Symptoms Of Psychiatric Disorders Research Articles

Critical Assessment of the Role of Diet and Nutrition in Mental Health Treatment Plans

It has been the focus of research for the last decade as to how nutritional intake interacts with the diet, and lots of faith is being given to dietary intervention in the management of mental health disorders. This paper critically examines the current evidence regarding the relationship between diet nutrition and mental health and discusses how nutritional therapies may be applied. Based on literature analysis and the present data, this paper is aimed at bringing insight into the promising effects of diets to manage some of the symptoms of anxiety, depression, and other psychiatric disorders. Moreover, the paper presents the limitations of the present study and directions for further research in nutritional psychiatry. It ends by arguing that diet and nutrition may or ought to be considered part of the fundamental care for mental health issues and could be useful additions to medication.

Prefrontal parvalbumin interneurons mediate CRHR1-dependent early-life stress-induced cognitive deficits in adolescent male mice.

Cognitive impairment, a core symptom of psychiatric disorders, is frequently observed in adolescents exposed to early-life stress (ES). However, the underlying neural mechanisms are unclear, and therapeutic efficacy is limited. Targeting parvalbumin-expressing interneurons (PVIs) in the medial prefrontal cortex (mPFC), we report that ES reduces mPFC PVI activity, which causally mediated ES-induced cognitive deficits in adolescent male mice through chemogenetic and optogenetic experiments. To understand the possible causes of PVI activity reduction following ES, we then demonstrated that ES upregulated corticotropin-releasing hormone (CRH) receptor 1 [CRHR1, mainly expressed in pyramidal neurons (PNs)] and reduced activity of local pyramidal neurons (PNs) and their excitatory inputs to PVIs. The subsequent genetic manipulation experiments (CRHR1 knockout, CRH overexpression, and chemogenetics) highlight that ES-induced PVI activity reduction may result from CRHR1 upregulation and PN activity downregulation and that PVIs play indispensable roles in CRHR1- or PN-mediated cognitive deficits induced by ES. These results suggest that ES-induced cognitive deficits could be attributed to the prefrontal CRHR1-PN-PVI pathway. Finally, treatment with antalarmin (a CRHR1 antagonist) and environmental enrichment successfully restored the PVI activity and cognitive deficits induced by ES. These findings reveal the neurobiological mechanisms underlying ES-induced cognitive deficits in adolescent male mice and highlight the therapeutic potentials of PVIs in stress-related cognitive deficits in adolescent individuals.

A transdiagnostic approach of negative symptoms in psychiatric disorders: replication of a two-factor structure in major depressive disorder and bipolar disorder.

Recent empirical findings suggest that negative symptoms are not limited to schizophrenia (SCZ) but also present in major depressive disorder (MDD) and bipolar disorder (BD) patients. Although SCZ patients generally showed a latent structure comprising the motivation and pleasure (MAP) and expression (EXP) factors, it remains unclear whether the same latent structure exists in MDD and BD patients. We administered the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS) to 179 MDD patients and 152 BD patients. Confirmatory Factor Analysis (CFA) was conducted to examine the one-factor model, the two-factor model of the MAP and the EXP domain, the five-factor model of anhedonia, avolition, asociality, alogia, and blunted affect, and the hierarchical model comprising the first-order five-factor, and the second-order two-factor (MAP and EXP factors). We further examined the correlations between demographics and the negative symptom dimensions found in the best factor model. The CFA showed that, when the CAINS and the BNSS were combined together, the two-factor model of MAP and EXP provided the best model fit than other competing models, in the MDD alone sample, BD alone sample, and the combined clinical sample. The two-factor model of the MAP and EXP appears to be a stable, transdiagnostic latent structure of negative symptoms across BD and MDD. Clarifying negative symptoms in MDD and BD can facilitate future research on the underlying neural mechanisms of the MAP and EXP dimensions.

