Psychosis Research Articles

Elevated serum IL-17 A and CCL20 levels as potential biomarkers in major psychotic disorders: a case-control study

BackgroundMajor psychotic disorders (MPD), including schizophrenia (SCZ) and schizoaffective disorder (SAD), are severe neuropsychiatric conditions with unclear causes. Understanding their pathophysiology is essential for better diagnosis, treatment, and prognosis. Recent research highlights the role of inflammation and the immune system, particularly the Interleukin 17 (IL-17) family, in these disorders. Elevated IL-17 levels have been found in MPD, and human IL-17 A antibodies are available. Changes in chemokine levels, such as CCL20, are also noted in SCZ. This study investigates the relationship between serum levels of IL-17 A and CCL20 in MPD patients and their clinical characteristics.MethodWe conducted a case-control study at the Ibn Sina Psychiatric Hospital (Mashhad, Iran) in 2023. The study involved 101 participants, of which 71 were MPD patients and 30 were healthy controls (HC). The Positive and Negative Symptom Scale (PANSS) was utilized to assess the symptoms of MPD patients. Serum levels of CCL20 and IL-17 A were measured using Enzyme-Linked Immunosorbent Assay (ELISA) kits. We also gathered data on lipid profiles and Fasting Blood Glucose (FBS).ResultsThe mean age of patients was 41.04 ± 9.93 years. The median serum levels of CCL20 and IL-17 A were significantly elevated in MPD patients compared to HC (5.8 (4.1–15.3) pg/mL and 4.2 (3–5) pg/mL, respectively; p < 0.001). Furthermore, CCL20 and IL-17 A levels showed a positive correlation with the severity of MPD. MPD patients also had significantly higher FBS, cholesterol, and Low-Density Lipoprotein (LDL) levels, and lower High-Density Lipoprotein (HDL) levels compared to HC. No significant relationship was found between PANSS components and blood levels of IL17 and CCL20.ConclusionThe current study revealed that the serum levels of IL-17 A and CCL20 in schizophrenia patients are higher than those in the control group. Metabolic factors such as FBS, cholesterol, HDL, and LDL also showed significant differences between MPD and HC. In conclusion, the findings suggest that these two inflammatory factors could serve as potential therapeutic targets and prognostic biomarkers for schizophrenia.

Psychotic symptoms associated increased CpG methylation of metabotropic glutamate receptor 8 gene in Chinese Han males with schizophrenia and methamphetamine induced psychotic disorder: a longitudinal study

Methamphetamine use can produce psychotic symptoms almost indistinguishable from schizophrenia (SCZ). Variation in DNA methylation may be closely implicated in the etiology and longitudinal development of psychiatric disorders. However, the relationship between psychotic symptoms, functional disability, and DNA methylation is still unclear. This study consists of three periods: discovery, validation, and follow-up. In the discovery stage, we employed genome-wide DNA methylation profiling (Illumina 450K) in peripheral blood mononuclear cells to test whether DNA methylation associates with psychotic symptoms and function state in representative SCZ and methamphetamine-induced psychotic disorder (MIP) patients. Then, we found seven differentially methylated regions/genes (DMRs, in UBA6, APOL3, KIF17, MLLT3, GRM8, CSNK1E, SETDB1) overlapping with genetic variants reported in previous studies of psychosis. In the validation stage, we compared the above-mentioned seven genes by MethLight qPCR method in Chinese Han males (N = 109 SCZ patients, N = 99 methamphetamine use disorder with MIP patients, N = 150 methamphetamine use disorder without MIP patients, N = 282 normal controls, age range: 18–50 years). GRM8 showed robustly altered methylation, which has passed rigorous filtration in subsequent validation, suggesting a remarkable contribution to SCZ and MIP. In addition, hypermethylation of GRM8 showed a significant association with the total scores of the Positive Negative Syndrome Scale and WHO disability assessment schedule II in both baseline and follow-up periods. Our findings suggest that increased CpG methylation in the promoter of GRM8 is a potential candidate epigenetic biomarker of psychotic symptoms in transdiagnostic samples of SCZ and MIP.

Characteristics of children and adolescents with recurrent mental health emergency visits and clinicians' intervention tendencies.

