The association between the intake of antipsychotic drugs and the occurrence of thromboembolic complications is widely described in the literature. The occurrence of this complication may call into question the medical responsibility of the attending physician.

The objective of this work is to describe the physiopathological mechanisms involved in the occurrence of thromboembolic complications in a patient under antipsychotic treatment, whether or not associated with physical restraint and to discuss the forensic implications.

Our study is retrospective on cases of fatal pulmonary embolism, discovered at autopsy, in connection with the taking of antipsychotics. The autopsies were carried out in the Department of Forensic Medicine of the Tahar Sfar University Hospital in Mahdia. The cases were collected over a period of 04 years. A review of the literature was carried out. We only selected articles published until February 2021 and dealing with cases of patients on antipsychotics, diagnosed with pulmonary embolism by performing a chest CT scan or during an autopsy.

915 autopsy cases were performed during the study period. Twenty cases of pulmonary embolism, discovered at autopsy, were collected. Four cases were related to the taking of antipsychotics (incidence 0.004%), including two men and two women, aged between 25 and 52 years. They were all on antipsychotic treatment for at least 5 years, with the exception of one case who was put on 3 antipsychotics, 7 days before his death, with indication of physical restraint.

After analysis of the memorial data, the external examination and the autopsy, the results of additional examinations, the death was attributed, in the 4 cases, to a massive fibrino-cruoric pulmonary embolism.

A selection of 45 studies regarding thromboembolic complications associated with taking antipsychotics, was included in the final review.

The reported cases provided additional evidence on the involvement of antipsychotics in the occurrence of thromboembolic complications. Psychiatrists should be careful when prescribing these treatments. The establishment of therapeutic guidelines, taking into account the thromboembolic risk factors, becomes essential, in order to avoid the occurrence of a complication which could engage both the vital prognosis of patients and the responsibility of the physician.

None Declared

Peer support work can be an effective way to support patients and their participation in psychiatric treatment. Unlike in general psychiatry there is less experience with peer support work in forensic mental health inpatient settings. Characteristics different from general psychiatry, e.g., regarding patient structure and background, might lead to different tasks of peer support workers and subjects of conversation.

We aim to present an overview of tasks and conversation topics of a peer support worker in a forensic mental health setting for addicted offenders during an 12 month period. We address tasks on regular and irregular basis and the most frequent conversation topics.

We used the anonymized work documentation about weekly working activities and conversation notes of the peer support worker to extract information. Extracted data were thematically analyzed and clustered into themes for tasks and conversation topics.

Results reveal several recurring and routine tasks, like joining ward rounds and changes of shift or leading a recovery patient group along with one-to-one conversations with patients according to their request. These topics were expanded by irregular tasks like group discussions for special occasions, e.g., after incidents. During one-on-one conversations, patients addressed topics, e.g., about their substance use history, thoughts and issues about their therapy or ways to achieve their goals in the future.

Peer support is a well-accepted offer that can contain various different tasks in groups and in one-on-one settings as well. Although the peer support worker is seated on one ward, there are many requests from other wards, too. There also exists a broad range of conversation topics, some might be also present in general psychiatric wards and others that might be more unique to forensic settings. The broad range of tasks and acceptance of peer support make it necessary to provide corresponding resources like peer support staff and payment.

None Declared

Demographic ageing in the world population is accompanied by increased negative social trends towards elderly persons, age discrimination, cruel treatment and violence.

There is an increase in crimes against the elderly related to fraud with their property, physical violence by children because of claims on the property of their parents.

We observe a growing number of property transactions committed under the influence of fraud, deceit, difficult life circumstances. There is an increasing number of elderly, deprived of legal capacity.

In order to identify the biological, socio-psychological, legal and victimological determinants we examined 235 patients of late age who underwent forensic psychiatric examination in a criminal and civil process.

Revealed: «non-dementia» mental disorders - in 45.5%, psychosis - in 7.7%, dementia - in 46.8%.

Patients can simultaneously and consistently participate in criminal and civil process in the status of accused, victims, plaintiffs, defendants, people in respect of whom the incapacity is determined.

The reasons for initiating these cases were often interrelated, the result of a long-term family conflict, often related to the disposal of property.

Such a change in the processual status of patients was characteristic of the late age, reflected their victimization.

This phenomenon was called “processual transformation”.

The probability of " processual transformation " imposes special requirements on the quality of examination of patients of later age. They should be as objective and reliable.

Since the previous expert opinions may affect the subsequent expert opinions in other processes.This phenomenon are legal determinants that can have a disadaptive effect on the late age.