Molecular modeling aided design, synthesis, and activity evaluation of N-arylindole derivatives as GPR52 agonists

G protein-coupled receptor 52 (GPR52) is considered to be a promising target to improve the symptoms of psychiatric disorders and its agonists are expected to treat schizophrenia without traditional side effects. Several research institutions have reported some small molecule GPR52 agonists, which can be the starting point for rational drug development. In this study, a series of N-arylindole derivatives were designed and synthesized based on 3g according to classical pharmacochemical methods and computer aided drug design (CADD). The designed compounds exhibited good to excellent activities and the structure-activity relationship (SAR) study was explored. The results show that the connection mode between the hydrophilic head (Part I) and the indole ring (Part II) plays an important role in the GPR52 agonist activity. Among these compounds, compounds 16 and 21 have good GPR52 agonist activity (EC50 = 93 nM and 75 nM) and can inhibit hyperactive behavior in mice induced by MK-801 (EC50 =7.94 mg/kg and 6.64 mg/kg). These designed small molecules will provide new options for the development of novel GPR52 agonists.

Multisensory temporal processing in schizophrenia and bipolar disorder: implications for psychosis

Structuring sensory events in time is essential for interacting with the environment and producing adaptive behaviors. Over the past years, the microstructure of temporality received increasing attention, recognized as a fundamental factor influencing cognitive, affective, and social abilities, whose alteration can underlie the etiopathogeneses of some clinical symptoms in psychiatric disorders. The present research investigated multisensory temporal processing in individuals with schizophrenia (N = 21), bipolar disorder (N = 20) and healthy controls (N = 21) in order to explore a plausible link between multisensory alterations in the temporal order of events and the psychopathological dimensions underlying psychosis. We asked participants to temporally order audio-tactile, visual-tactile, and audio-visual stimuli, and we administered different psychopathological scales to explore depressive, manic and psychotic symptoms. Results demonstrated that both subjects with schizophrenia and bipolar disorder are less precise in temporal order judgment independently of the sensory modalities involved. Interestingly, reduced precision in temporal processing of patients is positively associated with the presence and severity of positive symptoms. Our findings support the hypothesis that low-level sensory alterations in temporal structure may contribute to the emergence of clinical symptoms such as delusions, hallucinations, and disorganized behaviors.

Memory complaints after COVID-19: a potential indicator of primary cognitive impairment or a correlate of psychiatric symptoms?

Cognitive impairment and symptoms of psychiatric disorders have been reported frequently as features of post-acute sequelae of SARS-CoV-2 infection. This study aims to investigate subjective memory complaints in COVID-19 survivors and determine if these are more strongly associated with objective cognitive impairment related to sequelae of SARS-CoV-2 infection or with symptoms of psychiatric conditions. A total of 608 COVID-19 survivors were evaluated in-person 6–11 months after hospitalization, with 377 patients assigned to a “no subjective memory complaint (SMC)” group and 231 patients assigned to an SMC group based on their Memory Complaint Scale scores. Follow-up evaluations included an objective cognitive battery and scale-based assessments of anxiety, depression, and post-traumatic stress symptoms. We found the perception of memory impairment in COVID-19 survivors to be more strongly associated to core symptoms of psychiatric conditions rather than to primary objective cognitive impairment. Univariate analysis indicated significant differences between the “no SMC” and SMC groups, both for the psychiatric symptom evaluations and for the cognitive evaluations (p < 0.05); however, the psychiatric symptoms all had large partial eta-squared values (ranging from 0.181 to 0.213), whereas the cognitive variables had small/medium partial eta-squared values (ranging from 0.002 to 0.024). Additionally, multiple regression analysis indicated that only female sex and depressive and post-traumatic stress symptoms were predictors of subjective memory complaints. These findings may help guide clinical evaluations for COVID-19 survivors presenting with memory complaints while also serving to expand our growing understanding of the relationship between COVID-19, subjective memory complaints, and the risk of cognitive decline.

