Bipolar disorder (BD) is a chronic and often severe mental illness. Yet despite the well-documented complexities in its diagnosis and treatment, little research has been dedicated to understanding the complex inner landscape experienced by those living with BD. Even as qualitative research has explored the lived experience of BD across a variety of perspectives, i.e., what BD looks like, there is a lack of research exploring what BD means to those living with the condition.

We aimed to understand how people with BD perceive their condition, construct the meaning of their illness, and view BD in relation to their sense of self.

We conducted individual, semi-structured interviews with 20 adults with clinically stable BD. We coded the transcripts according to the principles of thematic analysis and analyzed the data using an interpretative phenomenological analysis approach.

We identified three overarching domains: (1) Benefit or burden: a dialectic through which participants weighed the valence of their illness over time; (2) Self or other: the internal or external locus through which they experienced BD; and (3) From ineffability to meaning making: the process of naming, understanding, and incorporating BD into their life’s whole. Within each domain, themes and subthemes outline nuanced and often conflicting perspectives of participants’ illness experiences.

Our work provides a framework of three domains central to the inner reality of lived bipolar experience. Thoughtful understanding of patients’ experiences, perspectives, and desires within these three domains may aid clinicians and loved ones alike in more sensitively and effectively addressing the unique individual needs of those living with BD. By exploring patients’ perspectives in each of the three domains we identified, those caring for people with BD may be better positioned to help identify the inner work and practical interventions needed to achieve a rich, meaningful life with BD.

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Negative symptoms pose a significant challenge for the treatment and management of schizophrenia. They refer to the loss or diminishment of normal emotional and behavioural functions, which profoundly impact one’s quality of life and socio-occupational outcomes. They are often persistent and difficult to treat.

To explore and assess different treatment strategies for addressing negative symptoms of schizophrenia, including pharmacological, psychosocial, and non-invasive neurostimulation interventions. The goal is to provide an overview of current evidence and recommendations for enhancing the quality of life and functional outcomes in individuals with schizophrenia.

We conducted a review of the extant literature to determine treatment strategies for negative symptoms in schizophrenia. We incorporated findings from randomised controlled studies, meta-analyses and systematic reviews.

We have identified several treatment strategies for negative symptoms in schizophrenia. The literature indicates that second generation antipsychotics such as Cariprazine and Amisulpride are associated with better functional outcomes with lower cognitive impairment. Adding on an anti-depressant, particularly to first-generation antipsychotics, has demonstrated positive effects. Psychosocial interventions including Cognitive Remediation (CR), Social Skills Training (SST) and exercise programs also alleviate negative symptoms. Additionally, non-invasive neurostimulation intervention such as rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) has shown encouraging results in reducing negative symptoms.

The findings highlight the important of comprehensive and holistic treatment approach integrating both pharmacotherapy and non-pharmacotherapy strategies to address the heterogeneity of negative symptoms. There is a need for further research into personalised treatments that address individual symptom profiles.

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Lyme borreliosis is one of the most common vector diseases transmitted by tick bites; it is caused by Borrelia burgdorferi. Mostly it manifests on the skin, in the nervous system or joints. It involves the nervous system in 10-15% of cases, of which 2-4 % affect the central nervous system. The most common manifestation is encephalitis, which has a diverse clinical picture.

We aim to describe a rare case and discuss the diagnostic challenges of a rapidly progressive disease.

A detailed description of the patient based on our interview and clinical findings, including blood work, imaging, microbiological testing, lumbar puncture, and treatment.

