EPA 2023SP-1290

Objective

In medicine, women are still understudied because they are considered less reliable research subjects than men, due to hormonal changes during the lifespan. Women with ADHD have been even more understudied, while exactly their hormonal mood changes and increased severity of ADHD urgently need our research attention.

Methods

In a selfreport questionnaire study (Dorani 2021) among 209 women with ADHD, hormonal mood changes during the menstrual cycle, after childbirth and during menopausal transition were investigated, and compared with available data from women of the general population, using the same instruments.

Results

The data showed that in every episode of hormonal changes, women with ADHD suffered from a 2-3 fold increase in frequency and severity of mood changes.

Conclusions

This first study points to increased severity of mood changes and probably also ADHD symptoms during episodes of hormonal changes in women with ADHD during the lifespan. During this talk, the findings and their etiological background will be clarified, such as interaction between the sex hormones estrogen and progesteron with dopamine and other neurotransmitters in the brain. Treatment options will be discussed as well.

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The UN Convention on the rights of people with disabilities (UN CRPD) raised awareness of the need to find alternatives to coercion in the process of care for people with mental illness and/or mental impairment. In order to promote the application of the CRPD the World Psychiatric Association (WPA) has undertaken to produce a document listing possible alternatives to coercion and proposed to the General Assembly of the WPA to support the recommendations of that document by a WPA Position Statement on the matter.

The presentation will discuss the suggestions included in the Position Statement and in the review of options to reduce coercion in the WPA materials.

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Patients with amnestic mild cognitive impairment (aMCI) have a high risk of transition to Alzheimer’s disease. Analysis of potential biomarkers of conversion to dementia in this clinical group is crucial for prognosis and early intervention.

The aim of the pilot study was to compare whole-brain functioning characteristics (fMRI, spontaneous activity and local coherence) in aMCI converters and non-converters to dementia.

Nine aMCI converters to dementia of the Alzheimer’s type (mean age 69.2 ± 8.2; 9 females) and ten aMCI non-converters (mean age 65.9 ± 6.1; 8 females) underwent resting-state fMRI (3T). All patients were followed up for three years. Baseline whole-brain amplitude of low-frequency fluctuations (ALFF) and local coherence (LCOR) were compared between groups (CONN-fMRI toolbox 19.с, https://web.conn-toolbox.org/; p < .001 voxelwise, p(FDR) < .05 clusterwise). Age was included in the analyses as a second-level covariate.

As compared to non-converters, aMCI converters were characterized by higher ALFF and LCOR values in the cluster located in the frontal medial cortex and frontal pole bilaterally.

Frontal medial cortex and frontal pole are involved in a wide range of cognitive functions, including episodic memory and “hot” (motivational) executive control (Rolls. ProgNeurobiol 2022; 217; Friedman, Robbins. Neuropsychopharmacology 2022; 47(1) 72-89). Both increased and decreased LCOR/ALFF values in aMCI converters compared to non-converters were found, although in the other regions (Mondragón et al. Dement Geriatr Cogn Dis Extra 2021; 11(3) 235–249; Khatri, Kwon. Front Aging Neurosci. 2022; 14). It seems reasonable to clarify if the brain functional features revealed in our study are the markers of conversion to dementia in aMCI.

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CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a cerebrovascular disease, tht appears in 1.98/100,000. It´s caused by a mutation of the Notch3 gene and is characterized by accumulation of granular osmiophilic material in the middle layer of the small and median sized cerebral arteries.

Sypmtoms are migraine, recurrent cerebral ischemic episodes, dementia, neuropsychiatric disorders (anosognosia, character disorders, apathy and cognitive impairment). It usually appears between 30-60 years, although there is an important variability. There is no curative treatment, only palliative.

Clinical review of anosognosia and its presence in CADASIL disease.

Clinical case and literatura review.

We presented the clinical case of a 68-year-old man, who was diagnosed with CADASIL after a stroke 3 years earlier. In his family, his brother was diagnosed also with CADASIL. The patient had previously presented disturbances in impulse control (hyperorality) and important executive failures. He currently presented anosognosia, deficits in verbal memory, spatial perception and executive functions, in addition to behavioral alterations and apathy. Due to these deficits he was prohibited from certain activities (driving, hunting).

The patient was not aware of these deficits and becouse of his “no knowledge of his illness”, he disagreed with these prohibitions, so he showed rage and anger at the impotence of not understanding why certain actions are prohibited.

In the consultation, mnesic errors and in naming objects were also objectified, for which it was recommended to carry out cognitive stimulation on a daily basis. In addition, he presented failures of sphincter incontinence, especially of urine and occasionally also of the anal sphincter. He had previously had episodes of myoclonus or fasciculations.