None Declared

Investigations into health and social care services offered to people who have died by suicide or who have committed a homicide have the potential to facilitate improvements in future practice. Such improvements are, however, dependent on the operationalizability of the recommendations of these investigations. Operationalizability in this context means the potential of the recommendations to alter the thinking/actions of practitioners involved in the areas of practice to which the recommendations relate. Critically, the proposed learning must make sense to practitioners in a multiplicity of single instance episodes of practice when the future is unknown. Although common content themes identified by investigations have been reported, no study has yet specifically examined how the framing of recommendations in investigation reports affects their operationalizability.

Primary objective: to pilot a novel approach to the thematic analysis of investigations into serious incidents which focuses on the operationalizability of recommendations for day-to-day practice. Secondary objective: to explore the operationalizability of the specific recommendations arising from a recent UK review of child homicides.

A publicly available UK national review of child homicides by parents under social care services was subjected to a two-stage thematic analysis (firstly, to identify the types of thinking/acting that were scrutinised; and secondly to characterise the ways in which these thoughts/actions were appraised). The frame of reference for the thematic analysis was that of a practitioner involved in typical instances of practice where there is uncertainty about outcomes (i.e. real-life practice).

Stage 1 - Four types of thinking/acting were identified: (i) information gathering, (ii) interpretation, (iii) judgement formation, and (iv) decision to act (figure 1).Stage 2 - The thoughts/actions were appraised according to three key themes: (a) occurrence of thoughts/actions at a pivotal moment, (b) erroneousness of thoughts/actions, and (c) thoroughness of thoughts/actions.

Image:

With regard to the specific report analysed, the recommendations were found to have differing degrees of operationalizability. For instance, examples of ‘erroneous thinking/acting’ were more readily applicable to future practice (since they can be operationalised in terms of general principles). However, the notion of ‘pivotal moments’ is less useful, since the labelling of moments as ‘pivotal’ is dependent on a knowledge of the outcome and therefore would not have been readily identified contemporaneously in these cases (or, by extension in future similar cases prior to any serious incident). This pilot demonstrates that the novel approach used is a feasible way to examine not just the content, but also the utility, of investigation recommendations.

None Declared

Studies of criminality among women are relatively poor because of its lower rate compared to men and its frequent association with mental illness.

The aim of this study is to determine the characteristics of female offenders referred for forensic psychiatric examination.

We studied the medical files of all the offenders referred to the forensic psychiatry unit in the Razi hospital for an examination between January 2010 and October 2020.

The number of people who have undergone a forensic psychiatric examination was 256. The offenders were female in 4.29% (11) of the cases. Their average age was 35 years with a range of 17-73 years. They were mostly single (54.5%) with no education (54%). Fifty four percent of the studied population were unemployed and 63% of them lived with their families.

One third of the studied population had a neurological history. Family history of psychiatric disorder was found in one case and only two had suicide attempts history.

Two women had personality disorder: a borderline and a histrionic personality disorder. An average number of one hospitalization was found in this group.

A criminal record was found in 47% of the cases with an average number of two offenses per person. The mean age of the first offense was 24 years old. The main crimes were: homicide (18.2%) and theft (18.2%).

Three offenders were found of intellectual disability, two of them personality disorders, one of schizophrenia, one of dementia and one of depression. No psychiatric disorder was found in the rest of the cases.

No drug abuse was found in this population.

The criminal and psychiatric profile of female inpatients differs from their male counterparts, which has important involvements in case management and validates the need of further searches in this field.

None Declared

Forensic studies often found high rates of major psychiatric and substance use disorders among inmates. These factors are linked to criminality in general, however, their involvement in recidivism among this population seems to be more important to determine.

The aim of this study is to determinesociodemographic, psychiatric and forensicfactors of criminal recidivism among prisoners

We studied the medical files of all the offenders referred to the forensic psychiatry unit in Razi hospital for an examination between January 2010 and October 2020 and we analyzed sociodemographic, psychiatric and forensic characteristics of this population.

The number of people who have undergone a forensic psychiatric examination was 256. Three files were not usable due to lacking data. The offenders were men in 95.7% (242) of the cases.

Male inmates were found to be more likely to be re-incarcerated (p=0.029). The study showed that the level of education was an important factor in the recidivism of criminal acts (p=0.001) whilst no impact of marital status and employment were found (p=0.848; p=0.088).

Family history of psychiatric illness was significantly higher among recidivist (p=0.022).

Psychiatric factors associated with multiple convictions were the presence of a major psychiatric discord (p=0.0013), a personality disorder (p=0) or a substance use disorder (p=0.025).)

The reason of conviction was linked with criminal recidivism as violent offense were factors of incarceration (p=0) as well as the age at first conviction (p=0) and the number of anterior incarcerations (p=0).

