Regarding last years, in German psychiatry the effects of the changed statutory framework conditions for the use of physical restraints [1,2,3] and the COVID-19 pandemic on the treatment in emergency psychiatry were discussed.

Against these background, changes in the severity of disease and regarding the use of coercive measures in our emergency psychiatry are to be analysed.

An internal retrospective study in the emergency psychiatry (2017=reference period; 2019=post changed statutory framework; 2021=post changed statutory framework and during the pandemic) was performed.

- The socio-demographic patient data (exception: gender) and the distribution of the main diagnoses groups remained stable. There was a reduction in the treatment volume by 4% in the pandemic period compared to 2019.

- Both in 2019 and 2021, significant increases regarding the number of patient characteristics of the intensive treatment according to the OPS code 9-61 [7,8,9] were measured.

- During pandemic period 2021, a significantly rise in the percentage of involuntarily committed treatment cases [10] imposed.

- Following changed framework conditions, there were decreases in the total duration of physical restraint and the number of restraint events per restrained treatment case [10] ratio of five-point/ seven-point restraint events reduced significantly and continuously.

The amendments in statutory framework for the use of physical restraints made personnel more aware of the issue and consequently led to changes in restraint practice at our emergency psychiatric unit. These effects were partially cancelled by the increases in the severity of diseases during the pandemic.

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Use of antipsychotics (APs) has increased worldwide during last decades. Main reason for this is off-label use, and especially the use of quetiapine for insomnia and anxiety. There is an insufficient amount of knowledge about the prescription habits and the effects of APs in off-label use. For example, APs have shown efficacy in the treatment of anxiety, but long term follow-ups are rare. Only two trials on effects of quetiapine in primary insomnia exist, without much evidence. Some small studies have indicated that even relatively small doses of APs may cause side-effects, such as increased weight and metabolic changes.

The aim of the APSY Oulu project is to analyse the prescriptions and use of APs off-label, and benefits and risks of APs in off-label use.

In 2019 a questionnaire study for doctors in different health care organisations in Finland was preformed. The purpose of the questionnaire was to find out the physicians’ prescription habits, thoughts and experiences concerning APs, especially in off-label use. In ongoing clinical study we will investigate whether the use of most frequently used off-label AP quetiapine will associate to changes in participants’ overall health, mental symptoms or cognitive functions during 6-12 months follow-up. In addition, in general population sample, we will compare characteristics and clinical outcomes of 137 persons being prescribed APs off-label and comparison groups.

Based on questionnaire for Finnish physicians (n=216), APs off-label prescriptions are mostly for insomnia and anxiety, most common drug being quetiapine. APs are being prescribed off-label by GPs, occupational health doctors and psychiatrists. The monitoring of metabolic values was not very common: 44% of the psychiatrists and 18% of other physicians reported to follow-up metabolic values of the patients (Pentinlehto J et al. Psychiatria Fennica 2021;52:22-). We have collected pilot sample of 10 individuals starting quetiapine for insomnia. They all had severe or very severe symptoms of insomnia, and used very small dose of quetiapine (mostly 12,5-25mg). Four of them used quetiapine still at the 12 months follow-up, and their insomnia symptoms decreased during the follow-up. Side effects were common (e.g. increase heart rate, drowsiness) and caused discontinuation of quetiapine for some persons. In the general population based Northern Finland Birth Cohort 1966 individuals who had been prescribed APs off-label had poorer health, lower socioeconomic status, consumed more alcohol and smoked more often compared with individuals with non-psychotic mental disorders without APs off-label (Pirhonen E et al. Acta Psychiatr Scand. 2022;146:227-).

Off-label prescriptions and use of APs is common. Further studies on APs off- label use and its safety are needed. There is a need for guideline on monitoring the patients during APs in off-label use.

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In modern society, mental health in the workplace is increasingly considered an im-portant issue and a major political agenda. Many studies have reported negative mental health risk factors or psychopathologies such as depression, anxiety, and suicidal inclination among workers. Accordingly, there are ongoing debates on the importance of establishing a system to screen and treat psychopathologies, such as the assessment of depression and anxiety. However, the absence of psychopathology or negative psychiatric factors does not guarantee good mental health. Mental health is a more comprehensive and complex concept. According to the World Health Organization, mental health is the state in which an individual can cope with routine stressors in life, work productively, and contribute to their organizations. Hence, it is needed to directly measure workers’ mental health in terms of happiness and life satisfaction.

To comprehensively investigate workers’ mental health, we explored factors associated with happiness and life satisfaction among workers using nationally representative data.

We performed multiple regression analysis, with happiness and life satisfaction set as the outcome measures, and sociodemographic factors and work-related factors as the predictive variables.