A genetic study by massive sequencing confirmed the heterozygous presence of the pathogenic variant c.1819C>T p.(Arg607Cys) in the NOTCH3 gene, a CADASIL disease.

The anosognosia that many patients with CADASIL disease present constitutes a problem because it contributes to the delay in consultation and, therefore, the delay in the adequate diagnostic approach, therapeutic possibilities and family genetic counseling. Due in part to anosognosia, CADASIL is considered an underdiagnosed entity. Due to the lack of awareness and the consequent lack of recognition of the deficit, these people are often seen as stubborn and difficult to deal with by people in their immediate environment.

In addition, there is general difficulty in the rehabilitation process, since patients do not think the neccesity to be treated. This can generate frustration and despair both in their relatives and in the health personnel.

For all these reasons, both in anosognosia and in CADASIL disease, adequate psychological support is needed for both those affected and their families.

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Obligate autoscopic mirror hallucinations of senescence have not heretofore been described.

To reveal that perception of looking older in the mirror may be the manifestation of Mirror Autoprosopometamorphopsia.

A 37 year old right handed female, with schizoaffective disorder, bipolar subtype She described that when she would gaze at herself in the mirror, she would not see her current face, but rather the visage of an “old person”. This would recur whenever she would directly look at herself in the mirror, and would avoid glancing at any mirrors because she was fearful of looking at her transform senescent countenance. She realised it was not another person but rather herself in the future, having become her geriartric self.

Abnormalities in Physical Examination: Mental Status Examination: Hyperverbal, grandiose with expansive affect, poor insight and judgment. Recalls 3 out of 4 objects in 3 minutes and all 4 with reinforcement. Proverb testing: correct abstraction. Neuropsychiatric Testing: The Patient Health Questionnaire 9:7 (mild depression). Other: Magnetic Resonance Imaging/ Magnetic Resonance Angiography of Brain with Infusion: Normal.

Autoscopic mirror hallucinations appearing only when embedded in a mirror are obligate autoscopic mirror hallucinations and suggest occipital and parietal lobe dysfunction (Virk, 2018). The inability to recognize the perception of another image or another person replacing the individual looking in the mirror, while defined as a mirror sign, may also be viewed as “a capgras syndrome for the mirror image” (Feinberg, 2005). Distortion of one’s own face only when viewed in a mirror is autoprosopometamorphopsia. With such distortion, this may be a misidentification of one’s own image. This phenomenon is classified as a form of delusional misidentification syndrome with inability to recognise one’s image in the mirror (Postal, 2005). Autoprosopometamorphopsia, obligate to mirror reflection, but metamorphosized to enhance perceived senescence, has not been specifically localized. Possibly a single lesion in the non dominant inferior parietal lobe may have caused this phenomenon. Somatoparaphrenia with somatosensory illusions involving body image are seen with parietal lobe dysfunction (Nightingale, 1982). In the general population, an individual’s focus on a mild facial imperfection often is associated with a negative view of their image. Exaggeration of this to involve the entire face, with projection of imperfection of aging, may be a somatic manifestation of such negative self image. It is possible that such senescent autoprospometamorphopsia may be prevalent, to a lesser degree, in the general population and may be a nidus for younger people seeking cosmetic and plastic surgical intervention of the face.

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Sleep related sexual behaviors or sexsomnias are unconscious behavioral activities that occur during sleep (e.g. parasomnias). Behaviors could range from sexual vocalizations, orgasms, sexualized movements, masturbation, or full sexual intercourse with a subsequent amnesia. Early epidemiological studies showed a prevalence of 7.1%, with a male predominance. While intended as a rare condition, leads to important physical and psychological consequences for both the patient and their bed partner. For our knowledge this is the first case of sexsomnia reported in Portugal.

To report the clinical and psychosocial impact of a Sexsomnia case in a young woman which was misdiagnosed with depression.

Patient´s clinical files consultation and literature review using Pubmedâ and the keywords: sexsomnia.

A 18-year-old female referred to a psychiatric consultation to be assessed and treated from a diagnostic of depressive disorder. This was a young woman with a previous history of sleepwalking during childhood, with no recurrent episodes since adolescence. A familiar positive history for sleepwalking was confirmed (mother). She reported the beginning of her sleep related sexual behavior six months before the consultation, conflicting with the moment in which she started pharmacological therapy for Chron Disease, diagnosed at that time.

