Kerri L. Kim

Developmental meta-analysis of the functional neural correlates of autism spectrum disorders

OBJECTIVE There is a pressing need to elucidate the brain-behavior interactions underlying autism spectrum disorders (ASD) given the marked rise in ASD diagnosis over the past decade. Functional magnetic resonance imaging (fMRI) has begun to address this need, but few fMRI studies have evaluated age-related changes in ASD. Therefore, we conducted a developmental analysis of activation likelihood estimation (ALE) meta-analysis to compare child versus adult ASD fMRI studies. We hypothesized that children and adolescents with ASD (<18 years old) would rely less on prefrontal cortex structures than adults (≥18 years old). METHOD PubMed and PsycInfo literature searches were conducted to identify task-dependent fMRI studies of children or adults with ASD. Then recent GingerALE software improvements were leveraged to perform direct comparisons of child (n = 18) versus adult (n = 24) studies. RESULTS ALE meta-analyses of social tasks showed that children and adolescents with ASD versus adults had significantly greater hyperactivation in the left post-central gyrus, and greater hypoactivation in the right hippocampus and right superior temporal gyrus. ALE meta-analyses of nonsocial tasks showed that children with ASD versus adults had significantly greater hyperactivation in the right insula and left cingulate gyrus, and hypoactivation in the right middle frontal gyrus. CONCLUSION Our data suggest that the neural alterations associated with ASD are not static, occurring only in early childhood. Instead, children with ASD have altered neural activity compared to adults during both social and nonsocial tasks, especially in fronto-temporal structures. Longitudinal neuroimaging studies are required to examine these changes prospectively, as potential targets for brain-based treatments for ASD.

Developmental meta-analyses of the functional neural correlates of bipolar disorder.

IMPORTANCE Bipolar disorder (BD) is a debilitating mental illness associated with high costs to diagnosed individuals and society. Within the past 2 decades, increasing numbers of children and adolescents have been diagnosed as having BD. While functional magnetic resonance imaging (fMRI) studies have begun to investigate the neural mechanisms underlying BD, few have directly compared differences in youths with BD and adults with BD (hereafter BD-youths and BD-adults, respectively). OBJECTIVE To test the hypothesis that BD-youths (<18 years old) would show greater convergence of amygdala hyperactivation and prefrontal cortical hypoactivation vs BD-adults. DATA SOURCES PubMed and PsycINFO databases were searched on July 17, 2013, for original, task-related coordinate-based fMRI articles. STUDY SELECTION In total, 21 pediatric studies, 73 adult studies, and 2 studies containing distinct pediatric and adult groups within the same study met inclusion criteria for our ALE analyses. DATA EXTRACTION AND SYNTHESIS Coordinates of significant between-group differences were extracted from each published study. Recent improvements in GingerALE software were used to perform direct comparisons of pediatric and adult fMRI findings. We conducted activation likelihood estimation (ALE) meta-analyses directly comparing the voxelwise convergence of fMRI findings in BD-youths vs BD-adults, both relative to healthy control (HC) participants. RESULTS Analyses of emotional face recognition fMRI studies showed significantly greater convergence of amygdala hyperactivation among BD-youths than BD-adults. More broadly, analyses of fMRI studies using emotional stimuli showed significantly greater convergence of hyperactivation among BD-youths than BD-adults in the inferior frontal gyrus and precuneus. In contrast, analyses of fMRI studies using nonemotional cognitive tasks and analyses aggregating emotional and nonemotional tasks showed significantly greater convergence of hypoactivation among BD-youths than BD-adults in the anterior cingulate cortex. CONCLUSIONS AND RELEVANCE Our data suggest that amygdala, prefrontal, and visual system hyperactivation is important in the emotional dysfunction present in BD-youths, as well as that anterior cingulate cortex hypoactivation is relevant to the cognitive deficits in BD-youths. Future studies are required to determine if the developmental fMRI differences between BD-youths and BD-adults identified by our ALE meta-analyses are useful as brain-based diagnostic or treatment markers of BD, including either longitudinal neuroimaging studies of BD-youths as they become adults or cross-sectional imaging studies directly comparing BD-youths with BD-adults.