Risks from Language Models for Automated Mental Healthcare: Ethics and Structure for Implementation (Extended Abstract)

In the United States and other countries exists a “national mental health crisis”: Rates of suicide, depression, anxiety, substance use, and more continue to increase – exacerbated by isolation, the COVID pandemic, and, most importantly, lack of access to mental healthcare. Therefore, many are looking to AI-enabled digital mental health tools, which have the potential to reach many patients who would otherwise remain on wait lists or without care. The main drive behind these new tools is the focus on large language models that could enable real-time, personalized support and advice for patients. With a trend towards language models entering the mental healthcare delivery apparatus, questions arise about how a robust, high-level framework to guide ethical implementations would look like and whether existing language models are ready for this high-stakes application where individual failures can lead to dire consequences. This paper addresses the ethical and practical challenges custom to mental health applications and proposes a structured framework that delineates levels of autonomy, outlines ethical requirements, and defines beneficial default behaviors for AI agents in the context of mental health support. We also evaluate fourteen state-of-the-art language models (ten off-the-shelf, four fine-tuned) using 16 mental health-related questions designed to reflect various mental health conditions, such as psychosis, mania, depression, suicidal thoughts, and homicidal tendencies. The question design and response evaluations were conducted by mental health clinicians (M.D.s) with defined rubrics and criteria for each question that would define "safe," "unsafe," and "borderline" (between safe and unsafe) for reproducibility. We find that all tested language models are insufficient to match the standard provided by human professionals who can navigate nuances and appreciate context. This is due to a range of issues, including overly cautious or sycophantic responses and the absence of necessary safeguards. Alarmingly, we find that most of the tested models could cause harm if accessed in mental health emergencies, failing to protect users and potentially exacerbating existing symptoms. We explore solutions to enhance the safety of current models based on system prompt engineering and model-generated self-critiques. Before the release of increasingly task-autonomous AI systems in mental health, it is crucial to ensure that these models can reliably detect and manage symptoms of common psychiatric disorders to prevent harm to users. This involves aligning with the ethical framework and default behaviors outlined in our study. We contend that model developers are responsible for refining their systems per these guidelines to safeguard against the risks posed by current AI technologies to user mental health and safety. Our code and the redacted data set are available on Github (github.com/maxlampe/taimh_eval, MIT License). The full, unredacted data set is available upon request due to the harmful content contained.

Impact of mentalization, identity diffusion and psychopathology on nonsuicidal self-injury among adolescents.

Nonsuicidal self-injury (NSSI) has become a major public health issue in adolescents. This cross-sectional case-controlled study aims to assess the impact of identity diffusion, psychopathology, and mentalization on NSSI in adolescence. The study sample consisted of 153 adolescents (76.5% girls; Mage = 15.6 years). The sample included 56 clinical cases of NSSI, 45 psychiatric cases without NSSI, and 52 healthy controls, all recruited in Ankara, Türkiye, from June 1, 2022, to August 31, 2022. Mentalization was assessed by "The Movie for the Assessment of Social Cognition" (MASC) which categorizes mentalizing as "correct mentalizing" "hypermentalizing" "undermentalizing" and "no-mentalizing". All participants filled in the Self-Injurious Behavior Screening Questionnaire, Assessment of Identity Development in Adolescence (AIDA), and Youth Self Report (YSR), and Inventory of Statements About Self-injury (ISAS). The NSSI group showed lower mentalizing capacity than the healthy control group (p = .011), and more no-mentalizing errors than the other two groups (p = .014). Identity diffusion scores were higher in the NSSI group than in the other two groups (p < .001). Multivariate logistic regression analysis showed that the presence of maternal psychiatric disorder (p = .019, OR = 5.21), identity diffusion (p = .007, OR = 1.02), no mentalizing (p = .049, OR = 1.28), and total psychopathology symptoms (p = .009, OR = 1.12) had a significant impact on NSSI. Current findings suggest that transdiagnostic approaches, including mentalization and identity diffusion, may contribute to a more comprehensive understanding of NSSI and to the development of clinical interventions.