After she slept with her boyfriend, she was told by him about the recurrence of masturbatory activity during sleep. These episodes were told to occur as often as 1 to 2 times a night, shortly after falling asleep, with posterior amnesia for the event.

As for medical or psychiatric history, only Chron’s disease is highlighted, being under control with azathioprine. Likewise, he took 1mg of melatonin/night.

Pittsburgh Sleep Quality Index at presentation was 7/21 and the STOP-Bang questionnaire revealed a low risk of Obstructive Sleep Apnea.

A Type I Polysomnographic study was performed revealing decreased sleep efficiency and fragmented sleep presenting an alternating cyclic pattern. The existence of significant respiratory events during sleep, as well as periodic movements, was excluded.

Cognitive behavioral therapy by means of highlighting the need of improvement on sleep hygiene measures was prescribed and the dose of melatonin was increased up to 3mg. Despite the good clinical response, the patient discontinued the melatonin treatment mainly due to familiar and personal reasons and failed to comply with the prescribed hygienic measures, with a further worsening of the clinical condition.

This particularly challenging case representing the emerging medicolegal issues and psychosocial aspects related with the still poorly understood sleep disorders like sexomnia, shows up how much awareness is required from psychiatric team members to better assist and refer patients, promoting both an assertive diagnostic and an effective management.

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In contrast to women, men do no experience a sudden cessation of gonadal function comparable to menopause. However, there is a progressive decline in hypothalamic-pituitary-gonadal function in aging men: testosterone level decline, and there is a loss of circadian rhythm of testosterone secretion.

By age 75 years, mean plasma testosterone levels have decreased 35% compared with young adults, and more than 25% of men of this age are clinically hypogonadal. Age related hypogonadism, which has been termed»andropause«, is thought to be responsible for variety of symptoms experienced by elderly men, including reduced muscle and bone mass, sexual dysfunction, depression, fatigue and irritability.

However, it has been difficult to establish correlations between these symptoms and plasma testosterone levels. Clinical trials of testosterone replacement have documented some symptoms relief (improved muscle strength and bone mineral density), yet studies to date on the specific relation between depression and testosterone level have been methodologically flawed.

Data are presented from systematic clinical and epidemiological studies with bearing on this relation:

1. 1. population-based assessments of the relation between testosterone level, genetic factors and depression in elderly men,

2. 2. placebo-controlled clinical trials of testosterone replacement in men with major depressive disorder.

Results suggest that age-related hypothalamo-pituitary-gonadal hypofunction may have particular etiologic importance in late-onset male dysthimia.

However, there is still the dilemma whether late-onset depression in older men is predominantly biological (in which testosterone decline certainly plays an important role), psychosocial, or stress-diathesis origin.

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Accumulating studies have pointed out that gut-blood and blood-brain barrier dysfunctions due to the alterations in permeability may play a role in the pathophysiology of neurodevelopmental disorders. Tight junctions are crucial components of these barriers and some peptides including claudin-5, occludin, zonulin and tricellulin are important components of these structures.

This study aimed to investigate the relationship between these molecules and attention deficit hyperactivity disorder (ADHD) in children and adolescents.

A total of 57 children with ADHD and 60 controls aged between 6 and 12 years were included in the study. The severity of ADHD symptoms was assessed through a parent-rated questionnaire and Conner’s Continuous Performance Test. Serum levels of biochemical variables were measured using enzyme-linked immunosorbent assay kits.

Serum claudin-5 and tricellulin levels were significantly lower in the ADHD group compared to the control group. The difference between the groups in terms of serum claudin-5 and tricellulin levels remained significant after controlling for confounding factors such as age, gender and autistic characteristics. There was no significant difference between the groups in terms of serum zonulin and occludin levels. (Table 1)Table 2.

Serum claudin-5, occludin, zonulin and tricellulin levels of ADHD and controls

These results suggest that claudin-5 and tricellulin may be involved in the etiopathogenesis of ADHD. Alterations in these peptides may affect the brain by leading a dysregulation in intestinal or blood-brain barrier permeability that eventually affects the gut-brain axis. The causal relationship between these peptides and ADHD requires further investigation.

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Mental illness is not uncommon among males. While the estimates of the males who are dissatisfied with their lives, die by suicide, become alcohol-dependent and drug users are high, low numbers seek mental health support.

In this study, we aimed to assess Text4Hope, a texting mental health support service, provided to people in Alberta during the COVID-19 pandemic, and examine its effectiveness among male subscribers.

