Gray and white matter differences in adolescents and young adults with prior suicide attempts across bipolar and major depressive disorders.

BACKGROUND: Findings regarding brain circuitry abnormalities in suicide attempters (SAs) converge across bipolar disorder (BD) and major depressive disorder (MDD), the most common disorders observed in suicides. These abnormalities appear to be present during adolescence/young adulthood when suicide rates increase steeply, and suicide is a leading cause of death in this age group. Identification of brain circuitry common to adolescent/young adult SAs with BD and MDD is important for generating widely effective early prevention strategies. We examined brain circuitry in SAs in adolescents/young adults across these two disorders. METHODS: Eighty-three participants (ages 14-25 years), 46 with BD (21 SAs) and 37 with MDD (19 SAs), underwent structural and diffusion-weighted magnetic resonance scanning. Whole-brain analyses compared gray matter (GM) volume and white matter (WM) fractional anisotropy (FA) between SAs and non-suicide attempters (NSAs) across and within BD and MDD (p < 0.005). RESULTS: Across and within BD and MDD, SAs showed differences compared to NSAs in ventral prefrontal cortex (PFC) GM volume and fronto-limbic (including uncinate fasciculus (UF)) WM FA. Exploratory analyses showed additional within-disorder differences for BD SAs in dorsolateral PFC (dlPFC) and hippocampus GM volume and UF FA, and for MDD SAs dorsomedial and dlPFC GM and dorsal frontal WM. However, there was no significant interaction between suicide attempt status and diagnosis. LIMITATIONS: Modest sample size. CONCLUSIONS: Common fronto-limbic gray and white matter alterations in adolescent/young adult SAs are potential targets for suicide prevention strategies across mood disorders. Preliminary findings of disorder-specific regional findings could suggest diagnostic-specific optimal targets may exist.

Preliminary examination of gray and white matter structure and longitudinal structural changes in frontal systems associated with future suicide attempts in adolescents and young adults with mood disorders.

BACKGROUND: Mood disorders are major risk factors for suicidal behavior. While cross-sectional studies implicate frontal systems, data to aid prediction of suicide-related behavior in mood disorders are limited. Longitudinal research on neuroanatomical mechanisms underlying suicide risk may assist in developing targeted interventions. Therefore, we conducted a preliminary study investigating baseline gray and white matter structure and longitudinal structural changes associated with future suicide attempts. METHODS: High-resolution structural magnetic resonance imaging, diffusion tensor imaging, and suicide-related behavioral assessment data for 46 adolescents and young adults with mood disorders [baseline agemean = 18 years; 61% female] were collected at baseline and at follow-up (intervalmean = 3 years). Differences in baseline and longitudinal changes in gray matter volume and white matter fractional anisotropy in frontal systems that distinguished the participants who made future attempts from those who did not were investigated. RESULTS: Seventeen (37%) of participants attempted suicide within the follow-up period. Future attempters (those attempting suicide between their baseline and follow-up assessment), compared to those who did not, showed lower baseline ventral and rostral prefrontal gray matter volume and dorsomedial frontal, anterior limb of the internal capsule, and dorsal cingulum fractional anisotropy, as well as greater decreases over time in ventral and dorsal frontal fractional anisotropy (p < 0.005, uncorrected). LIMITATIONS: Sample size was modest. CONCLUSIONS: Results suggest abnormalities of gray and white matter in frontal systems and differences in developmental changes of frontal white matter may increase risk of suicide-related behavior in youths with mood disorders. Findings provide potential new leads for early intervention and prevention strategies.

Multimodal Neuroimaging of Frontolimbic Structure and Function Associated With Suicide Attempts in Adolescents and Young Adults With Bipolar Disorder.

