Real-time drug testing of paediatric diffuse midline glioma to support clinical decision making: The Zurich DIPG/DMG centre experience.

Background: Children diagnosed with diffuse midline gliomas (DMG) have an extremely poor overall survival: 9-12 months from diagnosis with currently no curative treatment options. Given DMG molecular heterogeneity, surgical biopsies are needed for molecular profiling and as part of enrolment into molecular-based and precision medicine type clinical interventions. In this study, we describe the results of real time profiling and drug testing at the diffuse intrinsic pontine glioma/DMG Research Centre at University Children's Hospital Zurich.

Whole-spine dynamic magnetic resonance study of contortionists: anatomy and pathology.

Object: Whole-spine magnetic resonance (MR) images were obtained using a cylindrical 3-T MR imaging system in 5 contortionists to assess the pathological changes possibly associated with the practice of contortion. Whole-spine dynamic MR images were obtained using a 1-T open MR imaging system in 2 of these contortionists with the purpose of defining the range of motion (ROM) achieved during extreme contortion. The range of spinal motion in this unique population was then quantified.

Predicting recovery from episodes of major depression.

Background: This study examined psychosocial functioning as a predictor of recovery from episodes of unipolar major depression.

Methods: 231 subjects diagnosed with major depressive disorder according to Research Diagnostic Criteria were prospectively followed for up to 20 years as part of the NIMH Collaborative Depression Study. The association between psychosocial functioning and recovery from episodes of unipolar major depression was analyzed with a mixed-effects logistic regression model which controlled for cumulative morbidity, defined as the amount of time ill with major depression during prospective follow-up.

The naturalistic course of unipolar major depression in the absence of somatic therapy.

The goal of the study was to describe the naturalistic course of unipolar major depression in subjects not receiving somatic therapy for their depressive illness. Affectively ill individuals were recruited into the Collaborative Depression Study and followed prospectively for up to 15 years. One hundred thirty subjects who recovered from their intake episode of major depression subsequently experienced a recurrence that went untreated for at least 4 weeks following onset of the recurrence.

Sertraline treatment of co-occurring alcohol dependence and major depression.

Background: Major depressive disorder occurs commonly in association with alcohol dependence, both in clinical samples and in the community. Efforts to treat major depressive disorder in alcoholics with antidepressants have yielded mixed results. This multicenter, double-blind, placebo-controlled trial of sertraline was designed to address many of the potential methodological shortcomings of studies of co-occurring disorders.

Long-term use of benzodiazepines in participants with comorbid anxiety and alcohol use disorders.

Background: Although the only widely accepted role for benzodiazepines in alcohol dependence is the treatment of withdrawal syndromes, they are frequently prescribed outside of this clinical setting. There is little empirical evidence to guide the rational use of benzodiazepines in the common clinical situation where anxiety disorders are comorbid with alcohol use disorders (AUD). Since January 1989, the Harvard Anxiety Research Program has naturalistically monitored the prospective clinical course of people with anxiety disorders, some of whom had a history of AUD.

Tachyphylaxis in unipolar major depressive disorder.

Background: Major depressive disorder is usually a recurring illness, and maintenance treatment is used to forestall or prevent recurrent episodes of depression. This study describes recurrence of major depression despite maintenance pharmacotherapy, termed tachyphylaxis.

Method: The study sample consisted of 103 subjects who participated in the NIMH Collaborative Depression Study, a multicenter longitudinal observational study of the mood disorders.

Psychosocial impairment and recurrence of major depression.

Major depressive disorder is often marked by multiple recurrences. Unfortunately, it is difficult to predict specifically which patients will suffer a recurrence. This study examined whether psychosocial impairment is a risk factor for recurrence.

Motivational enhancement and coping skills training for cocaine abusers: effects on substance use outcomes.

Aims: This clinical trial investigated effects of motivational enhancement treatment (MET) and group coping-skills training (CST) tailored for cocaine dependence. Effects of MET were hypothesized to be greater with CST and for less motivated patients.

