Kiki D Chang

Stanford Medicine, Stanford, California, United States

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Publications (88)246.88 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pediatric onset bipolar disorder (BD) is a challenging diagnosis with potentially debilitating outcomes. This review aims to critically evaluate recently published literature relevant to the diagnosis of BD in youth, emphasizing interesting and important new findings characterizing pediatric BD and reporting updates in the diagnostic and statistical manual relevant to this disorder in youth. Challenges regarding the diagnosis of BD will be discussed, in addition to important distinctions with other childhood disorders, including other bipolar spectrum disorders; major depressive disorder; dysthymia; disruptive mood dysregulation disorder (DMDD); attention-deficit/hyperactivity disorder (ADHD) and other disruptive behavioral disorders; anxiety disorders, including post-traumatic stress disorder (PTSD); psychotic disorders; autism spectrum disorders; substance use disorders; and borderline personality disorder. The review concludes with a comment on past research limitations and future directions in the field.
    Current Psychiatry Reports 12/2014; 16(12):516. · 3.05 Impact Factor
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    ABSTRACT: Several genetic and environmental factors place youth offspring of parents with bipolar disorder (BD) at high risk for developing mood and anxiety disorders. Recent studies suggest that anxiety symptoms, even at subclinical levels, have been associated with an increased risk for developing BD. The brain-derived neurotrophic factor (BDNF) gene has been implicated in the pathophysiology of both BD and anxiety disorders. We aimed to explore whether anxiety in BD offspring was associated with the BDNF Val66Met polymorphism. 64 BD offspring (mean age: 13.73 (S.D. 3.45) M = 30, F = 34) and 51 HC (mean age: 13.68 (S.D. 2.68) M = 23, F = 28) were compared on presence of the met allele and on scores from the Multidimensional Anxiety Scale for Children (MASC). To assess family function, we used the Family Adaptability and Cohesion Evaluation Scales (FACES-IV). The Baron & Kenny method was the statistical approach used to examine the moderating effects between variables. BD offspring showed higher levels of overall anxiety than did the HC group. BD offspring with the val/val genotype showed higher levels of anxiety than BD offspring with other genotypes. No significant levels of anxiety or its association with BDNF genotype were found in the HC group. BD offspring group showed significantly more family dysfunction when compared with the HC group and the family dysfunction moderated the association between the BDNF genotype and anxiety symptoms. This study demonstrated the potential interplay of three factors: BD offspring, anxiety symptoms and family dysfunction. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Journal of Psychiatric Research 11/2014; · 4.09 Impact Factor
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    ABSTRACT: Psychotherapy for youth with mood dysregulation can help to stabilize mood and improve functioning, but the neural mechanisms of this improvement are not known. In this study we investigated changes in brain activation underlying improvement in mood symptoms.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 10/2014; · 4.03 Impact Factor
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    ABSTRACT: Bipolar disorder (BD) is highly familial and characterized by deficits in reward processing. It is not known, however, whether these deficits precede illness onset or are a consequence of the disorder.
    JAMA Psychiatry 08/2014; · 12.01 Impact Factor
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    ABSTRACT: Bipolar disorder (BD) has been associated with dysfunctional brain connectivity and with family chaos. It is not known whether aberrant connectivity occurs before illness onset, representing vulnerability for developing BD amidst family chaos. We used resting-state functional magnetic resonance imaging (fMRI) to examine neural network dysfunction in healthy offspring living with parents with BD and healthy comparison youth.