The configuration and management of “hearing music in the absence of stimuli” in professional musicians: clinical and social implications of the involuntary musical imagery. An exploratory study

ABSTRACT Background In the last decades, much research has shown that the phenomenon of “Hearing Voices” is not necessarily a symptom of psychiatric disorder but can also occur in the general population without causing serious mental health problems. Less attention has been paid to auditory experiences whose content is not verbal but musical. Although it has been hypothesised that both pathological and non-pathological phenomena, known as ”musical hallucinations” and “musical imagery’’, respectively, lie on a continuum, the boundary between these phenomena is not clear, nor why musicians experience them in a more positive way than non-musicians. Methods The following study involved 32 musicians to explore how they configure and manage the experience of hearing music in the absence of stimuli. Data were collected through semi-structured interviews and analysed using thematic analysis methodology. Results The findings suggest that musicians configure this phenomenon as a natural consequence of their musical education and seek to take professional advantage of them or to develop their ability to recall them. Discussion In conclusion, the experience of hearing music in the absence of corresponding stimuli may be configured as an adaptive phenomenon, especially in the musical context.

A Cellulose-Rich Diet Disrupts Gut Homeostasis and Leads to Anxiety through the Gut-Brain Axis.

It is widely said that a healthy intestinal environment plays an essential role in better mental condition. One known dietary nutrient that maintains the intestinal environment is dietary fiber. A recent study showed that maintaining the intestinal environment with dietary fiber alleviated symptoms of psychiatric disorders in animals. However, such effects have only been reported with soluble fiber, which is highly fermentable and promotes short-chain fatty acid (SCFA) production, and not with insoluble fiber. Therefore, we aimed to verify whether insoluble fiber, such as cellulose, can alter emotion via changes in the gut. We divided mice into two groups and fed either a standard diet (SD, which contains both insoluble and soluble dietary fibers) or a cellulose-rich diet (CRD, which contains cellulose alone as the dietary fibers). We found that CRD-fed mice display increased anxiety-like behavior. CRD-fed animals also showed decreased intestinal SCFA levels along with increased intestinal permeability, dysmotility, and hypersensitivity. This behavioral and physiological effect of CRD has been completely abolished in vagotomized mice, indicating the direct link between intestinal environment exacerbation to the emotion through the gut-brain axis. Additionally, we found that amygdalar dopamine signaling has been modified in CRD-fed animals, and the opioid antagonist abolished this dopaminergic modification as well as CRD-induced anxiety. Altogether, our findings indicate that consumption of cellulose alone as the dietary fiber may evoke intestinal abnormalities, which fire the vagus nerve, then the opioidergic system, and amygdalar dopamine upregulation, resulting in the enhancement of anxiety.

Environmental sensitivity moderates the longitudinal effect of fathers' positive parenting on mental disorders in Chinese adolescents

