Brain structural connectomic topology predicts medication response in youth with bipolar disorder: A randomized clinical trial.

Background: Response to pharmacotherapy varies considerably among youths with bipolar disorder (BD) and is poorly predicted by clinical or demographic features. It can take several weeks to determine whether medication for BD is clinically effective. Although neuroimaging biomarkers are promising predictors, few studies examined the predictive value of the brain connectomic topology.

Cognitive, Family, and Quality-of-Life Characteristics of Youth with Depression Associated with Bipolar Disorder.

Depression associated with bipolar disorder (BD) is more common compared to mania. Cognitive, family, and quality-of-life (QOL) factors associated with pediatric bipolar depression are understudied. The goal of this study was to evaluate cognitive, family environmental, and QOL characteristics of youth with bipolar depression.

Deficits in sustained attention in adolescents with bipolar disorder during their first manic episode.

Objectives: Evaluate differences in sustained attention (SAT) and associated neurofunctional profiles between bipolar disorder type I (BD), attention-deficit/hyperactivity disorder (ADHD), and healthy comparison (HC) youth.

Methods: Adolescent participants, aged 12-17 years, with BD (n = 30) and ADHD (n = 28) and HC adolescents (n = 26) underwent structural and functional magnetic resonance imaging (fMRI) while completing a modified Continuous Performance Task-Identical Pairs task. Attentional load was modifying in this task using three levels of image distortion (0 %, 25 % and 50 % image distortion).

Morphological abnormalities in youth with bipolar disorder and their relationship to clinical characteristics.

Objectives: To characterize the neuroanatomy of BD in youth and its correlation to clinical characteristics.

Methods: The current study includes a sample of 105 unmedicated youth with first-episode BD, aged between 10.1 and 17.

A Double-Blind Placebo-Controlled Pilot Study of Topiramate in Manic Adolescents Treated with Olanzapine.

To conduct a pilot study to examine topiramate for the treatment of weight gain associated with olanzapine in manic adolescents with bipolar disorder. We conducted a 12-week double-blind randomized placebo-controlled pilot study of topiramate (300-400 mg/day) versus placebo in manic youth (ages 10-18 years) with bipolar disorder who were treated with olanzapine (10-20 mg/day). The primary outcome measure was gender- and weight-normed change in body mass index (BMI z-score).

Brain functional activation and first mood episode in youth at risk for bipolar disorder.

Background: In order to identify biomarkers of prodromal mood disorders, we examined functional brain activation in children and adolescent at familial risk for bipolar disorder.

Methods: Offspring of parents with bipolar I disorder (at-risk youth; N = 115, mean ± SD age: 13.6 ± 2.

Effects of short-term quetiapine and lithium therapy for acute manic or mixed episodes on the limbic system and emotion regulation circuitry in youth with bipolar disorder.

Disruptions in the limbic system, and in emotion regulation circuitry that supports affect modulation, have been reported during acute manic episodes of bipolar disorder (BD). The impact of pharmacological treatment on these deficits, especially in youth, remains poorly characterized. 107 youths with acute manic or mixed episodes of bipolar I disorder and 60 group-matched healthy controls were recruited.

Changes in the structural brain connectome over the course of a nonrandomized clinical trial for acute mania.

Unlabelled: Disrupted topological organization of brain functional networks has been widely reported in bipolar disorder. However, the potential clinical implications of structural connectome abnormalities have not been systematically investigated. The present study included 109 unmedicated subjects with acute mania who were assigned to 8 weeks of treatment with quetiapine or lithium and 60 healthy controls.

Brain morphometric features predict medication response in youth with bipolar disorder: a prospective randomized clinical trial.

Background: Identification of treatment-specific predictors of drug therapies for bipolar disorder (BD) is important because only about half of individuals respond to any specific medication. However, medication response in pediatric BD is variable and not well predicted by clinical characteristics.