A 67-year old female patient came to the psychiatric emergency room in March 2024, because of persistent anxiety and unexplained somatic disorders, including weight loss, tremor and unstable gait, which began a few months ago. She had some somatic diagnostic procedures done, with no abnormal findings. 2 weeks before being admitted she was sent to the emergency neurological unit because of fatigue and tremor. They excluded focal neurological signs and concluded that she had an adjustment disorder and suggested psychiatric treatment. In March 2024 she was admitted to the geriatric psychiatry ward, where at first our main differential diagnosis was pseudodementia. In the next few days her condition worsened. She appeared psychotic, with ideas of persecution and reference. On the psychological exam she had moderate cognitive decline with a focus on impaired attention, memory and executive systems, misinterpretations of past and current events, misidentifications of people and possible complex visual hallucinations. At that time we suspected she might have prolonged delirium. Because of an uncommon clinical picture, we pursued further diagnostics. The lumbar puncture showed cerebral spinal fluid (CSF) pleocytosis, which confirmed the diagnosis of encephalitis. Blood tested for multiple infectious causes was positive for Lyme borreliosis. The brain CT scan showed an inflammatory or infiltrative process in both cerebral hemispheres. We then transferred her to the infectious disease clinic where she had a brain MRI with contrast and her CSF was tested for Borrelia and other possible causes. On the MRI they suspected she had rhombencephalitis with leptomeningitis. After the diagnosis of neuroborreliosis was confirmed, she received a 4-week parenteral treatment with ceftriaxone. Two months after completing the treatment she has fully recovered.

When faced with a patient with rapidly progressive dementia a wider range of possible diagnoses has to be considered. We have to be aware of the importance of recognising the cause of the disease sooner, as the patient may have a treatable condition.

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Bipolar disorder (BD) is a mental health disorder characterized by episodes of mania or hypomania alternating with depression, and it is known that seasonal changes can have an impact on the risk of relapse. Circadian rhythm - which works as an internal biological clock that regulates sleep-wake cycles, hormone production and mood stability -, plays a crucial role in the course of the disease, and it is likely that it influences relapse during seasonal changes, through mechanisms not entirely understood.

Review the relationship between seasonal changes and bipolar disorder relapse, focusing on circadian rhythm disruption, including possible pathophysiological pathways and treatment options.

Narrative review of articles published on Pubmed’s database using the following keywords and their combinations: bipolar disorder, circadian rhythms, seasonal and sleep disturbances, screening for relevance.

Several studies show us that manic episodes are associated with transition into spring and summer and depressive ones with transition into autumn and winter. Seasonal changes result in alterations in daylight exposure, which in turn, through the cardinal role of the suprachiasmatic nuclei in the hypothalamus, lead to disruptions in sleep-wake cycles, impacting melatonin and cortisol levels, which can contribute to mood instability. These hormones are also subjected to changes by other shifts in biological rhythms such as body temperature regulation, that come with seasonal transitions. On the other hand, light exposure also influences neurotransmission, particularly of serotonin and dopamine, with consequences on energy, mood and reward processing and arousal. There might also be a role for genetic polymorphisms like CLOCK, BMAL1 and PER, that influence sleep patterns and hormonal regulation, and therefore can predispose some people to mood disorders. Furthermore, there are important social factors related to seasonal changes, such as increases or decreases in social activities, that can impact mood. Therapeutic approaches that target circadian rhythm, such as light therapy and chronotherapy (including options like sleep deprivation and phase advance therapies), can be useful in decreasing relapse episodes. Additionally, simple psychoeducation on the matter, regarding maintenance of regular sleep schedules and social activities, might be helpful in preventing or, at the very least, decreasing relapses.

Seasonal changes play a relevant role in both manic and depressive relapses in BD through their role in circadian rhythm disruption, by way of a myriad of mechanisms. Future investigation should focus on these mechanisms and others that might possibly be involved, allowing us to reach more targeted treatment and even preventative measures to diminish relapse episodes in BD.

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Psychiatry has historically underserved Indigenous people. Earlier, cross-cultural psychiatry assumed that psychiatric disorders were universal and varied little across cultures. This approach has not worked well for Indigenous people who may have different views of mind and mental health. For example, Indigenous philosophy tend to explain the world and states of mental health from a storied approach encompassing relations to land, spiritual beings, ancestors, and the community which can result in different conclusions from conventional psychiatry.

We wanted to explore what modifications in their approach practicing psychiatrists have made to be successful in Indigenous communities and to determine what was common among how communities in which they worked conceptualized mind and mental health.