Mental disorders affect approximately 15%-20% of childhood. However, due to various factors, these individuals do not benefit sufficiently from mental health services. Therefore, psychiatry emergency services become a key system in the need of psychiatric care for these children. This study aims to reveal the factors that predict recurrent admissions in children and adolescents admitted to the emergency department of a psychiatric hospital and the tendencies of clinicians during management. In our study, the data of patients aged 0-18 years who applied to the emergency department between 1 March 2022 and 01 March 2023 were scanned retrospectively. Participants who applied once were included in the 'single applicant' group, whereas patients who applied two or more times were included in the 'repeated applicants' group. A total of 1563 emergency applications were recorded by 785 different patients. A total of 62.2% of the patients visited the emergency department once, while 37.8% applied two or more times. Non-suicidal self-injury, delusion/hallucination, irritability and depression were significantly higher in recurrent applicants (P < 0.05). Psychotic disorder, bipolar disorder, major depression and borderline personality traits were significantly frequent in these patients (P < 0.05). Additionally, it was determined that the number of psychiatric diagnoses, referral time, need for chemical restraint, having a diagnosis of psychotic disorder or borderline personality traits increased the likelihood of recurrence. Our results indicate some special risk factors that increase the likelihood of recurrent emergency admissions in children and adolescents. Further research with larger sample sizes may elucidate the unique needs of these children in order to use of community resources beneficially.

Change in care needs of people with severe mental illness with and without a non-Western migration background: are their needs equally served throughout treatment?

People with a non-Western migration background living in Western countries are more likely to experience psychiatric problems and have more severe symptoms when they do. Patients of non-Western origin also have more unmet needs for care. This study focuses on differences between Western and non-Western patients in care needs being met during the course of mental health treatment. The care needs of 1099 patients, 39% with and 61% without a non-Western migration background, recorded between 2017 and 2020 in Flexible Assertive Community Treatment, were compared. Non-Western migrants more often received psychotic disorder diagnoses, had more socio-economic problems, met, unmet and total needs for care and experienced less reduction in unmet needs during treatment. This was specifically the case for the rehabilitation areas: daily activities, treatment information, basic education, paid work and meaningful life and recovery. After controlling for socio-economic factors and diagnosis, group differences in change in number of unmet needs were no longer significant. However, the reduction in unmet needs in the areas of basic education, paid work and meaningful life and recovery remained significantly smaller for non-Western patients. Except for the rehabilitation domains of basic education, paidwork and meaningful life, the disadvantages in resolving the care needs of patients with a non-Western migration background do not remain significant after taking into account socioeconomic factors and diagnosis. Collaboration of mental health care and the social domain is warranted to improve socio-economic factors for patients with a non-Western migration background, to better address their unmet needs for care.

Positive Psychotic Symptoms after Escitalopram Treatment in a Female Adolescent with Peroxisome Spectrum Disorder Due to PEX-6 Gene Mutation

Introduction: In this case report, we present positive psychotic symptoms that developed after low-dose (5 mg/day) escitalopram treatment in a 16-year-old female adolescent with a peroxisome biogenesis disorder. Case presentation: Two weeks after starting escitalopram treatment for depression, the patient experienced vomiting attacks several times a day. About 2-3 days after the attacks began, the family stopped administering escitalopram. Five days after the onset of vomiting and 2-3 days after stopping escitalopram, the patient developed visual and auditory hallucinations and persecutory delusions. During the patient's follow-up period, the diversity of her hallucinations and delusions increased. When olanzapine treatment was gradually increased to 20 mg/day, the patient's psychotic symptoms disappeared. Conclusion: We discuss serotonin syndrome, drug-induced bipolar disorder, and psychotic disorder in the differential diagnosis. We believe that this case report is valuable as it is the first in the literature regarding the development of positive psychotic symptoms after SSRI use in a patient with a peroxisome biogenesis disorder.

Change in Clinical Risk Factors During Stay and Treatment in a Penitentiary Psychiatric Center.