BackgroundExposure to fathers' positive parenting has been associated reducing mental disorder symptoms during adolescence, evidence on the mechanisms underlying this association is lacking. One potential mechanism linking fathers' positive parenting and mental disorders is environmental sensitivity (ES). Here we studied whether the increased positive behaviors of both parents (1) separately, (2) relatively, (3) and jointly predict reduced depression, attention deficit hyperactivity disorder (ADHD) symptoms, suicidal ideation (SI), and increased well-being in Chinese adolescents. Additionally we investigated (4) whether ES moderates these relationships. MethodsThis study involving 7010 Chinese adolescents (55.6 % girls) aged 15 to 18 from six junior high schools in Shaanxi, China was conducted at four timepoints. ES was assessed using the Highly Sensitive Child (HSC) scale at ages 15 and 16, parental positive behaviors using the Parental Bonding Instrument (PBI) at ages 16 and 17, and psychopathology symptoms using the 9-item Patient Health Questionnaire (PHQ-9), Strengths and Difficulties Questionnaire (SDQ), and Positive and Negative Suicide Ideation (PANSI) Inventory at ages 17 and 18. Results(1) Multilevel analyses revealed that increased positive parenting predicted reduced psychiatric disorder symptoms and improved well-being; (2) trend interaction indicated that the compensatory effect of fathers' positive parenting was stronger in alleviating mental problems in adolescents than that of mothers'; (3) Simple slope analyses suggested that both high levels of fathers' and mothers' positive parenting predicted fewer subsequent psychiatric disorder symptoms, particularly for sensitive adolescents. LimitationsThis study was limited to its generalizability to the Western Chinese adolescents. ConclusionsSubstantial differences in the effects of positive paternal and maternal parenting highlight the important role of fathers' positive parenting in mental development, especially for highly sensitive adolescents.

Chronic Itch Affects Patients' Ability to Experience Pleasure: Anhedonia in Itchy Disorders.

Anhedonia, the reduced ability to experience pleasure, is a prevalent symptom in various psychiatric disorders, but has not been investigated in dermatological conditions, particularly those characterized by chronic itch. This study aimed to examine the prevalence and clinical correlates of anhedonia in patients with chronic itch. A cross-sectional study was conducted in 137 patients with chronic itch, classified according to the International Forum for the Study of Itch (IFSI) classification. Anhedonia was assessed using the Snaith-Hamilton Pleasure Scale (SHAPS) and Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS). Itch severity, quality of life, and psychological distress were assessed using the Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), ItchyQoL, and Hospital Anxiety and Depression Scale (HADS), respectively. The mean SHAPS score was 1.0 ± 1.7 points, and the mean ACIPS total score was 76.9 ± 16.2 points. In the study sample, 13.1% of patients were identified as anhedonic, with a higher prevalence observed in those with severe and very severe itch. Anhedonia was significantly correlated with itch severity (R = 0.2, p=0.02 for 24 h VASmean and SHAPS; R = 0.2, p = 0.01 for 24 h VASmax and SHAPS), anxiety symptoms (R = 0.3, p < 0.001 for SHAPS and HADS-anxiety), depression symptoms (R = 0.4, p < 0.001 for SHAPS and HADS-depression), and impairment in quality of life (R = 0.2, p = 0.014 for SHAPS and ItchyQoL). Anhedonia is a significant and prevalent aspect of psychological distress in patients with chronic itch. Addressing this symptom may not only improve patients' overall mental health but also enhance the effectiveness of treatments for chronic itch. Future research is needed to elucidate further the mechanisms underlying the relationship between anhedonia and chronic itch and to develop targeted interventions for this population.

Oral Supplementation of L-Carnosine Attenuates Acute-Stress-Induced Corticosterone Release and Mitigates Anxiety in CD157 Knockout Mice.

Corticosterone, an end product of the hypothalamic-pituitary-adrenal (HPA) axis, is a crucial stress hormone. A dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders, such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.

The Clinical Impact of Real-Time fMRI Neurofeedback on Emotion Regulation: A Systematic Review.