Methods: A total of 121 youth with early course BD (acute manic/mixed episode) were prospectively recruited and randomized to 6 weeks of double-blind treatment with quetiapine ( = 71) or lithium ( = 50).

Pretreatment Alterations and Acute Medication Treatment Effects on Brain Task-Related Functional Connectivity in Youth With Bipolar Disorder: A Neuroimaging Randomized Clinical Trial.

Objective: Disruptions in cognition are a clinically significant feature of bipolar disorder (BD). The effects of different treatments on these deficits and the brain systems that support them remain to be established.

Method: A continuous performance test was administered to 55 healthy controls and 71 acutely ill youths with mixed/manic BD to assess vigilance and working memory during task-based functional magnetic resonance imaging studies.

A Randomized, Double-Blind, Controlled Trial of Lithium Versus Quetiapine for the Treatment of Acute Mania in Youth with Early Course Bipolar Disorder.

To compare the efficacy and tolerability of lithium versus quetiapine for the treatment of manic or mixed episodes in youths with early course bipolar I disorder. Six-week, randomized, double-blind clinical trial of lithium versus quetiapine for the treatment of adolescents with acute manic/mixed episode. Target dose of quetiapine dose was adjusted to a target dose of 400-600 mg and target serum level for lithium was 1.

N-acetylcysteine for depression and glutamate changes in the left prefrontal cortex in adolescents and young adults at risk for bipolar disorder: A pilot study.

Aims: To investigate the mechanism of action of N-acetylcysteine (NAC) in depressive symptoms in young individuals at familial risk for bipolar disorder.

Methods: We conducted an 8-week open label clinical trial of NAC 2400 mg/days in 15-24 years old depressed offspring of a bipolar I disorder parent, with baseline and endpoint proton magnetic resonance spectroscopy acquired within the left ventrolateral prefrontal cortex (VLPFC).

Results: Nine participants were enrolled and finished the study.

Changes in the brain structural connectome after a prospective randomized clinical trial of lithium and quetiapine treatment in youth with bipolar disorder.

The goals of the current study were to determine whether topological organization of brain structural networks is altered in youth with bipolar disorder, whether such alterations predict treatment outcomes, and whether they are normalized by treatment. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. High-resolution MRI images were collected from children and adolescents with bipolar disorder who were experiencing a mixed or manic episode (n = 100) and healthy youth (n = 63).

Predicting Post-Concussion Symptom Recovery in Adolescents Using a Novel Artificial Intelligence.

This pilot study explores the possibility of predicting post-concussion symptom recovery at one week post-injury using only objective diffusion tensor imaging (DTI) data inputs to a novel artificial intelligence (AI) system composed of Genetic Fuzzy Trees (GFT). Forty-three adolescents age 11 to 16 years with either mild traumatic brain injury or traumatic orthopedic injury were enrolled on presentation to the emergency department. Participants received a DTI scan three days post-injury, and their symptoms were assessed by the Post-Concussion Symptom Scale (PCSS) at 6 h and one week post-injury.

Variation in rostral anterior cingulate functional connectivity with amygdala and caudate during first manic episode distinguish bipolar young adults who do not remit following treatment.

Objectives: Altered activity in the ventrolateral prefrontal and anterior cingulate cortices, as well as subcortical and amygdala projection sites, was previously reported during a first manic episode in youth with bipolar disorder and observed to be associated with treatment response. To extend these findings, we investigated functional connectivity among these regions in first-episode manic participants who remitted after 8 weeks of treatment compared to those who did not.

Methods: Forty-two participants with bipolar disorder (60% female) during their first manic episode were recruited and received 8 weeks of treatment.

Association between poor tolerability of antidepressant treatment and brain functional activation in youth at risk for bipolar disorder.

Objective: To investigate whether poor antidepressant tolerability is associated with functional brain changes in children and adolescents of parents with bipolar I disorder (at-risk youth).