Facial emotion recognition in childhood-onset bipolar I disorder: an evaluation of developmental differences between youths and adults

Bipolar disorder (BD) is a severe mental illness with high healthcare costs and poor outcomes. Increasing numbers of youths are diagnosed with BD, and many adults with BD report that their symptoms started in childhood, suggesting that BD can be a developmental disorder. Studies advancing our understanding of BD have shown alterations in facial emotion recognition both in children and adults with BD compared to healthy comparison (HC) participants, but none have evaluated the development of these deficits. To address this, we examined the effect of age on facial emotion recognition in a sample that included children and adults with confirmed childhood‐onset type‐I BD, with the adults having been diagnosed and followed since childhood by the Course and Outcome in Bipolar Youth study.

Self‐injurious implicit attitudes among adolescent suicide attempters versus those engaged in nonsuicidal self‐injury

BACKGROUND Suicide is among the most important mental health issues affecting adolescents today despite much research on its detection and prevention. Beyond suicide attempts (SAs), clinicians are increasingly confronted with another, potentially related problem: non-suicidal self-injury (NSSI)-defined as the deliberate destruction of body tissue without intent to die. NSSI may increase risk for making an SA by sevenfold, but many studies examining this link have involved youths engaging in both NSSI and SAs. Thus, there is a need to compare homogeneous groups of adolescents engaged in NSSI-only or SA-only, but not both, to advance what is known about each form of self-harm. The self-injurious implicit association task (SI-IAT) is a particularly important computerized behavioral task to study such adolescents because the SI-IAT provides objective behavioral data about problems for which people may lack insight or be motivated to conceal, such as SAs and NSSI. METHODS We evaluated implicit associations with cutting and death/suicide using the computerized SI-IAT in three mutually exclusive groups: (1) adolescents who made an SA but had never engaged in NSSI (n = 47); (2) adolescents who engaged in NSSI but had never made an SA (n = 46); and (3) typically developing control (TDC) adolescents without history of psychiatric problems (n = 43). RESULTS Nonsuicidal self-injury participants had stronger identification with cutting versus no cutting than either SA or TDC participants. Contrary to our hypothesis, NSSI participants had stronger identification with suicide/death versus life than either SA or TDC participants. CONCLUSIONS Strong implicit attitudes towards suicide/death among adolescents with NSSI without a prior SA suggest that clinicians should not dismiss NSSI as not serious. Further work is required to elucidate the mechanism by which youths engaged in NSSI acquire these stronger identifications and make a first-time SA to develop novel treatment and prevention strategies blocking this transformation, ultimately reducing youth suicide.

Cognitive Remediation: Potential Novel Brain-Based Treatment for Bipolar Disorder in Children and Adolescents

Bipolar disorder (BD) is among the most impairing psychiatric disorders affecting children and adolescents, despite our best psychopharmacological and psychotherapeutic treatments. Cognitive remediation, defined as a behavioral intervention designed to improve cognitive functions so as to reduce psychiatric illness, is an emerging brain-based treatment approach that has thus far not been studied in pediatric BD. The present article reviews the basic principles of cognitive remediation, describes what is known about cognitive remediation in psychiatric disorders, and delineates potential brain/behavior alterations implicated in pediatric BD that might be targets for cognitive remediation. Emerging data show that cognitive remediation may be useful in children and adults with schizophrenia, ADHD, and anxiety disorders, and in adults with BD. Potential targets for cognitive remediation in pediatric BD include face processing, response inhibition, frustration, and cognitive flexibility. Further study is warranted to determine if cognitive remediation for these targets, or others, may serve as a novel, brain-based treatment for pediatric BD.

Psychiatric and Self‐Injury Profiles of Adolescent Suicide Attempters versus Adolescents Engaged in Nonsuicidal Self‐Injury

To better delineate the unique correlates of self-injurious behaviors (SIB), psychiatric profiles of mutually exclusive groups of adolescents who made a suicide attempt (SA) versus those engaged in nonsuicidal self-injury (NSSI) were examined. Contrary to hypotheses, the NSSI group endorsed earlier onsets of SIB and suicidal ideation (SI), as well as higher rates of depression and anxiety compared with their SA counterparts. Future work is warranted to understand the role of SI, including duration of SI and anxiety in the development of NSSI, and to identify risk and resiliency factors useful in predicting an adolescents SIB status.

