Guiding Ethical Decisions in Cochlear Implantation for the Hearing Impaired with Comorbid Psychosis.

AbstractCochlear implants can restore hearing in people with severe hearing loss and have a significant impact on communication, social integration, self-esteem, and quality of life. However, whether and how much clinical benefit is derived from cochlear implants varies significantly by patient and is influenced by the etiology and extent of hearing loss, medical comorbidities, and preexisting behavioral and psychosocial issues. In patients with underlying psychosis, concerns have been raised that the introduction of auditory stimuli could trigger hallucinations, worsen existing delusions, or exacerbate erratic behavior. This concern has made psychosis a relative contraindication to cochlear implant surgery. This is problematic because there is a lack of data describing this phenomenon and because the psychosocial benefits derived from improvement in auditory function may be a critical intervention for treating psychosis in some patients. The objective of this report is to provide an ethical framework for guiding clinical decision-making on cochlear implant surgery in the hearing impaired with psychosis.

Aripiprazole-induced quasi-neuroleptic malignant syndrome: two case reports.

BACKGROUND: Significant elevation of creatine kinase levels (above three digits) and leucocytosis in the absence of muscle rigidity, tremors, or autonomic dysfunction can pose a real challenge in the context of antipsychotic treatment as an early herald of neuroleptic malignant syndrome. CASE PRESENTATION: We present here two cases of adult male patients of Black British heritage, ages 51 years and 28 years, respectively. Both received a diagnosis of schizoaffective disorder and presented with massive increase of creatine kinase blood level after aripiprazole depot administration, one with pernicious increase associated with silent neuroleptic malignant syndrome, and the second with asymptomatic benign enzyme elevation. CONCLUSION: Though aripiprazole use is less likely to cause neuroleptic malignant syndrome, on rare occasions it can produce massive symptomatic or asymptomatic increase in serum creatine kinase enzyme levels, raising the need for close monitoring, especially at the initial doses of the drug.

A case report of a patient with Turner syndrome who develops catatonia secondary to psychotic symptoms.

RATIONALE: Turner syndrome (TS) is a genetic disorder associated with partial or complete monosomy X abnormalities; some patients may have a higher risk of psychiatric symptoms. Catatonia is associated with a wide range of life-threatening complications with complex pathogenesis; However, It very rare for patients with TS to develop psychotic symptoms and eventually progress to catatonia. This case report describes the diagnostic and therapeutic course of catatonia-associated TS. PATIENT CONCERNS: In this study, we report the case of a patient with TS who initially developed sudden hallucinations, delusions, and emotional instability, followed by catatonia. DIAGNOSES: The patient was diagnosed with: unspecified catatonia; TS. INTERVENTIONS: Treatment included administering a combination of esazolam injections and olanzapine tablets, placing a gastric tube and urinary catheter, and providing nutritional support. OUTCOMES: After treatment, the patient's hallucinations, delusions, and catatonia disappeared, with no residual sequelae, and social functioning returned to normal. LESSONS: For patients with TS who present with psychotic symptoms and catatonia, a comprehensive evaluation is necessary, and treatment with antipsychotics and benzodiazepines is effective.

[Analysis of 9 patients with adolescence-onset methylenetetrahydrofolate reductase deficiency].

Objective: To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency. Methods: This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively. Results: The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 µmol/L) was found in all patients, and decreased to 20-70 µmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders. Conclusions: Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.

Modulation of mGlu5 reduces rewarding associative properties of nicotine via changes in mesolimbic plasticity: Relevance to comorbid cigarette smoking in psychosis.