This study examines the changes in clinical risk factors among individuals treated in Dutch Penitentiary Psychiatric Centers (PPCs). Using data from 874 patients with diverse psychiatric disorders, clinical risk factors were assessed at admission and discharge. Slight but significant improvements were observed in most risk factors, particularly psychotic symptoms, over an average stay of approximately 6 months. Patients with psychotic or substance use disorders showed the most improvement, while those with mood, personality, or developmental disorders showed minimal change. The study highlights the positive impact of PPCs' structured, secure environment and specialized treatment, especially for psychotic disorders. It also underscores the complexity of treating patients with high rates of comorbidity. The findings suggest that the duration of stay does not significantly predict the improvement in most clinical risk factors. Future research should explore specific diagnostic clusters and their impact on treatment outcomes in PPCs.

Exploring chitosan nanoparticles for enhanced therapy in neurological disorders: a comprehensive review.

Chitosan nanoparticles have emerged as a promising therapeutic platform for treating neurological disorders due to their biocompatibility, biodegradability, and ease of functionalization. One of the significant challenges in treating neurological conditions is overcoming the blood-brain barrier (BBB), which restricts the effective delivery of therapeutic agents to the brain. Addressing this barrier is crucial for the successful treatment of various neurological diseases, including Alzheimer's disease, Parkinson's disease, epilepsy, migraine, psychotic disorders, and brain tumors. Chitosan nanoparticles offer several advantages: they enhance drug absorption, protect drugs from degradation, and enable targeted delivery. These properties open new possibilities for non-invasive therapies for neurological conditions. Numerous studies have highlighted the neuroprotective potential of chitosan nanoparticles, demonstrating improved outcomes in animal models of neurodegeneration and neuroinflammation. Additionally, surface modifications of these nanoparticles allow for the attachment of specific ligands or molecules, enhancing the precision of drug delivery to neuronal cells. Despite these advancements, several challenges persist in the clinical translation of chitosan nanoparticles. Issues such as large-scale production, regulatory hurdles, and the need for further research into long-term safety must be addressed. This review explores recent advancements in the use of chitosan nanoparticles for managing neurological disorders and outlines potential future directions in this rapidly evolving field of research.

Functional observational battery (FOB) tests using caffeine and chlorpromazine hydrochloride in sprague-dawley rats.

Caffeine is believed to exert its therapeutic effects by acting as a nonselective, competitive antagonist of adenosine receptors. Chlorpromazine, a phenothiazine, is a classic psychotropic mediator extensively used in the clinical administration of psychotic disorders. This study aimed to validate the procedures used for performing Functional Observational Battery (FOB) tests, to demonstrate the proficiency and interobserver reliability during the FOB tests and also to assess effect on neurobehavioral parameters using positive controls in rats. The rats were administered with Caffeine in Milli-Q water as oral gavage at the dose of 20 mg/kg and Chlorpromazine HCl in 0.9% Saline as intraperitoneal route at the dose of 20 mg/kg. No inter-personnel variability was observed in home cage, handling, open field and sensory reactivity observations recorded in Proficiency test. In conclusion, the known effects of positive controls; caffeine and chlorpromazine HCl on neurobehavioral/Functional Observational Battery parameters including autonomic, neuromuscular and sensory reactivity tests were detected in the current study. FOB test procedures for neurobehavioral, grip strength and motor activity are adequate for the detection of neurotoxic effects of positive controls. No major inter-personnel variability was observed between study personnel in neurobehavioural observations.

Capgras Syndrome Accompanying Schizophrenia: An Adolescent Case Report

In Capgras syndrome, the patient believes that the original person or objects have been replaced by identical ones (fakes). The syndrome rarely occurs in its pure form. It often accompanies psychotic illness and organic pathology. Capgras syndrome can occur in all age groups and is more common in women. In this article, the case of a 16-year-old female patient who applied to the hospital with complaints of aggression, harming her environment and wanting to have a DNA test will be presented. During her first admission examination, she was found to have Capgras delusions, and she was hospitalized and monitored in a psychiatric clinic. The patient, who was followed up with a diagnosis of early-onset psychotic disorder, was determined to be a case of CS accompanying Schizophrenia. Early-onset Schizophrenia is already a rare condition, and the onset of CS at this age is uncommon. Our case is valuable as it shows that CS, a rare condition, can also be seen in adolescence.

