Autism-spectrum-disorder (ASD) is a heterogenous neurodevelopmental condition with a wide range of symptoms. Typical deficits, such as impairment in social communication and interactions, can lead to violent behaviours. However, ASD is often underdiagnosed and little is known about patients with ASD in forensic institutions.

To highlight the diagnostic challenges and offending behaviour of people with ASD in the context of the criminal justice system (CJS) through a case report.

The case report is based on exploration, third party anamnesis, medical documentations and court files

A 25-year-old man was placed in detention in 2021 after having committed a dangerous threat to unknown persons and was considered not guilty by reason of insanity. Since early childhood the patient presented with extreme mood swings and impulsive-aggressive outbursts that led to criminal mischief later on. During elementary school he developed concentration problems as well as specific learning deficits. Due to his deviant social behaviour, he was rejected from his peer group. Over the course of the years, he showed no significant responses to different psychopharmacological treatment approaches. His social anxiety grew and ultimately, he started experimenting with various drugs and drinking excessive amounts of alcohol, which induced multiple psychotic episodes. Due to the psychotic exacerbations, he was repeatedly admitted to psychiatric units for acute treatment, however the autistic disorder remained untreated. At the time of the crime an independent psychiatric assessor diagnosed schizophrenia simplex and multiple drug abuse. The patient had been in psychiatric treatment since the age of 5 and received multiple diagnoses such as combined personality disorder, different subtypes of schizophrenia, ADHD, Tourette syndrome, depressive disorder and ASD at the age of 14. Nevertheless, prior to his detention he had never received a complex therapy focusing on his ASD. According to the verdict he was admitted to a medium secure forensic ward in Lower Austria, where he was treated with antipsychotic and anxiolytic medication. Furthermore, he participated in the day-structuring treatment program ensuring routine.

Neurodevelopmental disorders such as ASD often impose a diagnostic challenge, particularly without intellectual disability. This can lead to under- and misdiagnosis, inadequate treatment or even criminal behaviour. Impaired theory of mind, poor emotional regulation and problems with moral reasoning should be recognized and treated specifically early on to prevent further damage to both the individual and society.

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The transgression of the law can be a deliberate act by a lucid adult, but it can also be the result of a deficiency in judgment and discernment due to lack of age or insanity. Psychiatric expertises are more and more solicited in the penal field with the objective of identifying the causal link between mental illness and the criminal act.

The objective of this work was to give an overview of the subjects expertised, the offences and the pathologies encountered through the report of a psychiatric expertise activity in criminal law.

It is a retrospective descriptive study carried out on the criminal psychiatric expertises made for a forensic act in the psychiatric department of Mahdia during the period from January 1, 2003 to March 30, 2022.

In total, we collected 101 defendants. The average age of our study population was 35±12.07 years. The majority of our study sample was male (98%), from an urban area (50%). 46.6% had primary education and only 11.2% had higher education. The defendants were single in 57.8% of the cases, and almost half (45.7%) had no occupation. Two-thirds of the accused (61.2%) had experienced emotional deprivation at a young age. The problematic use of psychoactive substances was found in 10.3%, as well as alcohol consumption in 46.6%. Moreover, 39.7% of the patients had a personal psychiatric history and 19% had been incarcerated at least once. The forensic acts were mostly against people (62.9%) dominated by physical aggression (33.6%) followed by homicide or its attempt in 19% of the cases. The majority of patients were not related to their victims (62.1%). The nosographic diagnosis found was a personality disorder in 32.75% of cases, followed by schizophrenic disorders in 22.4% of cases.

Psychiatric expertise is a useful, complex and noble clinical act. Determining the predictive factors of a possible acting out allows to specify the objectives of interventions aiming at limiting the acts of violence, hospitalizations and incarcerations of patients suffering from mental disorders.

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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.

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The psychopathology of female crime perpetrators is not well understood since female criminality rates have remained distinctly lower than male criminality.

This study draws on over 20 years of psychiatric expertises to identify sociodemographic, clinical, and forensic characteristics of female perpetrators.

• - To describe the epidemiological and clinical profile of female offenders examined for criminal psychiatric expertise.

• - Describe the criminological and forensic characteristics of these women.