In a naturalistic randomized controlled trial design, a comparison was run between two populations of Text4Hope male subscribers; an intervention group (IG, Text4Hope subscribers who received once-daily supportive text messages for 6 weeks) and a control group (CG, Text4Hope subscribers who joined the program in the same time frame but were yet to receive text messages). The severity and the prevalence of likely stress, anxiety, and depression were examined between the two groups, using the Perceived Stress Scale (PSS-10), the Generalized Anxiety Disorder 7-item (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9), and defined the Composite Mental Health (CMH) score as the sum of these three. T-test, Chi-squared association, and binary logistic regression analyses were applied.

There were 286 male subscribers to Text4Hope. The majority were above 40 years, white, employed, had postsecondary education, were in a relationship, and owned a home. Mean scores of PSS-10, GAD-7, and PHQ-9 scales and the CMH were significantly higher for the CG compared to the IG, 11.4, 28.8, 25.8, and 18.7%, respectively. Similarly, there was a statistically significant lower prevalence in IG, compared to the CG, on likely MDD (58.15 vs. 37.4%) and likely GAD (50 vs. 30.8%), with a small effect size. The IG was a significant predictor for lower odds of both likely MDD and likely GAD while controlling for sociodemographic characteristics.

Text4Hope is an effective tool for mental health support for male subscribers, during the COVID-19 pandemic. Compared to the subscribers who didn’t receive the service, those who received it were in a better mental health condition. Further efforts are still needed to encourage males to participate in such online services that can provide adequate support, particularly during crisis time.

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The clinical presentation and the course and outcome in Early-Onset Bipolar Disorder (EOBD) patients are found to be atypical compared to adult bipolar patients. Lithium and valproate are among the first-line maintenance treatments for bipolar disorder. Because of atypical features, in many patients, valproate is preferred over lithium. However, recent studies have shown that valproate results in more neurocognitive deficits than lithium. There have been very few Indian studies that assessed the prophylactic response to mood stabilizers in patients with early-onset bipolar disorder. BDNF has an important role in neurodevelopment, and it is shown that peripheral levels of BDNF are reduced in early-onset bipolar disorder.

To compare the effectiveness of lithium and valproate in attenuating manic, depressive, and mixed episodes in early-onset bipolar disorder.

This study was an observational (cross-sectional analytical) study conducted in the Affective Disorder clinic of a tertiary care hospital. We have recruited a total of 50 adult patients with a history of early-onset, i.e., onset at <18 years of age and in remission. Patients were divided into two groups based on the mood stabilizer drug they were receiving. There were 25 patients each in the lithium and valproate group. Montreal Cognitive Assessment (MoCA) scale was applied to assess cognitive functions.

The overall functioning was found to be significantly better in the patients receiving lithium than valproate, which was found by higher scores on the Global Assessment of Functioning (GAF) scale.We have found a statistically significant negative correlation between the number of episodes before starting a mood stabilizer and the time to recurrence after starting a mood stabilizer. However, the former cannot predict the latter. The age, educational status of the patient, total duration of illness and number of episodes before starting mood stabilizer correlated significantly with the MoCA score. Of all, the educational status could also predict the patient’s performance on the MoCA scale.

There were no significant differences between lithium and valproate in attenuating further episodes, the frequency of neurocognitive deficits and other adverse effects. Both drugs were equally effective and tolerable. The severity of illness was more in valproate-treated patients, and overall functioning was better in lithium-treated patients. BDNF levels did not correlate with neurocognitive deficits significantly. Future studies comprehensively assessing neurocognitive measures with a larger sample size in the early-onset bipolar disorder population would shed more light on the role of biomarkers in cognition in subjects with early-onset bipolar disorder.

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Maintenance electroconvulsive therapy (mECT) is an option in the treatment of affective disorders which progress is not satisfactory. It is certainly neglected and underused during the clinical practice.

To evaluate the efficacy of mECT in reducing recurrence and relapse in recurrent depression within a sample of three patients.

We followed up these patients among two years since they received the first set of electroconvulsive sessions. We applied the Beck Depression Inventory (BDI) in the succesives consultations for evaluating the progress.

The three patients were diagnosed with Recurrent Depressive Disorder (RDD). One of them is a 60 year old man that received initially a cycle of 12 sessions; since then he received 10 maintenance sessions. Other one is a 70 year old woman that received initially a cycle of 10 sessions; since then she received 6 maintenance sessions. The last one is a 55 year old woman that received initially a cycle of 14 sessions; since then she received 20 maintenance sessions.

All of them showed a significant reduction in depressive symptoms evaluated through BDI and clinical examination. In the first case, we found a reduction in the BDI from the first consultation to the last that goes from 60 to 12 points; in the second case, from 58 to 8 points; and in the last case, from 55 to 10 points. The main sections that improved were emotional, physical and delusional.