Fatores de risco para psicoses

The main objective of this article is to introduce undergraduate medical students to the concept of psychosis. The authors discuss the criteria for diagnosing psychosis and provide an overview of the epidemiology and risk factors for psychotic disorders such as: childhood trauma, cannabis use, migration, discrimination, social disadvantage, and skin color. The observation of these factors is essential in the evaluation of psychiatric patients, as it helps in predicting the development of psychosis.

Identificação e intervenção precoce de primeiro episódio psicótico em cenários não especializados

The diagnosis and early intervention of a first episode psychosis is directly related to its prognosis. It is the initial phase of a psychotic disorder, which is a severe mental illness characterized by delusions, hallucinations and/or disorganized behaviour or speech. Commonly, the first assistance to these patients are done by a non-psychiatrist in an emergency or primary care setting. The practitioners must be able to identify and properly manage this condition, without delaying the diagnosis, screening and initiation of the proper treatment.

Fitness to stand trial: 415 consecutive defendants assessed by a New Zealand forensic psychiatry service.

New Zealand defendants found unfit to stand trial following a Court-ordered forensic mental health assessment cannot be detained in prison and must either be released, or made subject to a mental health or intellectual disability order. There is increasing awareness of the need to identify these people and protect their rights. Retrospective audit of 8years of Court-ordered health assessor reports addressing fitness to stand trial prepared by a New Zealand regional forensic mental health service with a catchment area of around 850,000. Between 2014 and 2022, Courts referred 415 defendants for assessment of fitness to stand trial. The number of reports requested increased by 20% between 2014 and 2022. Report subjects were 81% male and had a median age of 31. Commonest primary diagnoses were psychotic disorders (37%), intellectual disability (13%) and acquired neurocognitive disorders (15%). Few people with foetal alcohol spectrum disorder were identified. Despite the increase in assessments, the number of defendants considered unfit by report writers remained stable over time. The increasing number of referrals for assessment of fitness to stand trial has resourcing implications for forensic mental health services.

Exploring associations between psychotic experiences and structural brain age: a population-based study in late adolescence.

Neuroimaging studies show advanced structural "brain age" in schizophrenia and related psychotic disorders, potentially reflecting aberrant brain ageing or maturation. The extent to which altered brain age is associated with subthreshold psychotic experiences (PE) in youth remains unclear. We investigated the association between PE and brain-predicted age difference (brain-PAD) in late adolescence using a population-based sample of 117 participants with PE and 115 without PE (aged 19-21 years) from the Avon Longitudinal Study of Parents and Children. Brain-PAD was estimated using a publicly available machine learning model previously trained on a combination of region-wise T1-weighted grey-matter measures. We found little evidence for an association between PEs and brain-PAD after adjusting for age and sex (Cohen's d = -0.21 [95% CI -0.47, 0.05], p = 0.11). While there was some evidence for lower brain-PAD in those with PEs relative to those without PEs after additionally adjusting for parental social class (Cohen's d = -0.31 [95% CI -0.58, -0.03], p = 0.031) or birth weight (Cohen's d = -0.29 [95% CI -0.55, -0.03], p = 0.038), adjusting for maternal education or childhood IQ did not alter the primary results. These findings do not support the notion of advanced brain age in older adolescents with PEs. However, they weakly suggest there might be a younger-looking brain in those individuals, indicative of subtle delays in structural brain maturation. Future studies with larger samples covering a wider age range and multimodal measures could further investigate brain age as a marker of psychotic experiences in youth.

Unmet Financial Needs of People with Psychotic Disorders-A Cross-Sectional Study in People with Psychotic Disorders, Parents, Siblings, and Controls.

Background. Psychotic disorders have a strong negative impact on people's lives, including their financial situation. This study aimed to examine differences in unmet financial needs between people with psychotic disorders, parents, siblings, and controls. Secondly, we aimed to examine whether family clustering contributes to unmet financial needs. Lastly, we aimed to examine to what extent demographic, economic, psychiatric, functional, and cognitive characteristics and substance use predict unmet financial needs in people with psychosis. Methods. Data from the first assessment of people with psychosis (n = 956), siblings (n = 889), parents (n = 858), and controls (n = 496) included in the Genetic Risk and Outcome of Psychosis study were used. Group differences were assessed with Kruskal-Wallis tests (aim 1), while a mixed-effects logistic regression analysis and explorative and confirmative ordinal logistic regression analyses were conducted for aims 2 and 3, respectively. Results. Twenty-four percent of people with psychotic disorders reported unmet financial needs. These levels of unmet financial needs were significantly higher than levels for siblings, parents, and controls. We found a negligible influence of (direct) familial clustering on unmet financial needs. Lastly, cannabis and tobacco use significantly and consistently predicted higher levels of unmet financial needs of people with psychosis. Conclusions. Relatively high levels of unmet financial needs occurred in a heterogeneous group of people with psychosis, especially when people used cannabis or tobacco. Unmet financial needs can have detrimental consequences for mental health, stigmatization, leisure time activities, and social engagement. Thus, it is pivotal to recognize unmet financial needs, especially combined with substance use, as a crucial stressor for people with psychosis.