A total of 7,797 participants (4,428 men [56.8%]) with a mean age of 46.58 years (SD = 13.50) were included in the analysis. Job satisfaction (β = 0.154, p < 0.001) and self-rated health (β = 0.175, p < 0.001) were the most strongly associated with happiness. Organizational commitment, region of work, average monthly income, education level, and number of guaranteed leaves were also strongly associated with happiness and life satisfaction. Life satisfaction had the highest adjusted R2 at 0.423. The adjusted R2 for happiness and the ladder approach were 0.283 and 0.213, respectively. The variance inflation factor was below 10, and residuals were below 0.1 for all predictor variables.

Our results indicated that personal and work-related factors were associated with the happiness and life satisfaction of workers. Among work-related factors, subjective, intrinsic rewards such as job satisfaction and organizational commitment were more strongly associated than external rewards such as average monthly income or guaranteed vacations. These findings may be useful foundational data in devising policies and interventions to promote workers’ happiness and life satisfaction.

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Adverse childhood experiences are common and have been linked to a number of physical illnesses, as well as socioeconomic problems. Moreover, it has been proven that ACEs can increase chances of people showing criminal behaviour. The question arises whether people with ACEs also have an increased chance of joining extremist groups or violent gangs.

The aim of this systematic review is to measure the ACE rates in violent extremists and gangs and to establish whether there is a pattern linking ACEs to violent extremist organizations and gangs.

The following databases were searched to retrieve relevant studies: the ProQuest Social Science database, Pubmed, Scopus. Eligible studies were articles of any study design that reported ACE rates in either extremists or gang members. Data was extracted and organized into a table and a quality assessment was performed using standardized tools (CASP and NHLBI). A narrative synthesis of the evidence was conducted. A meta-analysis could not be performed due to the heterogeneity of the studies.

22 studies (eight on extremists and fourteen on gang members) were included. The studies varied in terms of research design, sample size, location and measured ACEs. Quality also varied across the studies. The prevalence rates were heterogenous and ranged from 0% to almost 100%.

Physical abuse was the most addressed ACE (5 studies on extremists and 11 on gang members). Sexual abuse was the second most explored ACE (4 studies on extremists and 9 studies on gang members). Neglect and caregiver loss were also common ACEs, while the other ACEs were less represented in the two subpopulations. A comparison between the two subpopulations was difficult due to the differences in the studies.

While overall ACE rates were high in the two groups and some ACEs were salient in the two subpopulations, quality of evidence varied across the studies. No solid ACE pattern across the studies could be found. Moreover, there were only two prospective studies on gang members and none on extremists, so a causal relationship between ACEs and involvement in violent gangs or extremist organizations could not be established. Future research should concentrate on studies of this design, as well as on improving the quality of the evidence.

As ACEs are extremely common, researchers should also look beyond them when searching for causes of extremism or violent gang membership. Other negative events (bullying, racism) should also be explored.

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Poor social inclusion, as a cause and consequence simultaneously, has been associated with schizophrenia spectrum disorder (SSD). It can bring a substantial burden to individual families and the society. Previous studies lack 1) the quantitative exploration of (multidimensional) social inclusion which can enable the measurement and monitor of the level of social integration, 2) longitudinal and multivariate study designs, and 3) methodological comparison between the traditional and data-driven approaches for a better clinical suitability of monitoring and managing social inclusion.

To build and compare 3-year models predictive of multidimensional social inclusion (mSI) among the SSD patients, using standard and data-driven approaches.

We used the baseline and 3-year follow-up data of 1,119 patients from the Genetic Risk and Outcome in Psychosis. Social functioning (Social Functioning Scale, SFS) and quality of life (the brief version of the World Health Organization Quality of Life, WHOQOL-BREF) were used as a proxy of mSI. K-means clustering over the 13 subscales of SFS and WHOQOL-BREF was applied to identify mSI subgroups. Prediction models were built and internally validated via multinomial logistic regression (MLR) and random forest (RF). The MLR and RF model performance was compared by accuracy and the discriminability of mSI subgroups (i.e., p-value of one-sided binomial test between the accuracy and no information rate).

Five mSI groups were identified: 1) “very low (in SFS)/very low (in WHOQOL-BREF)” (8.58%), 2) “low/low” (12.87%), 3) “high/low” (49.24%), 4) “medium/high” (18.05%), and 5) “high/high” (11.26%). Both MLR and RF models included 22 predictors and demonstrated accuracies of 59.16% (95CI%: [55.75%, 62.58%], p = 0.994) and 61.61% (95%CI: [54.90%, 68.01%], p = 0.013) correspondingly. The mSI was robustly and mainly and robustly predicted by genetic predisposition, premorbid social functioning, symptoms (i.e., positive, negative and depressive), number of met needs and baseline satisfaction with the environment and social life.

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Notwithstanding comparable accuracies, we cautiously consider the RF model outperforming primarily due to its better discriminability. As the baseline conditions of the patients with SSD could indicate the 3-year mSI level, customized amount and types of resources and interventions can be designed to improve the level of multidimensional social inclusion of all SSD patients.

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Perinatal maternal depression and anxiety are associated with adverse maternal outcomes, and nutrition may play an important role in their emergence. Previous research shows that certain micro and macronutrients found in different dietary patterns may influence perinatal mood disorders.