Our study underlines that predictive factors of criminality in general are also involved in recidivism among prisoners which is useful in establishing strategies of secondary but also primary prevention of violent crimes in particular.

None Declared

Homicide is the most serious, radical and irreversible criminal act. It arouses a multitude of questions and fears. Committed by women, the homicide seems more unusual and weird.

Our objective is to describe the circumstances of the homicide committed by Tunisian women

This study was retrospective and descriptive. It focused on the files of criminal psychiatric expertise and involved female accused subjects.We have collected all the criminal expert reports carried out over a period of 24 years (from January 1, 1998 to December 31, 2021)

This study included 21 women who committed homicide.The majority of victims of homicide or attempted homicide (85.6%) belonged to the family circle of the accused.Five women (23.8% ) committed this act against their children and four women (19.1%) committed this act against their husbands.The means most used in homicide and its attempt were immolation (23.8%), strangulation (23.8%) and blows (23.8%).

Among those charged with homicide or its attempt, seven (33.3%) presented a personality disorder, 14.3% a depressive disorder, 14.3% a moderate intellectual disability, 4.8% a schizophrenia and 4. 8% mild intellectual disability.

This female criminality, in particular homicide, would find their explanations in different factors and the existence of a mental disorder at the origin of deviant behavior in women seems to be a significant factor in the determinism of such behavior. Much effort remains to be made to apply preventive measures.

None Declared

The female criminal phenomenon will gradually become a reality and the participation of women in criminogenic currents is clearly increasing .Tunisian society, like all other societies, has not escaped this phenomenon.

Our objective is to describe the criminological and forensic characteristics of the expertized women.

This study was retrospective and descriptive. It focused on the files of criminal psychiatric expertise carried out in the psychiatry department "C" at the Hedi Chaker hospital in Sfax and involved female accused subjects.

We have collected all the criminal expert reports carried out over a period of 24 years (from January 1, 1998 to December 31, 2021).

Out of a total of 864 criminal psychiatric expert opinions carried out over a period of 24 years, we collected 56 expert opinions in which the accused was a woman (6.48%).

Among the offenses committed, we identified 31 offenses against persons (55.4%) and 25 offenses against property (44.6%). Homicides represent 37.5% of offenses (N=21) and in second place are thefts (23.2%).

Twenty-seven offenses took place at the victim’s home (48.2%) and 13 (23.2%) at the accused’s home.

The offense was committed under the influence of a psychic disturbance (disorganization, delusional syndrome, psychic excitation, hallucinatory injunctions, cognitive deficit) in 30.4% of cases.

Dementia in the legal sense was retained in 30.4% of cases.

Given the frequency of mental illness among accused women, it would be interesting to optimize their psychiatric care in order to fight against violent acts.

None Declared

For many years, the crime of rape has been the focus of attention of numerous representatives of criminal law doctrines, psychologists and sexologists, and is also part of the considerations of courts and penitentiary centers.

Statistical reports made available by the police clearly indicate that in recent years the problem of sexual crime has been growing, especially crimes consisting in committing a forbidden act such as rape or sexual murder.However, complete and objective data on the prevalence of sexual offenses are very difficult to obtain. Data from the judiciary statistics reveal only a narrow part of the problem of rape.

The project involves the analysis of the collected research results, the result of which will be the preparation of a report - a psychological and sexological profile - the characteristics of the convicts. The indicated analysis will be the result of research conducted in several penal facilities in the territory of Poland, including: Kraków, Warsaw, Poznań and others. on a research group comprising about 15% of the total number of prisoners for this crime.

The source of data on sexual offenders will be data obtained as a result of direct examinations of persons charged with rape, forensic psychiatric opinions, forensic psychological opinions and sexological opinions issued in their cases based on psychiatric and sexological tests commissioned by the court. The research material comes from the files of the perpetrators made available for the purposes of the study by the Central Board of the Prison Service. The authors of the project created a comprehensive perpetrator questionnaire containing a range of data including items on life line, origin, education, work, sexual preferences, sexual life, sexual initiation, psychiatric diagnoses and disorders of sexual preferences and personality.

A preliminary review of the available material gives grounds to conclude that the data it contains is comprehensive and has enormous scientific value. The created tool (based on a comprehensive analysis of the material) by the research team also includes items on the course of the act itself, the method of searching for victims, the method of persuading or forcing victims to submit to sexual activities, the repetition of the act and, finally, the perpetrator’s relationship to the criminal act committed by him.

The final report will be presented at the EPA conference.

The presented report will allow to get to know the characteristic elements of the psychological and sexological profile is a necessary condition for developing an effective strategy of social rehabilitation interactions.