We interviewed psychiatrists working in Indigenous communities regarding what was effective and how they had changed their practice to work in those communities and how those communities had changed them. We used the iterative processing of constructivist grounded theory to find commonalities in their responses. We present from rural and remote Indigenous settings in Canada (Saskatchewan and Northern Ontario), New Zealand, and Maine (USA).

We found a modified approach to psychiatric services that emphasized Indigenous values and that determined positive aspects of the client’s history as well as problem areas and engaged the client in therapy from the beginning of the evaluation. Some key concepts that emerged from qualitative analysis of interviews and case histories using constructivist grounded theory as a method of analysis included (1) reframing the person’s self-story within a threat-power-meaning network, (2) working with stories about the spirit of the suffering, (3) exploring right relationships and meaningful conduct, (4)acknowledging the intergenerational transmission of suffering. Physicians came to understand that the client sets their goals and defines what recovery means for them in discussion with their family and important community members including elders. This led to a different understanding of what privacy meant to clients. Indigenous cultures encountered were different but appeared to share some similarities including a highly relational approach to defining the self, a collectivist mindset in which the needs of the group can supersede the needs of the individual, a reliance upon stories for transmission of knowledge and culture, and a commitment to a biopsychosocial and spiritual approach.

Psychiatry can form effective collaborative relationships with Indigenous communities requring modifications in the usual worldview and orientation to how psychiatry is practiced.

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Patients with End-Stage Renal Disease (ESRD) undergoing hemodialysis (HD) are particularly susceptible to psychological disorders, such as anxiety and depression, which can significantly affect their quality of life and clinical outcomes. However, in spite of its prevalence, psychiatric comorbidity in this population remains under-recognized, contributing to worse health outcomes and increased mortality.

The primary aim of this study is to explore the prevalence of psychiatric comorbidities, particularly depression and anxiety, among HD and PD patients. Insights into the different psychological effects of different dialysis treatments are offered, emphasizing the importance of integrated mental and physical healthcare in improving patient outcomes.

A narrative review was carried out using PubMed and Google Scholar to identify relevant articles with the keywords “dialysis,” “psychiatry,” and “comorbidities.”

The review underscores the important burden of psychiatric disorders among dialysis patients. Studies suggest that depression may affect up to 50% of these individuals. Both HD and PD patients exhibit varying degrees of psychological distress, exacerbated by factors such as the invasiveness of dialysis, comorbid medical conditions (e.g., diabetes), and socioeconomic challenges. The evidence suggests that HD patients may experience an even more heightened psychiatric burden due to the more invasive nature of HD compared to PD, which imposes greater restrictions on daily activities. Psychiatric disorders in these patients are often underdiagnosed, leading to treatment non-compliance, increased hospital admissions, and elevated mortality rates. The findings stress the necessity of regular mental health screenings and the integration of psychiatric care into routine dialysis practice.

Psychiatric comorbidities are prevalent among dialysis patients, with HD patients exhibiting a greater psychological burden. This review highlights the urgent need for routine mental health screening and intervention within the dialysis care framework. The integration of mental health support into dialysis treatment protocols could lead to improved patient outcomes, fewer hospitalizations, and better treatment adherence. Future research should focus on developing customized mental health interventions that address the specific challenges faced by dialysis patients, thereby enhancing their quality of life and clinical outcomes.

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Workplace violence, particularly in the healthcare sector, is on the rise and severely affects the quality of life and performance of healthcare workers. The psychological repercussions of such violence are particularly concerning, making it imperative to develop appropriate prevention strategies.

To evaluate the prevalence of assaults against healthcare staff at the Farhat Hached University Hospital in Sousse over a 20-year period, describing the characteristics of the victims, the circumstances of the assaults, and the psychological impacts observed.

This retrospective descriptive study, covering the years 2004 to 2023, analyzes workplace injury reports related to violence at the Farhat Hached University Hospital. The sample includes healthcare workers who were victims of reported assaults, with data collected on a synoptic sheet detailing sociodemographic aspects, the circumstances of the assaults, and their consequences.