RATIONALE: Antipsychotic medications that are used to treat psychosis are often limited in their efficacy by high rates of severe side effects. Treatment success in schizophrenia is further complicated by high rates of comorbid nicotine use. Dopamine D2 heteroreceptor complexes have recently emerged as targets for the development of more efficacious pharmaceutical treatments for schizophrenia. OBJECTIVE: The current study sought to explore the use of the positive allosteric modulator of the mGlu5 receptor 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) as a treatment to reduce symptoms related to psychosis and comorbid nicotine use. METHODS: Neonatal treatment of animals with the dopamine D2-like receptor agonist quinpirole (NQ) from postnatal day (P)1-21 produces a lifelong increase in D2 receptor sensitivity, showing relevance to psychosis and comorbid tobacco use disorder. Following an 8-day conditioning paradigm, brain tissue in the mesolimbic pathway was analyzed for several plasticity markers, including brain derived neurotrophic factor (BDNF), phosphorylated p70 ribosomal S6 kinase (phospho-p70S6K), and cadherin-13 (Cdh13). RESULTS: Pretreatment with CDPPB was effective to block enhanced nicotine conditioned place preference observed in NQ-treated animals. Pretreatment was additionally effective to block the nicotine-induced increase in BDNF and sex-dependent increases in cadherin-13 in the ventral tegmental area (VTA), as well as increased phospho-p70S6K in the nucleus accumbens (NAcc) shell found in NQ-treated animals. CONCLUSION: In conjunction with prior work, the current study suggests positive allosteric modulation of the mGlu5 receptor, an emerging target for schizophrenia therapeutics, may be effective for the treatment of comorbid nicotine abuse in psychosis.

Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis.

Increasing evidence points toward the role of the extracellular matrix, specifically matrix metalloproteinase 9 (MMP-9), in the pathophysiology of psychosis. MMP-9 is a critical regulator of the crosstalk between peripheral and central inflammation, extracellular matrix remodeling, hippocampal development, synaptic pruning, and neuroplasticity. Here, we aim to characterize the relationship between plasma MMP-9 activity, hippocampal microstructure, and cognition in healthy individuals and individuals with early phase psychosis. We collected clinical, blood, and structural and diffusion-weighted magnetic resonance imaging data from 39 individuals with early phase psychosis and 44 age and sex-matched healthy individuals. We measured MMP-9 plasma activity, hippocampal extracellular free water (FW) levels, and hippocampal volumes. We used regression analyses to compare MMP-9 activity, hippocampal FW, and volumes between groups. We then examined associations between MMP-9 activity, FW levels, hippocampal volumes, and cognitive performance assessed with the MATRICS battery. All analyses were controlled for age, sex, body mass index, cigarette smoking, and years of education. Individuals with early phase psychosis demonstrated higher MMP-9 activity (p < 0.0002), higher left (p < 0.05) and right (p < 0.05) hippocampal FW levels, and lower left (p < 0.05) and right (p < 0.05) hippocampal volume than healthy individuals. MMP-9 activity correlated positively with hippocampal FW levels (all participants and individuals with early phase psychosis) and negatively with hippocampal volumes (all participants and healthy individuals). Higher MMP-9 activity and higher hippocampal FW levels were associated with slower processing speed and worse working memory performance in all participants. Our findings show an association between MMP-9 activity and hippocampal microstructural alterations in psychosis and an association between MMP-9 activity and cognitive performance. Further, more extensive longitudinal studies should examine the therapeutic potential of MMP-9 modulators in psychosis.

Tobacco smoking and nicotine vaping in persons with first episode psychosis.

Tobacco smoking is highly prevalent in persons with psychosis and is the leading cause of preventable mortality in this population. Less is known about tobacco smoking in persons with first episode psychosis (FEP) and there have been no estimates about the prevalence of nicotine vaping in FEP. This study reports rates of tobacco smoking and nicotine vaping in young people with FEP enrolled in Coordinated Specialty Care programs in Pennsylvania and Maryland. Using data collected from 2021 to 2023, we examined lifetime and recent smoking and vaping and compared smokers and vapers to nonusers on symptoms, functioning, and substance use. The sample included 445 participants aged 13-35 with recent psychosis onset. Assessments were collected by program staff. Overall, 28 % of participants engaged in either smoking or vaping within 30 days of the admission assessment. Smokers and vapers were disproportionately male, cannabis users, and had lower negative symptom severity than non-smokers. Vapers had higher role and social functioning. Both smoking and vaping were related to a longer time from psychosis onset to program enrollment. We compare these findings to previous studies and suggest steps for addressing smoking and vaping in this vulnerable population.

Inflammatory blood cells and ratios at remission for psychosis relapse prediction: A three-year follow-up of a cohort of first episodes of schizophrenia.