7025 Acute Psychosis and the Diagnosis of Cushing’s Syndrome: Lessons Learned from a Patient with a Long History of Obesity

Abstract Disclosure: S. Modi: None. L. Belalcazar: None. Background: Although the association of hypercortisolism and psychosis is well established, acute psychosis remains a very rare manifestation of Cushing’s syndrome, especially in the absence of previous psychiatric history. We present lessons learned from a patient in whom the diagnosis of Cushing’s syndrome was missed until the onset of acute psychosis helped identify his underlying endocrine disorder. Clinical Case: A 31-year-old male presented to the Emergency Department after being found down on the street. The patient had superficial lacerations that were suspected to be self-inflicted due to a suicide attempt, but later found to be the result of auditory hallucinations. He had no previous psychiatric history and no history of suicidal ideation. His medical history was positive for obesity since adolescence and a recent diagnosis of hypertension. His family noted that for the past several months he had been experiencing headache, fatigue, muscle weakness and, more recently, insomnia, restlessness, and confusion. Weight gain was noted, but of unknown magnitude. On admission, he was agitated and hallucinating. He was initially sedated with dexmedetomidine and started on quetiapine. Physical examination revealed Cushingoid features with truncal obesity (body mass index of 35 kg/m2), facial plethora, and dorsocervical fat pad; no abdominal striae were present. Labs showed mild hypokalemia. His AM cortisol was markedly elevated at &amp;gt; 123 ug/dL (normal 4.5-23.0 ug/dL) with an ACTH level at 144 pg/mL (normal 7.2-63.3 pg/mL). MRI Brain showed a 1.9 cm pituitary macroadenoma with small suprasellar extension. With a diagnosis of Cushing’s disease, later confirmed by pathology, he underwent transsphenoidal resection. AM cortisol on post-operative day 3 was 3.2 ug/dL (normal 4.5-23.0 ug/dL). Maintenance-dose steroids were started due to evidence of post-surgical corticotroph suppression. Notably, there was marked improvement in his anxiety, paranoia, and confusion post-operatively. Quetiapine and blood pressure medications were discontinued after discharge. Conclusion: In this patient, the diagnosis of Cushing’s syndrome was missed when initially presenting with new onset hypertension in the setting of long-standing obesity. Despite months of symptoms compatible with the diagnosis, it was not until he developed acute psychosis and a careful history was obtained, that the diagnosis of Cushing’s syndrome was entertained. Psychosis is present in only 3-8% of reported cases of Cushing’s syndrome. This case illustrates the importance of including Cushing’s syndrome in the differential diagnosis of acute psychosis, especially in patients without previous psychiatric history. It also highlights the need of excluding secondary causes of hypertension in young adults, with particular attention to Cushing’s syndrome in those who present with obesity, even if long-standing. Presentation: 6/1/2024

