aim of the study was to identify associations of the GRIN2A gene rs11644461 polymorphism with features of the course of schizophrenia.

This study was carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki 1975). 805 patients with schizophrenia (ICD-10: F20) were included. Clinical examination and diagnostic evaluation were performed using the Positive and Negative Syndrome Scale (PANSS). From the general group of patients, 2 subgroups were distinguished according to the PANSS survey: 391 patients with leading negative symptoms and 414 patients with leading positive symptoms. Also 2 subgroups were distinguished from the general group of patients: 398 patients with a continuous course of schizophrenia and 257 patients with episodic schizophrenia. Genotyping was performed by real-time PCR.

An association of the C rs11644461 GRIN2A allele with the continuous course of schizophrenia was revealed (p<0,047). The rs11644461 polymorphism was not associated with the leading symptoms of the disease (positive or negative). At the same time, the values of the total score on the PANSS scale differed statistically significantly in carriers of different genotypes for this polymorphism. The sum of PANSS scores (Me [Q25 – Q75]) in carriers of the TC rs11644461 genotype was statistically significantly higher (106 [92–113]) than in carriers of the CC genotype (101 [87–108]) (p=0.006).

According to the results obtained, carriers of the TC rs11644461 GRIN2A genotype have a higher severity of schizophrenia symptoms according to the PANSS scale than carriers of the CC genotype. Also in the present study, it was shown that the C allele rs11644461 GRIN2A is associated with the continuous course of schizophrenia, which indicates the contribution of this locus to the formation of the course of the disease.

E. Poltavskaya Grant / Research support from: Russian Science Foundation # 21-15-00212, O. Fedorenko Grant / Research support from: Russian Science Foundation # 21-15-00212, E. Kornetova Grant / Research support from: Russian Science Foundation # 21-15-00212, I. Pozhidaev Grant / Research support from: Russian Science Foundation # 21-15-00212, D. Paderina Grant / Research support from: Russian Science Foundation # 21-15-00212

Three-dimensional chromatin interactions regulate gene expressions. The significance of de novo mutations (DNMs) in chromatin interactions remains poorly understood for autism spectrum disorder (ASD).

To investigate the genomic architecture of ASD in terms of non-coding de novo mutations and 3-dimensional chromatin interactions

We generated 813 whole-genome sequences from 242 Korean simplex families to detect DNMs, and identified target genes which were putatively affected by non-coding DNMs in chromatin interactions.

Non-coding DNMs in chromatin interactions were significantly involved in transcriptional dysregulations related to ASD risk. Correspondingly, target genes showed spatiotemporal expressions relevant to ASD in developing brains and enrichment in biological pathways implicated in ASD, such as histone modification. Regarding clinical features of ASD, non-coding DNMs in chromatin interactions particularly contributed to low intelligence quotient levels in ASD probands. We further validated our findings using two replication cohorts, Simons Simplex Collection (SSC) and MSSNG, and showed the consistent enrichment of non-coding DNM-disrupted chromatin interactions in ASD probands. Generating human induced pluripotent stem cells in two ASD families, we were able to demonstrate that non-coding DNMs in chromatin interactions alter the expression of target genes at the stage of early neural development.

Taken together, our findings indicate that non-coding DNMs in ASD probands lead to early neurodevelopmental disruption implicated in ASD risk via chromatin interactions.

None Declared

Brain-derived neurotrophic factor (BDNF) has been associated with both emotionally unstable personality disorder (EUPD) and suicidal behavior. No study has yet investigated BDNF-associated epigenetic alterations in severely impaired EUPD and suicidal patients.

The main goal of the present study was to investigate whether epigenetic dysregulation in BDNF, CRP, IL-1, IL-2 and IL-6 were associated with EUPD and severity of suicidal behavior.

The discovery cohort consisted of 97 women with emotionally unstable personality disorder (EUPD) with at least two serious suicide attempts (SA) and 32 healthy women. The genome-wide methylation pattern was measured by the Illumina EPIC BeadChip and analyzed by robust linear regression models to investigate mean BDNF methylation levels in a targeted analysis conditioned upon severity of suicide attempt. The validation cohort consisted of 60 female suicide attempters, stratified into low- (n=45)and high-risk groups (n=15) based on degree of intent-to-die and lethality of suicide attempt method, and occurrence of death-by-suicide at follow-up.

Mean BDNF methylation levels exhibited hypermethylation in relation to EUPD(p=0.0343, percentage mean group difference ~3.8%). Similarly, this locus was confirmed as hypermethylated in an independent cohort of women with severe suicidal behavior (p=0.0469). Results were independent of age and BMI.

This study elicits emerging evidence of epigenetic dysregulation of BDNF in relation to phenotypes known to increase risk of suicide (lethality of suicide-attempt method and presence of EUPD diagnosis with history of recent SA). Further studies investigating epigenetic and genetic effects of BDNF on severe suicidal behavior and EUPD are needed to elucidate the role of epigenetic regulatory mechanisms and neurotrophic factors in relation to suicide risk.

None Declared