None Declared

Homicide-suicide is a rarer phenomenon than homicides or suicides alone. However, this event shows a devastating psychological impact on relatives with effects on the mental health of survivors. The possibility of early intervention through the identification of psychopathological risk factors in offenders remains a challenge of current forensic psychiatry, also for the geographic heterogeneity of the phenomenon.

The purpose of the work is to offer a homogeneous review of the state of the art on the homicide-suicide phenomenon, focusing attention on the psychopathological characteristics of the offenders and related prevention.

A literature review was carried out through the PubMed NCBI search engine by entering the keywords “homicide-suicide” and psychiatry. A screening of the titles was carried out, with reading of the abstracts and full texts only in the selected papers that respected the research objectives.

The search evidenced 71 papers and only 20 met the inclusion criteria. The review revealed in the vast majority of offenders, most often male, the presence of mental disorders such as major depression and schizophrenia, especially in the context of relationship problems, with triggers such as the fear of separation or partner unfaithfulness. In these cases, the relationship between victim and killer shows pathological dependence or extreme possession. The event can involve children or relatives (filicide/familicide suicides). The review showed the frequent association with psychiatric depressive disorders, and obsessive-compulsive, paranoid, or narcissistic traits, with a lack of specialist consultations and very poor adherence to psychiatric treatment. Firearms were the most widely used means. In the history of perpetrators there were frequent episodes of domestic violence, previous suicide attempts and substance abuse. In rarer cases, the event takes place in the context of mass murder-suicides in which the offender assumes positions of responsibility (eg. Airplane pilot) or acts in extremist religious contexts.

The review showed an association with mental health disorders and the need for early identification of risk signals. Appropriate psychiatric prevention programs, through the close collaboration of the family, social community and the mass media, are necessary in the management of the phenomenon, especially through the reporting of episodes of domestic violence or self-harming attempts.

None Declared

Monoaminergic neurotransmitters affect motor control, emotions and cognitive functions. Their relative abundance depends on the action of monoamine oxidase A (MAOA) which catalyses their degradation into inactive metabolites. Brunner syndrome is a rare chromosome X-linked recessive inheritance genetic disorder, which causes loss of function of the MAOA gene, leading to a relative increase in monoamines in affected individuals (typically males). It manifests with moderate intellectual developmental disturbance associated with maladaptive externalising behaviours, low frustration tolerance and marked impulsivity.

To present a clinical case of patient diagnosed with Brunner Syndrome presenting with suicidal and homicidal ideation and to discuss it based on a non-systematic review of the literature.

Case report and non-systematic review of the literature.

Male born with neonatal asphyxia that consequently presented developmental retardation characterised by learning difficulties and emotional dysregulation. At 18 years of age, he began follow-up in Psychiatry due to self-injurious behaviours and several reactive suicide attempts (SA), being diagnosed with Intellectual Disability. At 22, he was hospitalised due to reactive depression, being discharged doing well with valproate, fluoxetine and olanzapine. Shortly after, he was arrested (aged 23-28) for attempted murder followed by SA. During imprisonment, he was diagnosed with Brunner’s Syndrome after his younger brother diagnosis. At 31, he was hospitalised for suicidal and homicidal ideation, revealing high impulsiveness and low frustration tolerance, and was discharged with compulsory psychiatric treatment. Three weeks later he was again hospitalised for symptoms recurrence having improved on Sertraline 50mg and Aripiprazole 400mg monthly.

Although scarce, the available evidence suggests that dietary modifications and the use of selective serotonin reuptake inhibitors may improve behaviour, reduce serotoninergic symptoms and possibly reverse some neurochemical abnormalities.

Brunner syndrome is a rare genetic disorder with neuropsychiatric manifestations, whose course, treatment and prognosis are currently poorly known. Thus, the current treatment is empirical and further studies are needed.

None Declared

aCGH determines pathogenic copy number variations (CNVs) in about 10% of patients with intellectual disability (ID). In another 20% of patients, probably pathogenic CNVs or variants with uncertain clinical significance are detected. It may be variants that do not fully explain the patient’s symptoms, aberrations with reduced penetrance or inherited from healthy parents. The use of a sequencing method for such cases is advisable.

Improvement of diagnosis of intellectual disability.

aCGH with 60K Agilent microarrays, qPCR, targeted sequencing, whole exome sequencing (WES).