Retrospective and descriptive study, which focused on 56 criminal psychiatric expertise files of female offenders, examined at the psychiatric department “C” at the CHU Hedi Chaker in Sfax, Tunisia, over a period of 24 years.

For each offender, we examined the expert report and the judicial research report. We then transcribed the socio-demographic and clinical information, as well as the criminological and forensic characteristics, onto a pre-established form.

The accused women in our study had an average age of 35 years and 06 months, and 67.86% of the cases were under 40 years of age, with an educational level no higher than primary school in 62.5% of cases. They were unemployed in 71.4% of cases. Among the accused examined, 76.8% had mental disorders, including 46.6% with personality disorders, 16.3% with intellectual disability, 16.3% with bipolar disorder, 9.3% with depressive disorder, 9.3% with psychotic disorder, and 2.3% with substance use disorder (anxiolytic). We recorded 55.4% offences against persons, including 37.5% homicides and attempted homicides, and 44.6% offences against property, including 23.2% thefts. Dementia in the legal sense was identified in 30.4% of cases. Bipolar disorder accounted for 41.1% of legally demented subjects.

It emerges that the profile of the female criminal is that of a woman under 40, with a low educational and economic level, and most often with an antisocial personality or intellectual disability. It would therefore be important to step up primary prevention work by better educating these at-risk women and to combat the factors contributing to dangerousness among the mentally ill by optimizing their psychiatric care.

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Previous studies showed, that reduced executive function can be associated with antisocial and aggressive behavior. For the measurement of executive functions numerous standardized neuropsychological tests are available.

We thought to compare the results of an executive function examination with Wisconsin Card Sorting Test (WCST) of patients observed at the Semmelweis University’s Department of Psychiatry and Psychotherapy to normative data from published database. We also performed a subgroup analysis between the violent and non-violent groups of the patients.

After data clearance our dataset consisted of 20 patients, who were divided into two groups based on whether the crime they committed before their admission was violent according to the Cornell scale.The analyzed parameters were the number of perseverative errors, the percentage of perseverative errors, and the number of completed categories. For comparison, the data bank from the 1993 edition of the WCST manual as normative data was used. The deviation from the healthy average for all three parameters was compared between the violent and non-violent groups using a two-sample T-test.

There was significant difference between the patient and normal populations in all the 3 analyzed WCST parameters: the mean difference was 9,37+2,764, (p=0,0008) in the number of perseverative errors, 14,04+2,21 (p<0,0001) in the percentage of perseverative errors and -2,39+0,34 (p<0,0001) in the number of completed categories (Table 1).Table 1:

The difference between the average scores of healthy individuals grouped by age (from the 1993 WCST manual) and the scores of the patients.

On the other hand, there were no significant differences between the violent and non-violent subgroups in the average deviations (from the normative data) of the number of perseverative errors, the percentage of perseverative errors and the number of completed categories (with p-values of 0.092, 0.34 and 0.59, respectively).

As a limitation, it is important to note that due to the low sample size, and our sample’s heterogeneity in terms of psychiatric diagnosis, drawing reliable conclusions is not possible. However, our results were in line with previous similar research in the forensic psychiatric population (though not under forensic mental state observation) regarding the significant deviations in two examined WCST parameters when compared to normative data. Additionally our study did not find significant difference between the violent and non-violent subgroups of the patients.

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Severe schizophrenia is often closely related to delinquency resulting in relative overrepresentation of these manifestations of disease in forensic institutions.

The aim of the present work is to report the therapeutic challenges in a case of severe schizophrenia in a forensic institution from a clinical viewpoint as a basis for discussion.

The case report is based on the available clinical documentation, exploratory interviews as well as a structured clinical interview (PANSS).