This study aims to explore relationships between nutrition during pregnancy and perinatal maternal depression and anxiety symptoms using network analyses.

Using data from the French EDEN mother-child cohort, the sample consisted of 1438 women with available perinatal mental health outcomes (CES-D, STAI and EPDS) and nutritional markers collected from food frequency questionnaires. Four networks were constructed to explore the relationships between prenatal nutrient status, dietary patterns, and perinatal mental health, while accounting for important confounders.

The Healthy dietary pattern was associated with the presence of vital micronutrients, while the Western dietary pattern was consistently associated with poorer intake of vital micronutrients and contained an excess of certain macronutrients. Western dietary pattern and symptoms of postnatal depression were connected by a positive edge in both the macronutrient and micronutrient networks. Lower education levels were associated with higher Western dietary pattern scores, from which a positive edge linked to postnatal depression symptoms in both models.

A Western dietary pattern was associated with increased symptoms of postnatal depression in our adjusted network models; The Healthy dietary pattern was associated with essential micronutrients but not with symptoms of depression or anxiety. Perinatal mental health might be impacted by specific dietary patterns in the context of psychosocial and physical stress associated with pregnancy.

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Psychiatrists need access to professional resources to care for their patients. In mental health settings, clinical innovations such as a new therapeutic approach, clinical guidelines or new drugs can diffuse more or less, depending on the social capital of these clinicians. The Resource Generator developed by Snijders & Van Der Gaag (2004) measures access to resources within a social network for the general population. It may therefore not capture access to social capital in the professional field of psychiatry.

We aimed to develop and validate the Resource Generator for Psychiatrists and to detect factors influencing the social capital of clinicians.

The development of the final 11-item questionnaire followed multiple steps. First, the items were selected and adapted by an expert in the sociology of mental health to match the sector of psychiatry. Content validity and detection of important issues or misunderstandings were ensured by cognitive interviews with a panel of 6 clinicians. Each item has a 6-point response scale, rated from 0 to 6. Answers were coded “0” when the respondent did not need a certain resource or it was not applicable to their situation, while answering the closest resource was coded “6”. The online self-completion questionnaire was administered through a link sent by email to all adult psychiatrists and psychiatric residents licensed to work in Belgium. Additional warm contacts were performed for psychiatrists working in ambulatory care. An exploratory factor analysis was conducted. Internal consistency was ensured with Pearson’s correlation, item-total correlation and Cronbach’s alpha. Test-retest reliability was also measured. Multivariable linear regression analysis assessed the association between psychiatrist demographics and the RG-Psy total score.

The Resource Generator for Psychiatrists questionnaire completed by 152 psychiatrists showed a normal distribution with a mean of 32.5 (SD=12), good test-retest reliability (ICC=0.81), and good total Cronbach’s alpha (0.74). Exploratory factor analysis revealed two main subtypes in psychiatrists’ social capital: “attention and access to advice” and “practical assistance, knowledge and expertise”, with Cronbach’s alpha of 0.62 and 0.7 respectively. Clinicians attending institutional seminars (β=5.5221, p=0.013) and working in multidisciplinary settings such as hospitals (β=4.7448, p=0.023) or a mobile team (β=8.7475, p=0.014) were more likely to have higher social capital.

Psychiatrists’ access to professional resources can be reliably measured by a 11-item questionnaire and can be used to test the influence of their professional social capital on different outcomes.

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Affective episodes often emerge in adolescence and young adulthood. Identification of factors subjectively associated with their onset may improve aetiological models and targeted intervention.

To examine precipitating conditions of (hypo-)manic and depressive episodes in adolescents and young adults from the general population.

A random sample of 14-21 year-olds was drawn from the population registry of Dresden, Germany, and N=1180 were assessed in 2015/2016 (response rate: 21.7%). Lifetime depressive and (hypo-)manic symptoms as well as full-threshold depressive and (hypo-)manic episodes (DSM-5) were identified using standardized interview. Participants reporting depressive or (hypo-)manic symptoms were asked whether and which events or conditions they associate with episode onset. Besides responses on a list providing potential triggering conditions a free answer was possible. Qualitative content analysis preceded quantitative logistic regression analyses (significance level p<.05). Considered categories were: negative life events (further divided for depression into loss/danger events, burdensome life conditions, and interpersonal factors), events requiring adaptation, positive life events, internal factors, and other factors.

The vast majority of participants reporting depressive (n=682) respectively (hypo-)manic (n=200) symptoms also reported a precipitating condition (94.7%, 83.1%). There was no significant association between any triggering condition and the occurrence of a full-threshold depressive (n=206) or (hypo-)manic (n=25) episode. However, the number of reported categories of precipitating conditions was associated with full-threshold depressive and (hypo-)manic episodes. Among those with depressive or (hypo-)manic symptoms and at least one reported precipitating condition, multiple regression models including all condition categories showed that in particular internal factors, interpersonal problems and other factors were associated with the occurrence of a full-threshold depressive episode (n=199) and positive life events as well as internal factors were associated with the occurrence of a full-threshold (hypo-)manic episode (n=21).