Out of a total of 5695 workplace accidents, 110 were recorded as assaults, representing a prevalence of 1.9%. The victims had an average age of 46.8 ± 6.72 years, with a strong female predominance (69.1%). The most affected professions were nurses (50%) and workers (25.5%), with the most impacted departments being maternity (15.5%), emergency (13.6%), and psychiatry (11.8%). The majority of assaults (68.2%) occurred in the morning, and the perpetrators were primarily patients themselves (38.2%) or their relatives (33.6%).

Regarding the psychological aspects of the assaults, 42.7% of incidents involved psychological violence, such as verbal abuse, intimidation, or threats. The psychological consequences were significant: 26.4% of the victims developed disorders such as post-traumatic stress disorder (PTSD) and sleep disturbances.

The high prevalence of assaults and their psychological repercussions highlight the urgent need to strengthen preventive measures. Specific training on conflict management and psychological support strategies should be implemented to improve the safety and well-being of healthcare staff.

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Case management is a model of community intervention in people with severe mental illness.

To explore the treatment adherence and effectiveness of patients with severe schizophrenia undergoing treatment in a community-based, case management program (CMP) with an integrated pharmacological and psychosocial approach compared to the standard treatment.

An observational, longitudinal study was conducted with a ten-year follow-up of patients with severe schizophrenia (CGI-S ≥ 5) treated in mental health units (MHUs) or on a CMP (N = 688). All causes of treatment discontinuation, psychiatric hospital admissions, suicide attempts, and antipsychotic (AP) medications were recorded. Clinical severity was assessed with the CGI-S.

Adherence to the CMP was higher than to the standard treatment (p < 0.001). There were fewer hospital admissions and suicide attempts on the CMP than in standard care (p < 0.001). Clinical severity decreased more in the CMP than in MHUs (p < 0.005). Long-acting injectable (LAI) AP medication was more closely related to these outcomes than oral APs (p < 0.001) in both settings, but especially on the CMP.

Treatment clinical outcomes after 10-year follow-up

N: number of patients %: percentage of patients Av: average SD: standard deviation

*: basal (at beginning of program) **: standard treatment ***: Program treatment

The treatment of patients with severe schizophrenia in a multicomponent, case-managed program recorded higher compliance and effectiveness compared to standard care. Treatment with LAI antipsychotics was linked to these outcomes. A combination of case management, psychosocial approach, and LAI AP medication contributed more to the achievement of clinical goals in these patients than the standard treatment and oral APs.

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Tattooing is a mode of bodily expression that belongs to both tradition and modernity. This form of expression is rich in variant and variable meanings for women in general, and women with psychiatric disorders in particular. Their popularity and prevalence are increasing rapidly, particularly among young people. However, despite this expansion, the social perception of tattoos, particularly among women, remains a complex and often stigmatized subject. Hence the interest in knowing the characteristics of tattoos among women in Morocco, the different perceptions of the latter as well as the correlation of tattooing with psychiatric disorders.

To study the characteristics, meaning and perception of tattoos among Moroccan women, past and present. In an attempt to better understand the potential health implications of this mode of expression and its correlation with mental health.

A descriptive cross-sectional study was carried out among women of different profiles. Data were collected using a form sent online and distributed in paper form. The form collected socio-demographic data, descriptive characteristics of the tattoos and the women’s mental health status. Statistical analysis was performed using Jamovi 2.3.

Our results focused on the socio-demographic characteristics of our population, it was carried out on 52 women, 57.7% of whom were aged between 25 and 40, 62% of our sample were single and the majority(92%) had a level of education higher than the baccalaureate. Also, almost 30% were unemployed. ours study results focused essentially on the tattoo characteristics, summarized in Image 1. Image 2 shows the results concerning the psychiatric history of our population.

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Tattooing is a means of expression and a form of body modification, rich in cultural and personal significance, with a dual affiliation to tradition and modernity. It is highly prevalent among women, and has implications for both mental and physical health.

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Schizophrenia is one of the most disabling mental disorders, affecting around 1% of the population. Although most patients respond to antipsychotic treatment, one third have a limited response to antipsychotic medication, being considered treatment resistant schizophrenia (TRS). Clozapine is the only effective medication for TRS, but 30-40% of TRS patients do not respond to it. Patients with schizophrenia who do not respond to clozapine experience more severe disability, persistent symptoms, a lower quality of life and incur higher economic costs compared to those who respond to treatment.