Presenting a case of a 41-year-old, male Caucasian inpatient suffering from a catatonic schizophrenia, we report the challenges in treatment of chronic, major schizophrenic disease resistant to antipsychotic medication. Without any previous criminal convictions, he has been instutionalized in a forensic psychiatry after a bodily harm to a random stranger about three years ago. Regarding medical history, information is limited to a few inpatient admissions prior to detention documenting intravenous opioid and cocaine abuse. Initially, the patient presented sexual disinhibition and ongoing endangerment of others with frequent assaults to other patients and prison guards. From a psychopathological viewpoint several phenomenona such as delusional intuition, acoustic, tactile and coenaesthetic hallucinations, echolalia, mannerisms and thought diffusions reflect the severe course of the disease (PANSS: P 34/49, N 38/49, G 73/112; total 145/210). Therapeutic attempts with an antipsychotic combination of risperidone, olanzapine and quetiapine as well as valproic acid resulted in insufficient recovery with persistent physical assaults and florid psychosis. In reaction to that zuclopenthixol for impulse control was added. As from the beginning of this year a switch of medication by gradually replacing risperidone and zuclopenthixol with haloperidol and clozapine showed modest success. Under the current medication and therapeutic drug levels the patient does not pose endangerment to others. However, regular tonic-eye fits require supplementary treatment with biperiden, and the patient still presents frequent periods of self-harm punching himself, verbal lack of impulse control and the psychopathological phenomenona described before. In addition to pharmacological treatment the patient receives psychotherapeutic one-on-one conversations. Despite approaching all limits of the available antipsychotic repertoire, psychopathology is only insufficiently controlled leading considerations to electroconvulsive therapy as a treatment of last resort.

Certainly, the present case is exemplary for a severely ill population of patients reaching – after a long and untreated course of disease - a chronic stage that does not sufficiently respond to a multitude of treatment attempts despite proper compliance raising the urgent need for further treatment options.

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Despite promising research there is still hesitation in implementing peer support work in some hospitals. Especially in forensic hospitals reservations are held against peer support workers.

We aim to give an overview of reviews about the effects of peer support work in psychiatric settings and its implementation. Special emphasis on implications for forensic psychiatric settings shall be given.

Five electronic databases and archives of four relevant journals were searched in December 2019 and updated in April 2022. In addition, references of articles were searched and relevant authors were contacted for unpublished data. Results of reviews were clustered by one author and checked by another.

22 reviews were identified of which 15 reported on effects of peer support work and six on factors influencing its implementation and one review on both. Several effects of peer support work on clinical, psychosocial, organizational and other outcomes (e.g., cost savings) were described. Psychosocial outcomes were the most promising ones whereas no effects were described in most reviews for clinical, organizational and other outcomes. Factors influencing the implementation of peer support work were described during preparation, recruitment, early employment and further development of the peer support worker’s roles. Most factors, beneficial and challenging, were described for the preparation stage of the implementation process.

The authors of the reviews often reported concerns about the low quality of the included studies. Therefore, the present results have to be considered as preliminary. Nevertheless, it is clear that peer support has a positive influence on psychosocial factors and thus complements classic therapeutic approaches. To achieve the best possible effect, the implementation of peer support needs to be carefully planned. Further studies are necessary in order to be able to consider the effect of recovery support in a more differentiated way.

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Nowadays, following the increasing digital technologies, the cyber aspect of violence is becoming more common (Willard, Journal of Adolescent Health 2007; 41) At this point, we can think that cyber violence victimization, environmental factors such as childhood traumas, exposure to violence, and moreover psychological and biological factors play a role (Fan et al., Front. Psychol 2921;12)

Our aim was to conduct a study to determine the prevalence of cyber violence victimization among university students and to examine whether this prevalence would be related to negative childhood traumas.

We reached university students in many cities of Turkey through an online survey between 01 January 2023 and 31 March 2023. A total of 600 students participated. In our survey, we used the Turkish forms of the Childhood Adverse Experiences Scale and the Cyber Victimization Scale, for which sociodemographic data, validity and reliability studies have been completed in Turkish.

University students from 8 different provinces participated in our study. According to the results of our study, it was evaluated that university students who had negative childhood experiences were more likely to become cyber victims. We are exposed to many traumas from the moment we are born, and this exposure is the relationship with the mother, then relatives, friends, teachers, colleagues, etc. It continues throughout life through relationships. There is a moderate relationship between victimization of blocking and damaging behaviors in cyberspace and negative childhood relationships (r = 0.304), a low level relationship between victimization of sexual bullying in cyberspace and negative childhood relationships (r = 0.289), and victimization of spreading rumors in cyberspace. A low degree of correlation (r = 0.277) was found between and negative childhood relationships. (p <0.05)

The widespread use of technology today facilitates the digitalization of violence, as in every field. As a result, cyber violence, like other types of violence, may be associated with childhood traumas, and this can be prevented by being exposed to the least trauma during childhood, and moreover, if we look from Bronfenbrenner’s perspective, if the next generation grows up in a suitable ecological environment, cyber violence victimization can be prevented to that extent.