As side-effects of the treatment, we found anterograde amnesia, lack of concentration and loss of focus at all of them.

We find mECT as a very useful treatment for resistant cases of affective disorders like RDD.

It should be considered as a real therapeutic option when the first option drugs have been proved without success.

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Cognitive symptoms in psychosis represent a major unmet clinical need (Acuna-Vargas et al. Cog in Psych 2019; 21(3), 223–224). Deficit in memory has been largely described in first episode early onset psychosis (Mayoral et al. Eur Psych 2008; 23(5), 375-383) and has been associated to a worse functionality (Øie et al. Neuropsychology 2011; 25(1), 25–35). However, results from existing studies are quite mixed on memory deficits of early psychosis patients, particularly in terms of memory contents and storage resources.

The aims of this study were 1) to examine the nature and extent of cognitive impairment in early-onset psychosis and 2) to analyze which type of memory (verbal and visual) is more affected in the disorder.

The present systematic review and meta-analysis was conducted according to the PRISMA criteria (Moher et al. Systematic Reviews 2015; 4(1), 1 - 9). A systematic search of CINAHL, PsycInfo, PubMed, Redalyc, SCOPUS and Web of Science (published from 2000 to 2020) identified case-control studies of early onset psychotic disorder (under 18 years old). Those studies focused on both verbal and visual memory performance.

Twenty articles were included in the review. A deficit in memory in child and adolescent psychotic disorders was obtained displaying a large effect size in memory tasks (g = -0.83). Also, a medium effect size was found in visual memory tasks (g = - 0.61) and a large effect size was found in verbal memory tasks (g = -1.00).

It was observed a strong memory deficit on early psychotic disorders already present at the onset of the illness. This deficit was stronger when verbal memory tasks were used compared to the effect found with visual memory tasks. Based on previous literature (García-Nieto et al. Jou Cli Child & Ado Psych 2011; 40(2), 266-280; Lepage et al. Eur Psych 2008; 23(5):368- 74; Hui et al. Psych Med 2016; 46(11):2435-44), these results contribute to describe and characterize the cognitive symptoms in the first-episode psychosis in a youth population.

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Prof. dr. sc. Slađana Štrkalj Ivezić, psychiatrist, University psychiatric hospital Vrapče, Croatia

The aim is to present the importance of educating psychiatrists to acquire competencies relate to knowledge, attitudes and behavior in holistic understanding of patients, implementation of principles of recovery and respect for human rights and use of alternative interventions to coercion in order to eliminate or reduce coercive practice such as involuntary hospitalizations and coercive measures. All the necessary competences such as clinical assessment, skills to form therapeutical relationship and application of evidence base interventions that can prevent or significantly reduce the use of coercive measures: de-escalation; availability of a comfort room with sensory modulation; a trained response team; joint crisis intervention, advance directives and successful multimodal strategies will be presented including the elimination of potential environmental triggers of aggression in the hospital setting. The training and education of psychiatrists on human rights, recovery and alternatives to coercive practice can abolish or significantly reduce coercion.

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After the war in Bosnia-Herzegovina that lasted from 1992 to 1995, the populations gradually rebuilt their lives haunted by the spectrum of personal and collective painful souvenirs. Regarding the children who were born after the war, some mothers would rather not talk about it to protect their children from what they might be feeling while others would definetely share what they have experienced to protect their children. Because the intergenerational transmission of war trauma from mother to baby has been poorly explored among populations who recently lived in a warzone, we seeked to highlight the particularity of the interpersonal relations between the mother and her child in connection with maternal psychotrauma, by searching the factors of influence on the functioning of the dyad.

The main objective of this study is to determine and conceptualize the modes of transmission of trauma from the study of mother-baby interactions in a Bosnian environment, after the war in Bosnia-Herzegovina.

In 2003, 40 mothers and their babies aged 2 to 36 months living in Sarajevo were enrolled in the study. Among these mothers, 31 lived in or near the warzone and 9 were either displaced in other areas of the country or were refugees in foreign countries. We assessed the level of severity of post-traumatic stress disorder (PTSD) using the Clinician Administered PTSD Scale (Blake et al, 1998). In order to examine the quality of the mother-child dyads of mothers who lived through the war, we videorecorded a 10-minute free play of 23 dyads in their home environment. Then the interactions were coded using the National Institute of Child Health and Human Development observation grid by two independent raters.