The aim of the present study is to review evidence for therapeutic strategies for patients with treatment-resistant schizophrenia not responding to clozapine.

Review of the literature regarding treatment-resistant schizophrenia not responding to clozapine. The research was carried out through the PubMed® database, using the terms “treatment resistant schizophrenia”, “schizophrenia resistant to clozapine” and “clozapine augmentation”.

For patients with treatment-resistant schizophrenia who do not respond to clozapine, several therapeutic strategies have been explored. These include pharmacological approaches, non-pharmacological interventions and brain stimulation procedures [Electroconvulsive Therapy (ECT) and Transcranial Magnetic Stimulation (TMS)]. However, the evidence is weak and the reported benefits were modest.

The current evidence is weak for efficacy of pharmacological augmentation strategies to clozapine. There are contradictory data regarding ECT and clozapine augmentation. More studies are necessary to clarify the potential of these strategies in order to manage these complex patients.

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The prevalence of extreme temperature is increasing largely due to the progression of climate change globally (LaSorte et al. Climate Change 2021; 166 1-2). Existing research indicates extreme temperatures have an impact on mental health, including its effect on mood disorders (Rony & Alamgir. Health Sci Rep 2023; 6 12). While there is evidence to suggest that mood disorders can be influenced by various environmental, biological, and social factors (Zhang et al. Environmental International 2020; 143), no study has synthesized findings on the relationship between extreme temperature and mood disorders in existing literature.

The study aims to: investigate the linkage between extreme temperature and mood disorders in terms of symptom severity, hospital admissions and adverse events; describe factors moderating the relationship between extreme temperature and mood disorders; outline study-defined interventions and make policy recommendations.

This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Major databases (Medline/PubMed, PsychINFO, Scopus, Web of Science) were searched for eligible reports using a search strategy developed for the study. This was supplemented by snowball searching for references in relevant studies. Title and abstract screening and data extraction were completed by at least two independent investigators and conflicts were resolved by discussion amongst investigators or consulting the senior author. All included studies will be assessed with the National Institutes of Health Study Quality Assessment Tools.

As seen in Image 1, 468 articles were identified from searching databases. Following screening and full-text review, 22 articles were selected for data extraction. Preliminary findings showed that the included studies were conducted in North America, Europe, Asia, and Oceania-Australia among others. The included studies were of different designs, including case-crossover, cohort and cross-sectional studies. Findings across studies indicate that extreme temperatures have a complex and significant impact on mood disorders. High temperatures were associated with increased hospital admissions, with adolescents, women, and the elderly especially vulnerable. Individuals with bipolar disorder and depression showed increased sensitivity to heat exposure. While some studies found increased emergency department visits for mood disorders during periods of extreme heat, others revealed insignificant correlations. Moreover, short-term exposure to humidity was also linked to elevated risk for mood disorders.

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This study underscores the impact of extreme temperatures on mood disorders and highlights the need for real-world solutions, like policy implementation, to reduce exposure to such conditions due to climate change.

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Delusions in schizophrenia have been theoretically linked to probabilistic reasoning bias (‘jumping to conclusions’, JTC), although experimental support has been mixed (Garety et al BJP 2013; 203 327-333). Ward and Garety (Schiz Res 2019; 203 80-87) recently proposed a reformulation of the theory in terms of Kahneman’s concepts of ‘fast’ and ‘slow’ thinking. This proposes that decision-making involves two cognitive processes: a fast, heuristic-based approach which is prone to errors, and a slow, deliberate process that carefully evaluates all the relevant evidence. According to this view, an overreliance on fast thinking and/or reduced engagement of slow thinking underlies the initial development of delusional interpretations of everyday events and also makes them harder to be corrected.

Our aim was to develop a novel task to investigate the fast and slow thinking hypothesis of delusions in patients with schizophrenia, for use in behavioural and functional imaging studies. As a preliminary step, we tested this task on healthy participants.