BACKGROUND: The clinical course following a first episode of schizophrenia (FES) is often characterized by recurrent relapses, resulting in unfavorable clinical and functional outcomes. Inflammatory dysregulation has been implicated in relapse risk; however, the predictive value of inflammatory blood cells in clinically remitted patients after a FES has not been previously explored. METHODS: In this study, we closely monitored 111 patients in remission after a FES until relapse or a three-year follow-up endpoint. The participants were recruited from the multicenter 2EPS Project. Data on inflammatory blood cells and ratios were collected at baseline and at the time of relapse or after three years of follow-up. RESULTS: Monocyte counts (OR = 1.91; 95 % CI = 1.07-3.18; p = 0.009) and basophil counts (OR = 1.09; 95 % CI = 1.01-1.12; p = 0.005) at baseline were associated with an increased risk of relapse, while the platelet-lymphocyte ratio (OR = 0.98; 95 % CI = 0.97-0.99; p = 0.019) was identified as a protective factor. However, after adjusting for cannabis and tobacco use during the follow-up, only monocyte counts (OR = 1.73; 95 % CI = 1.03-2.29; p = 0.027) and basophil counts (OR = 1.08; 95 % CI = 1.01-1.14; p = 0.008) remained statistically significant. ROC curve analysis indicated that the optimal cut-off values for discriminating relapsers were 0.52 × 10^9/L (AUC: 0.66) for monocytes and 0.025 × 10^9/L (AUC: 0.75) for basophils. When considering baseline inflammatory levels, no significant differences were observed in the inflammatory biomarkers at the endpoint between relapsers and non-relapsers. CONCLUSION: This study provides evidence that higher monocyte and basophil counts measured at remission after a FES are associated with an increased risk of relapse during a three-year follow-up period.

Association between neutrophil to lymphocyte ratio and inflammatory biomarkers in patients with a first episode of psychosis.

Neutrophil to lymphocyte ratio (NLR) has been proposed as an emerging marker of the immune system alterations in psychotic disorders. However, it is not entirely clear whether NLR elevation is a characteristic of the psychotic disorder itself, which inflammatory pathways activation is detecting, or which possible confounding variables could alter its interpretation. We aimed to analyze the relationship of NLR values with a panel of inflammatory and oxidative/nitrosative stress biomarkers and main potential confounding factors in a well-characterized cohort of 97 patients with a first episode of psychosis (FEP) and 77 matched healthy controls (HC). In the FEP group, NLR values presented a moderate, positive correlation with the pro-inflammatory mediator Prostaglandin E2 levels (r = 0.36, p < 0.001) and a small but significant, positive correlation with cannabis use (r = 0.25, p = 0.017). After controlling for cannabis use, the association between NLR and PGE2 remained significant (beta = 0.31, p = 0.012). In the HC group, NLR values negatively correlated with body mass index (BMI, r = -0.24, p = 0.035) and positively correlated with tobacco use (r = 0.25, p = 0.031). These findings support a relationship between the elevation of NLR values and an elevated expression of proinflammatory pathways related to stress response in patients with a FEP. In addition, our study highlights the importance of considering variables such as cannabis or tobacco consumption, and BMI when interpreting the results of studies aimed to establish a clinical use of NLR. These considerations may help future research to use NLR as a reliable biomarker to determine immune system status in this population.

Mixed Connective Tissue Disease Presenting With Psychosis-A Case Report.

ABSTRACT: Mixed connective tissue disease (MCTD) is a systemic autoimmune disease with features overlapping multiple autoimmune disorders. One study found that over 55% of patients with MCTD experienced neuropsychiatric symptoms, the most common of which was an "aseptic meningitis-like syndrome." We present a case of a 17-year-old adolescent girl presenting with abnormal speech and behavior, auditory hallucinations, and paranoid delusions after an isolated episode of fever. She was treated for her psychotic symptoms but later developed symptoms resembling neuroleptic malignant syndrome. An antibody screen revealed elevated anti-U1-ribonucleoprotein antibodies with a possible diagnosis of MCTD. She finally responded to steroid therapy. To our knowledge, this is the first reported case of MCTD initially presenting with psychosis. A diagnosis of autoimmune disorders should be kept in the differential of similar clinical presentations including connective tissue disorders and autoimmune thyroid conditions.

A proposal for reducing maximum target doses of drugs for psychosis: Reviewing dose-response literature.