Design And Interventions: A 2 x 2 design investigated two individual sessions of MET compared to meditation-relaxation (MRT), followed by four group sessions of CST versus drug education (ED), as daily adjuncts to intensive treatment.

Association of a long-chain fatty acid-CoA ligase 4 gene polymorphism with depression and with enhanced niacin-induced dermal erythema.

Hypotheses about relationships between changes in membrane lipids and mental illness have focused primarily on three long-chain polyunsaturated fatty acids: arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Membrane deficiencies of these fatty acids have been reported in schizophrenia (AA, EPA, and DHA) and in depression (EPA and DHA). Long-chain fatty acid-CoA ligase type 4 (FACL4; MIM 300157) is a key enzyme involved in the metabolism of AA, EPA, and DHA.

The course of depression in elderly patients.

Objective: Studies on the course of major depressive disorder (MDD) among elderly persons are limited to short periods of follow-up, seldom provide comparisons with younger cohorts, and raise other methodological concerns.

Methods: Utilizing 15 years of prospective data from the NIMH Collaborative Depression Study, the authors examined the index episode of MDD and the time until first observed recurrence in those who recovered for subjects in four age-groups defined by age at intake: 17-30, 31-50, 51-64, and 65-79 years. Assessments were conducted every 6 months for 5 years and annually thereafter.

Unipolar mania over the course of a 20-year follow-up study.

Objective: Using data from a longitudinal study of the mood disorders, the investigators address the phenomenon of unipolar mania.

Method: Subjects diagnosed as having Research Diagnostic Criteria mania at intake into the study were prospectively followed for up to 20 years.

Results: Twenty-seven subjects had the diagnosis of unipolar mania at the time they entered the study and had no history of major depression before enrolling in the study.

Alleles of a functional serotonin transporter promoter polymorphism are associated with major depression in alcoholics.

Background: Serotonergic neurotransmission has been implicated in the pathogenesis of both alcohol dependence and mood disorders and may therefore be important in understanding the pathophysiology of comorbid alcohol dependence and major depression. Studies of the association of these disorders with a functional polymorphism in the promoter region of the gene encoding the serotonin transporter protein (locus SLC6A4) have yielded inconsistent results. Because the convergence of these disorders may provide a refined phenotype, we examined the association of serotonin (5-HT) transporter linked polymorphic region (5-HTTLPR) alleles to comorbid alcohol dependence and major depression.

The long-term course of rapid-cycling bipolar disorder.

Background: Rapid cycling among patients with bipolar affective disorders is important because of its implications for long-term prognosis and for the use of antidepressants. To our knowledge, no prospective study has, as yet, described the course of this phenomenon beyond 5 years.

Methods: From 345 patients with bipolar I or bipolar II disorder followed up for a mean (SD) of 13.

A 20-year longitudinal observational study of somatic antidepressant treatment effectiveness.

Objective: This observational study examined the effectiveness of somatic antidepressant treatments as administered in the community.

Method: The study group consisted of 285 subjects with an intake diagnosis of major depressive disorder who had entered the National Institute of Mental Health Collaborative Depression Study as early as 1978, had at least one additional affective episode, and had been followed for up to 20 years, as recently as 1999. The characteristics that distinguished subjects receiving various levels of somatic antidepressant treatment were accounted for in what was called a propensity for treatment intensity model.

Negative mood, depressive symptoms, and major depression after smoking cessation treatment in smokers with a history of major depressive disorder.

Negative mood, depressive symptoms, and major depressive episodes (MDEs) were examined in 179 smokers with a history of major depression in a trial comparing standard smoking cessation treatment to treatment incorporating cognitive-behavioral therapy for depression (CBT-D). Early lapses were associated with relatively large increases in negative mood on quit date. Mood improved in the 2 weeks after quit date among those returning to regular smoking but not among those smoking moderately.