Management of neuropsychiatric symptoms in adults treated with elexacaftor/tezacaftor/ivacaftor.

INTRODUCTION: Reports of neuropsychiatric symptoms proximal to cystic fibrosis transmembrane conductance regulator (CFTR) modulator initiation are emerging, but their prevalence and management remain poorly characterized. METHODS: Retrospective chart review was used to categorize symptom trajectories of all adults at a single CF Center who initiated elexacaftor/tezacaftor/ivacaftor (ETI) before March 2022 and subsequently had ≥1 outpatient visit with the consulting CF psychiatrist. For those who developed neuropsychiatric symptoms probably related to ETI and modified treatment in response, the strategy resulting in greatest improvement with acceptable physical course and tolerability was identified. Ratings were made by a psychiatrist not involved in clinical care. RESULTS: Of 148 adults initiating ETI, 31 were psychiatrically evaluated, 16 of whom developed new/worsening and unexpected neuropsychiatric symptoms probably related to ETI, including neurocognitive (word finding, brain fog, memory, attention/concentration), insomnia, depression, anxiety, fatigue/low energy, mania/hypomania, other distress. This group had higher maximum lifetime Generalized Anxiety Disorder-7 scores (14.42 ± 0.96; p = 0.05) than those with improved, unchanged, or worsening/possibly related symptoms (N = 15; 9.9 ± 1.82). Treatment strategies resulting in much/very much improvement included pharmacologic interventions, psychotherapy, and dose reduction/discontinuing ETI. CONCLUSIONS: Although many people initiating ETI experience improved physical and mental health and quality of life, a subset report worsening neurocognition, mood, and anxiety. As novel therapies are developed, ascertaining and evaluating neuropsychiatric symptoms in clinical and research settings is advisable. Larger studies are needed to characterize prevalence, course, and risk factors (e.g., age, gender, clinical status, pharmacokinetics/pharmacogenomics, drug-drug interactions) for neuropsychiatric adverse events related to CFTR modulators and guide effective management.

Examining the impact of ADHD polygenic risk scores on ADHD and associated outcomes: A systematic review and meta-analysis.

Early identification of attention-deficit/hyperactivity disorder (ADHD) is critical for mitigating the many negative functional outcomes associated with its diagnosis. Because of the strong genetic basis of ADHD, the use of polygenic risk scores (PRS) could potentially aid in the early identification of ADHD and associated outcomes. Therefore, a systematic search of the literature on the association between ADHD and PRS in pediatric populations was conducted. All articles were screened for a priori inclusion and exclusion criteria, and, after careful review, 33 studies were included in our systematic review and 16 studies with extractable data were included in our meta-analysis. The results of the review were categorized into three common themes: the associations between ADHD-PRS with 1) the diagnosis of ADHD and ADHD symptoms 2) comorbid psychopathology and 3) cognitive and educational outcomes. Higher ADHD-PRS were associated with increased odds of having a diagnosis (OR = 1.37; p<0.001) and more symptoms of ADHD (ß = 0.06; p<0.001). While ADHD-PRS were associated with a persistent diagnostic trajectory over time in the systematic review, the meta-analysis did not confirm these findings (OR = 1.09; p = 0.62). Findings showed that ADHD-PRS were associated with increased odds for comorbid psychopathology such as anxiety/depression (OR = 1.16; p<0.001) and irritability/emotional dysregulation (OR = 1.14; p<0.001). Finally, while the systematic review showed that ADHD-PRS were associated with a variety of negative cognitive outcomes, the meta-analysis showed no significant association (ß = 0.08; p = 0.07). Our review of the available literature suggests that ADHD-PRS, together with risk factors, may contribute to the early identification of children with suspected ADHD and associated disorders.

A Child Psychiatry Perspective on Encopresis.

Fecal incontinence, known as encopresis, is the repetitive, intentional or unintentional passage of stool in inappropriate places in children who are developmentally four years old or older. Incontinence can have a chronic course and is associated with emotional distress and a substantial negative impact on quality of life. We review how a medical and behavioral health multidisciplinary approach provides the optimal clinical care for this condition, and we discuss how the unique skill set of the child psychiatrist may address the complex family dynamics and psychiatric comorbidities which may be preventing remission from this condition. Identifying and understanding these factors is essential in developing a comprehensive and effective treatment plan.