BACKGROUND: Presently, there is limited guidance on the maximal dosing of psychosis drugs that is based on effectiveness rather than safety or toxicity. Current maximum dosing recommendations may far exceed the necessary degree of dopamine D2 receptor blockade required to treat psychosis. This may lead to excess harm through cognitive impairment and side effects. AIMS: This analysis aimed to establish guidance for prescribers by optimally dosing drugs for psychosis based on efficacy and benefit. METHODS: We used data from two dose-response meta-analyses and reviewed seven of the most prescribed drugs for psychosis in the UK. Where data were not available, we used appropriate comparison techniques based on D2 receptor occupancy to extrapolate our recommendations. RESULTS: We found that the likely threshold dose for achieving remission of psychotic symptoms was often significantly below the currently licensed dose for these drugs. We therefore recommend that clinicians are cautious about exceeding our recommended doses. Individual factors, however, should be accounted for. We outline potentially relevant factors including age, ethnicity, sex, smoking status and pharmacogenetics. Additionally, we recommend therapeutic drug monitoring as a tool to determine individual pharmacokinetic variation. CONCLUSIONS: In summary, we propose a new set of maximum target doses for psychosis drugs based on efficacy. Further research through randomised controlled trials should be undertaken to evaluate the effect of reducing doses from current licensing maximums or from doses that are above our recommendations. However, dose reductions should be implemented in a manner that accounts for and reduces the effects of drug withdrawal.

[Lifestyle in young adults with and without a psychotic disorder]. / Leefstijl bij jongvolwassenen met en zonder psychotische stoornis.

Background Patients with psychotic disorders have a higher risk of physical illnesses on account of genetic predisposition, poorer access to healthcare, medication use, environmental factors and lifestyle. Because healthy lifestyle behaviour is established at young age, it is important to signal problems in good time. A lifestyle screening might be useful in this respect. Aim To describe the lifestyle characteristics of patients in a mental health clinic for young adults (age: 18-28 years) with early psychotic disorder based on parts of the instrument ‘Lifestyle-in-the-picture’ compared to healthy controls. We also discuss experiences of lifestyle coaches in applying ‘Lifestyle-in-the-picture’. Method Lifestyle characteristics and lifestyle behaviour of 90 patients with a psychotic disorder and 137 young adults from the general population were compared quantitatively. Additionally, interviews were held with lifestyle coaches as to the use of the instrument ‘Lifestyle-in-the-picture’. Results The young adult patients had considerably poorer results on lifestyle aspects than controls: increased body mass index (BMI 53% versus 18%), smoking, addiction and unhealthy eating and activity patterns. They were more dissatisfied with their physical and mental health. According to the lifestyle coaches, the ‘Lifestyle-in-the-picture’ instrument was a good starting point to work on improvement with patients since the instrument provided insight in the healthy and unhealthy aspects of their lifestyle and gave directions to set goals. Conclusions Young adults with a psychotic disorder have an unhealthy lifestyle and also more risk factors compared to controls. Lifestyle screening programmes are important to discuss health risks in time and which steps for improvement can be taken. The step from insight to actual more healthy behaviour is challenging.

A naturalistic cohort study of first-episode schizophrenia spectrum disorder: A description of the early phase of illness in the PSYSCAN cohort.

BACKGROUND: We examined the course of illness over a 12-month period in a large, international multi-center cohort of people with a first-episode schizophrenia spectrum disorder (FES) in a naturalistic, prospective study (PSYSCAN). METHOD: Patients with a first episode of schizophrenia, schizoaffective disorder (depressive type) or schizophreniform disorder were recruited at 16 institutions in Europe, Israel and Australia. Participants (N = 304) received clinical treatment as usual throughout the study. RESULTS: The mean age of the cohort was 24.3 years (SD = 5.6), and 67 % were male. At baseline, participants presented with a range of intensities of psychotic symptoms, 80 % were taking antipsychotic medication, 68 % were receiving psychological treatment, with 46.5 % in symptomatic remission. The mean duration of untreated psychosis was 6.2 months (SD = 17.0). After one year, 67 % were in symptomatic remission and 61 % were in functional remission, but 31 % had been readmitted to hospital at some time after baseline. In the cohort as a whole, depressive symptoms remained stable over the follow-up period. In patients with a current depressive episode at baseline, depressive symptoms slightly improved. Alcohol, tobacco and cannabis were the most commonly used substances, with daily users of cannabis ranging between 9 and 11 % throughout the follow-up period. CONCLUSIONS: This study provides valuable insight into the early course of a broad range of clinical and functional aspects of illness in FES patients in routine clinical practice.