A battery of 137 experimental questions (where fast thinking leads to incorrect answers) was generated from multiple sources, including examples of the base rate and conjunction fallacies, the cognitive reflection test (CRT), trick questions, and syllogisms. Example questions included: If it takes 5 machines 5 minutes to make 5 widgets, how long would it take 100 machines to make 100 widgets? [Correct answer = 5 minutes; intuitive answer = 100 minutes; category: cognitive reflection] A farmer had 15 sheep and all but 8 died. How many are left? [intuitive answer: 7; correct answer: 8, category: trick question]. 137 control questions (where both fast and slow thinking give the correct answer) were adapted from the experimental questions. The questions were administered online to 176 healthy volunteers using PsychoPy software, with 15 experimental and 15 control questions randomly assigned to each participant.

The sample had a mean age of 40.3 years (range 17-77 years); 55.1% were female and 65.9% had a university education. Correct answers to experimental questions were markedly fewer than answers to control questions in all categories (overall p < 0.001). Response latency for the experimental questions was slightly higher than for the control questions, apart from in one category (CRT) (overall p = 0.004).

Results from a large sample of healthy participants indicate that a battery of questions can be feasibly developed to reliably detect fast thinking.

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Individuals with neurodevelopmental disorders, such as ADHD and autism spectrum disorder, often experience higher rates of chronic pain compared to the general population. Potential shared mechanisms could be central sensitization, muscular dysregulation and altered pain experiences. Individuals with ADHD and chronic pain frequently have a lower health-related quality of life, including higher pain interference and depressed symptoms. Psychological inflexibility, insomnia and hypermobility are identified as mediators in the relationship between neurodevelopmental symptoms and chronic pain. Understanding these connections can aid in developing targeted interventions to improve the quality of life for individuals with neurodevelopmental disorders experiencing chronic pain.

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While most individuals adhere to preventive measures during pandemics, a subset engages in behaviors that may intentionally spread COVID-19, presenting unique challenges to public health efforts.

This study explores the psychological, social, and environmental factors influencing deliberate virus-spreading behavior in the Saudi Arabian population during the initial phase of the COVID-19 pandemic.

A cross-sectional online survey was conducted between April 3 and May 5, 2020, with 1,817 participants. The survey collected demographic information and variables related to virus-spreading inclinations. Descriptive statistics and Pearson’s chi-squared tests were used to analyze associations between deliberate virus-spreading behavior and various characteristics, with statistical significance set at p < 0.05.

Individuals who intentionally spread the virus (2% of the sample) were younger (mean age 22.9 vs. 29.3 years, p < 0.001), predominantly female (81.1% vs. 65.6%, p = 0.033), and more likely to have a history of mental health issues (24.3% vs. 8.5%, p < 0.001) and conspiracy beliefs (45.9% vs. 26.2%, p = 0.003) compared to those who did not engage in virus-spreading behaviors. No significant differences were found regarding marital status, education level, or traumatic life events.

This study highlights key factors associated with intentional virus-spreading behaviors, such as younger age, mental health history, and conspiracy beliefs, underscoring the need for integrated mental health support and targeted misinformation interventions. Public health strategies should include age-appropriate messaging and digital outreach to mitigate the risks posed by intentional spread behaviors and enhance pandemic response efforts. Further research with larger, more diverse samples is recommended to expand understanding and improve intervention strategies

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Obsessive-Compulsive Disorder (OCD) and psychotic disorders are traditionally considered distinct entities; however, there is increasing evidence of a spectrum where these conditions overlap. In some cases, OCD presents with poor insight, leading to obsessive thoughts and behaviors that resemble psychotic features. These “schizo-obsessive” phenomena challenge standard diagnostic categories and suggest a continuum between OCD and psychosis, necessitating a more integrated approach to diagnosis and treatment.

We report the case of a 69-year-old male evaluated in the emergency department for severe obsessive symptoms, including intrusive images and compulsive behaviors, accompanied by low insight and depressive symptoms, such as suicidal ideation. Initial management with selective serotonin reuptake inhibitors (SSRIs) led to only partial improvement, highlighting the complexity of distinguishing obsessive from psychotic symptomatology and supporting the concept of a continuum between OCD and psychosis.