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Recently, the new therapeutic approach based on genome editing using the CRISPR/Cas9 system has been applied to treat cancer and other monogenetic disorders. CRISPR/Cas9 allows specific correction of the altered gene without affecting the rest of the genome.

The aim of this study was to report the current CRISPR/Cas9 genome editing clinical trials in neurodevelopmental and mental disorders.

We conducted a search via the ClinicalTrials platform to describe clinical trials that have been conducted using the CRISPR/Cas9 genome-editing tool in neurodevelopmental disorders.

Our research revealed three clinical trials that used the CRISPR/Cas9 tool for diagnostic and therapeutic purposes. The first study aimed to investigate the pathological role of KMT2D mutations in 40 Kabuki syndrome patients in order to facilitate the identification and characterization of therapeutic strategies to improve symptoms, to identify the consequences of KMT2D mutations on epigenetic marker changes and cellular structural changes and to finally attempt gene correction by CRISPR/Cas9. The therapeutic approach was an epigenome editing approach aimed at increasing the expression of the wild-type KMT2D allele to restore the functional activity of a histone H3-lysine 4 (H3K4)-methyltransferase (MLL4) in treated mesenchymal stem cells. The second clinical trial aimed to validate gene editing based on CRISPR/Cas9 technology combined with AAV delivery for the correction of the most common MECP2 mutations in Rett syndrome both in vitro and in vivo. The third GENEPI clinical trial aimed to identify acetylation profiles as epigenetic markers to assess the causality of CREBBP and EP300 variants in Rubinstein-Taybi syndrome, which is considered as a genetic model of neurodevelopmental abnormality with an epigenetic component.

CRISPR/Cas9 clinical trials in polygenic conditions, such as psychiatric disorders, could be envisaged at the level of the epigenetic component of these pathologies. This therapy could be applied ex vivo to perform tissue-specific gene editing.

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In females, congenital adrenal hyperplasia (CAH), a spectrum of inherited genetic conditions related to the disruption of adrenal steroidogenesis, is among the most common conditions leading to inappropriate virilization. For adolescent and adult women, progression of hirsutism may have many psychological concerns.

To explore the psychological distress of a young Tunisian woman who sought medical help and psychological support at a late stage, after suffering from genital ambiguity and severe virilization.

Harboring phenotypic male transformation at puberty, our patient attended genetic counselling for cytogenetics assessment. Clinical, biological, psychological and genetic explorations were thus carried out.

A 17-year-old female was born from first-degree consanguineous parents, and had healthy siblings (a sister and three brothers). After a single menstrual episode at puberty, she developed amenorrhea and an unexpected progressive virilization, including hirsutism with an inappropriate beard that she had to shave every day and a male voice. Clinical examination revealed a male morphotype with an enlarged clitoris that resemble a penis, male-type pubic hair, underdeveloped of breasts, abnormal cutaneous hyperpigmentation, and a short stature. Pelvic ultrasound revealed a small uterus, but with no visualized gonads. Genetic exploration showed a female 46,XX karyotype and the absence of Y chromosome sequences. Diagnosis of a non-classic CAH was confirmed. Psychological assessment found that the psychological development of the sexual identity corresponded to the assignment of the female sex. A severe psychological suffering due to the non-acceptance of her virile appearance impaired the quality of her daily personal and social life. Stigmata of a depressive syndrome were also revealed.

Particular attention to the psychological assessment of patients with CAH is recommended, as changes in physical appearance have a detrimental impact on psychological and mental well-being.

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After the success of polygenic risk scores (PRS) that embed a useful summary of genomic information in a comprehensive score, the wish to develop summary statistics for DNA methylation had become more pressing. Developing such a score faces challenges, as the score has to be specific and sensitive as well. Epidemiological research on DNA methylation and depression would benefit from such score.

Here, we test a score trained on incident depression (case-control), i.e., a list of published weights for particular CpGs, for its validity in the context of depression severity as measured using MADRS in our sample with depressed patients only.

