Enigmatic missense mutations can cause disease via creation of nuclear export signals.

Disease-causing missense mutations that occur within structurally and functionally unannotated protein regions can guide researchers to new mechanisms of protein regulation and dysfunction. Here, we report that the thrombocytopenia-, myelodysplastic syndromes-, and leukemia-associated P214L mutation in the transcriptional regulator ETV6 creates an XPO1-dependent nuclear export signal to cause protein mislocalization. Strategies to disrupt XPO1 activity fully restore ETV6 P214L protein nuclear localization and transcription regulation activity.

Impulsive aggression with irritability and responsive to divalproex: a pediatric bipolar spectrum disorder phenotype?

Background: The objective of this retrospective chart review was to evaluate the phenomenology and response to divalproex in a sub-population of children admitted to an inpatient setting with severe impairing symptoms of irritability and aggression. In addition, we examined whether the symptomatology of this group was consistent with a pediatric divalproex-responsive bipolar spectrum disorder.

Methods: The charts of 46 child and adolescent patients with prominent impulsive aggression with irritability admitted to a crisis stabilization center were assessed retrospectively.

Treatment challenges and safety considerations for antipsychotic use in children and adolescents with psychoses.

With increased prescribing of psychotropic medications to children and adolescents, more attention should be given to the safety and tolerability of these drugs in this population. Compared with adults, children are especially vulnerable to adverse effects, including extrapyramidal symptoms (EPS), sedation, weight gain, and prolactin elevation. The prevalence of EPS is much higher in children treated with conventional antipsychotics than in those given atypical antipsychotics.

Long-term safety, tolerability, and clinical efficacy of quetiapine in adolescents: an open-label extension trial.

Quetiapine is a novel, atypical antipsychotic agent that has been shown to provide long-term efficacy without serious adverse effects in adults. This is the first study of the extended use of quetiapine in adolescents. Five boys and 5 girls, ages 12.

Transdermal nicotine and haloperidol in Tourette's disorder: a double-blind placebo-controlled study.

Background: Preclinical animal and open-trial clinical trials using nicotine gum and the transdermal nicotine patch found that treatment with nicotine potentiates the effects of neuroleptics in reducing the dyskinetic symptoms of Tourette's disorder. We sought to verify and expand these findings in a prospective double-blind placebo-controlled trial.

Method: Seventy patients with DSM-IV Tourette's disorder were treated with either transdermal nicotine (7 mg/24 hours) or placebo patches in a 33-day, randomized, double-blind study.

Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial.

Objective: To determine the safety and efficacy of fluvoxamine for the treatment of children and adolescents with obsessive-compulsive disorder (OCD) with a double-blind, placebo-controlled, multicenter study.

Method: Subjects, aged 8 to 17 years, meeting DSM-III-R criteria for OCD were recruited from July 1991 to August 1994. After a 7- to 14-day single-blind, placebo washout/screening period, subjects were randomly assigned to fluvoxamine 50 to 200 mg/day or placebo for 10 weeks.

Pharmacokinetics, tolerability, and clinical effectiveness of quetiapine fumarate: an open-label trial in adolescents with psychotic disorders.

Background: This is the first investigation of the pharmacokinetics, tolerability, and efficacy of quetiapine fumarate in adolescents with chronic or intermittent psychotic disorders.

Method: Ten patients with DSM-IV chronic or intermittent psychotic disorders (ages 12.3 through 15.

Twelve-month outcome in bipolar patients with and without personality disorders.

Background: We studied the 12-month course of illness after hospitalization for patients with a DSM-III-R diagnosis of bipolar disorder, manic or mixed episode, to identify the impact of a co-occurring personality disorder on measures of outcome.

Method: Fifty-nine patients with bipolar disorder hospitalized for the treatment of a manic or mixed episode were recruited. Diagnostic, symptomatic, and functional evaluations were obtained at the index hospitalization.

Lower dosages of phentermine-fenfluramine given in the afternoon: five cases with significant weight loss.

Phentermine and fenfluramine are widely used in the treatment of obesity. Despite the fact that primary pulmonary hypertension and mitral valve insufficiency have been associated with fenfluramine use, many of these patients need medication to achieve weight loss. Small degrees of weight loss have been shown to significantly improve obesity-related medical conditions such as hypertension, hypercholesterolemia, and noninsulin-dependent diabetes mellitus.