1. 1) To describe the clinical presentation and management of a patient with OCD and psychotic features.

2. 2) To review the evidence regarding the clinical characteristics and management of the schizo-obsessive spectrum.

A review of the patient’s clinical history, psychiatric assessments, and treatment responses was conducted. A literature review was also performed to provide an overview of OCD with low insight and schizo-obsessive phenomena.

The schizo-obsessive spectrum concept suggests an overlap between obsessive-compulsive symptoms and psychotic features, particularly when insight is impaired. In OCD with poor insight, obsessions can lose their typical egodystonic quality and appear more like delusions. This challenges traditional diagnostic boundaries and indicates a continuum between OCD and psychosis, where insight fluctuates and symptoms may shift from obsessive to delusional states. Clinical management is complex; combining SSRIs with antipsychotics can be effective, particularly in cases with minimal insight. In our case, the introduction of low-dose aripiprazole led to significant improvement, supporting a combined pharmacological strategy addressing both obsessional and psychotic dimensions and aligning with the schizo-obsessive spectrum framework.

1. 1. This case highlights the difficulty in distinguishing psychotic from obsessive symptoms when insight is poor, emphasizing the need for careful differential diagnosis.

2. 2. The overlap of obsessive and psychotic features in this patient indicates the need for further study of “schizo-obsessive” phenomena.

3. 3. The patient’s positive response to combined SSRIs and antipsychotics suggests this approach may be effective for similar cases with overlapping symptoms.

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Previous studies show the aggregation of major psychiatric disorders (MPDs; a combined category of schizophrenia, bipolar disorder, depression, and anxiety) among siblings. However, few studies have examined whether MPDs in childhood and early adulthood are associated with siblings’ future socioeconomic status (SES).

To assess subsequent SES outcomes among siblings of individuals with an MPD diagnosed at age 5–25.

This cohort study included 54,742 full siblings, 4,490 paternal, and 4,858 maternal half siblings of individuals born in Finland between 1975–1985 with MPDs diagnosed at ages 5–25 (affected probands). We defined the reference groups as identical types of siblings of individuals without any MPD diagnosis (matched unaffected probands). The siblings of both the affected and the unaffected probands were followed from the diagnosis date of affected probands until December 31, 2020. MPD diagnoses were obtained from the Finnish Care Register. SES was measured through employment status, annual disposable income (measured in EUR), and educational achievement derived from the FOLK module of Statistic Finland. Conditional logistic regression, median regression, and Generalized Estimating Equations (GEE) models were applied to estimate the adjusted associations.

The median age (interquartile range, IQR) at baseline was 20 years (16–24) for full siblings, 17 years (12–26) for maternal half-siblings, and 18 years (12–26) for paternal half-siblings of the affected and unaffected probands. Compared to siblings of the unaffected probands, the odds of unemployment were 50% higher (95% CI: 1.46-1.55) in full siblings of affected probands with any MPD; this association was particularly pronounced in full siblings of an affected proband diagnosed before age 15 (aOR: 1.68, 95% CI 1.49-1.90). Full siblings of the affected probands were more likely not to attain a university degree (aOR: 1.37, 95% CI 1.33-1.41). The median annual disposable income was 1,518.3 EUR lower (95% CI: -1647.4, -1389.3) in full siblings of affected probands. Similar but weaker associations were observed in maternal and paternal half-siblings. For example, compared with the half siblings of the unaffected probands, the odds of unemployment were 29% (95%CI 1.16-1.44) and 23% (95%CI 1.10-1.38) higher in maternal and paternal half-siblings of affected probands with any MPD, respectively.

Our findings suggest that the unfavorable socioeconomic consequences of MPDs might extend to siblings.

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Current ketamine-based therapies for treatment-resistant depression (TRD) can induce dissociative symptoms. A novel oral prolonged-release ketamine formulation (KET01) results in a lower and delayed peak concentration of ketamine, and a higher concentration of the metabolites norketamine and hydroxynorketamine than after intravenous administration. KET01 has limited dissociative properties, compared to other ketamine formulations.