Methods: Seventy-three at-risk youth (ages 9-20 years old) who participated in a prospective study and had an available baseline functional magnetic resonance imaging (fMRI) scan were included. Research records were reviewed for the incidence of adverse reactions related to antidepressant exposure during follow-up.

Medication exposure and predictors of first mood episode in offspring of parents with bipolar disorder: a prospective study.

Objectives: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder.

Methods: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74).

Asenapine in the Treatment of Bipolar Depression.

Objectives: Asenapine, a potent serotonin 7 (5-HT) receptor antagonist, was examined for efficacy as an antidepressant in depressed bipolar subjects. It was predicted that subjects with the genetic variant of the short form of the serotonin transporter (5HTTR) would be more likely to respond.

Experimental Design: A subset of patients participating in a randomized, placebo-controlled study of the efficacy of asenapine in bipolar I depression also underwent genetic testing for the 5HTTR.

Individual prediction of symptomatic converters in youth offspring of bipolar parents using proton magnetic resonance spectroscopy.

Children of individuals with bipolar disorder (bipolar offspring) are at increased risk for developing mood disorders, but strategies to predict mood episodes are unavailable. In this study, we used support vector machine (SVM) to characterize the potential of proton magnetic resonance spectroscopy (H-MRS) in predicting the first mood episode in youth bipolar offspring. From a longitudinal neuroimaging study, 19 at-risk youth who developed their first mood episode (converters), and 19 without mood episodes during follow-up (non-converters) were selected and matched for age, sex and follow-up time.

Efficacy and Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression-TRANSFORM-3.

Background: Elderly patients with major depression have a poorer prognosis, are less responsive to treatment, and show greater functional decline compared with younger patients, highlighting the need for effective treatment.

Methods: This phase 3 double-blind study randomized patients with treatment-resistant depression (TRD) ≥65 years (1:1) to flexibly dosed esketamine nasal spray and new oral antidepressant (esketamine/antidepressant) or new oral antidepressant and placebo nasal spray (antidepressant/placebo). The primary endpoint was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to day 28.

Neurophysiological effects of multiple mood episodes in bipolar disorder.

Objectives: Bipolar disorder is marked by progressive symptomatic changes, which have been linked with episode-related structural findings-particularly in the prefrontal cortex. However, few studies have examined neurofunctional and neurochemical effects of disease burden. In this study, we compared first- and multi-episode bipolar individuals.

Effect of lisdexamfetamine on emotional network brain dysfunction in binge eating disorder.

We examined the effects of lisdexamfetamine (LDX) treatment on ventral prefrontal cortex (VPFC) and striatal brain activation in binge eating disorder (BED). We hypothesized that participants with BED have an abnormal brain response to palatable food cues, and that VPFC and striatal regions would respond to such cues after LDX treatment. Twenty women with moderate to severe BED consented to a 12-week, open-label trial of LDX with fMRI before and after treatment.

Longitudinal proton spectroscopy study of the prefrontal cortex in youth at risk for bipolar disorder before and after their first mood episode.

Objectives: To investigate neurochemical abnormalities in the left and right ventrolateral prefrontal cortex (VLPFC) and anterior cingulate cortex (ACC) of youth at risk for bipolar disorder using proton magnetic resonance spectroscopy before and after their first mood episode.

Methods: Children and adolescents offspring of parents with bipolar I disorder (at-risk group, n = 117) and matched healthy controls (HC group, n = 61) were recruited at the University of Cincinnati. At-risk subjects had no lifetime major mood and psychotic disorders at baseline, and were followed up every 4 months to monitor for development of a major depressive, manic, hypomanic, or mixed mood episode.

Capacity to provide informed consent among adults with bipolar disorder.

Background: Identifying correlates of capacity to provide informed consent among individuals with bipolar disorder is essential for patient protection. As part of a clinical trial involving approved, standard treatments, we investigated relationships between clinical characteristics and capacity to provide informed consent in adults with bipolar disorder using the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). After administering the MacCAT-CR, continuing participants in the trial were capable of and provided informed consent.