Adolescents and young adults from the general population usually associate the onset of phases with affective symptoms with precipitating conditions but these do not necessarily signal the emergence of a diagnostically relevant episode. Nevertheless, a greater number of and the presence of particular precipitating conditions may indicate the emergence of full-blown depressive or (hypo-)manic episodes. Thus, asking for subjective triggers appears relevant and may guide early identification and intervention.

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Screening for early detection of health issues and support are provided to children needing developmental support. In Japan, a significant percentage of infants requiring support are identified during health checkups. Sometimes, however, problems are first observed when children are of school age. It is, therefore, important to identify the age at which children need early support.

Of the children born in 2005 in Kanie-cho, in Japan, 106 participated in the survey at all time points: age 5, first grade, fifth grade, and eighth grade.

The medical checkup results of the participants at age 5 were used to determine who among them needed support After entering school, the participants who scored less than 70 points on the Children’s Global Assessment Scale, where their adjustment was assessed based on the interview with the homeroom teacher, were considered maladjusted.

The results are presented in Table 1.

Thirty participants needed supports at age 5; of these, 20 (66.7%) were maladjusted at any point in their school years—19 (95%) in the first grade, 14 (70%) till the fifth grade, and five (25%) till the eighth grade.

Of the 76 participants who did not need support in early childhood, 24 (31.6%) were maladjusted at some point in their school years—nine (37.5%) experienced maladjustment in the first grade, but none of them continued to be maladjusted till the fifth grade, and 14 (58.3%) who were not maladjusted in the first grade experienced it in the fifth or eighth grade (adolescents).

Thus, the participants maladjusted in their school years were categorized as follows:

1. The developmental disorders group (experiencing maladjustment throughout since early childhood): 19

2. The “first grade problem” group (experiencing transient problems only in the first grade): 9

3. The adolescent group (experiencing problems during adolescence): 14

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Since maladjusted children with developmental disabilities are identified in early childhood, support can be provided before they reach school age. Many children with developmental disabilities improve their adjustment as they grow up. It is thus advisable to take a long-term perspective in dealing with problematic behaviors.

From late school age to adolescence, problems unrelated to developmental disabilities emerge. By listening to the child’s upbringing, it may be possible to ascertain whether or not the problem stems from a developmental disability.

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Although studies have demonstrated that younger people are at high-risk of instigating alcohol, substance use and development of related disorders, the trend is gradually changing. An observed gradual initiation and substance use among older persons, especially during the COVID-19 pandemic. However, there is dearth of data on about the prevalence and determinant of substance use during COVID-19 pandemic in Uganda.

Determine the prevelence and determinants of susbstance use during COVID-19 pandemic in Uganda

A cross-sectional design and probability based sampling was applied. Data was collected among 474 older persons aged 50 years and above, that resided in the central region of Uganda. A multivariate logistic regression was used to assess the socio-economic, demographic and health related correlates of alcohol and tobacco use.

9.2% and 5.4% of older persons were taking alcohol and smoking before the COVID-19 pandemic. However, an observed increase of 14% of smoking and alcohol intake among older persons during the pandemic. Being male had higher odds of substance use than their female counterparts. Older persons with tertiary education and low (poor) wealth quantile, had lower odds of substance use than their counterparts.

Our finding highlights increased substance use among older persons during the COVID-19 pandemic. Designing targeted measures and policies to deter the substances use among older persons is critical to address this vice, especially during the pandemic and possible future disease outbreaks.

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Endogenous psychoses, e.g. schizophrenia, are a pressing problem of modern medicine and biology. Among various neurobiological models of schizophrenia,much attention is paid to disturbances in the brain neural activity and metabolism.

The aim of this study was to analyze dynamics of motor cortex metabolites in the norm and in early stage of schizophrenia in period of BOLD response to event related single stimulus using MRI methods (fMRI and NMR).

Study was performed on clinical Phillips Achieva 3.0 T MRI scanner. Volume of interest in motor cortex was localized on the base of fMRI study (EPI FFE, TR = 3000 ms, TE = 30 ms) as the zone of activation (Fig 1) caused by bottom push with the forefinger in response to single auditory stimuli transmitted with the 18 s periodicity. The BOLD signal was measured each 3 sec. 1Н МR spectra (PRESS, TE = 30 ms TR = 3000 ms) were run; FID signals for time points t = 0, 3, 6, 9, 12, 15, 18 s after stimulus were summarized (Fig 2). Thus, the synchronization of BOLD and metabolic responses to single stimulus was achieved. The same method was applied for spectra accumulation in resting state. For FID processing custom made software was used (with apodization filtering (LB = 20, GB = -5), FT and manual phase correction).

NAA, Cho, Cr signal intensities for each time point were normalized to their values at t = 0 and to the volume of activated cells containing in the voxel (segmented manually). Intergroup difference and time points differences were estimated using Mann-Whitney criterion with the level of significance p<0.05.

