Patient-reported outcomes and quality of life in PMM2-CDG.

Patient-reported outcomes (PROs) measure important aspects of disease burden, however they have received limited attention in the care of patients with Congenital Disorders of Glycosylation (CDG). We evaluated the PROs and correlation between clinical disease severity scoring and reported quality of life (QoL) in a PMM2-CDG patient cohort. Twenty-five patients with diagnosis of PMM2-CDG were enrolled as part of the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC) natural history study. Patient- Reported Outcomes Measurement Information System (PROMIS) was completed by caregivers to assess health-related QoL. Clinical disease severity was scored by medical providers using the Nijmegen Progression CDG Rating Scale (NPCRS). The domains such as physical activity, strength impact, upper extremity, physical mobility, and a satisfaction in social roles (peer relationships) were found to be the most affected in the PMM2-CDG population compared to US general population. We found a strong correlation between NPCRS 1 (current functional ability) and three out of ten PROMIS subscales. NPCRS 2 (laboratory and organ function) and NPCRS 3 (neurological involvement) did not correlate with PROMIS. Mental health domains, such as anxiety, were positively correlated with depressive symptoms (r = 0.76, p = 0.004), fatigue (r = 0.67, p = 0.04). Surprisingly, patients with severely affected physical mobility showed low anxiety scores according to PROMIS (inverse correlation, r = -0.74, p = 0.005). Additionally, there was a positive correlation between upper extremity and physical mobility (r = 0.75, p = 002). Here, we found that PROMIS is an informative additional tool to measure CDG disease burden, which could be used as clinical trial outcome measures. The addition of PROMIS to clinical follow-up could help improve the quality of care for PMM2-CDG by facilitating a holistic approach for clinical decision-making. SYNOPSIS: We recommend PROMIS as an informative tool to measure disease burden in PMM2-CDG in addition to traditional CDG disease severity scores.

Factors Associated With Postictal Agitation After Electroconvulsive Therapy.

OBJECTIVE: This study investigated the occurrence of postictal agitation (PA) in patients undergoing an acute series of electroconvulsive therapy (ECT) and further explored patient and treatment variables associated with PA. METHODS: Charts were retrospectively searched for patients undergoing an acute series of ECT. Postictal agitation was identified by the administration of a sedative after ECT. Demographic, diagnostic, medication, and ECT variables that could also be associated with PA were collected and accounted for in statistical analysis. RESULTS: In this population, 22 of 156 patients experienced PA. Associations that reached statistical significance included sex, weight, active substance use disorder, seizure duration (as observed by motor movements), and waking time. Only seizure duration and waking time maintained significance after multivariable analysis. CONCLUSIONS: These data identify clinical factors that could help predict PA. Patients with greater weight, male sex, or an active substance use disorder ought to be carefully monitored for PA, and staff in the recovery suite should be especially vigilant about such patients with longer seizures and waking times.

Correlates to Improvement in Sleep Duration in Acute Mania and Depression.

Objective: To examine sleep duration at admission and discharge and change in sleep duration during hospitalization in patients experiencing a manic episode and compare these parameters to patients hospitalized for major depressive disorder (MDD) during the same time frame. The correlation between sleep duration parameters in those with mania and MDD with length of hospital stay, after accounting for possible confounders, was also examined.Methods: This retrospective study examined patients admitted to an acute care psychiatric unit from 2018 to 2021 with an episode of mania or MDD. Sleep duration was determined based on nursing observer report.Results: The study included 41 patients with mania (32.9 ± 1.7 years) and 38 patients with MDD (32.7 ± 1.8 years). Mania patients had longer hospitalization and received higher antipsychotic and benzodiazepine doses, but fewer hypnotics (all P < .005). No differences were found in sleep duration at admission (P = .109) and discharge (P = .623) in the mania and MDD groups. Change in sleep duration was 1.14 ± 0.27 and 0.37 ± 0.28 hours (P = .05) in the groups, respectively. In those with mania, sleep duration at admission negatively correlated with length of stay (r = -0.033; P = .03). Sleep duration parameters were not correlated with length of stay in patients with MDD.Conclusion: There was a trend toward greater improvement in sleep duration in inpatients with mania versus MDD. Sleep duration at admission correlated with length of hospitalization in patients with mania. Future studies should examine whether attempts to increase sleep duration can improve patient outcomes.Prim Care Companion CNS Disord 2024;26(1):23m03620. Author affiliations are listed at the end of this article.