The results showed that all mothers who lived through the war presented post-traumatic symptoms but only half of them showed a PTSD. Videotaped observations of mother-child interactions during playtimes revealed that their interactions are less linked to the mother’s PTSD than to the influence of PTSD on maternal attitudes and thereby extending to those of their infant. They are less sensitive to their children’s signals. They are also more intrusive and detached. Overall, they are more focused on themselves than on their child when they are interacting. As a result, their children are more focused on play and less actively engaged in communicating with their mothers.

The interactions between the mother and her child cover a set of relatively complex processes during which the two partners influence each other. When a mother lives through the war, she will pass on to her child an often painful life story. And thus, it is not only the content but also the way she transmits it that influences how the child receives the objects of the transmission.

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Negative thoughts towards mental illness are a global problem for health care professionals. Mainly it leads to late help seeking which aggravates the prognosis of the problem, denial of this situation, refusing long term medication etc.…

We aim to identify the determinants leading to negative attitudes towards psychiatric problems among medical students.

This is a descriptive and analytical cross-sectional study conducted at the Faculty of Medicine of Sfax through an anonymous questionnaire via google Forms. The degree of stigmatization was evaluated by the score « The Attribution Questionnaires AQ-27 ».

One hundred and seven students completed the questionnaires. The Sex-ratio was 0.30 (M/F). The percentage of first- and second-year students was 24.42%, third to 6th year students was 34.57% and residents was 41.01%. Students with a personal history of psychiatric disorders presented 45.8% of our population and those with a family history of mental health problems 40.2%. Medical students who studied psychiatry as a discipline and students who had internship in the psychiatry department (third to 6th year students and residents) had lower scores of the Attribution Questionnaires AQ-27 (p=0,003 and p=0,002 respectively). Sixty per cent of the students reported that spreading listening cells when needed, media coverage of mental illness and campaigns of awareness can help us reduce mental disease’s related stigma.

To conclude, in order to lower rates of stigmatization of mentally sick people, spreading awareness among medical students can be an important tool in order to understand this situation and to provide a better health care.

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Among the cases usually referred to Pain Clinics, the existence of cases of medically unexplained symptoms (MUS) is frequent, which are defined as those physical symptoms that present little or no basis that they respond to an underlying organic disease or that even when organic disease exists the symptoms are inconsistent or disproportionate to it.

The main objective of this study is to know the proportion of patients who present MUS among those referred to a Pain Clinic. Secondarily, an attempt will be made to classify those patients with MUS in different diagnostic categories.

Observational study. All those patients referred to the Pain Unit of the Complejo Asistencial Universitario de León for 18 months were included in the study. All patients are evaluated in real clinical conditions, without any experimental control of variables, initially by a multidisciplinary team made up of Anesthesiologist, Psychiatrist and Rehabilitator and, in those who suspect a MUS condition, individually by part of psychiatry in order to confirm and characterize the syndrome.

462 patients were evaluated in a multidisciplinary way. 174 (37.7%) were male and 288 (62.3%) females. The mean age was 59.06 + 16.30 years. After the multidisciplinary assessment, two groups of patients were formed, one of 313 patients (67.75%) in whom there was no suspicion of MUS and the other of 149 patients (32.25%) in whom the existence of a MUS condition was suspected and who were referred for evaluation by psychiatric interview. After the psychiatric interview, it is observed that psychopathological and social factors explain the painful condition in 23.7% of the cases. The diagnoses found were Somatoform Disorders and Central Sensitization (N = 49, 10.6%), Malingering (N = 23, 5%), Factitious Disorders (N =21, 4.5%) and Other Diagnoses (N = 38, 8.2%).

The psychological and social factors are relevant to explain the condition of up to

23.7% of the patients referred to the pain unit.

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Waiting and stopping are essential and distinct elements of appropriate behavioral control with its dysfunction implicated in various impulsivity related mental disorders. Although rodent and human studies have investigated both phenomena, the role of preparing to stop in waiting impulsivity has rarely been investigated. Furthermore, convergent evidence from multi-modal investigation tools remains a poorly utilized approach in addressing such questions.