The psychiatric diagnoses of twenty-two adolescents who have sexually molested other children.

The purpose of this study was to assess the prevalence of specific psychiatric disorders in adolescents who have sexually molested other children. Twenty-two adolescent males (aged 13 to 17 years) who sexually molested a child at least once were evaluated with structured clinical interviews for DSM-III-R axis I disorders. All subjects met lifetime DSM-III-R criteria for pedophilia (with the exception of the age requirement), 21 (95%) for two or more paraphilias, 18 (82%) for a mood disorder (12 [55%] for a bipolar disorder), 12 (55%) for an anxiety disorder, 11 (50%) for a substance use disorder, and 12 (55%) for an impulse-control disorder.

Newer antidepressants. Beyond selective serotonin reuptake inhibitor antidepressants.

This article outlines the use of alternative agents to TCAs and SSRIs. Features of the more commonly used alternative antidepressant agents are outlined. In addition, antidepressant agents that are currently either under development or used in other countries are indicated for completeness because it seems likely that many of these will be introduced in the United States within the next few years.

An adolescent male with multiple paraphilias successfully treated with fluoxetine.

Little is known about the psychiatric diagnosis and treatment of adolescents who sexually offend. We therefore describe an adolescent sex offender who met DSM-IV criteria for multiple paraphilias (except for the age criterion), bipolar type II disorder, and OCD, whose paraphilic urges and behaviors, depression, and violent obsessions responded to open label fluoxetine after failing to respond to long-term residential treatment. Although only a single and uncontrolled observation, this case suggests that some adolescent sex offenders may in fact have paraphilias, and that paraphilias in adolescents, like those in adults, may respond to serotonin reuptake inhibitors.

Nicotine for the treatment of Tourette's syndrome.

Recent evidence has demonstrated that nicotine may obtund the symptoms of Tourette's syndrome (TS). TS is a neuropsychiatric disorder characterized by motor and vocal tics, obsessions and compulsions, and frequently with impulsivity, distractibility, and visual-motor deficits. While neuroleptics, such as haloperidol, are most effective for treatment of the motor and vocal tics of TS, these medications have many side effects.

Control of oxygen cytotoxicity with allopurinol and superoxide dismutase: a canine model of global myocardial ischemia-reperfusion injury.

The purpose of this study was to assess the effects of acute pharmacological interventions on the ischemia-reperfusion damage in a canine model of hypothermic global myocardial ischemia. Three experimental groups each consisting of seven animals were subjected to 2 h of global ischemia followed by 1 h of reperfusion. Group A (control) used Tyers' iso-osmolar potassium cardioplegia solution; group B received allopurinol (40 mg/kg), 95% intravenously (IV) systemically with 5% added to the final infusion of Tyers' solution.

Phenomenology of adolescent and adult mania in hospitalized patients with bipolar disorder.

Objective: Although available data suggest that bipolar disorder most commonly begins in adolescence, it has often been underrecognized and misdiagnosed in this age group. The authors hypothesized that this might in part be because adolescent mania is phenomenologically different from adult mania. To test this hypothesis, they compared a cohort of adolescents hospitalized for acute mania with a group of hospitalized acutely manic adults.

Personality disorders in first- and multiple-episode mania.

We compared rates of DSM-III-R personality disorders in 33 first-episode and 26 multiple-episode bipolar patients. Patients were evaluated with the patient and personality disorders versions of the Structured Clinical Interview for DSM-III-R. Significantly more multiple-episode patients (65%) met DSM-III-R criteria for a personality disorder than did first-episode patients (33%).

An open study of the effects of sertraline on adolescent major depression.

This open study investigated the effects of sertraline in treating 13 adolescents, ages 12 to 18, who were hospitalized for treatment of a major depressive episode. The sample included 7 adolescents with nonendogenous depression and 6 with endogenous depression, as diagnosed by both Research Diagnostic Criteria (RDC) and Kiddie-SADS-P DSM-III-R endogenous subtype criteria. These patients were followed for an inpatient length of stay ranging from 9 to 38 days (mean 19 days), with later outpatient follow-up for a total of 12 weeks.