Six patients with ID and inherited deletions/duplications detected by aCGH and their parents if available were further examined by sequencing. Four patients had maternal CNVs: (1) del1q41 (SPATA17, LINC00210, RRP15), (2) del7q35 (TCAF2, exon 8), (3) dup8p22p21.3 (PSD3, exons 1-11), and (4) del12p11.1 (SYT10, exons 1-2). Two patients had paternal CNVs: (5) dup1q44 (SMYD3, exons 2-5) and (6) del15q11.2 (TUBGCP5, CYFIP1, NIPA1, NIPA2, LOC283683). The severe phenotype of patient (5) with dup1q44 could not be explained by the paternally inherited disruption of the single SMYD3 gene. WES determined probably pathogenic SNV in the MID1 gene associated with Opitz GBBB syndrome (OMIM 300000), which corresponds better to the patient’s phenotype and is likely to be the cause of the disease. Although del1q41 is included in the region of chromosome 1q41-q42 deletion syndrome (OMIM 612530) the phenotype of the patient (1) is much milder; WES in the patient detected two pathogenic (MPO, MAN2C1) and one probably pathogenic (ARID1B) SNVs. In patient (6) with del15q11.2 pat WES detected additional pathogenic SNV in exon 7 of the ARSE gene. In patient (3) with dup8p22p21.3 WES determined two SNVs with uncertain significance in the KIDINS220, FOXG1 genes. No SNVs were detected by WES in patient (2) with del7q35. For patient (4) with del12p11.1 targeted SYT10 sequencing revealed no pathogenic SNVs as well.

Sometimes aCGH-analysis is sufficient to identify the causes of ID, however, in the case of detection of CNVs with uncertain clinical significance and/or inherited from healthy parents, it may be necessary to further examine the patient using sequencing methods. So, the accurate diagnosis was made by WES for one patient of eight. For another two patients the combination of CNVs and SNPs should be considered. For the last three patients the described aberrations could not explain the phenotype and whole genome sequencing may be the solution.This study was supported by the Russian Science Foundation, grant 21-65-00017, https://rscf.ru/project/21-65-00017/

None Declared

The deductive method: from karyotyping to aCGH and WES is an important aspect in the diagnosis and search for the causes of intellectual disability due to congenital brain anomalies. There is recommendation to exclude the presence of CNV or monogenic variants for patients with a normal karyotype, but with a clinical picture of syndromic disease.

Improvement of diagnosis of intellectual disability.

aCGH with 60K Agilent microarrays, WES with SureSelect Human All Exon V8

Pathogenic or potentially pathogenic CNVs were excluded previously by aCGH for 10 families (total 32 people, 2 families had 2 children) with intellectual disability and congenital brain anomalies (for example, polymicrogyria, pachygyria, lissencephaly). The WES identified candidate variants for all families that can lead to impaired neurodevelopment, including 3 pathogenic variants in 3 families, 3 likely pathogenic in three other families, and 10 variants with uncertain clinical significance for 4 families. Almost all of these variants were identified de novo, except for one family, where the proband has been a compound heterozygous for two variants in the RELN gene. The first case of pathogenic mutation de novo was detected in a girl with agenesis of the corpus callosum. It was a missense mutation DYNC1H1 (NM_001376.5): c.4868G>A (p.Arg1623Gln), which leads to impaired intellectual development in autosomal dominant type 13 (OMIM 614563). The second variant was detected in a boy with corpus callosum agenesis, pontine hypogenesis, pachygyria in the frontal lobes. It was a missense variant MACF1 (ENST00000567887.5): c.21989A>G(p.Asp7330Gly), which leads to lissencephaly 9 with complex brainstem malformation (OMIM 614563). The third variant was found in a girl with epilepsy and impaired myelination of the white matter of the parietal-occipital areas of the cerebral hemispheres. It was a missense variant CDKL5 (NM_001323289.2):c.404-1G>A that leads to developmental and epileptic encephalopathy 2 (OMIM 300672).

Sixteen candidate variants potentially responsible for mental health were reported in this study. Most of these variants were missense changes in genes. All except one anomalies arisen de novo. Trio-based WES has been shown to be an important step in making a genetic diagnosis if other chromosomal and subchromosomal abnormalities had been excluded. The clinical description of the patient is the most important step for the correct interpretation of WES results, which allows to establish the exact genetic cause of the disease if several variants with unclear clinical significance were previously identified.

This study was supported by the Russian Science Foundation, grant 21-65-00017, https://rscf.ru/project/21-65-00017/

None Declared

Haploinssufficiency of AUTS2 gene has been associated with a syndromic form of neurodevelopmental delay called AUTS2 Syndrome (AUTS2S). It is characterized for having attention/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), mild global development delay (GDD) and intellectual disability (ID). Clinicians also reported microcephaly, feeding difficulties, generalized hypotonia and ptosis.Due to its great variability, the AUTS2 Syndrome Severity Scoring System (ASSS) was established to assess the severity of the syndrome presentation. It is based on 32 characteristics including items of growth, feeding, neurodevelopment and congenital anomalies.

