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.

Aberrant brain network topology in youth with a familial risk for bipolar disorder: a task-based fMRI connectome study.

Background: Youth with a family history of bipolar disorder (BD) may be at increased risk for mood disorders and for developing side effects after antidepressant exposure. The neurobiological basis of these risks remains poorly understood. We aimed to identify biomarkers underlying risk by characterizing abnormalities in the brain connectome of symptomatic youth at familial risk for BD.

Aberrant Neurofunctional Responses During Emotional and Attentional Processing Differentiate ADHD Youth With and Without a Family History of Bipolar I Disorder.

Objective: To compare neurofunctional responses in emotional and attentional networks of psychostimulant-free ADHD youth with and without familial risk for bipolar I disorder (BD).

Methods: ADHD youth with (high-risk, HR,  = 48) and without (low-risk, LR,  = 50) a first-degree relative with BD and healthy controls ( = 46) underwent functional magnetic resonance imaging while performing a continuous performance task with emotional distracters. Region-of-interest analyses were performed for bilateral amygdala (AMY), ventrolateral (VLPFC) and dorsolateral (DLPFC) prefrontal cortex, and anterior (ACC) and posterior cingulate cortex (PCC).

Brain network structural connectome abnormalities among youth with attention-deficit/hyperactivity disorder at varying risk for bipolar I disorder: a cross-sectional graph-based magnetic resonance imaging study.

Background: Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent among youth with or at familial risk for bipolar-I disorder (BD-I), and ADHD symptoms commonly precede and may increase the risk for BD-I; however, associated neuropathophysiological mechanisms are not known. In this cross-sectional study, we sought to investigate brain structural network topology among youth with ADHD, with and without familial risk of BD-I.

Methods: We recruited 3 groups of psychostimulant-free youth (aged 10-18 yr), namely youth with ADHD and at least 1 biological parent or sibling with BD-I (high-risk group), youth with ADHD who did not have a first- or second-degree relative with a mood or psychotic disorder (low-risk group) and healthy controls.

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).

Different brain functional network abnormalities between attention-deficit/hyperactivity disorder youth with and without familial risk for bipolar disorder.

Attention-deficit/hyperactivity disorder (ADHD) commonly precedes the initial onset of mania in youth with familial risk for bipolar disorder (BD). Although ADHD youth with and without BD familial risk exhibit different clinical features, associated neuropathophysiological mechanisms remain poorly understood. This study aimed to identify brain functional network abnormalities associated with ADHD in youth with and without familial risk for BD.

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.

Regional microstructural differences in ADHD youth with and without a family history of bipolar I disorder.

Background: Having a first-degree relative with bipolar I disorder (BD) in conjunction with prodromal attention deficit/hyperactivity disorder (ADHD) may represent a unique phenotype that confers greater risk for developing BD than ADHD alone. However, underlying neuropathoetiological mechanisms remain poorly understood. This cross-sectional study compared regional microstructure in psychostimulant-free ADHD youth with ('high-risk', HR) and without ('low-risk', LR) a first-degree relative with BD, and healthy controls (HC).

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.

Symptom Profiles, But Not Prefrontal Neurochemistry, Differentiate ADHD Youth With and Without a Family History of Bipolar I Disorder.

To identify clinical and central features that differentiate ADHD youth with and without familial risk for bipolar I disorder (BD). Psychostimulant-free ADHD youth (10-18 years) with and without a first-degree relative with BD and healthy controls were enrolled. Bilateral ventrolateral prefrontal cortex (VLPFC) proton magnetic resonance spectroscopy (H MRS) scans and a range of symptom ratings were performed.

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.

Familial risk for bipolar I disorder is associated with erythrocyte omega-3 polyunsaturated fatty acid deficits in youth with attention-deficit hyperactivity disorder.