    Bipolar Disorders 06/2014; · 4.89 Impact Factor
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    ABSTRACT: Objectives The aim of the present study was to systematically evaluate the prodrome to mania in youth. Methods New-onset/worsening symptoms/signs of ≥ moderate severity preceding first mania were systematically assessed in 52 youth (16.2 ± 2.8 years) with a research diagnosis of bipolar I disorder (BD-I). Youth and/or caregivers underwent semi-structured interviews, using the Bipolar Prodrome Symptom Scale–Retrospective. ResultsThe mania prodrome was reported to start gradually in most youth (88.5%), with either slow (59.6%) or rapid (28.8%) deterioration, while a rapid-onset-and-deterioration prodrome was rare (11.5%). The manic prodrome, conservatively defined as requiring ≥ 3 symptoms, lasted 10.3 ± 14.4 months [95% confidence interval (CI): 6.3–14.4], being present for ≥ 4 months in 65.4% of subjects. Among prodromal symptoms reported in ≥ 50% of youth, three were subthreshold manic in nature (irritability: 61.5%, racing thoughts: 59.6%, increased energy/activity: 50.0%), two were nonspecific (decreased school/work functioning: 65.4%, mood swings/lability: 57.7%), and one each was depressive (depressed mood: 53.8%) or subthreshold manic/depressive (inattention: 51.9%). A decreasing number of youth had ≥ 1 (84.6%), ≥ 2 (48.1%), or ≥ 3 (26.9%) ‘specific’ subthreshold mania symptoms (i.e., elation, grandiosity, decreased need for sleep, racing thoughts, or hypersexuality), lasting 9.5 ± 14.9 months (95% CI: 5.0–14.0), 3.5 ± 3.5 months (95% CI: 2.0–4.9), and 3.0 ± 3.2 months (95% CI: 1.0–5.0) for ≥ 1, ≥ 2, or ≥ 3 specific symptoms, respectively. Conclusions In youth with BD-I, a relatively long, predominantly slow-onset mania prodrome appears to be common, including subthreshold manic and depressive psychopathology symptoms. This suggests that early clinical identification and intervention may be feasible in bipolar disorder. Identifying biological markers associated with clinical symptoms of impending mania may help to increase chances for early detection and prevention before full mania.
    Bipolar Disorders 03/2014; · 4.62 Impact Factor
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    ABSTRACT: This article reviews work published by the ENIGMA Consortium and its Working Groups (http://enigma.ini.usc.edu). It was written collaboratively; P.T. wrote the first draft and all listed authors revised and edited the document for important intellectual content, using Google Docs for parallel editing, and approved it. Some ENIGMA investigators contributed to the design and implementation of ENIGMA or provided data but did not participate in the analysis or writing of this report. A complete listing of ENIGMA investigators is available at http://enigma.ini.usc.edu/publications/the-enigma-consortium-in-review/ For ADNI, some investigators contributed to the design and implementation of ADNI or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators is available at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ ADNI_Acknowledgement_List.pdf The work reviewed here was funded by a large number of federal and private agencies worldwide, listed in Stein et al. (2012); the funding for listed consortia is also itemized in Stein et al. (2012).
    Brain Imaging and Behavior 01/2014; · 3.39 Impact Factor
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    ABSTRACT: We wished to determine whether decreases in N-acetyl aspartate (NAA) and increases in myoinositol (mI) concentrations as a ratio of creatine (Cr) occurred in the dorsolateral prefrontal cortex (DLPFC) of pediatric offspring of parents with bipolar disorder (BD) and a healthy comparison group (HC) over a 5-year period using proton magnetic resonance spectroscopy ((1)H-MRS). Paticipants comprised 64 offspring (9-18 years old) of parents with BD (36 with established BD, and 28 offspring with symptoms subsyndromal to mania) and 28 HCs, who were examined for group differences in NAA/Cr and mI/Cr in the DLPFC at baseline and follow-up at either 8, 10, 12, 52, 104, 156, 208, or 260 weeks. No significant group differences were found in metabolite concentrations at baseline or over time. At baseline, BD offspring had trends for higher mI/Cr concentrations in the right DLPFC than the HC group. mI/Cr concentrations increased with age, but no statistically significant group differences were found between groups on follow-up. It may be the case that with intervention youth at risk for BD are normalizing otherwise potentially aberrant neurochemical trajectories in the DLPFC. A longer period of follow-up may be required before observing any group differences.
    Psychiatry research. 09/2013;
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    ABSTRACT: Smaller amygdalar volumes have been consistently observed in pediatric bipolar disorder subjects compared to healthy control subjects. Whether smaller amygdalar volume is a consequence or antecedent of the first episode of mania is not known. Additionally, smaller volume has not been localized to specific amygdala subregions. We compared surface contour maps of the amygdala between 22 youths at high risk for bipolar disorder, 26 youths meeting full diagnostic criteria for pediatric familial bipolar disorder, and 24 healthy control subjects matched for age, gender, and intelligence quotient. Amygdalae were manually delineated on three-dimensional spoiled gradient echo images by a blinded rater using established tracing protocols. Statistical surface mesh modeling algorithms supported by permutation statistics were used to identify regional surface differences between the groups. When compared to high-risk subjects and controls, youth with bipolar disorder showed surface deformations in specific amygdalar subregions, suggesting smaller volume of the basolateral nuclei. The high-risk subjects did not differ from controls in any subregion. These findings support previous reports of smaller amygdala volume in pediatric bipolar disorder and map the location of abnormality to specific amygdala subregions. These subregions have been associated with fear conditioning and emotion-enhanced memory. The absence of amygdala size abnormalities in youth at high risk for bipolar disorder suggests that reductions might occur after the onset of mania.