Emotion dysregulation has long been considered a key symptom in multiple psychiatric disorders. Difficulties in emotion regulation have been associated with neural dysregulation in fronto-limbic circuits. Real-time fMRI-based neurofeedback (rt-fMRI-NFB) has become increasingly popular as a potential treatment for emotional dysregulation in psychiatric disorders, as it is able to directly target the impaired neural circuits. However, the clinical impact of these rt-fMRI-NFB protocols in psychiatric populations is still largely unknown. Here we provide a comprehensive overview of primary studies from 2010 to 2023 that used rt-fMRI-NFB to target emotion regulation. We assessed 41 out of 4001 original studies for methodological quality and risk of bias and synthesised concerning the frequency of significant rt-fMRI-NFB-related effects on the neural and behaviour level. Successful modulation of brain activity was reported in between 25 and 50 percent of study samples, while neural effects in clinical samples were more diverse than in healthy samples. Interestingly, the frequency of rt-fMRI-NFB-related behavioural improvement was over 75 percent in clinical samples, while healthy samples showed behavioural improvements between 0 and 25 percent. Concerning clinical subsamples, rt-fMRI-NFB-related behavioural improvement was observed in up to 100 percent of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) samples. Substance use samples showed behavioural benefits ranging between 50 and 75 percent. Neural effects appeared to be less frequent than behavioural improvements: most neural outcomes ranged between 25 and 50 percent for MDD and substance use and between 0 and 25 percent for PTSD. Using multiple individualised regions of interest (ROIs) for rt-fMRI-NFB training resulted in more frequent behavioural benefits than rt-fMRI-NFB solely based on the amygdala or the prefrontal cortex. While a significant improvement in behavioural outcomes was reported in most clinical studies, the study protocols were heterogeneous, which limits the current evaluation of rt-fMRI-NFB as a putative treatment for emotional dysregulation.

Polygenic Scores and Networks of Psychopathology Symptoms

Studies on polygenic risk for psychiatric traits commonly use a disorder-level approach to phenotyping, implicitly considering disorders as homogeneous constructs; however, symptom heterogeneity is ubiquitous, with many possible combinations of symptoms falling under the same disorder umbrella. Focusing on individual symptoms may shed light on the role of polygenic risk in psychopathology. To determine whether polygenic scores are associated with all symptoms of psychiatric disorders or with a subset of indicators and whether polygenic scores are associated with comorbid phenotypes via specific sets of relevant symptoms. Data from 2 population-based cohort studies were used in this cross-sectional study. Data from children in the Avon Longitudinal Study of Parents and Children (ALSPAC) were included in the primary analysis, and data from children in the Twins Early Development Study (TEDS) were included in confirmatory analyses. Data analysis was conducted from October 2021 to January 2024. Pregnant women based in the Southwest of England due to deliver in 1991 to 1992 were recruited in ALSPAC. Twins born in 1994 to 1996 were recruited in TEDS from population-based records. Participants with available genetic data and whose mothers completed the Short Mood and Feelings Questionnaire and the Strength and Difficulties Questionnaire when children were 11 years of age were included. Psychopathology relevant symptoms, such as hyperactivity, prosociality, depression, anxiety, and peer and conduct problems at age 11 years. Psychological networks were constructed including individual symptoms and polygenic scores for depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), body mass index (BMI), and educational attainment in ALSPAC. Following a preregistered confirmatory analysis, network models were cross-validated in TEDS. Included were 5521 participants from ALSPAC (mean [SD] age, 11.8 [0.14] years; 2777 [50.3%] female) and 4625 participants from TEDS (mean [SD] age, 11.27 [0.69] years; 2460 [53.2%] female). Polygenic scores were preferentially associated with restricted subsets of core symptoms and indirectly associated with other, more distal symptoms of psychopathology (network edges ranged between r = -0.074 and r = 0.073). Psychiatric polygenic scores were associated with specific cross-disorder symptoms, and nonpsychiatric polygenic scores were associated with a variety of indicators across disorders, suggesting a potential contribution of nonpsychiatric traits to comorbidity. For example, the polygenic score for ADHD was associated with a core ADHD symptom, being easily distracted (r = 0.07), and the polygenic score for BMI was associated with symptoms across disorders, including being bullied (r = 0.053) and not thinking things out (r = 0.041). Genetic associations observed at the disorder level may hide symptom-level heterogeneity. A symptom-level approach may enable a better understanding of the role of polygenic risk in shaping psychopathology and comorbidity.