The BOLD signal in both groups demonstrated maximum at the 6th s after target stimulus, however its value was reliably lover in schizophrenia in comparison with the control group.

The only [NAA] in normal motor cortex was changed after the stimulation (Fig D). In schizophrenia [NAA], [Cr] and [Cho] were constant. The stable values of [NAA], [Cr] and [Cho] were observed in dynamics in resting state as well. [NAA] in normal cortex statistically significantly decreased at the 12th s after stimulus presentation and returned to initial value at the 15th s (Fig 3). Thus [NAA] minimum delayed relative to maximum of BOLD by 6 s.

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The reversible decrease of NAA observed for the norm in the study could provide a short-term activation of neuronal Krebs cycle through a synthesis of Ac CoA using acetate obtained in ASPA reaction. Different behavior of [NAA] in the norm and schizophrenia might be related with a difference in location (or activity) of ASPA. Decreased expression of glutamate transporters in schizophrenia could also reduce consumption of NAA as a source of acetate in synthesis of Ac CoA which is used for restoration of ATP.

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The kynurenine pathway of tryptophan catabolism has come into the spotlight of schizophrenia research since its catabolites exert neuroactive effects. A strong body of evidence suggests that kynurenic acid, a catabolite of kynurenine pathway, acts as the only endogenous NMDA receptor antagonist leading to the weakening of circuits in layer III of dorsolateral prefrontal cortex of schizophrenia patients. Studies exploring the levels of kynurenic acid and other metabolites of tryptophan in peripheral blood did not yield any definite conclusions.

Primary objective of this study was to assess differences in concentrations of key constituents of kynurenic pathway in blood plasma – tryptophan (TRP), kynurenine (KYN) and kynurenic acid (KYNA) between schizophrenia patients (SCZ) and healthy controls (HC). Secondary objective was to explore correlations between these concentrations and clinical characteristics.

In our two-centre prospective case-control study we measured plasma concentrations of TRP, KYN and KYNA in 36 healthy controls (HC) and 38 schizophrenia (SCZ) patients during acute exacerbation and remission and explored the correlations with clinical parameters using PANSS scale. The patients were matched with HC by age, sex and body mass index and exclusion criteria included obesity class 2 or higher, any concomitant organic mental or neurological disorder, acute or chronic inflammatory disease, and use of immunomodulatory drugs or psychoactive substances.

TRP concentrations were significantly higher in HC than in SCZ patients in acute phase (p<0,001) and remission (p<0,001), while SCZ patients in acute phase had significantly higher TRP levels than in remission (p<0,01). Levels of KYNA and KYN were significantly lower in SCZ patients than in HC both in acute phase and remission, all with high statistical significance (p<0,001). There was no statistically significant difference between acute phase and remission neither for KYN (p>0,05), nor for KYNA (p>0,05). There was no correlation of plasma levels of TRP, KYN and KYNA with total PANSS score, PANSS positive scale score, PANSS negative scale score and PANSS general psychopathology scores, both in acute phase and remission (p>0,05). Also, there was no correlation between plasma levels of TRP, KYN and KYNA in SCZ patients in remission with improvements measured with PANSS scale (p>0,05).

Although there are concerns about the value of measurement of metabolites of kynurenine pathway in the peripheral blood, our data suggest that significantly decreased levels of KYN and KYNA could suggest that disrupted TRP degradation in SCZ patients may be reflected in the peripheral blood as well. Further studies of peripheral levels of kynurenine pathway metabolites on larger samples should also explore effects of antipsychotic therapy, but also their correlation with other clinical parameters such as neurocognition.

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Despite replicated cross-sectional evidence of aberrant levels of peripheral inflammatory markers in individuals with major depressive disorder (MDD), there is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies.

To assess associations between plasma levels of pro-inflammatory markers and treatment response to escitalopram and adjunctive aripiprazole in adults with MDD.

In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10– 20 mg daily for 8 weeks. Responders continued on escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers – C-reactive protein, Interleukin (IL)-1β, IL-6, IL-17, Interferon gamma (IFN)-Γ, Tumour Necrosis Factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2) - measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyses to assess associations between inflammatory markers and treatment response.

Pre-treatment levels of IFN-Γ and CCL-2 were significantly higher in escitalopram non-responders compared to responders. Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.

Pre-treatment levels of IFN-Γ and CCL-2 were predictive of response to escitalopram. Increasing levels of these pro-inflammatory markers may predict non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.

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Identifying the specific brain pattern characterizing psychiatric disorders could lead us to precise diagnostic process, better treatment plan and outcome prediction. Structural covariance is a graph-analysis method with which disruptions in large scale brain network organization can be observed. More studies, employing this method in psychiatry, are still needed.

The current study aims to investigate how the main psychiatric disorders – schizophrenia, major depressive disorder, bipolar disorder, affect brain circuitry by means of multivariate graph theory, more specifically – structural covariance. We hypothesized that specific abnormalities in the brain circuits would be found in separate diagnostic entities.