Are clinical trials for insomnia recruiting real-world patients?

Recent Phase III trials of hypnotic medications that have led to Food and Drug Administration approval have severely restrictive eligibility criteria. One hundred patients referred for insomnia who received a hypnotic medication at a large tertiary referral center were identified. Data were extracted to evaluate whether these patients would be eligible to be included in any of the recent Phase III trials. Of the 100 patients identified, only 3 were eligible. Most were excluded because of a prior or concurrent trial of cognitive behavioral therapy for insomnia. If this criterion were set aside, only 12% would have been eligible to participate. The remaining top reasons for exclusion were medical comorbidities, daytime napping, and sleep apnea. These findings question the generalizability of the regulatory studies and suggest that future trials should enroll patients with less-restrictive criteria to help determine the effectiveness of these medications in real-world settings. CITATION: Golebiowski R, Mansukhani MP, Kolla BP. Are clinical trials for insomnia recruiting real-world patients? J Clin Sleep Med. 2023;19(8):1553-1555.

Association between early childhood sleep difficulties and subsequent psychiatric illness.

STUDY OBJECTIVES: Chronic disruptions to sleep in childhood are associated with increased prevalence of psychiatric disease later in development. When sleep disruptions remit before adolescence, the increased prevalence of psychiatric disease is no longer observed, highlighting the importance of early detection and intervention. Clinicians typically rely on caregivers' reports for diagnosis and management of childhood sleep challenges. We examined whether findings on polysomnogram (PSG) can offer similar insight into childhood sleep difficulties and the risk of subsequent psychiatric illness. METHODS: A cohort was identified of 348 children ages 5 years 11 months and younger with sleep difficulties rising to the level of formal clinical workup. A retrospective review of caregiver-reported sleep concerns, PSG results, and subsequent psychiatric illness was completed. PSG findings were compared to presence of psychiatric illness later in life as well as caregivers' reported concerns. Chi-squared and Fisher's exact tests were completed to evaluate correlations and Cohen's kappa was used to evaluate agreement. RESULTS: With only a few exceptions, comparisons between clinician findings on PSG and subsequent psychiatric diagnoses were statistically nonsignificant. Similarly, the relationship between caregivers' subjective reports about sleep and clinicians' findings on PSG demonstrated only slight to fair agreement, suggesting reported concerns were not predictive of PSG results. CONCLUSIONS: Parental reports of subjective sleep concerns are indicative of different sleep pathologies compared to sleep pathologies detected on PSG. The addition of PSG to caregiver-reported data appears to have limited clinical utility in understanding sleep concerns associated with the risk of subsequent psychiatric illness in young children. CITATION: Pease E, Shekunov J, Savitz ST, et al. Association between early childhood sleep difficulties and subsequent psychiatric illness. J Clin Sleep Med. 2023;19(12):2059-2063.

Antecedents to first episode psychosis and mania: Comparing the initial prodromes of schizophrenia and bipolar disorder in a retrospective population cohort.

OBJECTIVE: We aim to compare the psychiatric antecedents of schizophrenia (SZ) and bipolar disorder (BD). METHODS: Using the Rochester Epidemiology Project, we searched for residents of Olmsted County that had a diagnosis of SZ or BD. We confirmed each case using DSM-5 criteria and obtained the psychiatric antecedents. RESULTS: We identified 205 cases with first episode psychosis or mania (SZ = 131; BD = 74). The mean age at first visit for mental health reasons was 12.3 ± 6.3 years for SZ and 13.9 ± 5.6 years for BD. The duration of the initial prodrome (time from first mental health visit to first episode) was similar for both groups (SZ 8.3 ± 6.2 years vs BD 7.3 ± 5.9 years). We found that SZ and BD have overlapping antecedents, but SZ was more common in males and in foreign born and had more learning deficits before the first episode. BD was more common in white population and had higher rates of depressive and adjustment disorders prior to first episode. BD also had more affective symptoms, nightmares, and panic attacks before the first episode. Both groups had similarly high rates of substance use (SZ 74 % vs BD 74.3 %), prescription of antidepressants (SZ 46.6 % vs BD 55.4 %) and stimulants (SZ 30.5 % vs BD 22.9 %). CONCLUSIONS: The psychiatric antecedents of SZ and BD usually start during adolescence, overlap, and present in unspecific ways. The initial prodromes are more alike than distinct. Further studies are encouraged to continue looking for specific factors that distinguish the antecedents of these two disorders.