Although attention-deficit/hyperactivity disorder (ADHD) and a family history of bipolar I disorder (BD) increase the risk for developing BD, associated pathoetiological mechanisms remain poorly understood. One candidate risk factor is a neurodevelopmental deficiency in omega-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This study investigated erythrocyte EPA+DHA biostatus in psychostimulant-free ADHD youth with ('high-risk', HR) and without ('low-risk', LR) a first-degree relative with BD, and healthy controls (HC).

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 preliminary study of the effects of mindfulness-based cognitive therapy on structural brain networks in mood-dysregulated youth with a familial risk for bipolar disorder.

Background: Mindfulness-based cognitive therapy for children (MBCT-C), as a psychotherapeutic intervention, has been shown to be effective for treating mood dysregulation (MD). While previous neuroimaging studies of MD have reported both pre-treatment structural and functional alterations, the effects of MBCT-C on brain morphological network organisation has not been investigated.

Methods: We investigated brain morphological network organisation in 10 mood-dysregulated youth with familial risk for bipolar disorder and 15 matched healthy comparison youth (HC).

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.

Fish oil supplementation alters emotion-generated corticolimbic functional connectivity in depressed adolescents at high-risk for bipolar I disorder: A 12-week placebo-controlled fMRI trial.

Objective: To evaluate the effects of fish oil (FO), a source of the omega-3 polyunsaturated fatty acids (n-3 PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on emotion-generated corticolimbic functional connectivity in depressed youth at high risk for developing bipolar I disorder.

Methods: Thirty-nine antidepressant-free youth with a current depressive disorder diagnosis and a biological parent with bipolar I disorder were randomized to 12-week double-blind treatment with FO or placebo. At baseline and endpoint, fMRI (4 Tesla) scans were obtained while performing a continuous performance task with emotional and neutral distractors (CPT-END).

Emotion-Related Network Reorganization Following Fish Oil Supplementation in Depressed Bipolar Offspring: An fMRI Graph-Based Connectome Analysis.

Introduction: Mood disorders are associated with fronto-limbic structural and functional abnormalities and deficits in omega-3 polyunsaturated fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Emerging evidence also suggests that n-3 PUFA, which are enriched in fish oil, promote cortical plasticity and connectivity. The present study performed a graph-based connectome analysis to investigate the role of n-3 PUFA in emotion-related network organization in medication-free depressed adolescent bipolar offspring.

Network-level functional topological changes after mindfulness-based cognitive therapy in mood dysregulated adolescents at familial risk for bipolar disorder: a pilot study.

Background: Given that psychopharmacological approaches routinely used to treat mood-related problems may result in adverse outcomes in mood dysregulated adolescents at familial risk for bipolar disorder (BD), Mindfulness-Based Cognitive Therapy for Children (MBCT-C) provides an alternative effective and safe option. However, little is known about the brain mechanisms of beneficial outcomes from this intervention. Herein, we aimed to investigate the network-level neurofunctional effects of MBCT-C in mood dysregulated adolescents.

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).

A Preliminary Study of the Effects of Treatment with Lithium Versus Quetiapine on Attention of Adolescents with Bipolar Disorder.

Despite attentional deficits being a prominent feature of bipolar disorder, there are limited data on the effects of common treatments for bipolar disorder on attention. Thus, we sought to compare the effects of lithium versus quetiapine on attention in adolescents with bipolar disorder. Adolescents ages 10-17 with bipolar disorder, type I, who were experiencing a manic or mixed episode, were recruited from outpatient settings and the inpatient psychiatric units at Cincinnati Children's Hospital Medical Center during their first manic episode.

Brain structural correlates of familial risk for mental illness: a meta-analysis of voxel-based morphometry studies in relatives of patients with psychotic or mood disorders.

Schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are heritable psychiatric disorders with partially overlapping genetic liability. Shared and disorder-specific neurobiological abnormalities associated with familial risk for developing mental illnesses are largely unknown. We performed a meta-analysis of structural brain imaging studies in relatives of patients with SCZ, BD, and MDD to identify overlapping and discrete brain structural correlates of familial risk for mental disorders.