164 subjects were included with schizophrenia-SCH (n=17), bipolar disorder-BD(n=25), major depressive disorder–MDD(n=68) and a healthy control group-HC(n=54). Each participant provided a written informed consent and the study protocol was approved by the University’s Ethics Committee. High resolution structural MRI was acquired, and preprocessing was performed using SPM 12 toolbox. The structural covariance method was applied consisting of calculation of the correlation across subjects between the different pairs of regions by using the gray matter average volume. We used the threshold statistic to binarize the covariance matrix and transform it into an adjacency matrix. This allows us to compare psychiatric disorders at a network level by calculating measures such as authorities, hubs and outdegree.

61 statistically significant regions were found for the whole sample. The matrices of the four groups were compared according to their ‘authorities’ ,‘hubs’ and ‘outdegree’ as first, second and third ranking variables, respectively. In the group comparison between HC and BD patients the top five significant regions were Planum temporale (PT), Putamen, Precuneus (PreCu), Calcarine cortex (Calc_cor) and Postcentral gyrus medial segment (PostCGms). The MDD group demonstrated the following regions with most significant difference including Precentral gyrus (PreCG), Entorhinal area (EntA), Amygdala (Amy), Anterior cingulate gyrus (ACC), Anterior insula (AI). While SCH grop was charachterized by ACC, PreCG – medial segment, PostCGms, anterior orbital gyrus, and frontal pole.

The results of our study demonstrated that schizophrenia and mood disorders have specific disturbances in brain network structural organization, affecting hubs of default mode network, salience network, motor, sensory and visual cortex, as well as limbic system. These alterations might elucidate the pathophysiological mechanisms of common symptoms of the disorders under investigation including perceptual, affective and cognitive disturbances.

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Schizophrenia is a neuropsychiatric disorder characterised by positive, negative and cognitive behavioral symptoms. Despite years of research, the need for suitable therapy remains elusive. Nigella sativa oil (NSO) is a medicinal plant notable for its dietary, neuroprotective and anti-inflammatory properties. However, there is paucity of information on its neuroprotective potentials in schizophrenia.

This study was designed to investigate the modulatory effects of NSO on the hippocampus of dizocilpine-induced schizophrenia in mice.

Sixty 14-weeks old male BALB/c mice (23-25g) were divided into five groups (n=12); control (normal saline, 1 mL/kg), NSO (1 mL/kg), dizocilpine-control (0.5 mg/kg) all for 7 days, while NSO (1 mL/kg for 7 days) + dizocilpine (0.5 mg/kg, for another 7 days) for preventive measure, and dizocilpine (0.5 mg/kg for 7 days) + NSO (1 mL/kg for another 7 days) for reversal. Dizocilpine and NSO were administered intraperitoneally and orally, respectively. Open field box was used for stereotypic popping. Animals were euthanised after behavioral studies, and harvested brains were weighed. Hippocampal glutamate was determined spectrophotometrically. Neuronal arrangement, sizes and densities were determined in perfused brain tissues using haematoxylin and eosin stain. Dendritic arborisations were assessed using Golgi stain. Metabotropic glutamate receptor-II (mGluR-2) and Glia Fibrilliary Acidic Protein (GFAP) were evaluated immunohistochemically. Data were analysed using descriptive statistics and ANOVA at α0.05.

Stereotypic popping was observed in dizocilpine-control but not in the preventive and reversal NSO-treated animals. The NSO increased glutamate levels in the reversal (0.19±0.00 μM/μg tissue) but not in the preventive (0.18±0.00 μM/μg tissue) groups relative to dizocilpine-control (0.18±0.00 μM/μg tissue). Hippocampal neuronal density was significantly increased by dizocilpine (21.25±1.11neurons/100μm2) but modulated by NSO in the preventive (17.25±0.51 neurons/100μm2) and reversal groups (12.00±0.71 neurons/100μm2). Significant neuronal de-arborisation that occurred in the dizocilpine-control (989.90±253.9 μm2/2.5mm2area) was inhibited by NSO in the preventive (1678±370.90 μm2/2.5mm2area) and reversal (1639±314.80 μm2/2.5mm2area) treatments. Compared to dizocilpine-control (4219±127.3 ODU), NSO increased mGluR-2 expression in the preventive (4945±17.00 ODU) and reversal (4116±24.97 ODU) groups. The GFAP expression in NSO-treated animals relative to dizocilpine-control (5510±38.45 ODU) was significantly reduced in the preventive (4945±17.00 ODU) and reversal (4116±24.97 ODU) measures.

Nigella sativa oil mitigated schizophrenic symptoms induced by dizocilpine in mice via modulation of hippocampal glutamate, metabotropic glutamate receptor–II upregulation, astrogliosis inhibition and neuroprotective mechanisms.