At the molecular level, the AUTS2 gene consists of 19 exons that are divided into a non-conserved N-terminal region and a conserved 3’ terminal end. There is a short isoform expressed primarily in the brain that initiates at an alternative transcription site and includes the last 11 exons. Variants that disrupt this final part of the gene have been associated with a severe phenotype.

To describe and compare 3 patients affected with AUTS2 syndrome using the ASSS.

(1) Case series: Comparison of the patients diagnosed with AUTS2 Syndrome using the AUTS2 Syndrome Severity Score.

(2) Narrative review of the AUTS2 syndrome and the genotype-phenotype correlation through PubMed database (1990-2020). Key terms: “AUTS2”, “AUTS2 syndrome”, “ADHD”, “neurodevelopmental disorder”, “autism”.

1 (ASSS score: 12). Interstitial duplication long arm of chromosome 7. Characteristics: microcephaly, GDD, ASD features, ADHD, auditory hypersensitivity. Finger flexion and syndactylia, arched eyebrows, palpebral fissures, epicanthus, nares, micrognathia, narrow mouth.

2 (ASSS score: 13). Pathogenic variant exon 9. Characteristics: GDD, feeding problems, ID, ASD features, auditory hypersensitivity, ADHD, hypotonia, cerebral anomalies, hypertelorism, anteverted nostrils, broad nasal bridge, micrognathia, low-set ears, narrow mouth.

3 (ASSS score: 13). Pathogenic variant exon 16. Characteristics: ID, short stature, feeding problems, auditory hypersensitivity, ADHD, hypotonia, umbilical hernia, hypertelorism, proptosis, short palpebral fissures, epicanthus, prominent nasal tip, anteverted nares, low-set ears.

Currently, 65 patients with pathogenic variants in AUTS2 are described in the literature. Significantly higher ASSS values have been found in patients with pathogenic variants affecting the 3’ end of the gene. Further research is needed, since genetic diagnosis of affected patients contributes to improved clinical protocols and personalized treatment.

None Declared

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social interaction and communication, whose etiology is heterogeneous, including genetic, epigenetic, and environmental factors. It is associated with restricted interests and stereotyped behaviors with high prevalence rates in general population, neurobiological bases and high heritability.

The aim of our study is to identify the possible phenotype-genotype relationships regarding neurodevelopmental disorders and to evaluate a correlation between genomic alterations and the manifestations of the overt and subthreshold ASD in a family administered psychiatric clinical evaluations at our hospital.

The family M underwent a psychiatric evaluation through the MINI interview according to the SCID-5 criteria, the AQ, ADAS, PAS-SR, SHI-SHY,SHY-OBS to assess respectively the subthreshold traits of ASD in adulthood, the panic-agoraphobic, social-phobic and obsessive-compulsive spectrum and CAT-Q Italian version, to evaluate social camouflage behaviors typical of ASD individuals. Array Comparative Genomic Hybridization was used for studying DNA imbalances in this family.

We found that Mrs.A, her father, her brothers and her older sister had a microduplication, very likely pathogenic, since it has been never reported in healthy subjects and harbors several genes. It could be related with overt and subthreshold traits of ASD. From the questionnaires administered and from the clinical interview, it emerged that Mrs.A is affected by ASD and Bipolar Disorder. Her twin brothers have been evaluated at early ages by child neuropsychiatric clinic and they were diagnosed with ASD and mental and psychomotor impairment. Her father was reported a significant trend in ADAS, AQ, PAS-SR, SHI-SHY and SHY-OBS scores. Finally, about her older sister, even if our results were not significant for an ASD diagnosis, we speculated that she performed a high score in some ADAS items and in the CAT-Q but not in the AQ. Females generally tend to attract fewer attention than males thanks to their better coping and camouflaging mechanisms as well as their ability to “disappear” in large groups.

Genetic knowledge can have a relevant clinical impact; a genetic etiology can be identified in individuals with ASD, leading to the identification of treatable psychiatric comorbidities. Furthermore, knowing the causative genetic variants of ASD could provide crucial information for genetic counseling as well as to understand the neurobiology of these disorders and to contribute to an early diagnosis.

None Declared

Turner syndrome characterized by total/partial and/or homogeneous/mosaic X chromosome monosomy is associated with various physical health concerns, including facial dysmorphism, short stature, infertility, and other organ defects such as heart, kidney, bone, skin, … as well as variable degrees of cognitive impairments. Besides, social skills, communication and relationships are usually disordered.

The aim of this study was to report social challenges of Turner syndrome particularly related to discrimination regarding physical and cognitive impairments.

A retrospective analysis of clinic data and karyotypes were carried out for the patients diagnosed with Turner syndrome among patients who consulted at our genetic counselling at the medical University of Sfax, during the last two decades.

