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Abstract Background Current evidence suggests that high concentrations of pro-inflammatory markers are associated with bipolar disorder characterized by severe impairment during inter-episodic periods, reduced treatment response and persistent subsyndromal symptoms. We tested whether persistent subsyndromal symptoms in euthymic bipolar patients were associated with markers of an ongoing chronic pro-inflammatory process. Methods Forty-five euthymic bipolar patients (22 with subsyndromal symptoms (BD+) and 23 without subsyndromal symptoms (BD-) and 23 well controls (WC) were recruited for assessment of soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble interleukin-6 receptor (sIL-6R) and soluble interleukin-2 receptor (sIL-2R) concentrations. Soluble cytokine receptor concentrations were assessed using enzyme-linked immunosorbent assay. Results In comparison to WC, sTNF-R1 concentration was higher in both BD- and BD+ (age and sex adjusted standardized β, respectively: β = 0.34, p = 0.012 and β = 0.41, p = 0.003). Similarly, compared to WC, sIL-6R concentration was higher in both BD- and BD+ (age and sex adjusted standardized β, respectively: β = 0.44, p = 0.001 and β = 0.37, p = 0.008). There was no difference between BD- and BD+ in the concentration of either sTNF-R1 or sIL-6R; plasma concentration of sIL-2R was not analyzed as 75% percent of the samples were non-detectable. Conclusions Although bipolar patients present with a pro-inflammatory shift compared to well controls, subsyndromal symptoms are not associated with additive increasing effects. Longitudinal studies with larger samples are required to clarify the relationship between illness course and inflammatory markers in bipolar disorder.

Damage zones are common around faults, but their effects on earthquake mechanics are still incompletely understood. Here, we investigate how damage affects rupture patterns, source time functions (STF) and ground motions in 2D fully‐dynamic cycle models. We find that back‐propagating rupture fronts emerge in large faults and can be triggered by residual stresses left by previous ruptures or by damage‐induced pulse‐to‐crack transitions. Damage‐induced back‐propagating fronts are modulated by slip rate oscillations, amplify high‐frequency radiation, and sharpen the multiple peaks in STF even in the absence of frictional heterogeneity or fault segmentation. Near‐field ground motion is predominantly controlled by stress heterogeneity left by prior seismicity, and further amplified within the damage zone by trapped waves and outside it by secondary rupture fronts. This study refines our knowledge on damage zone effects on earthquake rupture and identifies their potentially observable signatures in the near and far field. Plain Language Summary: Faults are surrounded by layers of fractured rocks, known as damage zones, which can affect earthquakes and related hazards, but in ways that are still not well understood. Here, by running computer simulations, we investigate how damage zones influence earthquake ruptures and consequent ground motions. Our models fully account for seismic wave effects, produce multiple earthquake cycles, and span a large range of fault lengths and damage zone properties that are representative of natural faults. We identify characteristic patterns of earthquake rupture produced by damage zones: back‐propagating fronts that re‐rupture the fault, and oscillatory fault motions that affect ground shaking amplitude and frequency content. We identify which of these effects might be observable in seismograms recorded near and far from the fault. Overall, our computational study highlights significant effects of damage zones on earthquakes and on the shaking they produce. These results can guide us to better interpret earthquake source and ground motion observations, and to predict the potential characteristics of future events. Key Points: Reduction of nucleation size and pulse‐crack transitions are two distinct damage zone effects that induce back‐propagating rupture frontsDamage effects can enhance high‐frequency radiation and complexity of source time functions, potentially observable in the far fieldBack‐propagating fronts have potential signatures in near‐field seismograms and can affect peak ground motions [ABSTRACT FROM AUTHOR]

Introduction: Childhood maltreatment(CM) can precipitate a range of psychiatric disorders in individuals. Some research show that CM rates are as high as 85% in schizophrenia spectrum disorders (Larsson et al. 2013). This case report explores an instance of acute catatonic psychosis in an adolescent following a significant episode of physical and emotional abuse. Objectives: The aim is to elucidate the clinical presentation, diagnosis, and treatment of trauma-induced acute catatonic psychosis in an adolescent. The report seeks to emphasize the potential link between acute trauma and severe psychiatric disorders in young individuals. Methods: A thorough review of the patient's clinical records was undertaken, focusing on psychiatric history, symptoms, treatment trials and responses. In parallel, an extensive literature review was conducted to understand the current knowledge on the association between acute traumatic stress and acute psychosis with catatonia. Results: The patient, a 16-year-old female, presented with severe symptoms of catatonia and psychosis including mutism, posturing, stupor, negativism, auditory hallucinations and persecutory delusions, in addition; eating refusal, urinary and fecal incontinence. Symptoms started immediately following physical and emotional abuse that occurred 10 days ago. She was hitted, insulted and detained for 2 days by her parent's friends. Abuse reported to social services and judicial authorities. All laboratory and neurologic examinations performed to exclude an organic pathology. No pathologic results founded. Olanzapine 5 mg/day and lorazepam 0.5 mg/day started and titrated to 30 mg/day and 3.75 mg/day doses. Biperiden 4 mg/day started due to extrapyramidal side effects. A significant improvement observed about her catatonic and positive psychotic symptoms but she still had acute stress disorder