DNA methylation was assessed using the Illumina Infinium MethylationEPIC 850k BeadChip on a sample of 119 patients with a diagnosis of MDD. After data cleaning, 113 participants were included in the analysis (Mage= 47 years, 57.98% women, MMADRS=27.7). Data processing was conducted using the RnBeads package. From the published reference for the overall sample, a list of 196 CpGs was provided, 170 of these were present in our dataset and used for the score. The list of non-smokers comprised 144 CpGs, of which 124 were available. The score per individual was built using M-values, using the formula: S(weight*DNA methylation value). The score was tested in association with depression and other typical confounders using multiple regression in R. Confounders included ancestry, BMI, age, sex, and 6 cell types. We tested both scores in our sample: smokers and non-smokers.

In contrast to our expectations, none of the regression analyses showed a significant association with depression (MADRS-score). Nonetheless, a significant association was seen with biological sex for both analysis (overall: p=0.036, non-smokers: p=0.026). A reduced model with only this predictor explained 5% and 4% of the variance of the summary score calculated (R2), respectively (overall: p=0.013; non-smokers: p=0.019). One of the ancestry components was marginally significant too in the non-smoker summary score (p=0.065). This was not the case anymore in the reduced model.

Our results show that caution is still in place when using methylation risk scores as specificity and sensitivity might not yet be optimized. The score built for depression incidence does not seem fitting for depression severity at this moment. The use of DNA methylation, a marker that is generally sensitive to confounding factors, for a risk score, might pose more challenges in the context of reliable summary statistics, in particular also for cross-trait examination, which is currently a typical use of polygenic risk scores.

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Crigler-Najjar 1 (CN1) due to exon 3 mutations of the UGT1A1 gene is a not rare genetic disease in Tunisia with a founder effect. CN1 syndrome is very severe, and most of CN1 Tunisian patients die soon after birth, within a maximum of one year, due to kernicterus. Liver transplantation, which is the only available therapeutic method for CN1, remains unreachable.

The aim of this study was to report behavioral and neurocognitive phenotypes in CN1 patients who survived to school enrollment.

We have selected all patients evaluated from 2004 to 2010, both clinically and molecularly, for a deficiency of bilirubin-UGT enzyme activity leading to a pathological elevation of unconjugated bilirubin with a suspicion of CN1 syndrome. Direct sequencing of targeted PCR amplification products was performed for molecular analysis of UGT1A1. Behavioral and mental features of patients were studied through our genetic counselling.

We identified 15 patients with the homozygous c.1070 A>G Tunisian mutation. Their age at diagnosis ranged from one week to 9 months for 13 patients. Six of them died within a month of molecular investigation. Only two boys were of school age, i.e. 6 and 9 years. The first had been hospitalized at 3 months year-old for a prolonged jaundice treated with phenobarbital and phototherapy. His psychomotor and neurological development was normal, with school attendance at the age of six. The second patient presented with an unexplored jaundice at the age of 3 days, which was later complicated by seizures and treated with phenobarbital. Despite neurological and motor sequelae associated to language impairments with slurred speech, he attended school at the age of six.

The neurological and behavioral profile of CN1 patients depends on familial and medical management. Quick diagnosis, close follow up and early liver transplantation can improve prognosis.

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Neurobiological studies have shown that genetic variations affecting the intensity of monoamine neurotransmission play an important role in aggressive behavior and borderline personality traits. Also, the effect of family environment has been repeatedly shown on aggressive behavior and interpersonal functioning. Population-based longitudinal studies pointed out interactions between the so-called monoaminergic sensitivity alleles and childhood adversities.

Our study aimed to analyze the associations between the most studied variable number tandem repeats of monoaminergic genes and the different psychological factors in adult patient and healthy control groups, checking for the moderating effects of the parental occupation and education, childhood abuse and trauma.

The recruited 73 patients with BPD diagnosis and 98 healthy controls were assessed by the Structured Clinical Interview for DSM-5. Participants filled out online questionnaires including the Level of Personality Functioning Scale – short version (LPFS-SR) and the Buss-Perry Aggression Questionnaire (BPQ). Childhood social environment and traumatic experiences were assessed by the Barratt Simplified Measure of Social Status and the Early Trauma Inventory or the Childhood Trauma Questionnaire. Genomic DNA samples were obtained either from peripheral blood, saliva or buccal swabs using the desalting technique. Functional dopaminergic and serotonergic polymorphisms were chosen based on previous findings, implicating them as sensitivity gene variants, e.g., the variable-number tandem-repeats of the dopamine D4 receptor, serotonin transporter and the monoamine oxidase-A (MAO-A) genes. Since the MAO-A gene is located on the X chromosome, sex-stratified analyses were also carried out.