Cytogenetic analysis were carried out using conventional methods and RHG banding with analysis of at least 20 metaphases and 3 karyotypes for each patient. Social challenges were recorded for each patient during pre-cytogenetic consultation and oriented questioning.

We identified 23 cases referred with a cytogenetic diagnosis of monsomy X. The karyotyping was indicated for dysmorphism, primary or secondary amenorrhea, female infertility and recurrent pregnancy losses. Homogeneous X chromosome monosomy was recorded in 13% of cases, whereas mosaic forms with and without structural X/Y abnormalities were more frequent (82%). The mean age of patients in the study was twenty years. When the 45,X population was the predominant one (56,5%), dysmorphism and primary amenorrhea were constant. In the mosaic forms, clinical traits of Turner syndrome were insignificant. Discrimination based on physical appearance, intellectual disability, and failure to conceive were the three types of social challenges revealed by patients of our study. Parents of Turner patients were also concerned at the psychological level. They in fact revealed their emotional distress face to stressful experiences of their children with Turner syndrome regarding the social discrimination they encountered particularly in schools.

Social challenges related to discrimination based on physical appearance, intellectual disability, and failure to conceive in Turner syndrome lead to depression, low self-esteem and anxiety.

None Declared

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by the deficit in communication and social interaction as well as restricted and repetitive interests and behaviors. In addition to the involvement of the environmental component in ASD, it is currently established the significant contribution of genetic factors such us the 16p13.11 duplication. We report the case of a patient carrying this anomaly in whom an ASD was diagnosed, the genetic study of the parents objectified the same anomaly in a clinically healthy father.

This case report aims to expand the clinical findings associated to this genomic abnormality and provide further knowledge of the pathogenic involvement of this duplication.

Our patient, aged 4 years and 10 months, presented developmental peculiarities from birth. The difficulties became more evident with the language delay, the deficit of social interactions and the appearance of motor stereotypies as well as sensory specificities. The diagnosis of ASD was confirmed by the passation of the ADI and the ADOS.

Further genetic exploration with a CGH-Array request was performed due to a normal 46 XY karyotype. She objectified a 16p13.11 duplication comprising 25 genes including NDE1. The assessment was completed by the search for potentially associated malformations, particularly cardiac and skeletal. We continued the family investigation with genetic samples for the parents and the siblings finding the same anomaly in the father who does not present any particular phenotype.

The 16p13.11 duplication is associated with a variable clinical spectrum including behavioral disorders, attention deficit/ hyperactivity disorder, intellectual disability, cardiac and skeletal malformation, epilepsy as well as ASD and language delay presented by our patient. Eight annotated genes are present in this region including NDE1, the candidate gene for the neurocognitive phenotype. This microduplication can be found in the normal population, but it is increasingly detected in patients with ASD, schizophrenia or presenting cognitive disorders due to incomplete penetrance that can explain the presence of the duplication despite the absence of any disorders in the patient’s father.

The link between the 16p13.11 duplication and ASD is increasingly recognized in the literature. The heterogeneity of its clinical expression and especially its incomplete penetrating make genetic counseling difficult. Collaboration between child psychiatrists and geneticists remains essential to detect, link their clinical evaluation and optimize care.

None Declared

Schizotypy is conceptualized to be on the continuum of the risk for psychosis. However, previous studies that used the dimensional approach to schizotypy failed to confirm the expected relations between schizotypal traits and polygenic risk scores (PRS) for schizophrenia. A taxonic approach is an alternative way of looking at schizotypy, but to the best of our knowledge it has not been used to explore the genetic architecture of this construct.

The present study aimed to fill this gap by comparing groups with different profiles of schizotypal traits on PRS for schizophrenia and related phenotypes.

To find clusters with different combinations of schizotypal traits, we conducted data mining of an ethnically homogeneous cohort of 1377 healthy individuals completed the Schizotypal Personality Questionnaire. Four clusters emerged, termed low, positive, negative, and high mixed schizotypy. Approximately equal groups from each cluster were selected for genotyping. After quality control, PRS for schizophrenia, depression, neuroticism, and educational attainment were calculated for 320 individuals (mean age = 31.74, SD 12.25 years, 59% women) based on the summary statistics of the largest genome-wide association studies of the respective traits. The groups from different clusters were then compared on PRS.

The schizotypy groups were similar in age and sex composition but differed in educational attainment and neuroticism (as measured by the Eysenck Personality Inventory), with the high mixed schizotypes having the lowest education and highest neuroticism scores among the schizotypy groups. There were no statistically significant differences between the groups in any PRS. However, the high mixed schizotypy group showed the largest PRS for schizophrenia, neuroticism, and depression. At a nominally significant level, it differed from negative and positive schizotypes in schizophrenia PRS and from low schizotypy in neuroticism PRS. The positive and negative schizotypal groups had non-significantly lower schizophrenia PRS than low schizotypy subjects.