OBJECTIVE: Bipolar disorder is associated with high risk for suicidal behavior that often develops in adolescence and young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents and young adults with bipolar disorder with and without a history of suicide attempts combines structural, diffusion tensor, and functional MR imaging methods to investigate implicated abnormalities in the morphology and structural and functional connectivity within frontolimbic systems. METHOD: The study had 26 participants with bipolar disorder who had a prior suicide attempt (the attempter group) and 42 participants with bipolar disorder without a suicide attempt (the nonattempter group). Regional gray matter volume, white matter integrity, and functional connectivity during processing of emotional stimuli were compared between groups, and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors. RESULTS: Compared with the nonattempter group, the attempter group showed significant reductions in gray matter volume in the orbitofrontal cortex, hippocampus, and cerebellum; white matter integrity in the uncinate fasciculus, ventral frontal, and right cerebellum regions; and amygdala functional connectivity to the left ventral and right rostral prefrontal cortex. In exploratory analyses, among attempters, there was a significant negative correlation between right rostral prefrontal connectivity and suicidal ideation and between left ventral prefrontal connectivity and attempt lethality. CONCLUSIONS: Adolescent and young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral frontolimbic neural system subserving emotion regulation. Among attempters, reductions in amygdala-prefrontal functional connectivity may be associated with severity of suicidal ideation and attempt lethality.

Brain circuitry associated with the development of substance use in bipolar disorder and preliminary evidence for sexual dimorphism in adolescents.

Substance use disorders and mood disorders are highly comorbid and confer a high risk for adverse outcomes. However, data are limited on the neurodevelopmental basis of this comorbidity. Substance use initiation typically occurs during adolescence, and sex-specific developmental mechanisms are implicated. In this preliminary study, we review the literature and investigate regional gray matter volume (GMV) associated with subsequent substance use problems in adolescents with bipolar disorder (BD) and explore these associations for females and males. Thirty adolescents with DSM-IV-diagnosed BD and minimal alcohol/substance exposure completed baseline structural magnetic resonance imaging scans. At follow-up (on average 6 years post baseline), subjects were administered the CRAFFT interview and categorized into those scoring at high ( ≥ 2: CRAFFTHIGH ) vs. low ( < 2: CRAFFTLOW ) risk for alcohol/substance problems. Lower GMV in prefrontal, insular, and temporopolar cortices were observed at baseline among adolescents with BD reporting subsequent alcohol and cannabis use compared to adolescents with BD who did not (P < 0.005, clusters ≥ 20 voxels). Lower dorsolateral prefrontal GMV was associated with future substance use in both females and males. In females, lower orbitofrontal and insula GMV was associated with future substance use, while in males, lower rostral prefrontal GMV was associated with future use. Lower orbitofrontal, insular, and temporopolar GMV was observed in those who transitioned to smoking tobacco. Findings indicate that GMV development is associated with risk for future substance use problems in adolescents with BD, with results implicating GMV development in regions subserving emotional regulation in females and regions subserving executive processes and attention in males. © 2016 Wiley Periodicals, Inc.

Anterior Cortical Development During Adolescence in Bipolar Disorder.

BACKGROUND: Increasing evidence supports a neurodevelopmental model for bipolar disorder (BD), with adolescence as a critical period in its development. Developmental abnormalities of anterior paralimbic and heteromodal frontal cortices, key structures in emotional regulation processes and central in BD, are implicated. However, few longitudinal studies have been conducted, limiting understanding of trajectory alterations in BD. In this study, we performed longitudinal neuroimaging of adolescents with and without BD and assessed volume changes over time, including changes in tissue overall and within gray and white matter. Larger decreases over time in anterior cortical volumes in the adolescents with BD were hypothesized. Gray matter decreases and white matter increases are typically observed during adolescence in anterior cortices. It was hypothesized that volume decreases over time in BD would reflect alterations in those processes, showing larger gray matter contraction and decreased white matter expansion. METHODS: Two high-resolution magnetic resonance imaging scans were obtained approximately 2 years apart for 35 adolescents with bipolar I disorder (BDI) and 37 healthy adolescents. Differences over time between groups were investigated for volume overall and specifically for gray and white matter. RESULTS: Relative to healthy adolescents, adolescents with BDI showed greater volume contraction over time in a region including insula and orbitofrontal, rostral, and dorsolateral prefrontal cortices (p < .05, corrected), including greater gray matter contraction and decreased white matter expansion over time, in the BD compared with the healthy group. CONCLUSIONS: The findings support neurodevelopmental abnormalities during adolescence in BDI in anterior cortices, including altered developmental trajectories of anterior gray and white matter.