Family environment indexed by the Barratt Simplified Measure Social Status had significant effect on anger, hostility and interpersonal functioning (p < 0.01). In the pooled sample of patients and controls, individuals carrying the high activity alleles of MAOA had elevated scores on the BPQ subscales. When analysis was limited to female participants, the genetic effect stayed significant only at the anger scale of the BPQ.

Family environment had pronounced effect on aggressive behavior and personality functioning, interaction with common monoaminergic genetic variants was detected only in women.

This study was supported by the National Research Development and Innovation Office grants NKFI K 129195 and NKFI K 135437.

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The purpose of predictive genetic tests is to identify carriers or the onset of a disease in pre-symptomatic individuals. Prediction is linked to a negative psychological impact (anxiety, depression, etc.), depending on the perception of risk, the severity of the disease, and the availability and effectiveness of treatments.

Here, we report on genetic counselling during predictive genetic testing offered to an Arab family affected by fragile X condition (FXS) caused by the unstable expansion of a CGG repeat (CGGR) in the FMR1 gene.

A 10-year-old boy who harbored a mental retardation was referred to our genetic counselling for genetic testing as he was suspected to be affected by FXS. Screening of FMR1 gene mutations was conducted for the index case and his mother. A predictive genetic testing for the family members (brothers, sisters and others) was offered, focusing on knowledge of genetics and medical risks of FXS.

FMR1 molecular analysis showed a full mutation (300 to 2000 CGGR) for the boy and a large premutation (100 CGGR) for the mother. During genetic counselling, the family was informed about the significance of the genetic results. In FXS initiated by an expansion of over 200 CGGR. While mental retarded males usually harbor the full mutation, the mother carry a premutation (70 to 200 CGGR). The deficiency of FMR protein (FMRP) in the neurons of affected males leads to brain developmental abnormalities. Some pre-mutated children may show signs of the autism spectrum disorder and females may develop FMR1-related premature ovarian insufficiency. An increased risk of a late onset fragile X tremor ataxia syndrome is identified in pre-mutated men (55 to 200 CGGR) and less in women.

The reduction or loss of FMRP leads to multisystem damage. Neuropsychiatric disorders such as mental retardation, speech and language delay, autism spectrum disorder, sensory hyperexcitation, social anxiety, abnormal eye contact, shyness and aggressive behaviour are common in individuals with the mutation. Affected women are often under-diagnosed because mental retardation is not constant, but minor disorders including a borderline IQ with learning difficulties and emotional disturbances have been reported. Conditions associated with fragile X premutation, a term proposed by the European Fragile X Network (FXPAC), seem to be characterized by many physical and psychological health symptoms. Anxiety, depression, sleep disorders and mood disorders are more common in permutated individuals. However, new reports suggested that FXS patients could be at unusually low risk of cancers, because FMRP is over-expressed in multiple cancer tissues.

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Klippel-Feil abnormality (KFA) is an association of bone defects characterized by a triad: fusion of the cervical vertebrae and consequent short neck, low hairline and a limited motion in the neck. KFA may be a feature of another disorder, such as MURCS association. Familial mutations in the GDF6 (KFS1 8q22), MEOX1 (KFS2 17q21), GDF3 (KFS3 12p13) and MYO18B (KFS4 22q11) genes cause inherited KFA.

The aim of this study was to report dysmorphic features and psychological burdens in two sisters with Klippel-Feil condition.

Two sisters with amenorrhea and dysmorphic clinical features were examined at our genetic counselling. Assessment of dysmorphic and behavioral features and karyotyping using RHG banding were performed.

Familial history revealed consanguineous parents and seven other healthy sisters. Physical examination shown typical triad of KFA. Karyotyping showed 46,XX formula in both patients. The first 22-year-old sister had body asymmetry with size difference between the two sides at the level of bones, pectus excavatum of the sternum, an ascent of the left scapula, scoliosis, dental position abnormalities and facial dysmorphism. The second 28-year-old sister had size difference between the two legs and scoliosis, vitiligo and facial dysmorphism. Anxious and depressed, the two sisters had normal learning abilities but shared many personal psychological concerns regarding their physical appearance and their amenorrhea. They were also exposed to significant discrimination and stigma making them feel excluded and ignored because of their visible difference.