symptoms. Trauma-focused cognitive-behavioral therapy added to her treatment. Family-based interventions examined for CM. She discharged in full remission after eight weeks of hospital stay. Lorazepam dose reduced and stopped before discharge. Conclusions: Neurobiological models are trying to enlight the association between experiencing highly stressful or traumatic events, such as child abuse, may impact on later expression of psychotic disorders by increasing stress sensitivity to later adversity (Fares-Otero et al. 2023). This case underscores the potential of acute traumatic stress to precipitate severe psychiatric disorders, including catatonia. It highlights the importance of comprehensive clinical evaluations and the inclusion of trauma history in children presenting with acute psychiatric symptoms. The findings advocate for the integration of trauma-focused interventions in the treatment of similar cases. Further research is needed to understand the pathophysiological mechanisms underlying this association and to develop effective treatment strategies for this vulnerable population. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Early-Onset Schizophrenia (EOS) is a rare and severe form of schizophrenia that begins in childhood and it is often associated with genetic risk factors, poorer prognosis, and increased treatment resistance compared to adult-onset schizophrenia (Hatzimanolis et al.  Eur Psychiatry 2020;63(1):e44). This case report presents two siblings diagnosed with EOS and treated at the same inpatient clinic in different years. Objectives: The aim is offering a perspective on the clinical characteristics, genetic and environmental implications, and treatment challenges of two siblings with EOS and seeking to enhance understanding of EOS's complexity, particularly in the context of treatment resistance. Methods: A comprehensive retrospective review of the siblings' all medical records was conducted, focusing on their psychiatric history, symptoms, treatment trials, and responses of treatment. Both cases' current clinical situations were evaluated cross-sectionally. Results: Older sibling: 19 year-old male, was diagnosed with EOS following the onset of symptoms as social withdrawal, negativism and suspiciousness at the age of 14. He referred to the inpatient clinic with the cause of drug intake refusal. Risperidone treatment started but there was no significant response. Risperidone to olanzapine switch made and clinical remission observed. After his discharge, 4 more hospitalisations in 5 years needed due to low socioeconomic status, parental neglect and him having no insight and stopped taking his medications repeatedly. Several depot form antipsychotic injections started to prevent recurrent hospitalisation. Despite that he needed several hospitalisations to adult psychiatry inpatient clinics. Younger sibling: 14 year-old female, were diagnosed with EOS following the symptoms as auditory hallucinations, suspiciousness, disorganised speech and behaviours at the age of 13. She referred to the same inpatient clinic with suicidal risk after 2 years of his brother's last hospital stay. She responded good to olanzapine treatment like her brother's, during her first stay. After 2 weeks of her discharge, her psychotic symptoms started again with no specific reason. Second hospitalisation needed due to her homicidal and suicidal risk. Clozapine and aripipirazole treatment started and she discharged in partial remission. She is being followed in outpatient clinic, with low functioning. Conclusions: Despite trials of multiple antipsychotic medications and adjunctive treatments, both siblings demonstrated significant treatment resistance. These sibling cases underscore the complexity and challenges in managing EOS, particularly when it presents with treatment resistance. The shared familial environment and potential genetic factors demand further investigation to elucidate the pathogenesis of EOS and optimize therapeutic approaches. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Involuntary treatments in forensic psychiatry represents a complex intersection of mental health, legal systems and ethics. Judicial authorities may compulsorily refer children to inpatient clinics for receiving necessarily treatment. Despite its importance, there is limited research on the reasons behind and effectiveness of such interventions in minors. Objectives: The objectives of this study were to describe the clinical characteristics of minors who have risks of harming themselves and/or others so receiving involuntary treatment due to a court order. It is aimed to assess the effectiveness of involuntary treatment. Methods: A follow-up case series was conducted on 9 minors who hospitalized by court orders in a secure inpatient child and adolescent psychiatry clinic, in the year of 2023. Data collected from medical records, including demographic information, clinical presentation, diagnosis and discharge treatment. After one, three and six month of the discharge, interviews made with the patients and their families. Current data collected on treatment regimen, compliance, behavioral outcomes and reoffending rates. All data were anonymized to maintain patient confidentiality. Results: The case series consisted of 3 males and 6 females, with a mean age of 16.5 years at the time of admission. The most common reason to hospitalization was homicide risk 88%, followed by substance use 66%. Conduct Disorder was the most common diagnosis with the rate of 88%, followed by Substance Use Disorder(66%) and Attention Deficit and Hiperactivity Disorder(50%). 44% of minors had a history of juvenile delinquency. School dropout rates were 100%. Treatment consisted of a combination of individual and group therapy and medication. Treatment refusal rates were 88% so in terms of treatment, 88% of the minors in this sample treated with depot form antipsychotic medications, with the most common medication being risperidone. Overall all of the sample showed a significant reduction in disruptive behaviors during their hospital stay. Follow-up data collecting is still continue and preliminary statistics show us that relapse rates are low and treatment compliance is relatively high of the sample. Conclusions: The findings suggest that involuntary hospitalization can be effective in reducing disruptive behaviors and increasing treatment compliance in minors with conduct disorders, substance abuse disorders and a history of juvenile delinquency. These results underscore the need for comprehensive, multidisciplinary approaches that integrate psychiatric treatment, psychoeducation and social support. Given the relatively small sample size and short-term follow-up, further research is needed to determine the long-term effects of involuntary treatment and to identify factors that predict treatment response. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: This case report elaborates an unconventional approach to the management the use of clozapine, typically used in treatment-resistant Schizophrenia, in a 17-year-old female patient with treatment-resistant Conduct Disorder, Attention Deficit and Hyperactivity Disorder and Intellectual Disability. Objectives: The aim is to demonstrate the potential effectiveness and applicability of clozapine in treating severe, treatment-resistant behavioral problems associated with Conduct Disorder, even without the presence of psychosis, by detailing the clinical course, treatment strategy and outcome of this unique case. Methods: A 17-year old female patient was referred to inpatient clinic due to escalating aggression towards her family members and risky sexual behaviors despite undergoing treatments before as risperidone, haloperidole, olanzapine, lithium, clonidin or aripipirazole. She was running away from home repeatedly and under the risk of sexual abuse. After comprehensive clinical and psychopathological assessment, a decision was made to initiate treatment with clozapine, closely monitoring the patient for adverse effects, and assessing its impact on the patient's aggressiveness and other behavioral problems. During her stay, clozapine dose titrated to 250 mg/day in addition to her current treatment as amisulpiride 800 mg/day and valproic acid 500 mg/day. Atropine solution as mouthwash used for salivary hipersecretion. No other side effects observed. Cognitive and behavioural therapy interventions made for anger management and impulsivity. Also focused on family-based interventions about establishing healthy boundaries. Results: A significant reduction in aggressive behavior was noted under the treatment of clozapine. The patient's overall conduct and interaction with family improved remarkably. The treatment was well-tolerated except sialorrhea, leading to a successful integration back into her family and community. Conclusions: This case highlights the potential of clozapine as a viable treatment option for managing severe, treatment-resistant behavioral problems in patients with conduct disorder, even in the absence of psychosis. A randomized-controlled trial showed that clozapine was more effective than risperidone in conduct externalization factors, delinquency trait and global functioning in children and adolescents(Juárez-Treviño et al. Clin Psychopharmacol Neurosci. 2019;17(1):43-53). While it necessitates careful monitoring due to its side-effect profile, this unconventional use of clozapine may open up new avenues for the management of treatment-resistant conduct disorder, thereby improving patient outcomes and quality of life. Further controlled studies are warranted to ascertain the safety and efficacy of this approach. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Schizo-obsessive disorder (SOD) is a complex psychiatric condition characterized by exhibiting symptoms of schizophrenia and obsessive-compulsive disorder (OCD)(Schirmbeck et al. Front Pharmacol. 2013 Aug 9;4:99). Some researchers prefer to describe this condition as a spectrum called "schizo-obsessive spectrum" and state that clinical represantations such as OCD with poor insight, OCD with schizotypal personality disorder, schizophrenia with obsessive-compulsive symptoms and schizophrenia with OCD are included in this spectrum(Poyurovsky et al. J Psychiatr Res. 2005 Jul;39(4):399-408). There is limited literature available on early on-set schizo-obsessive disorder in child and adolescent sample. Objectives: This case series aimed to describe the clinical characteristics, phenomenology, diagnostic process and treatment response of SOD in a sample of inpatient adolescents and illuminate the intricate symptomatology between schizophrenic and obsessive-compulsive features. Methods: A retrospective review was conducted of 7 adolescent patients who met DSM-V criteria for both schizophrenia and OCD in our inpatient clinic over the past year. Data were collected from medical records, including demographic information, clinical presentation, treatment history and response to treatment. All data were anonymized to maintain patient confidentiality. Results: The sample consisted of 5 females and 2 males, with a mean age of 15,4 years. All patients presented with a mixed symptomatology of hallucinations, delusions and obsessive-compulsive symptoms. Many common points observed about clinical characteristics and psychiatric history of the patients. In most of the patients, the first psychiatric complaints started with obsessive-compulsive symptoms. It was observed that obsessions evolved into over-valued ideas and delusions in the course of time. Patients responded late and inadequately to pharmacological treatment, multiple drug use was necessary. Hospitalization lasted longer, the average time was 53 days. Most of the patients required augmentation with cognitive-behavioral therapy due to partial response or intolerable side effects. Unfortunately, no patient experienced full remission or returned to premorbid functioning. Conclusions: This case series underscores the complexity of diagnosing and treating schizo-obsessive disorder in a pediatric population. It appears that a combined approach using both pharmacotherapy and psychotherapy may yield the most beneficial results. However, given the small sample size and retrospective design, these findings need to be interpreted with caution. Further research are crucial to corroborate our findings and refine treatment strategies. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]