SIPD or psychotic disorder with stimulant use

SIPD or psychotic disorder with stimulant use

7173 Cabergoline Induced Psychosis in a Patient with no Previous History of Psychiatric Disorder

Abstract Disclosure: B. Aryal: None. K. Kim: None. A. Shafi: None. M. Ganesh: None. Introduction: Cabergoline is a dopamine agonist (DA) used to treat prolactinomas. It is well established that DAs may cause psychotic symptoms. However, very few cases report cabergoline-associated psychosis in patients without personal or family history of psychiatric disorders. We report a rare case of cabergoline-induced psychosis in a patient with a prolactinoma without any underlying psychiatric disorder, which was managed with the addition of olanzapine. Case: A 41 year old male with no history of psychiatric disorder was started on cabergoline 0.5mg twice a week for a newly diagnosed prolactinoma. 4 weeks later, he presented to the emergency room for aggressive behavior and confusion for the past 2 weeks. He endorsed visual and auditory hallucinations. Cabergoline was discontinued. During hospitalization, he attempted suicide and required 1:1 observation. He was started on olanzapine per the inpatient psychiatry team. Surgical resection of the prolactinoma was considered given his acute psychosis associated with cabergoline. However, complete resection of the tumor was deemed impossible given encasement of the internal carotid arteries. After discussion with the patient, he underwent re-challenge with cabergoline 0.25mg weekly while on olanzapine under 1:1 observation in the ICU. He was monitored for 2 weeks and eventually discharged home on cabergoline 0.25mg twice a week and olanzapine with improvement in prolactin levels to 4973.7 ng/mL after 4 weeks. He continued to remain free of psychotic symptoms upon follow up as an outpatient. Discussion: Psychosis is a rare side effect of DA mediated via D2/D3 receptors in the mesocortical and mesolimbic pathways. Several cases report psychosis associated with cabergoline in patients with a history of psychiatric disorders. However only one case reports de novo psychosis. Our patient developed severe psychosis while on low-dose cabergoline for 4 weeks. This rare case of de novo cabergoline-associated psychosis re-emphasizes that psychosis may occur regardless of previous history of psychiatric disorder and independent of the dose or duration of cabergoline. Treatment of a prolactinoma in the setting of cabergoline-associated psychosis requires a multidisciplinary approach. Alternative treatment of surgical resection was considered for our patient. However surgical resection was not plausible given difficult surgical anatomy. Therefore he was monitored closely to re-initiate cabergoline while on olanzapine. Several cases report successful use of clozapine, aripiprazole, and quetiapine for patients with psychiatric symptoms while on cabergoline. Patients who are on cabergoline should be closely monitored for any psychotic symptoms. Further studies are warranted to identify patients at risk of developing psychosis while on cabergoline to tailor an individualized approach to therapy and monitoring. Presentation: 6/2/2024

6419 Cushing’s Syndrome due to Metastatic Pancreatic Neuroendocrine Neoplasm With Incidental Pituitary Microadenoma

Abstract Disclosure: A. Ibrahim: None. L. Esper: None. R. Jain: None. N. El Asmar: None. Introduction: Pancreatic neuroendocrine neoplasms (PNENs) are rare with a reported incidence of 1-2/100,000. While the majority are non-functional, insulinomas and gastrinomas are the most common functional PNENs. Our case of ACTH-producing PNENs is extremely rare. Case presentation: A previously healthy 47-year-old female was hospitalized for worsening dyspnea. Her symptoms included rapid weight gain, skin hyperpigmentation, and lower extremity edema. Her exam was notable for elevated blood pressure of 181/120 mmHg, moon facies, purple abdominal striae, and proximal myopathy. Her lab analysis showed a cortisol level of 42 mcg/dL (6.2-19.4), ACTH of 254 pg/ml (7.2-63), DHEA sulfate of 171 mcg/dl (41-243), HbA1C 7%, K of 3 mmol/l and 24H urine cortisol &amp;gt;2100 mcg/24hrs. A post low-dose DST cortisol level was 42.7 mcg/dl. CT chest demonstrated an ill-defined hypodense lesion in the region of the pancreatic head. MRI abdomen revealed a 3 x 2.3 x 2.3 cm mass in the pancreatic head and many small enhancing lesions within the right lobe of the liver. Adrenal glands appeared normal. Subsequent PET CT scan with GA 68 DOTOTATE showed increased uptake in the pancreatic head mass and in the right hepatic lobe. Her pituitary MRI revealed a right pituitary gland 6 mm hypointense lesion, possibly a microadenoma. A high dose DST resulted in a cortisol level of 80 mcg/dl mostly consistent with ectopic ACTH secretion. EUS-guided biopsy of the pancreatic mass showed a well-differentiated neuroendocrine tumor that stained positive for ACTH, chromogranin, synaptophysin, and CD56. Treatment with Ketoconazole 600mg q6h and Octreotide 50mg q6h was started 3 days before surgery to control acute hypercortisolism as she developed acute psychosis. The patient subsequently underwent a Whipple procedure with successful resection of the pancreatic mass. Post-op, her ACTH levels dropped to 19 pg/ml with a cortisol level of 6 mcg/dl. Final pathology showed a well-differentiated grade 3 neuroendocrine tumor with a KI-67 labeling index greater than 20%. After surgery, the patient received a short course of stress dose hydrocortisone which was tapered off over the following 2 months. The patient is being followed for planning further intervention given the aggressive grade of the tumor and hepatic metastases. Conclusion: Ectopic ACTH-producing PNENs are rare. An accurate and timely diagnosis, while challenging, is key. Patients usually present with rapidly progressing symptoms that could cause life-threatening complications such as thrombosis and sepsis. We demonstrated the importance of utilizing a multidisciplinary team approach and starting cortisol-lowering medications early given the complexity of the disease, requiring rapid intervention and lifelong follow-up. Presentation: 6/3/2024