Physical appearance has a profound impact on a person’s life. To our knowledge, there is no reports that describe specific psychological burdens of KFA. Self-esteem, body image, and quality of life is negatively impacted in the case of dysmorphic physical appearance, always associated to social discrimination. Patients with KFA should be assessed not only for associated congenital defects but also for psychological distresses.

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Patients with Brugada Syndrome (BS), a rare inherited cardiac channelopathy, with an increased risk of developing arrhythmias, syncope and sudden cardiac death, also present serious adverse psychological outcomes that require medical support to improve their health and well-being as well as those of their families.

Here we report psychological concerns of a Tunisian patient who presented to our genetic counselling, with his three children, for molecular exploration of BS type 1.

Clinical, electrical, biological and psychological characteristics of the patient and his offspring were identified. Cytogenetic exploration using RHG banding and molecular screening of SCN5a gene mutations using High Resolution Melting and sequencing were carried out. Subsequently, genetic counselling was undertaken for all the family members and psychological concerns were reported.

A 51-year-old married man with an academic career was born from a consanguineous couple, with a family history of sudden cardiac death. He was diagnosed with BS1 based on the pathognomonic ST-segment elevation in leads V1–V3, after experiencing palpitations and syncope. He was treated by implantable cardioverter defibrillator. The patient was also being treated for diabetes and dyslipidemia. His children, a girl and two boys, were investigated by ECG, which revealed no electrical disorders. However, both boys reported chest pain on exertion. The 18-year-old girl presented with primary amenorrhea and infantilism, along with a Turner syndrome formula. Molecular analysis revealed none of the targeted mutations in the SCN5a gene. Psychologically, the patient had a phobia of death and reported painful sensations of imminent death at each palpitation. He was anxious about the clinical outcome of his children. The children reported anxiety about their autosomal dominant fathers’ disorder.

Approximately 16% of BS patients experience depression and anxiety. More attention needs to be indorsed to the psychological distress of BG patients and their families.

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Schizophrenia (SZ) is a common psychiatric neurodevelopmental disorder with a complex genetic architecture. Genomic association studies indicate the involvement of transcription factors in the pathogenesis of SZ. A recent GWAS showed a significant association of ZNF536 with SZ. To date, the molecular functions of ZNF536 are poorly understood and its possible role in the pathogenesis of SZ is unclear.

The aim of this work was to develop a model cell line for study ZNF536-mediated pathogenic mechanisms associated with SZ.

To assess the spatial interaction of ZNF536 with SZ risk loci, we used the Capture-C method. For ZNF536 deletion, SH-SY5Y was sequentially transduced with two lentiviral vectors. The first expressed Cas9 under the control of a tetracycline regulated promoter and the second expressed a pair of sgRNAs for ZNF536 deletion. Puromycin was used to select transduced cells. Stably transduced cells were then treated with oxytetracycline to induce Cas9 expression. In parallel, SH-SY5Y were transduced with lentiviral constructs of Cas9 and sgRNA carrying a spacer lacking targets in the human genome to obtain a negative control. Individual clones were obtained by the limiting dilution method. The ZNF536 deletion was confirmed by PCR and Sanger sequencing.

A spatial interaction of ZNF536 with SZ risk loci was found, suggesting its involvement in SZ pathogenesis. Using the CRISPR/Cas9 system, we obtained several clones with heterozygous deletion of ZNF536. We observed that their growth and proliferation were significantly slowed down. In addition, the mutant clones spontaneously differentiate into a neuron-like phenotype in low-serum medium.

We established a cellular model to study ZNF536-mediated mechanisms associated with SZ.

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Accordingly, the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) working committee, composed of domestic experts, developed Korea’s first KMAP-BP in 2002 and later in 2006, 2010, and 2010. A revised version of KMAP-BP was announced every four years four times in 2014 and 2018.6-10). The treatment strategy considering the safety and tolerability of KMAP-BP 2022 was developed by collecting opinions from domestic bipolar disorder experts.