Brain Imaging in New Onset Psychiatric Presentations.

We report two cases of patients who presented with psychiatric symptoms and were found to have brain changes on magnetic resonance imaging. In the first case, a 19-year-old man presented with erratic behavior and odd, paranoid ideas. Imaging of the brain revealed a focus of high FLAIR signal involving the left globus pallidus. The second case was a 21-year-old woman who presented with irritability, racing thoughts, and suicidal ideation. Brain imaging revealed nodules of heterotopic grey matter in the right inferior frontal white matter and foci of subcortical heterotopia with thickening of the adjacent cortex. Both patients received psychotropic medications and showed improvement of their symptoms. Integrating neuroimaging in the evaluation of new onset or atypical psychiatric presentations might be of value in specific cases. It is important to develop clear guidelines for the use of imaging modalities in clinical psychiatric practice.

Suicidality among Lebanese adolescents: Prevalence, predictors and service utilization.

Suicide and self-harm in young people is a global public health issue, although epidemiological evidence remains scant in many parts of the world. The aims of the present study are to describe the prevalence, comorbidity patterns, and the clinical and demographic correlates of suicidality among a representative sample of adolescents from Beirut, Lebanon. We recruited 510 adolescents aged 11-17 and one of their parents/legal guardians using a multistage random cluster design. The validated Arabic version of the Development and Well-Being Assessment (DAWBA) was administered independently to the parent/legal guardian, and adolescents, who also self-completed the Strengths and Difficulties Questionnaire (SDQ), and the Peer-Relations Questionnaire (PRQ). The parent/legal guardian also completed the SDQ and provided demographic and clinical information. A total of 22 adolescents (4.3%) have experienced suicidal ideation or attempt. Correlates of suicidality were female gender, alcohol use in the past 4 weeks, lifetime exposure to a stressful life event, suffering from a major depressive disorder and having bipolar disorder within the last 4 weeks. Only 1 suicidal participant reported ever seeking professional mental health help. Our findings highlight an alarming treatment gap in Lebanese adolescents experiencing suicidality. Future studies should aim at investigating barriers to care and at developing community-based interventions to improve access to care.

Characteristics and dispositional determinants of psychiatric emergencies in a University Hospital in Beirut.

Mental health problems are common in Lebanon, and so are psychiatric emergencies. In order to show the characteristics of psychiatric emergencies in Lebanon along with their dispositional determinants, we conducted this retrospective, single-center, chart-review study of patients who presented to the Emergency Department between July 1, 2016 until December 31, 2016 and required an official psychiatrist consultation. Our sample included 195 patients of all age groups. The most common diagnosis was depression (75 patients) followed by anxiety (61 patients). 107 patients (54.8%) required admission for adequate treatment; however only 72 (67.3%) of those were actually admitted, and the rest (32.7%) left the hospital against medical advice. Increased hospital admission was associated with being a female (OR = 3.042), having family history of psychiatric disease (OR = 2.040) and having suicidal ideations (OR = 12.949). In a country that has inadequate health coverage, financial coverage can also be a determining factor in whether or not patients get the admission they need.

Case series: Salvia divinorum as a potential addictive hallucinogen.

BACKGROUND AND OBJECTIVE: Recreational use of salvia divinorum (salvia), a potent, naturally occurring hallucinogen, is on the rise internationally. Despite the paucity of information about its long-term health effects, salvia is readily available and generally portrayed as a safe non-addictive substance. METHODS AND RESULTS: We report on two patients who presented with an enduring and pervasive pattern of salvia use. DISCUSSION AND CONCLUSIONS: Evaluating patients for salvia use during clinical assessment is strongly encouraged, especially among young polysubstance users. SCIENTIFIC SIGNIFICANCE: Clinicians should be mindful of the multifaceted psychiatric effects of salvia, including the potential for a use disorder. (Am J Addict 2018;27:163-165).