Child & Adolescent Anxiety: Psychopathology and Neuroscience

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1 bbrfoundation.org Child & Adolescent Anxiety: Psychopathology and Neuroscience Daniel S. Pine, M.D. Chief, Child & Adolescent Research Mood & Anxiety Disorders Program National Institute of Mental Health (NIMH)

2 Child & Adolescent Anxiety: Psychopathology & Neuroscience Daniel S. Pine, MD Section on Development and Affective Neuroscience

3 Clinical Advances Longitudinal studies Family studies Treatment studies Neuroscience Outline Circuitry involved in fear among animals Extensions to children & novel treatment

4 Epidemiology of Major Depression Very common 5-20% of adolescents might be affected Normal vs. Abnormal Significantly impairing Missed school, friendships, family life Relationship to age, gender Frequently recurrent Bipolar disorder controversy

5 Epidemiology of Anxiety Types of Anxiety OCD PTSD Phobias, GAD, Separation Anxiety, Others More common than MDD Normal vs. abnormal The impairment & extreme distress criteria Relationship to age, gender Often predicts MDD

6 Any Adolescent Anxiety Disorder & Any Adult Mood/Anxiety Disorder Disorder as Adults? Disorder as Adolescents? No Yes No Yes Pine et al. 1998, 2001, 2002

7 Any Adolescent Anxiety Disorder & Any Adult Mood/Anxiety Disorder Disorder as Adults? Disorder as Adolescents? No Yes No Yes Pine et al. 1998, 2001, 2002

8 Any Adolescent Anxiety Disorder & Any Adult Mood/Anxiety Disorder Disorder as Adults? Disorder as Adolescents? No Yes No Yes Pine et al. 1998, 2001, 2002

9 Any Adolescent Anxiety Disorder & Any Adult Mood/Anxiety Disorder Disorder as Adults? Disorder as Adolescents? No Yes No Yes Pine et al. 1998, 2001, 2002

10 Family-Genetic Associations Studies of psychopathology Childhood anxiety and parental MDD Studies of Temperament Behavioral inhibition and parental MDD Familial aggregation Genetics & Environment

11 Treatment Major Depression SSRI Medications Psychotherapy: CBT? & IPT? Anxiety Disorders SSRI Medications Psychotherapy: CBT

12 Treatment Major Depression SSRI Medications Psychotherapy: CBT? & IPT? Anxiety Disorders SSRI Medications Psychotherapy: CBT

13 SSRIs and Pediatric MDD: Efficacy fluoxetine works (3 of 3½ studies) Weak evidence for sertraline (not really), citalopram (2 of 4 studies) Some (very weak) evidence for paroxetine Virtually no evidence for other agents What gives? Data in adults that strong? Differences among the SSRIs? Differences in placebo response, sample, assessment

14 Results Fluoxetine vs. placebo CBT vs. placebo What does this mean? Strong role of expectancy What do we recommend to patients? First Line Treatments?

15

16 Treatment Major Depression SSRI Medications Psychotherapy: CBT? & IPT? Anxiety Disorders SSRI Medications Psychotherapy: CBT

17

18 Meta-Analysis: Rates of Improvement Rates of Improvement Study Difference PBO SSRI RUPP Anxiety Study (2001) 47% 29% 76% Birmaher et al. (2003) 25% 36% 61% Rynn et al. (2001) 80% 10% 90% Wagner et al. (2004) 40% 38% 78% Walkup et al. (2008) 31% 24% 55% Rynn et al. (2007) 12% 24% 36% Total 30% 31% 61% NNT=3.3

19 Walkup J et al. N Engl J Med 2008; /NEJMoa

20 Treatment Anxiety vs. MDD Response rates Higher in anxiety than MDD Relapse rates Higher in MDD than anxiety

21 Antidepressants and Thoughts About Suicide FDA Analysis from December, 2006

22 Conclusions SSRIs are very effective in the treatment of pediatric anxiety. Of the SSRIs, only fluoxetine and citalopram have been clearly shown to be effective in pediatric MDD. Increased risk of suicidality with SSRI treatment is real, but the magnitude of the effect is small.

23 Advances in in Neuroscience Research on emotion has just begun Advantages More precise understanding of brain circuit Better handle on cause Generate new treatments, diagnostic tests Suitable models Basic science in rodents & primates Cognitive neuroscience

24 Treatment Neuroscience Anxiety vs. MDD Implications for Diagnosis Brain imaging in affected children Brain imaging and genes in those at risk Implications for Treatment Novel treatments for anxiety

25 Treatment Neuroscience Anxiety vs. MDD Implications for Diagnosis Brain imaging in affected children Brain imaging and genes in those at risk Implications for Treatment Novel treatments for anxiety

26

27 Amygdalar Activation Exposure to Fearful Face Amygdala hyperactivity in MDD and anxiety VS. Breiter et al. 1996; Whalen et al Bilateral Amygdala Activation

28 Treatment Neuroscience Anxiety vs. MDD Implications for Diagnosis Brain imaging in affected children Brain imaging and genes in those at risk Implications for Treatment Novel treatments for anxiety

29 VISUAL CORTEX VISUAL THALAMUS AMYGDALA HEART RATE BLOOD PRESSURE MUSCLE LeDoux. Sci Am. 1994;270:50.

30 Anxiety Score Attention Retraining Therapy Train to Neutral Train to Angry Altered Response to Stress Training of Attention Eldara, Ricona, & Bar-Haim

31

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33 NMDA manipulations? Ressler & Davis 2003

34 Conclusions Clinical Research Longitudinal course Familial aggregation Treatment Basic Science Research Developing better diagnostic markers? Producing novel treatments?

35 For any questions: To refer patients call:

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