Safety and tolerability of drugs are very important factors in the treatment of bipolar disorder. An expert opinion survey was conducted on treatment strategies in various special clinical situations, such as significant weight gain, characteristic drug side effects, low drug adherence, pregnant and reproductive women, and genetic counseling.

A written survey about treatment strategies related to safety and tolerability was prepared and focused on significant weight gain, characteristic drug side effects, low drug adherence, pregnant and reproductive women, and genetic counseling. Ninety-three experts of the review committee completed the survey.

In the case of weight gain occurring during drug treatment, it was preferred to replace it with a drug that caused less weight gain, such as lamotrigine, aripiprazole, or ziprasidone. If there was a significant weight gain due to the treatment drug, it was preferred to intervene as soon as possible. In the case of hyperprolactinemia, it was selected to change the medication and discontinue it for benign rash caused by lamotrigine. In improving drug adherence, the preference for long-acting injections increased. Antipsychotics can be used with great caution in pregnant or reproductive women.

Treatment strategies in various clinical situations related to safety and tolerability in drug treatment for bipolar disorder were described. It is hoped that it will be useful in practical clinical situations.

None Declared

Down’s syndrome often requires specialized rehabilitation methods in order to effectively improve cognitive and motor functioning. The growing interest in technologies to support rehabilitation is opening up new and promising perspectives for improving the quality of life of people diagnosed with this syndrome. One of these technologies is the Computer Assisted Rehabilitation Environment (CAREN) system from Motek.

The aim of the planned research project is to explore the potential of using the CAREN system in the rehabilitation of people with Down’s syndrome.

The study included 10 participants with Down’s syndrome (men and women aged 18 to 50 years) without the presence of organic musculoskeletal disease or other somatic causes impairing motor performance. Before the training test, the participants were assessed by two psychological tests: 1) ACE III - Addenbrooke’s Cognitive Examination III Scale (ACE-III), which assesses attention and orientation, memory, verbal fluency, language and visuospatial functions and 2) the TONI 4 Non-Verbal Intelligence Test, which is a test used to measure general intelligence. The tests were carried out using the MOTEK CAREN device, which consists of a treadmill for motor training and a virtual reality screen on which different scenes are displayed for the participant to see during the test. Integrated motion capture technology was used to assess movement capabilities of the patients.. The screen displayed different types of applications in the form of virtual reality, in which the participant had to cope with various tasks accommodating different psychomotor skills, for example:crossing a virtual bridge, walking through a forest. The test took about 45 minutes per person. Two training sessions were conducted for each of the 10 patients with a one-month interval between them.

The Motek Caren System has proven to be a promising rehabilitation method for people with Down’s syndrome, compared to previous experience with different rehabilitation methods and existing research in the field.

Results emphasize the necessity for further investigations and future research should involve more participants. The project has the potential to integrate modern technology with traditional forms of therapy to improve the quality of life and functioning of people affected by this syndrome.

None Declared

There are few studies about how people with intellectual disability (ID) perceive their own quality of life (QoL), with research being focus, mainly, in the opinion of caregivers and/or family. Thinking about QoL, the World Health Organization developed an instrument that measures QoL, the WHOQOL. In Brazil, this instrument was adapted, validated and translated for people with ID and their caregivers.

The aim of this study was to increase knowledge and understanding of how people with ID perceive their own QoL.

This study was approved by the Ethics and Research Committee. Sample of 51 individuals aged between 19 and 54 years (G1), with medical diagnosis of ID, who did not present physical/mental disabilities and/or mental disorders and 31 caregivers (G2). G1 answered the WHOQOL-DIS-ID questionnaire and G2 answered the WHOQOL-DISID Proxy questionnaire. The results were statistically analyzed considering p-value ≤ 0.05.

The individuals with ID presented higher score on the psychological and lower score in the discrimination domain. The caregivers presented higher scores on the physical and lower scores in the autonomy domain. Regard the comparison between self-perception and the perception of caregivers, on Table 1, it was possible to observe significant differences in Psychological, Social, Environmental and all domains for the Disabilities Module.Table 1.

Correlation between Domains

It is critical that people with ID participate in the creation and/or changes of inclusion policies and actions. Since the relationship between the perception of self-reported QoL and reported by caregivers are different and converge only in the physical domain.

None Declared