    Bipolar Disorders 09/2013; · 4.62 Impact Factor
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    ABSTRACT: Depressive and anxiety disorders are common in youth who are at risk for bipolar disorder (i.e., youth who have at least one parent with bipolar disorder) and antidepressants are commonly prescribed as treatment. However, there are few data regarding the safety and tolerability of antidepressants in this population. Therefore, we sought to prospectively examine the effects of these medications in children and adolescents who are diagnosed with depressive or anxiety disorders and have a parent with bipolar I disorder. Youth aged 9-20 years, with at least one parent with bipolar I disorder [high risk (HR)], were recruited (n = 118) and assessed using semi-structured diagnostic interviews. Participants were prospectively evaluated using a modified version of the Longitudinal Interval Follow-up Evaluation to assess changes in affective and anxiety symptoms and were treated naturalistically. Over the course of 43-227 weeks (mean duration of follow-up: 106 ± 55 weeks), 21% (n = 25) of youth had antidepressant exposure and, of these, 57% (n = 12) had an adverse reaction (e.g., irritability, aggression, impulsivity, or hyperactivity) that led to antidepressant discontinuation. Those patients who experienced an adverse reaction were significantly younger than those who did not (p = 0.02) and discontinuation of antidepressant therapy secondary to an adverse event occurred at an average of 16.7 ± 17.4 weeks (median: 11 weeks, range: 2-57 weeks). Cox proportional hazard analyses yielded a hazard ratio of 0.725 (p = 0.03), suggesting that there is a 27% decrease in the likelihood of an antidepressant-related adverse event leading to discontinuation with each one-year increase in age. Antidepressant medications may be poorly tolerated in youth with a familial risk for developing mania. Controlled studies further assessing treatments for depression and anxiety in HR youth are urgently needed.
    Bipolar Disorders 08/2013; · 4.62 Impact Factor
  • The Journal of Clinical Psychiatry 07/2013; 74(6):628-629. · 5.81 Impact Factor
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    ABSTRACT: Depression in children and adolescents with bipolar disorder is more commonly observed than mania or hypomania, and is associated with significant functional disability in multiple environmental realms. Optimal management of pediatric bipolar depression is often defined by its multimodal nature with emphasis on both psychopharmacological and psychosocial treatment. This article provides a brief overview of the epidemiology and clinical course of pediatric bipolar depression, a clinically-oriented guide to the evidence-based psychopharmacological and psychosocial management of bipolar depression in youth, and suggestions on how best to integrate medication and therapy. Recommended treatment for bipolar depression in pediatric populations usually includes both medication and psychosocial interventions given a paucity of double-blind, placebo-controlled psychopharmacological studies. Lithium and lamotrigine are feasible and tentatively efficacious options; however, treatment with quetiapine monotherapy may be no better than placebo. Furthermore, some youth may be at heightened risk for developing manic symptoms after treatment with selective serotonin reuptake inhibitors (SSRIs). Psychotherapy, either alone or adjunctively with medications, provides practitioners with a safe and feasible alternative. Interpersonal and Social Rhythm Therapy for Adolescents (IPSRT-A), Child- and Family-Focused Cognitive Behavioral Therapy (CFF-CBT), Dialectical Behavior Therapy for Adolescents (DBT-A), family psychoeducation, and Family Focused Therapy for Adolescents (FFT-A) are evidence-based treatments available to clinicians treating youth with bipolar depression.