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Autism Spectrum Disorder (ASD) includes a group of developmental disabilities characterized by patterns of delay and deviance in the development of social, communicative, cognitive skills and the presence of repetitive and stereotyped behaviors as well as restricted interests (APA, 2013 DSM 5th ed.). Although the etiopathogenesis of autism has not yet been elucidated, past literature has highlighted an imbalance between glutamatergic and gamma-aminobutyric acid (GABA)-ergic neurotransmission (Harada et al. J Autism Dev Disord 2011;41:447-54.). A cortical deficiency of GABA in young people with ASD has been reported (Rojas et al. Neuroimage 2013;86:28-34.). Endocannabinoids act in numerous synapses of the central nervous system, maintaining an adequate synaptic homeostasis, preventing excess stimulation at the level of excitatory or inhibitory synapses. They therefore appear to be fundamental for the short- and long-term control of synaptic plasticity (Castillo et al. Neuron 2012;76,70-81). The endocannabinoid system appears to play an important role in some clinical presentations of autism, such as socialization. Indeed, Autism Spectrum Disorder seems to be characterized by a hypo-functionality of the endocannabinoid system (Aran et al. Mol Autism 2019;10, 2).

The present work aims to describe the current state of the art regarding the possible role of cannabinoids in the modulation of the excitatory and inhibitory systems in individuals with ASD.

We carried out a search on PubMed concerning the randomized clinical trials on the modulating effect of excitatory and inhibitory cannabinoid systems in autism. Three eligible articles were found according to the purpose of the present study.

The results of the three articles considered highlighted a cannabinoid (CBD)-related increase in glutamate in subcortical regions (basal ganglia) and a decrease in cortical regions (dorsomedial prefrontal cortex), both in subjects with and without ASD. CBD increased GABA transmission in the subcortical regions of neurotypical subjects, while it decreased it in the same areas of the ASD group. Furthermore, CBD modulated low-frequency activity, used as a measure of brain activity and functional connectivity in the brains of adults with ASD.

Data from the three functional MRI studies demonstrated that CBD influences cortical and subcortical connectivity on an adult sample. This effect was notable only in the ASD group but not in the controls. However, further studies are needed to confirm the results obtained so far.

None Declared

Alzheimer’s disease (AD) is the most prevalent form of age-related dementia in the world. The body of evidence suggesting that its main pathological features consist of amyloid-β (Aβ) plaque deposits and neurofibrillary tangles formed by hyperphosphorylated tau protein is robust. The drugs currently on the market have no effect on disease progression and provide only partial symptomatic relief, which creates a large unmet medical need. Anti-Aβ monoclonal antibodies (mAbs) have been shown to reduce amyloid plaques. Therefore, passive immunization is a major hope for treatment of AD.

This review aims to summarize the up to date knowledge and experience with Anti-Aβ mAbs with positive clinical or biomarker effects in long-duration trials.

A narrative review was conducted based on a search in Google Scholar and Pubmed, using the following terms or combinations “anti-aβ protofibril antibody”; “early alzheimer’s disease”; “immunotherapy for Alzheimer’s disease”. Peer-reviewed literature published between 2016 and April 2022 was screened on full-text for this purpose.

Aducanumab surpassed a successful Phase 1B trial demonstrating a dose and time dependency for Aß reduction with a beneficial impact on some clinical measures after 1 year of treatment. Two large Phase 3 clinical trials were initiated and already discontinued based on futility analysis done and not based on safety concerns. Further analyses including participants exposed for longer periods of time at higher doses indicated that aducanumab reduced brain amyloid and decreased the rate of decline.

Lecanemab (BAN2401) completed a Phase 2 trial (2018) with evidence of amyloid reduction and slowing of cognitive decline and has now entered Phase 3. Aducanumab and BAN2401 showed significant efficacy on both clinical and biomarker outcomes.

Crenezumab Phase 2 trial results suggested efficacy in mild AD; a Phase 3 program was recently halted due to futility. This mAb is currently being assessed in a prevention trial involving a Colombian kindred with autosomal dominant AD.

Gantenerumab showed significant biomarker effects, with no clinical efficacy reported to date and is being assessed in Phase 3 trials after a trial in prodromal disease stopped for futility suggested that higher doses might be efficacious. Gantenerumab and solanezumab showed no drug-placebo differences in clinical outcomes of specific studies included in this review.

Therapies with anti-Aβ mAbs have been developed successively and conducted in clinical trials signaling a promising new era for AD drug development and providing compelling evidence for the prominent role of neurotoxic soluble amyloid oligomers in the pathogenesis of AD and as therapeutic targets. Lessons learned from these studies may also be a bridge to more efficacious, safe drugs in AD.

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Depressive symptoms are a common feature of schizophrenia (SCH) and define bipolar disorder and major depressive disorder (MDD). Their emergence is related to altered neurotransmission at the serotonin receptors and potentially at dopamine D3 receptors.

The aim of this analysis was to examine the efficacy of cariprazine (CAR) in treating depressive symptoms in SCH, bipolar depression (BD) and MDD.