A pilot study of maudsley family therapy with group dialectical behavior therapy skills training in an intensive outpatient program for adolescent eating disorders.

OBJECTIVE: The goal of this study was to provide pilot clinical data on the effectiveness of an intensive outpatient treatment model for adolescent eating disorders that combines Maudsley-based family therapy and group dialectical behavior therapy skills training. METHOD: Measures of physical and psychological status were gathered upon admission, discharge, and at 3 follow-up intervals. RESULTS: Adolescents who completed the program gained a significant amount of weight and experienced a significant decrease in eating disorder psychopathology. At the 1-year follow-up, 64% of adolescents were weight restored and menstruating normally. Measures of eating disorder psychopathology continued to improve up to a year after treatment. CONCLUSIONS: This pilot, multimodal program warrants further investigation and may be an effective intermediate level of care treatment option for adolescent eating disorders.

Neurobiological risk factors for suicide: insights from brain imaging.

CONTEXT: This article reviews neuroimaging studies on neural circuitry associated with suicide-related thoughts and behaviors to identify areas of convergence in findings. Gaps in the literature for which additional research is needed are identified. EVIDENCE ACQUISITION: A PubMed search was conducted and articles published before March 2014 were reviewed that compared individuals who made suicide attempts to those with similar diagnoses who had not made attempts or to healthy comparison subjects. Articles on adults with suicidal ideation and adolescents who had made attempts, or with suicidal ideation, were also included. Reviewed imaging modalities included structural magnetic resonance imaging, diffusion tensor imaging, single photon emission computed tomography, positron emission tomography, and functional magnetic resonance imaging. EVIDENCE SYNTHESIS: Although many studies include small samples, and subject characteristics and imaging methods vary across studies, there were convergent findings involving the structure and function of frontal neural systems and the serotonergic system. CONCLUSIONS: These initial neuroimaging studies of suicide behavior have provided promising results. Future neuroimaging efforts could be strengthened by more strategic use of common data elements and a focus on suicide risk trajectories. At-risk subgroups defined by biopsychosocial risk factors and multidimensional assessment of suicidal thoughts and behaviors may provide a clearer picture of the neural circuitry associated with risk status-both current and lifetime. Also needed are studies investigating neural changes associated with interventions that are effective in risk reduction.

Frontotemporal White Matter in Adolescents with, and at-Risk for, Bipolar Disorder.

Frontotemporal neural systems are highly implicated in the emotional dysregulation characteristic of bipolar disorder (BD). Convergent genetic, postmortem, behavioral and neuroimaging evidence suggests abnormalities in the development of frontotemporal white matter (WM) in the pathophysiology of BD. This review discusses evidence for the involvement of abnormal WM development in BD during adolescence, with a focus on frontotemporal WM. Findings from diffusion tensor imaging (DTI) studies in adults and adolescents are reviewed to explore possible progressive WM abnormalities in the disorder. Intra- and interhemispheric frontotemporal abnormalities were reported in adults with BD. Although evidence in children and adolescents with BD to date has been limited, similar intrahemispheric and interhemispheric findings have also been reported. The findings in youths suggest that these abnormalities may represent a trait marker present early in the course of BD. Functional connectivity studies, demonstrating a relationship between WM abnormalities and frontotemporal dysfunction in BD, and DTI studies of vulnerability in first-degree relatives of individuals with BD, are discussed. Together, findings suggest the involvement of abnormal frontotemporal WM development in the pathophysiology of BD and that these abnormalities may be early trait markers of vulnerability; however, more studies are critically needed.