Pharmacological Management of Insomnia.

Insomnia is a highly prevalent condition associated with significant morbidity, reduction in quality of life, and increase in healthcare costs, and is a risk factor for multiple physical and mental disorders. The primary treatment modality is cognitive behavioral therapy for insomnia (CBT-I) but this is associated with difficulties with access and higher cost as well as poor response in some patients. Therefore, pharmacotherapy for insomnia is common and hypnotic agents are among the most frequently prescribed medications in the United States. Older medications for insomnia are limited by their side effect burden and narrow therapeutic window. Newer hypnotics, on the other hand, have been shown to have a better safety profile and longer term efficacy. While some studies have shown that long-term hypnotic use is associated with adverse outcomes, the current evidence is equivocal. The decision to treat chronic insomnia disorder with long-term hypnotics should be individualized and balance the potential risks of continuing hypnotic medication use with the risks of untreated persistent insomnia and associated functional limitations. This clinical review discusses the currently available medication options to treat insomnia, their mechanisms of action, dosing, and side effect profiles. This review also provides guidance on long-term management of hypnotics and the use of these medications in the elderly, those with medical comorbidities, and other special populations.

A systematic review of microbiome changes and impact of probiotic supplementation in children and adolescents with neuropsychiatric disorders.

OBJECTIVES: In recent decades, the diagnostic and therapeutic implications of the microbiome changes and the impact of probiotic supplementation have increased rapidly. However, the potential for clinical translation of microbiome research for children and adolescents with psychiatric disorders is unclear. This review examined available evidence related to gut microbiota as well as the impact of probiotic supplementation on psychiatric disorders in the pediatric population reported to date. METHODS: We performed a literature search for the gut microbiota in child and adolescent population (0-18 years old) with mental health disorders from July 1999 through July 2019 in several databases: ClinicalTrials.gov, Ovid EBM Reviews, Ovid Embase, Ovid Medline, Ovid PsycINFO, Scopus, and Web of Science. RESULTS: A total of 7 studies met inclusion criteria consisting of randomized controlled trials and cohort studies that examined various associations between psychiatric disorders and gut microbiota in youth. Six studies examined the effects of various treatment interventions such as probiotic supplementation on microbiota composition and behaviors. One study showed an increase in prosocial behavior in children with Autism Spectrum Disorder (ASD) and an increase in the Lachnospiraceae family following prebiotic supplementation. Another study suggested that prebiotic supplementation increased bifidobacterial populations for ASD and healthy controls. A study evaluating infant supplementation of prebiotics showed both a decreased likelihood of developing Attention Deficit Hyperactivity Disorder (ADHD) or ASD and decreased gut Bifidobacterium. One study did not find significant differences in microbiome composition after micronutrient treatment. CONCLUSION: The main goal of this systematic review was to comprehensively examine and summarize the current evidence focused on the potential effect of the relationship between microbiota gut composition as well as the effects of probiotic supplementation on psychiatric disorders in children and adolescents. This is a relatively new area of research and the number of included studies is limited. More studies are needed to determine whether gut dysbiosis leads to the development and/or contributes to the severity of mental disorders or whether gut dysbiosis is a result of other processes that accompany mental disorders. CLINICAL SIGNIFICANCE: A better understanding of the specific bacteria contributions, gut-brain pathways, and role in pathophysiological mechanisms in neuropsychiatric disorders in the child and adolescent populations can possibly provide alternative tools for a clinical psychiatrist. Moreover, it may ultimately aid the clinician with intervention strategies, or detect populations at risk for developing neuropsychiatric disorders.