Reversal-learning deficits in childhood-onset bipolar disorder across the transition from childhood to young adulthood

BACKGROUND Bipolar disorder (BD) is a severe mental illness that can have high costs for youths (<18 years old) and adults. Relative to healthy controls (HC), individuals with BD often show impaired attention, working memory, executive function, and cognitive flexibility (the ability to adapt to changing reward/punishment contingencies). In our study of youths and young adults with BD, we investigated 1) how cognitive flexibility varies developmentally in BD, and 2) whether it is independent of other executive function deficits associated with BD. METHODS We measured errors on a reversal-learning task, as well as spatial working memory and other executive function, among participants with BD (N=75) and HC (N=130), 7-27 years old. Regression analyses focused on the effects of diagnosis on reversal-learning errors, controlling for age, gender, IQ, spatial span, and executive function. Similar analyses examined non-reversal errors to rule out general task impairment. RESULTS Participants with BD, regardless of age, gender, or cognitive ability, showed more errors than HC on the response reversal stages of the cognitive flexibility task. However, participants with BD did not show more errors on non-reversal stages, even when controlling for other variables. LIMITATIONS Study limitations include the cross-sectional, rather than longitudinal, design; inability to measure non-linear age effects; and inclusion of medicated participants and those with psychiatric comorbidity. CONCLUSIONS Individuals with BD show a specific impairment in reversing a previously rewarded response, which persists across the transition from childhood to young adulthood. Tailored interventions targeting this deficit may be effective throughout this developmentally turbulent time.

Circadian Phase Preference in Pediatric Bipolar Disorder

Pediatric bipolar disorder (BD) rates have notably increased over the past three decades. Given the significant morbidity and mortality associated with BD, efforts are needed to identify factors useful in earlier detection to help address this serious public health concern. Sleep is particularly important to consider given the sequelae of disrupted sleep on normative functioning and that sleep is included in diagnostic criteria for both Major Depressive and Manic Episodes. Here, we examine one component of sleep—i.e., circadian phase preference with the behavioral construct of morningness/eveningness (M/E). In comparing 30 BD and 45 typically developing control (TDC) participants, ages 7–17 years, on the Morningness-Eveningness Scale for Children (MESC), no between-group differences emerged. Similar results were found when comparing three groups (BD−ADHD; BD+ADHD; TDC). Consistent with data available on circadian phase preference in adults with BD, however, we found that BD adolescents, ages 13 years and older, endorsed significantly greater eveningness compared to their TDC peers. While the current findings are limited by reliance on subjective report and the high-rate of comorbid ADHD among the BD group, this finding that BD teens demonstrate an exaggerated shift towards eveningness than would be developmentally expected is important. Future studies should compare the circadian rhythms across the lifespan for individuals diagnosed with BD, as well as identify the point at which BD youth part ways with their healthy peers in terms of phase preference. In addition, given our BD sample was overall euthymic, it may be that M/E is more state vs. trait specific in latency age youth. Further work would benefit from assessing circadian functioning using a combination of rating forms and laboratory-based measures. Improved understanding of sleep in BD may identify behavioral targets for inclusion in prevention and intervention protocols.

Translational neuroscience in pediatric bipolar disorder.

Evaluation of: Pavuluri MN, Passarotti AM, Lu LH, Carbray JA, Sweeney JA. Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder: fMRI outcomes. Psychiatric Res. 193(1), 28–37 (2011). While controversial and often confounded with other forms of psychopathology, recent studies have shown that bipolar disorder (BD) is on the rise in children and adolescents. Research has made important strides in advancing our understanding of the phenomenology, neural underpinnings and treatment outcomes for BD youths. However, there is an increasing need to unite these domains to identify potential neural effects and predictors of treatment outcome. Pavuluri et al. have conducted such a study, evaluating the neural effects of divalproex or risperidone for pediatric BD. The future is likely to bring more of such studies, potentially resulting in a biomarker augmented approach to the diagnosis and treatment of pediatric BD.

Emotion Dysregulation Mediates the Relationship Between Child Maltreatment and Non-Suicidal Self-Injury

ABSTRACT One risk factor for non-suicidal self-injury (NSSI) in adolescents is exposure to traumatic experiences, particularly child maltreatment. However, the mechanisms through which childhood maltreatment predicts NSSI are largely unknown. Emotion dysregulation (ED) is likely an important mechanism in this relationship. Therefore, this study examined the relationship between childhood maltreatment, ED, and NSSI in a sample of adolescent inpatients (n = 53). Results demonstrated that child physical and emotional maltreatment, but not child sexual abuse, was significantly associated with NSSI frequency. More specifically, ED mediated the relationship between child physical and emotional maltreatment and NSSI frequency. Findings support the importance of ED as a mediating factor in the relationship between childhood maltreatment and NSSI behaviors and highlight the need for teaching emotion regulation skills to youth affected by trauma.