Association between electronic nicotine product use and subsequent first episode psychosis.

Tobacco use has been established as a possible risk factor for psychosis, but the effect of electronic nicotine delivery systems (ex. nicotine vapes) has not been independently established. Using the Population Assessment of Tobacco and Health study, we found that use of electronic nicotine products was significantly associated with later first episode psychosis after controlling for substance use and other confounders, and that this relationship was only significant among the heaviest users (>20 puffs/day). Given the rapid rise in electronic nicotine products use, clinicians and public health professionals should consider potential impacts and closely monitor trends in the coming years.

Pediatric anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis: Exploring psychosis, related risk factors, and hospital outcomes in a nationwide inpatient sample: A cross-sectional study.

OBJECTIVE: Our study aims to examine the risk factors for comorbid psychosis in pediatric patients hospitalized for anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and its impact on hospital outcomes. METHODS: We conducted a cross-sectional study using the nationwide inpatient sample (NIS 2018-2019). We included 3,405 pediatric inpatients (age 6-17 years) with a primary discharge diagnosis of anti-NMDAR encephalitis. We used binomial logistic regression model to evaluate the odds ratio (OR) of variables (demographic and comorbidities) associated with comorbid psychosis. RESULTS: The prevalence of comorbid psychosis in anti-NMDAR encephalitis inpatients was 5.3%, and majorly constituted of adolescents (72.2%) and females (58.3%). In terms of race, Blacks (OR 2.41), and Hispanics (OR 1.80) had a higher risk of comorbid psychosis compared to Whites. Among comorbidities, encephalitis inpatients with depressive disorders (OR 4.60), sleep-wake disorders (OR 3.16), anxiety disorders (OR 2.11), neurodevelopmental disorders (OR 1.95), and disruptive behavior disorders (OR 2.15) had a higher risk of comorbid psychosis. Anti-NMDAR encephalitis inpatients with comorbid psychosis had a longer median length of stay at 24.6 days (vs. 9.8 days) and higher median charges at $262,796 (vs. $135,323) compared to those without psychotic presentation. CONCLUSION: Adolescents, females, and Blacks with encephalitis have a higher risk of psychotic presentation leading to hospitalization for anti-NMDAR encephalitis. Identification of demographic predictors and comorbidities can aid in early recognition and intervention to optimize care and potentially reduce the healthcare burden.

[Intended utilization of health care services in cases of mental illnesses with varying urgency]. / Intendierte Inanspruchnahme von Versorgungsangeboten bei psychischen Erkrankungen mit unterschiedlicher Dringlichkeit.

OBJECTIVE: To investigate variations in intended utilization in cases of an acute psychotic episode, an alcohol related or depressive disorder depending on different case characteristics. METHODS: A telephone survey with case vignettes was conducted (N=1,200). Vignettes varied in terms of urgency of symptoms, daytime, sex of the afflicted person and age/mental disorder. The respondents were asked to indicate whom they would contact first in the described case. RESULTS: Outpatient physicians were named most frequently as the first point of contact (61.1%) while only 6.5% of the respondents named emergency medicine including the medical on call service (8.1% in high urgency cases, i. e. emergencies that did not tolerate any delay). Intended utilization varied by urgency and age/mental illness. CONCLUSION: More Information about the need to seek medical help immediately in cases of mental illnesses with high urgency should be provided.

The impact of menarche on hippocampal mechanisms of severity of psychotic-like experiences in the ABCD study.