Vitamin D in tuberous sclerosis complex-associated tumors

Mammalian target of rapamycin inhibitors (mTORi) have been used to treat pediatric tuberous sclerosis complex (TSC)-associated tumors, particularly in cases with contraindications to surgery or difficulties in complete tumor resection. However, some patients experience side effects and tumor regression after discontinuation of the treatment. Therefore, there is an urgent need to develop drugs that can be used in combination with mTORi to increase their efficacy and minimize their side effects. 1,25-Dihydroxyvitamin D3 (1,25-D), which has anticancer properties, may be a promising candidate for adjuvant or alternative therapy because TSC and cancer cells share common mechanisms, including angiogenesis, cell growth, and proliferation. Vitamin D receptor-mediated signaling can be epigenetically modified and plays an important role in susceptibility to 1,25-D. Therefore, vitamin D signaling may be a promising drug target, and in vitro studies are required to evaluate the efficacy of 1,25-D in TSC-associated tumors, brain development, and core symptoms of psychiatric disorders.

Botulinum Toxin Injections for Psychiatric Disorders: A Systematic Review of the Clinical Trial Landscape.

Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders to identify relevant trends in the field and discuss the refinement of therapeutic techniques. A comprehensive search for published clinical trials using BONT-A injections for psychiatric disorders was performed on 4 May 2023 through OVID databases (MEDLINE, Embase, APA PsycINFO). Unpublished clinical trials were searched through the ClinicalTrials.gov and International Clinical Trial Registry Platform public registries. The risk of bias was assessed using the JBI Critical Appraisal tools for use in systematic reviews. We identified 21 studies (17 published, 4 unpublished clinical trials) involving 471 patients. The studies focused on evaluating the efficacy of BONT-A for major depressive, borderline personality, social anxiety, and bipolar disorders. BONT-A was most commonly injected into the glabellar area, with an average dose ranging between 37.75 U and 44.5 U in published studies and between 32.7 U and 41.3 U in unpublished trials. The results indicated significant symptom reductions across all the studied psychiatric conditions, with mild adverse effects. Thus, BONT-A appears to be safe and well-tolerated for psychiatric disorders of negative affectivity. However, despite the clinical focus, there was a noted shortage of biomarker-related assessments. Future studies should focus on pursuing mechanistic explorations of BONT-A effects at the neurobiological level.

Unlocking insights from actigraphy: examining feature selection and activation detection approaches for enhanced data interpretation

IntroductionAlterations in motor activity are an extremely important characteristic and one of the leading symptoms of major functional psychiatric disorders. These pattern disturbances can be observed in schizophrenia. Actigraphy is a non-invasive method that can be used to monitor these changes, and recent studies emphasize its significance in the early identification of disorders like schizophrenia.ObjectivesThis study uniquely focuses on distinguishing latent liabilities for schizotypy from manifested schizophrenia using specific actigraphy features.Methods Actigraphy data were collected using specialized devices from the University of Szeged and Haukeland University Hospital datasets (Berle et al., 2010). At Haukeland University Hospital patients with chronic schizophrenia (N=23) (so-called: manifested group) were collected, separately, at the University of Szeged, healthy university students were recruited and screened for latent tendencies towards shizotypic pathological development. In the latter study, two main groups were formed based on their scores: a positive schizotypy factor group (so-called: latent group) (N=22) and a control group (N=25), with actigraphy data. Utilizing the pyActigraphy library (Hammad et al., 2021) and wavelet analysis, features such as activity mean, interdaily stability and sleep movement characteristics were derived. Feature selection employed machine learning algorithms, notably Logistic Regression, Random Forest, ANN, and AHFS aided by Shapley values and Click Forming Feature Selection for insight into the most influential features.ResultsThe three models exhibited similar performance with a 60% accuracy threshold. In the latent group, sleep-related movements have a substantial impact, while in the manifested group, in addition to sleep characteristics, features like RA, IV, ADAT, M10, the mean activity level (all of which decreased), and the ratio of zero values also play a significant role. In the latent group, features related to the length of small amplitude movements were dominant, particularly the increased values, along with a decrease in the density of large movements.Conclusions Our study indicates that in the latent phase of schizophrenia, actigraphy features related to sleep are most significant, but as the disease progresses, both sleep and daytime activity patterns are crucial. Sleep disturbances may signal early susceptibility, with nighttime movements offering clearer insights. These variations might be influenced by medication effects in the manifested group, reflecting the broader challenges in schizophrenia research where the drug-free study of patients remains elusive. Further studies should explore these features in the Clinical High Risk and prodromal groups to refine our understanding of the development of the disorder.Disclosure of InterestNone Declared

