The transcription factor PPARα is overexpressed and is associated with a favourable prognosis in IDH-wildtype primary glioblastoma.

AIMS: PPARα agonists are in current clinical use as hypolipidaemic agents and show significant antineoplastic effects in human glioblastoma models. To date however, the expression of PPARα in large-scale glioblastoma datasets has not been examined. We aimed to investigate the expression of the transcription factor PPARα in primary glioblastoma, the relationship between PPARα expression and patients' clinicopathological features and other molecular markers associated with gliomagenesis. METHODS AND RESULTS: With protein immunoblotting techniques and reverse transcription quantitative real-time PCR, PPARα was found to be significantly overexpressed in glioblastoma compared with control brain tissue (P = 0.032 and P = 0.005). PPARA gene expression was found to be enriched in the classical glioblastoma subtype within The Cancer Genome Atlas (TCGA) dataset. Although not associated with overall survival when assessed by immunohistochemistry, cross-validation with the TCGA dataset and multivariate analyses identified PPARA gene expression as an independent prognostic marker for overall survival (P = 0.042). Finally, hierarchical clustering revealed novel, significant associations between high PPARA expression and a putative set of glioblastoma molecular mediators including EMX2, AQP4, and NTRK2. CONCLUSIONS: PPARα is overexpressed in primary glioblastoma and high PPARA expression functions as an independent prognostic marker in the glioblastoma TCGA dataset. Further studies are required to explore genetic associations with high PPARA expression and to analyse the predictive role of PPARα expression in glioblastoma models in response to PPARα agonists.

The Use of Transdermal Therapeutic Systems in Psychiatric Care: A Primer on Patches.

BACKGROUND: Numerous currently available medications that act in the central nervous system can be delivered transdermally. Such medications include cholinesterase inhibitors for dementia, methylphenidate (MPH) for attention-deficit hyperactivity disorder, monoamine oxidase inhibitors (MAOIs) for depression, dopamine agonists for Parkinson disease and restless leg syndrome, and clonidine for attention-deficit hyperactivity disorder and impulse-control disorders. OBJECTIVE: This article aims to review the literature related to transdermal delivery systems from the perspective of clinical practice and research related to their use in the treatment of psychiatric conditions. RESULTS: Most of the currently available transdermal systems have psychotropic properties or utility in the behavioral health arena and, therefore, are of clinical relevance to consultation-liaison psychiatrists or practitioners of psychosomatic medicine. We discuss their efficacy and safety profiles. We provide a table of these agents and their uses. CONCLUSIONS: Transdermal delivery (i.e., patches) for medicines with psychotropic properties allows mental health providers to customize therapy for patients by altering the duration of therapy, minimizing first-pass metabolism and the potential for drug-drug interactions, and decreasing the risk for gastrointestinal irritation.

Strategies for the prescription of psychotropic drugs with black box warnings.

BACKGROUND: The Black Box Warning (BBW) is the Food and Drug Administration's highest level of drug warning. It signifies that a medication has serious (or potentially life-threatening) side effects and is prominently displayed on a medication's package insert. It literally consists of the medication warning and is surrounded by a bold black border. OBJECTIVE: This article aims to review data related to BBWs on psychotropic medications currently used in clinical practice, with special attention to clinical situations and questions relevant to consultation-liaison psychiatrists. RESULTS: We review 3 clinical advisories or BBWs for psychotropic medications (i.e., antidepressant medication and suicidality in the pediatric population, stimulant medication and sudden death in the pediatric population, and antipsychotic medication and increased mortality in the elderly) and discuss the effect they have had on prescribing practices. We provide a table of current BBWs relevant to psychotropic medications. CONCLUSIONS: BBWs can have unintended and far-reaching consequences, albeit with a limited ability to target specific populations and practice patterns. Although it is critical for clinicians to be aware of these serious potential side effects and to inform patients about these warnings, medications with boxed warnings remain Food and Drug Administration-approved and may have critically important therapeutic roles.

Clinical Barriers to Effective Treatment of Eating Disorders and Co-occurring Psychiatric Disorders in Transgendered Individuals.

Eating disorders (EDs) are complex and difficult to treat illnesses that are often chronic and disabling on their own accord or due to comorbidity with other psychiatric conditions. Historically, EDs have been viewed as illnesses of heterosexual, affluent white females. This stereotype increases the likelihood that these disorders will be underrecognized in the lesbian, gay, bisexual, and transgender community, as well as in different gender, socioeconomic, and ethnic populations. Our case report illustrates the clinical difficulties of managing a patient who presented to inpatient treatment with complaints of depression and suicidality, but who also had an active ED and was transgender.

Elevated prolactin levels in male youths treated with risperidone and quetiapine.

The aim of this study was to report on the serum prolactin levels in 70 male youths at a residential treatment center who were treated with either risperidone or quetiapine. This is a cross-sectional retrospective medical chart review of 50 males (mean age, 13.5+/-2.8 years) treated with risperidone (mean dose, 2.4+/-1.6 mg/day) and 20 males (mean age, 13.5+/-2.4 years) treated with quetiapine (mean dose, 317.5+/-238 mg/day). Serum prolactin levels were drawn according to a protocol, after at least 6 weeks of treatment. Prolactin was above the upper limit of normal for 68% of the patients on risperidone and 20% of the patients on quetiapine (chi2 analysis: R>Q; p<0.001). Both risperidone and quetiapine produced dose-related increases in serum prolactin levels (R, r=0.34, p=0.017; Q, r=0.45, p=0.05). No correlation was found between duration of treatment and prolactin levels. Given that hyperprolactinemia secondary to antipsychotic treatment may result in reproductive and growth irregularities, periodic long-term monitoring during treatment with these two atypical antipsychotics (and perhaps others as well) may be warranted.

Schooling students with psychotic disorders.

The term psychosis is generally used to describe the abnormal behaviors of children and adolescents with grossly impaired reality testing. This article discusses evaluation of psychotic symptoms in students and psychosocial school interventions for students with psychosis, including the roles of teachers and school administrators. Psychoeducation provided by clinicians and school staff to enhance coping and cognitive strategies is described.

Plasma methylphenidate concentrations in youths treated with high-dose osmotic release oral system formulation.

BACKGROUND: Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications. OBJECTIVE: We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment. METHODS: Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e.g., measures of blood pressure and heart rate) were also examined. RESULTS: Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5 mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >or=50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs. CONCLUSIONS: High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness.

Neuropsychiatric effects of prescription drug abuse.

Prescription drugs have become a major category of abused substances, and there is evidence that the prevalence of prescription drug abuse may soon overtake that of illicit drugs. Study of prescription drugs has been hampered by vague terminology, since prescription drugs are only separated from other drugs of abuse by social and legal constructs. Reviewed herein is published literature on the abuse of four major categories of abused prescription drugs: sedative-hypnotics, stimulants, anabolic steroids, and anticholinergics. The review emphasizes evidence regarding the effects of these drugs on neural systems. Other abused prescription drugs that fall outside of the major categories are also briefly addressed.