Accumulating evidence suggests that estrogens play an important modulatory role in the pathogenesis of psychosis. Estrogens come online within a dynamic developmental context of emerging psychopathology and neurodevelopment. As a result, estradiol (the primary form of estrogen) may influence psychosis lability directly or indirectly through its neurodevelopmental influence on estrogens-sensitive areas like the hippocampus. Understanding this influence may provide novel insight into mechanisms of psychosis lability. This study included baseline and year 2 timepoints from 4422 female participants from the Adolescent Brain Cognitive Development (ABCD) study (age 8-13), who varied in estradiol availability (pre-menarche, post-menarche, pre- and post-menarche timepoints). Estradiol availability was related to psychotic-like experiences (PLE) severity both directly and as an interactive effect with hippocampal connectivity using menarche status (pre/post) in a multilevel model. PLE severity was highest in individuals with early menarche emphasizing the importance of the developmental timing. Although PLE severity decreased over time in the sample, it stayed clinically-relevant over 2 years. Lower hippocampal connectivity was related to elevated PLE severity. This effect was moderated by estradiol; before the availability of estradiol (pre-menarche), lower hippocampal connectivity significantly contributed to the PLE severity, but when estradiol was available (post-menarche) hippocampal dysconnectivity did not account for PLE severity. This moderation suggests that the estrodiol's influence on hippocampal plasticity also reduced the mechanistic role of the hippocampus on PLE severity. Further, the lack of a significant direct reduction of PLE severity post-menarche, may suggest an increased role for other interacting psychosis lability factors during this critical developmental period.

Assessing Pharmacokinetic Correlates of Escitalopram-Related Adverse Drug Reactions.

BACKGROUND: To assess the pharmacokinetic correlates of reported adverse drug reactions (ADRs) under antidepressant treatment with escitalopram (ESC) using a large therapeutic drug monitoring database. METHODS: A large naturalistic sample of inpatients and outpatients prescribed ESC was analyzed. ADRs were classified using the Udvalg for Kliniske Undersogelser side effect rating scale. We compared ESC-treated patients with (n = 35) and without ADRs (n = 273) using ESC plasma concentrations as the primary outcome. We also compared ADR rates in the 2 groups based on 2 cut-off ESC levels reflecting the recommended upper thresholds of the therapeutic reference range of 80 ng/mL, suggested by the consensus therapeutic drug monitoring guidelines, and 40 ng/mL, based on recent meta-analysis data. The effects of age, sex, smoking, daily ESC dose, plasma concentrations, and concentrations corrected for daily dose were included in a binary logistic regression model to predict ADRs. RESULTS: No differences in clinical, demographic, or pharmacokinetic parameters were observed between patients with and without ADRs ( P > 0.05). Patients with ESC-related ADRs were more frequently diagnosed with psychotic disorders than those without (25% vs. 7.1%, P = 0.004). None of the variables was associated with ADR risk. Overall, ADR rates were not significantly different in patients above versus below thresholds of ESC concentrations (ESC concentrations >40 [n = 59] vs. ≤40 ng/mL [n = 249] and >80 [n = 8] vs. ≤80 ng/mL [n = 300]; P = 0.56 and P = 1.0, respectively). CONCLUSIONS: No distinct pharmacokinetic patterns underlying ESC-associated ADRs were observed. Further studies with more specific assessments of ADRs in larger cohorts are required to better identify potential underlying patterns.

A whole-brain neuromark resting-state fMRI analysis of first-episode and early psychosis: Evidence of aberrant cortical-subcortical-cerebellar functional circuitry.

Psychosis (including symptoms of delusions, hallucinations, and disorganized conduct/speech) is a main feature of schizophrenia and is frequently present in other major psychiatric illnesses. Studies in individuals with first-episode (FEP) and early psychosis (EP) have the potential to interpret aberrant connectivity associated with psychosis during a period with minimal influence from medication and other confounds. The current study uses a data-driven whole-brain approach to examine patterns of aberrant functional network connectivity (FNC) in a multi-site dataset comprising resting-state functional magnetic resonance images (rs-fMRI) from 117 individuals with FEP or EP and 130 individuals without a psychiatric disorder, as controls. Accounting for age, sex, race, head motion, and multiple imaging sites, differences in FNC were identified between psychosis and control participants in cortical (namely the inferior frontal gyrus, superior medial frontal gyrus, postcentral gyrus, supplementary motor area, posterior cingulate cortex, and superior and middle temporal gyri), subcortical (the caudate, thalamus, subthalamus, and hippocampus), and cerebellar regions. The prominent pattern of reduced cerebellar connectivity in psychosis is especially noteworthy, as most studies focus on cortical and subcortical regions, neglecting the cerebellum. The dysconnectivity reported here may indicate disruptions in cortical-subcortical-cerebellar circuitry involved in rudimentary cognitive functions which may serve as reliable correlates of psychosis.