Here, we conducted two separate, but hierarchical studies, using functional magnetic resonance imaging (fMRI) to map the neural circuit involved in waiting impulsivity and proactive stopping, and subsequently provide mechanistic and causal evidence of disruption of this circuit by transcranial magnetic stimulation (TMS). In the second study, based on our fMRI study data, we attempted to investigate possible causation between the LIFG and waiting impulsivity by modulating LIFG, i.e. non-invasively producing a “virtual lesion” with an inhibitory transcranial magnetic stimulation (TMS) protocol called continuous theta burst stimulation

We recruited 41 healthy volunteers who performed an adapted version (1CSRT) of the well-established 5 choice serial reaction time task to capture waiting impulsivity. We developed a novel task measuring proactive inhibition. We scanned participants while completing these two tasks. Our fMRI data showed a strong association between LIFG activity and waiting impulsivity on the 1CSRT task. We conducted a single-blind, randomized, between-subjects design of cTBS of the LIFG on a sample of 51 healthy volunteers who completed an adapted version of the 1CSRT task (2CSRT task). Our a priori hypothesis was that cTBS would transiently decrease local cortical activity of the LIFG and increase the frequency of premature responses on both fixed and delayed cue-target interval trials on the 2CSRT task.

We first show a shared neural network comprising the pre-supplementary motor area and bilateral anterior insula underlying both waiting impulsivity and proactive stopping. We further demonstrate activity in dorsomedial prefrontal cortex and left inferior frontal gyrus (LIFG) negatively correlated with waiting impulsivity in trials with additional target onset delay. We demonstrate active stimulation significantly increased waiting impulsivity.

In these two studies, we validated a novel task measuring proactive inhibition. We further validated the significance of task structure for assessing distinct aspects of impulsivity, which is of translational interest. We further established a causal role of lIFG for waiting impulsivity thus highlighting the integrity of LIFG and related neural circuitry required in waiting impulsivity.

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The most common liver diseases associated with the fat accumulation in the hepatic tissue are metabolic associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH). Many studies previously reported several key mechanisms tying hepatic injury to extrahepatic manifestations. In this way, the co-occurrence of cognitive decline, mood, and affective changes could suggest the existence of a strong neurological component predisposing to neuropsychiatric comorbidities.

In this study, we aimed to describe the neurological and neuropsychiatric comorbidities of MALFD, NAFLD, and NASH.

The main scientific databases were screened for English-written studies using the following key words: ”cognitive decline”, ”neuronal loss”, ”affective disorders”, ”anxiety”, ”depression”, ”MAFLD”, ”NAFLD”, ”NASH”. Exclusion criteria: (1) studies not focussing on fatty liver diseases; (2) not describing comorbid conditions; (3) not providing correlative analysis of disease co-occurrence or mechanistic associations.

Hepatic encephalopathy (HE) is the main NAFLD/NASH extrahepatic manifestation commonly characterized by impaired cognition, rapid mood swings, depressive and anxious behaviours, and defective sleep. It is currently reported that more than 70% of the cirrhotic patients develop HE. Cognitive impairments and brain tissue reduction were found in NAFLD patients, while MAFLD patients’ cognitive dysfunctions (mild cognitive impairment and hippocampal-dependent memory impairment) were not associated with the presence of metabolic syndrome. Similarly Alzheimer’s disease (AD) was not described as comorbid in MAFLD. By contrast, since NAFLD and NASH are often characterized by insulin resistance and dyslipidaemia – significant triggers of dementia. By far the most prevalent neuropsychiatric comorbidity in NAFLD and NASH is the major depressive syndrome, diagnosed in almost 30% of the cases. Also, a correlation between the anxiety manifestation and the progression from NAFLD to NASH was described. In this context, as a response to the vast evidence that connect liver dysfunction to cognitive impairments, the liver-brain axis function was hypothesized.

MAFLD, NAFLD, and NASH are frequently associated with cognitive decline. The main NASH neurological comorbidity is hepatic encephalopathy, but it could also be seen in NAFLD. While Alzheimer’s disease occurs in NAFLD and NASH, more studies are needed to explain the severity-dependent association. Depression and anxiety were also reported in NAFLD and NASH.

Acknowledgements: B.I.-M. and R.M.-A. is currently supported through the Project entitled “Platformă multidisciplinară de cercetare-dezvoltare medicală în regiunea N-E” (CENEMED, code: 127606), cofinanced through the Operational Program of Competitivity, Prioritary Axis: Research, Technological development, and Inovation (CDI).