Comparative Risk of Neuropsychiatric Adverse Events Associated With Leukotriene-Receptor Antagonists Versus Inhaled Corticosteroids

Leukotriene-receptor antagonists (LTRA) and inhaled corticosteroids (ICS) are common controller medications for asthma, but limited studies examine their comparative risks on neuropsychiatric adverse events (NAEs) in asthma patients. To investigate the comparative risks of LTRA versus ICS on seven distinct categories of NAEs in asthma patients at a nationwide level. We conducted a nationwide cohort study during 2010-2021. Incident NAEs and its clinical subgroups (e.g., psychotic disorders, anxiety disorders, movement disorders, behavioral and emotional disorders, mood disorders, sleep-related disorders, and personality disorders) were assessed. Cox proportional hazards regressions were employed to quantify the comparative risks. There were 1,249,897 asthma patients aged 6-64 years. Incidence rates for NAEs were 25.10 per 1000 person-years among patients treated with LTRA, and 23.46 per 1000 person-years among those treated with ICS. The incidence rate difference was 1.64 [95%CI: 0.30-2.98] per 1000 person-years. Positive associations of NAEs and three clinical subgroups were found in patients treated with LTRA compared to ICS (hazard ratios (HR): 1.06 [95%CI: 1.00-1.12] for NAEs; HR: 1.88 [95%CI: 1.24-2.84] for psychotic disorders; HR: 1.10 [95%CI: 1.01-1.20] for anxiety disorders; and HR: 1.27 [95%CI: 1.02-1.58] for behavioral and emotional disorders), but not for movement disorders, mood disorders, sleep-related disorders, and personality disorders. This nationwide cohort study identified heightened risks, ranging from 6% to 88%, of NAEs and three clinical subgroups in asthma patients treated with LTRA compared to ICS. These findings underscore the necessity for clinicians to communicate with patients regarding potential neuropsychiatric harms when prescribing LTRA.

Exploring the role of TNF-α, TGF-β, and IL-6 serum levels in categorical and noncategorical models of mood and psychosis

Psychotic and mood disorders are discussed as part of the same continuum. The potential role of immune dysregulation in defining their clinical presentations, however, remains unclear. Differences in TNF-α, IL-6 and TGF-β levels were investigated in 143 patients with schizophrenia (SCH = 63) and bipolar disorder (BD = 80), in remission. Cytokines were evaluated against the dimensional assessment of psychosis and affective symptoms using the schizo-bipolar scale, together with the severity of the same symptom domains measured by the brief psychiatric rating scale (BPRS). Lower TGF-β was associated with more lifetime episodes, family risk for psychosis, and more severe mood and psychotic symptoms in all patients. BPRS Affect symptoms domain correlated with lower TGF-β levels in BD, and higher TGF-β levels in SCH patients. Using moderated mediation analysis, TGF-β was a relevant predictor only in the setting of non-categorical symptom distribution, with familial risk for psychosis confirmed as a significant moderator. Severity of BPRS Affect symptoms domain was an independent predictor of inclination towards the psychosis spectrum. The underlying immune dysregulation may be shared by the disorders, rather than a unique characteristic of each, having significant implications for our understanding of the continuum vs. categorical approach to psychosis and mood disorders.