    Paediatric Drugs 03/2013; · 1.72 Impact Factor
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    ABSTRACT: Depression and brief periods of (hypo)mania are linked to an increased risk of progression to bipolar I or II disorder (BD) in children of bipolar parents. This randomized trial examined the effects of a 4-month family-focused therapy (FFT) program on the 1-year course of mood symptoms in youth at high familial risk for BD, and explored its comparative benefits among youth in families with high versus low expressed emotion (EE). Participants were 40 youth (mean 12.3±2.8 years, range 9-17) with BD not otherwise specified, major depressive disorder, or cyclothymic disorder who had a first-degree relative with BD I or II and active mood symptoms (Young Mania Rating Scale [YMRS]>11 or Child Depression Rating Scale>29). Participants were randomly allocated to FFT-High Risk version (FFT-HR; 12 sessions of psychoeducation and training in communication and problem-solving skills) or an education control (EC; 1-2 family sessions). Youth in FFT-HR had more rapid recovery from their initial mood symptoms (hazard ratio = 2.69, p = .047), more weeks in remission, and a more favorable trajectory of YMRS scores over 1 year than youth in EC. The magnitude of treatment effect was greater among youth in high-EE (versus low-EE) families. FFT-HR may hasten and help sustain recovery from mood symptoms among youth at high risk for BD. Longer follow-up will be necessary to determine whether early family intervention has downstream effects that contribute to the delay or prevention of full manic episodes in vulnerable youth. Clinical trial registration information-Early Family-Focused Treatment for Youth at Risk for Bipolar Disorder; http://www.clinicaltrials.gov/; NCT00943085.
    Journal of the American Academy of Child and Adolescent Psychiatry 02/2013; 52(2):121-31. · 6.97 Impact Factor
  • Manpreet K Singh, Kiki D Chang
    Biological psychiatry 01/2013; 73(2):109-10. · 8.93 Impact Factor
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    ABSTRACT: Bipolar disorder (BD) is a debilitating psychiatric condition that commonly begins in adolescence, a developmental period that has been associated with increased reward seeking. Because youth with BD are especially vulnerable to negative risk-taking behaviors, understanding the neural mechanisms by which dysregulated affect interacts with the neurobehavioral processing of reward is clearly important. One way to clarify how manic symptoms evolve in BD is to "prime" the affect before presenting rewarding stimuli. The objective of this study was to investigate the neural effects of an affective priming task designed to positively induce mood before reward processing in adolescents with and without BD. Neural activity and behaviors during the anticipation of and response to monetary reward and loss after an affective prime were compared using functional magnetic resonance imaging in 13- to 18-year-old adolescents with a recent onset of BD-I (n = 24) and demographically matched healthy comparison youth (n = 24). Compared with the healthy control youth, youth with BD had speeded reaction times and showed decreased activation in the thalamus and inferior temporal gyrus while anticipating gains after priming but increased activations in the middle frontal gyrus and parietal cortices while anticipating losses after priming. Youth with BD also showed less activation in the inferior parietal lobule, thalamus, and superior frontal gyrus while receiving losses after priming. Aberrant prefrontal and subcortical activations during reward processing suggest mechanisms that may underlie disordered self-awareness during goal pursuit and motivation in BD. Longitudinal studies are needed to examine whether this pattern of neural activation predicts a poorer long-term outcome.
    Journal of the American Academy of Child and Adolescent Psychiatry 01/2013; 52(1):68-83. · 6.97 Impact Factor
  • 59th Meeting of American Academy of Child and Adolescent Psychiatry; 10/2012
  • 59th Meeting of American Academy of Child and Adolescent Psychiatry; 10/2012
  • 59th Meeting of American Academy of Child and Adolescent Psychiatry; 10/2012
  • 59th Meeting of American Academy of Child and Adolescent Psychiatry; 10/2012
  • 59th Meeting of American Academy of Child and Adolescent Psychiatry; 10/2012

Publication Stats

854 Citations
246.88 Total Impact Points

Institutions

  • 2005–2014
    • Stanford Medicine
      • • Department of Psychiatry and Behavioral Sciences
      • • Division of Child and Adolescent Psychiatry
      Stanford, California, United States
  • 2013
    • University of California, Los Angeles
      • Division of Child and Adolescent Psychiatry
      Los Angeles, California, United States
  • 2002–2013
    • Stanford University
      • • Department of Psychiatry and Behavioral Sciences
      • • Division of Child and Adolescent Psychiatry
      Palo Alto, CA, United States
  • 2012
    • Vanderbilt University
      Nashville, Michigan, United States
  • 2008
    • University of Colorado at Boulder
      Boulder, Colorado, United States
  • 2007
    • University of Nebraska Medical Center
      Omaha, Nebraska, United States
  • 2006
    • UConn Health Center
      Farmington, Connecticut, United States