Psychosis Due to Osmotic (Pontine) Myelinolysis in Non-Hodgkin’s Lymphoma: Case Report

Introduction: central pontine myelinolysis (CPM) is rare neurological condition. The severe symptoms of neurologic and psychiatric disorders accompanying this condition are not sufficiently disclosed in the literature. Most often CPM develops on infusion therapy and forced correction of hyponatremia. The complexity of diagnosis and the lack of certain algorithms for the management of this category of patients cause a high frequency of disability, persistent neurological and psychiatric symptoms, and lethal outcomes.The aim was to present and analyze clinical picture of psychosis in CPM on the example of non-Hodgkin’s lymphoma case report. Patient and method: clinical analysis of disorders in 14-years old patient with diagnosis of non-Hodgkin’s lymphoma.Results: clinical polymorphism of psychotic features, catatonic disorders, neurological symptoms at the end stage and development of psychosis associated with CPM during cytotoxic treatment. A year and a half follow-up of the first generation antipsychotics administration is presented.Conclusion: CPM may occur on cytotoxic infusion therapy in patients with non-Hodgkin’s lymphoma and be accompanied by severe psychotic disorders. Thus, practitioners should be aware of the risks of this condition, its diagnostic and therapeutic options when working with these patients.

MM165 - A Small Hybrid Molecule Modulates the Kynurenine Pathway and Attenuates Lipopolysaccharide-Induced Memory Deficits and Inflammation.

Cognitive dysfunctions are now recognized as core symptoms of various psychiatric disorders e.g., major depressive disorder. Sustained immune activation may leads to cognitive dysfunctions. Proinflammatory cytokines shunt the metabolism of tryptophan towards kynurenine and quinolinic acid may accumulate at toxic concentrations. This acid triggers an increase in neuronal nitric oxide synthase function and promotes oxidative stress. The searching for small molecules that can regulate tryptophan metabolites produced in the kynurenic pathway has become an important goal in developing treatments for various central nervous system diseases with an inflammatory component. Previously we have identified a small hybrid molecule - MM165 which significantly reduces depressive-like symptoms caused by inflammation induced by lipopolysaccharide administration. In the present study, we investigated whether this compound would mitigate cognitive deficits induced by lipopolysaccharide administration and whether treatment with it would affect the plasma or brain levels of quinolinic acid and kynurenic acid. Neuroinflammation was induced in rats by administering lipopolysaccharide at a dose of 0.5mg/kg body weight for 10 days. We conducted two tests: novel object recognition and object location, to assess the effect on memory impairment in animals previously treated with lipopolysaccharide. In plasma collected from rats, the concentrations of C-reactive protein and tumor necrosis factor alfa were determined. The concentrations of kynurenic acid and quinolinic acid were determined in plasma and homogenates obtained from the cerebral cortex of rats. Interleukin 6 in the cerebral cortex of rats was determined. Additionally, the body and spleen mass and spontaneous activity were measured in rats. Our study shows that MM165 may mitigate cognitive deficits induced by inflammation after administration of lipopolysaccharide and alter the concentrations of tryptophan metabolites in the brain. Compounds exhibiting a mechanism of action analogous to that of MM165 may serve as foundational structures for the development of a new class of antidepressants.