Clinical trials with randomised, double-blind, placebo (PLB)-controlled designs were included in these analyses. Data from 3 SCH [NCT00694707, NCT01104766, NCT01104779; 1.5-9 mg/d] and 3 BD [NCT01396447, NCT02670538, NCT02670551; 1.5-3 mg/d] studies were pooled. In MDD, add-on CAR to antidepressant treatment was evaluated against PLB in two studies [NCT03738215: 1.5 and 3 mg/d; NCT01469377: 1-2 mg/d and 2-4.5 mg/d).

Least square (LS) mean changes were analysed using Mixed Model Repeated Measures: from baseline (BL) to Week 6 in the Positive and Negative Syndrome Scale (PANSS)-derived Marder anxiety/depression factor items (schizophrenia); from BL to Week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total scores (bipolar depression); and from BL to Week 6 [NCT03738215] and Week 8 [NCT01469377] in MADRS total score (major depressive disorder).

Altogether, 1466 SCH (PLB=442, CAR=1024) patients were included in the pooled analysis. In the BD analysis, data from 1383 (PLB=460, CAR=923) patients were pooled. In the MDD trials, there were 502 CAR (1.5mg/d=250, 3 mg/d=252) and 249 PLB-treated patients [NCT03738215], and 544 CAR (1-2 mg/d=273, 2-4.5 mg/d=271) and 264 PLB patients in the other study [NCT01469377]. In SCH, CAR achieved significantly greater reductions than PLB on the Marder anxiety/depression factor domain (LS mean change: PLB= -2.66, CAR= -3.26, p<0.01): the effect was driven by 3 out of 4 items. In BD, CAR yielded significantly greater improvement on the MADRS compared to PLB (LS mean change: PLB= -12.05, CAR= -14.69, p<0.001), which was driven by 9 out of 10 items. In MDD [NCT03738215], CAR 1.5 mg/d add-on significantly alleviated depressive symptoms compared to PLB (LS mean change: PLB= -11.5, CAR 1.5mg/d= -14.1, p<0.01), while in the other MDD trial [NCT01469377], CAR 2-4.5 mg/d add-on produced significantly greater reductions than PLB (LS mean change: PLB= -12.5, CAR 2-4.5 mg/d= -14.6, p<0.01).

These findings indicate that CAR is an effective treatment option for the treatment of depressive symptoms independent of disease (in SCH, BD and MDD), being a transdiagnostic broad-spectrum treatment option.

R. McIntyre Grant / Research support from: CIHR/GACD/National Natural Science Foundation of China (NSFC), the Milken Institute, Consultant of: Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Gedeon Richter, Recordati, Atai Life Sciences, Speakers bureau of: Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Gedeon Richter, Recordati, Atai Life Sciences, R. Csehi Employee of: Gedeon Richter Plc., G. Németh Employee of: Gedeon Richter Plc.

Burnout is a topical issue, which concerns all fields and more particularly our health field.

Our descriptive study aims to evaluate the prevalence of burnout and describe its risk factors among nurses, health technicians and midwives in the regional hospital of Beni Mellal. It is being carried out from February to June 2022, with 113 participants.

Given the nature of our research, the data collection tool consists of two questionnaires, the first to study personal, professional data and risk factors for burnout, and the second to assess burnout among our participants, based on the MBI in its French version.

Our study showed that burnout affected more than three quarters of our sample, 59.3% of them had high emotional exhaustion, 26.5% had high depersonalization and 41.6% had low personal accomplishment.

The occurrence of this syndrome was the result of several risk factors, the most frequent being: stress related to the Covid-19 pandemic, poor organization and management of services, insufficient means and personnel, lack of recognition and motivation, unsatisfactory salary/effort, degraded interpersonal relations and confrontation with suffering.

In conclusion, burnout is a palpable reality among nurses, health technicians and midwives.Our alarming results must lead to the implementation of preventive actions while insisting on the organization of work and the valorization of the Moroccan caregiver.

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Work ability can be influenced by numerous factors, particularly psychosocial ones. These latter can be individual psychosocial factors but also psychosocial factors at the workplace.

This study aimed to explore psychosocial determinants of work ability among workers in a Tunisian electricity and gas company.

We conducted a cross-sectional survey among 83 male workers in a Tunisian electricity and gas company. We used a self-administered questionnaire that included socio-demographic profile, psychosocial factors assessment through the Job content questionnaire (JCQ) and General Health Questionnaire (GHQ-12), and Work Ability Index (WAI) questionnaire. Data were analysed using SPSS software. We used the student’s test to compare means between two groups.

The mean WAI score among workers in the studied electricity and gas company was 8.96 (SD=1.37). At the time of the survey, one person out of 3 among the participants suffered from a psychological distress (37.3% with a GHQ-12 score ≥ 3). These Workers had a weaker work ability compared to those with not (p=0.033). We found also that having low social support and passive jobs were associated with low work ability (p=0.003 and p=0.005 respectively).

Most personal and occupational psychosocial factors had significant associations with WAI in the studied company. Thus, enhancing the psychosocial environment in the workplace can promote work ability in such occupations.

None Declared