To explore the relation between dissociative and antidepressant effects of KET01.

KET01-02 (EudraCT 2021-004927-34) was a randomized, double-blind phase 2 trial in outpatients with TRD comparing adjunct 120 mg (n=42) or 240 mg (n=40) oral KET01 once-daily for 3 weeks to placebo (PBO, n=40). The primary endpoint was change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score on day 21. Dissociation was assessed using the Clinician-Administered Dissociative States Scale (CADSS).

The association between CADSS scores at 7 hours after first dosing and MADRS scores on day 4 was investigated with a statistical mediation analysis. The 7-hour timepoint was selected since it coincides with the average Tmax (time-to-peak) when the highest dissociation is expected. Depression scores at the first subsequent visit (on day 4) were selected for the analysis. It was also the time point where change in MADRS score from baseline differentiated the most between KET01 and placebo with a difference of 4.32 (p=0.006) to the benefit of KET01 – based on the model used in the mediation analysis.

The antidepressant effect of KET01 that was mediated through dissociation was estimated to the negligible -1.28% (CI: (-28%) – (+11%)).

The antidepressant effect of KET01 was achieved with minimal to no dissociation and with no significant mediation through dissociation. Our findings challenge the commonly held clinical view that some degree of dissociation is necessary to guarantee ketamine’s antidepressant effect. Instead, it appears that dissociative symptoms are merely adverse events associated with certain formulations of ketamine.

L. Arvastson Consultant of: HMNC Brain Health, E. Papanastasiou Employee of: HMNC Brain Health, K. Schmid Employee of: Develco Pharma, A. Damyanova Employee of: HMNC Brain Health, A. Glas Employee of: HMNC Brain Health, C. Strote Employee of: HMNC Brain Health, C. Eulenburg Consultant of: HMNC Brain Health, D. Gehrlach Employee of: HMNC Brain Health, K. Maiboe Consultant of: HMNC Brain Health, H. Eriksson Employee of: HMNC Brain Health

In the ESCAPE-TRD study, esketamine nasal spray (ESK-NS) significantly increased chance of remission at Week 8 versus (vs) quetiapine extended release (Q-XR) in patients (pts) with treatment resistant depression (TRD; Reif et al. NEJM 2023; 389:1298–309). Changes in disability and functional impairment due to depressive symptoms assessed with the Sheehan Disability Scale (SDS) are reported.

To assess the effect of ESK-NS vs Q-XR on pts’ daily functioning using SDS, considering their symptom evolution.

ESCAPE‑TRD was a randomised phase IIIb trial comparing the efficacy of ESK-NS vs Q-XR, both alongside an ongoing selective serotonin/serotonin-norepinephrine reuptake inhibitor, in pts with TRD. Clinical response (CRes) was defined as ≥50% improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline or total score ≤10, clinical remission (CRem) was defined as total MADRS score of ≤10, and functional remission (FRem) was defined as SDS total score ≤6. The Kaplan-Meier method was used for time to event analyses, and hazard ratios (HRs) were estimated using Cox regression models. Time in each state was estimated by treatment arm and compared between arms using analysis of covariance.

336 and 340 pts were randomised to ESK-NS and Q-XR, respectively. Significantly more ESK-NS treated pts achieved CRes, CRem and FRem (HRs: 1.848, 1.711 and 1.819, respectively; all p<0.001), and achieved these faster, compared to Q-XR (Figure 1). In each arm and at each time point, more pts reached CRes than CRem, and more reached CRem than FRem, illustrating that FRem is more difficult to achieve (Figure 1). Total time in CRes was 5.4 weeks greater for ESK-NS compared with Q-XR; total time in CRem was 3.7 weeks greater and in FRem 2.0 weeks greater for ESK-NS vs Q-XR, respectively (Table 1).

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These data support a temporal cascade of events from CRes to CRem to FRem; ESK-NS improved time to, and in, each outcome vs Q-XR. Treatments that reduce clinical symptoms better and faster provide the best chance of improving functional impairment.

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