Our study showed no reliable difference between groups with different schizotypal profiles in PRS of schizophrenia and related phenotypes. At the same time, a number of trends were observed suggesting that only the high mixed schizotypy might be viewed as a condition with an elevated genetic risk of schizophrenia. This is in line with Meehl’s quasi-dimensional model of schizotypy and warrants further investigation in larger samples. This work was supported by the Russian Foundation for Basic Research under Grant 20-013-00230.

None Declared

Schizophrenia (SZ) is an inherited mental illness that affects 1% of the world’s population. Schizophrenia is a common functional psychosis with some unifying features that appears to have a universal distribution. Much of the research on SZ seeks to identify physiological, biochemical, or genetic features that differ between patients and healthy individuals. Biochemical factors represent an imbalance of certain biochemical substances in the brain, especially neurotransmitters. Early studies focused on the brain biochemistry of patients with SZ in terms of dysregulation of the neurotransmitter network. There is evidence that elevated dopamine concentrations are associated with positive symptoms (i.e., hallucinations, delirium) of the disease. For example, L-DOPA decarboxylase (DDC) is an enzyme involved directly in dopamine and serotonin synthesis and indirectly in noradrenaline synthesis. Therefore, the DDC gene can be considered a candidate gene for schizophrenia and its activity is a good candidate for functional analysis via epigenetic repression.

We aimed to create a cellular model with a deregulated DDC gene.

We constructed two lentiviral vectors, one expressing the dCas9-KRAB-MeCP2 repressor under the control of a synthetic tetracycline inducible promoter, and the other carrying a cassette expressing two sgRNAs with spacers against the DDC promoter. The SH-SY5Y cell line was sequentially stably transduced with both lentiviral constructs, and cells carrying both constructs were selected by the fluorescence of the GFP and RFP reporter proteins encoded in the lentiviral construct backbones.

Methyl-sensitive real-time PCR followed by high-resolution fusion showed methylation of the DDC promoter. Correspondingly, real-time PCR showed a two-fold decrease in DDC expression in SH-SY5Y during tetracycline-induced expression of the CRISPR repressor.

We developed a cellular model to study the contribution of DDC deregulation to SZ-related molecular mechanisms.

None Declared

Schizophrenia is a severe mental disorder mainly caused by genetic risk factors. Many studies have demonstrated that both multiple genetic variants and rare mutations are associated with schizophrenia risk. The next step is to study the causal effect of the gene on the phenotype. Recently, a large family-based study identified de novo mutations, which may increase liability to schizophrenia (Rees et al 2020). In particular, a mutation in the GABA transporter (SLC6A1) gene (rs756927822 C/T) was identified in one patient from our subsample.

Here, we present a case report of this patient and describe the procedure of derivation of induced pluripotent stem cells (iPSCs) from fibroblast cultures.

Clinical, psychometric and neuropsychological methods were used. iPSCs were derived from patients’ and both unaffected parents’ fibroblasts. Human fibroblasts, cultured in fibroblast medium, are infected with lentivirus vectors expressing the transcription factors Oct4, Sox2, c-Myc, and KLF4. All iPSCs were immunocytochemical stained for intracellular (Oct4, Sox2) and extracellular (SSEA4, Tra-1-81, Tra-1-60) pluripotency markers. An qPCR analysis for pluripotency markers (TDGF1, Sox2, Oct4, REX1, LIN28, NANOG, KLF4, GDF3, DPPA4, DNMT3) was performed. All four iPSC lines formed embryoid bodies before the differentiating into three germ layers. Differentiation was confirmed by immunostaining for mesoderm (aSMA), ectoderm (Nestin, Desmin) andendoderm (FoxA2, Pax6) markers.

A 47-year-old male patient was presented to psychiatry at the age of 16. There was no personal or family history of psychiatric disorder, the premorbid functioning was normal, the patient had no somatic diseases, showed high performance in sport (mountain skiing). On his first admission, he was diagnosed with schizoaffective psychosis. The patient showed signs of mania and catatonia. Neuropsychological testing revealed a decrease of cognitive functioning (short-term and associative memory). The patient was followed up for more than 20 years. The diagnosis was changed for schizophrenia at the age of 43 years. There was a deterioration in cognitive function (the apparent decrease in performance on neurocognitive tests (attention, memory, executive functions) from the first examination (1997) till last one (2019). The patient refused or was not able to perform most of the tasks. During follow-up, the patient shows good adherence to treatment.

For this patient, obtained lines might be valuable for investigating the disease mechanisms and screening candidate drugs.

None Declared