I. M. Balmus Grant / Research support from: Project entitled “Platformă multidisciplinară de cercetare-dezvoltare medicală în regiunea N-E”(acronym: CENEMED, mySMIS code: 127606), cofinanced through the Operational Program of Competitivity, Prioritary Axis: Research, Technological development, and Inovation (CDI)., M. -.-A. Robea Grant / Research support from: Project entitled “Platformă multidisciplinară de cercetare-dezvoltare medicală în regiunea N-E”(acronym: CENEMED, mySMIS code: 127606), cofinanced through the Operational Program of Competitivity, Prioritary Axis: Research, Technological development, and Inovation (CDI)., R. Lefter: None Declared, A. Ciobica: None Declared, L. Huiban: None Declared, C. Stanciu: None Declared, A. Trifan: None Declared

In the past few years, there has been a considerable amount of evidence that cannabis use can cause structural and functional brain abnormalities.Structural imaging studies of cannabis users have revealed reduced prefrontal cortex volumes and white matter damage that may be involved with impulsivity.Objectives: To Determine the level of dependence on cannabis among cannabis users consulting the detoxification center of Sfax, Tunisia To assess in addition the impact of cannabis on impulsivity and motor control.

This is a cross-sectional, descriptive and analytical study that was conducted over a period of 13 months between September 15, 2020 and October 1, 2021 among cannabis users consulting the detoxification center of Sfax, Tunisia.A short form of the Barratt Impulsiveness Scale (the BIS-15) and a Cannabis Abuse Screening Test (CAST) were used to assess impulsivity and to determine cannabis abuse.Results: Thirty Eight cannabis users agreed to participate in this study. The distribution of CAST scores showed that 36 users (94.7%) had problematic cannabis use at the time of the study. The mean BIS 15 score was 38.2. In our sample, The level of impulsivity was highest in people with a high level of cannabis dependence. A higher level of impulsivity was found in younger subjects. However, a greater level of impulsivity was found in subjects with a lower socio-economic level. Concerning employment status, unemployment was significantly correlated with a higher level of impulsivity.

Impulsivity is often associated with a variety of problematic behaviors such as aggressive behavior, smoking, drug abuse, pathological gambling or compulsive buying.

A higher frequency of cannabis use and earlier age of onset use have been shown to be associated with the highest rates of impulsivity.

Therefore, cannabis addiction represents a real public health problem, both because of the serious complications and heavy repercussions that it causes.

None Declared

Early life stress (ELS) associates with unfavourable outcome in Major depressive disorder (MDD) and treatment-resistant depression (TRD). Trauma-focused psychotherapy benefits TRD patients exposed to ELS. Epigenetic processes are altered in stress-related disorders, but few studies show epigenetic signatures associated with trauma.

We performed an epigenome-wide association study (EWAS) to explore the relation between methylation changes in TRD patients characterized for recent and ELS and trauma-focused psychotherapy outcomes.

Thirty TRD patients participated. They underwent psychotherapy, from which 12 cognitive behavioural therapy and 18 Eye Movement Desensitization and Reprocessing (EMDR). We used validated interviews and questionnaires for symptom evaluation and stress exposure. Patients were evaluated at T0 (baseline), T8 (end of psychotherapy), T12 (follow-up) and T26. Methylation was profiled with Illumina Infinium EPIC array for T0, T8 and T12. Methylation levels were quantified after quality control and normalization using ChAMP R package. We tested the association between B-values for each CpG site (each probe set) and each phenotype/condition using a linear model approach (with paired values) as implemented in the Limma R package. P-values were adjusted using Benjamini & Hochberg method. Probe sets were considered significant with an adjusted p-value q ≤ 0.05. CpG site annotation was performed using IlluminaHumanMethylationEPICanno.ilm10b2.hg19 R package (hg19 genome reference).

Association analyses between baseline methylation levels and emotional abuse resulted in two significant probe sets annotated in SLCO4A1 (p=1,72E-08; q=0,008), involved in sodium independent transmembrane substrate transport, and GPNMB (p=1,53E-07; q=0,022), involved in cell differentiation. Associations between baseline methylation levels and physical abuse resulted in one significant probe set annotated in DDIT4L (p=4,77E-08; q=0,035), involved in cell growth.

In longitudinal analyses, association between T0-T8 methylation levels and response at T8 resulted in two significant probe sets annotated in PLEKHB1 (p=3,54E-08; q=0,013), involved in cell differentiation, and NUDT4P2 (p=1,34E-07; q=0,032). Longitudinal T12-T0 EWAS analyses in patients undergoing EMDR resulted in 44 significant probe sets annotated in genes, highlighting MAD1L1 (p=6,28E-07; q=0,035), involved in cell division, and TNFAIP3 (p=3,00E-06; q=0,045), which regulates immunity.

We identified epigenetic signatures of ELS in TRD patients, suggesting that ELS may modulate the intensity of epigenetic alterations. Longitudinal methylation analyses along psychotherapy showed significant genes in relation to response, especially for patients undergoing EMDR. Some genes are associated with post-traumatic stress disorder (MAD1L1) and anxiety disorders and MDD (TNFAIP3).

None Declared