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)
Child & Adolescent Anxiety: Psychopathology & Neuroscience Daniel S. Pine, MD Section on Development and Affective Neuroscience
Clinical Advances Longitudinal studies Family studies Treatment studies Neuroscience Outline Circuitry involved in fear among animals Extensions to children & novel treatment
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
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
Any Adolescent Anxiety Disorder & Any Adult Mood/Anxiety Disorder Disorder as Adults? Disorder as Adolescents? No Yes No 390 36 426 Yes 191 62 253 581 98 679 Pine et al. 1998, 2001, 2002
Any Adolescent Anxiety Disorder & Any Adult Mood/Anxiety Disorder Disorder as Adults? Disorder as Adolescents? No Yes No 390 36 426 Yes 191 62 253 581 98 679 Pine et al. 1998, 2001, 2002
Any Adolescent Anxiety Disorder & Any Adult Mood/Anxiety Disorder Disorder as Adults? Disorder as Adolescents? No Yes No 390 36 426 Yes 191 62 253 581 98 679 Pine et al. 1998, 2001, 2002
Any Adolescent Anxiety Disorder & Any Adult Mood/Anxiety Disorder Disorder as Adults? Disorder as Adolescents? No Yes No 390 36 426 Yes 191 62 253 581 98 679 Pine et al. 1998, 2001, 2002
Family-Genetic Associations Studies of psychopathology Childhood anxiety and parental MDD Studies of Temperament Behavioral inhibition and parental MDD Familial aggregation Genetics & Environment
Treatment Major Depression SSRI Medications Psychotherapy: CBT? & IPT? Anxiety Disorders SSRI Medications Psychotherapy: CBT
Treatment Major Depression SSRI Medications Psychotherapy: CBT? & IPT? Anxiety Disorders SSRI Medications Psychotherapy: CBT
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
Results Fluoxetine vs. placebo CBT vs. placebo What does this mean? Strong role of expectancy What do we recommend to patients? First Line Treatments?
Treatment Major Depression SSRI Medications Psychotherapy: CBT? & IPT? Anxiety Disorders SSRI Medications Psychotherapy: CBT
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
Walkup J et al. N Engl J Med 2008;10.1056/NEJMoa0804633
Treatment Anxiety vs. MDD Response rates Higher in anxiety than MDD Relapse rates Higher in MDD than anxiety
Antidepressants and Thoughts About Suicide FDA Analysis from December, 2006
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.
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
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
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
Amygdalar Activation Exposure to Fearful Face Amygdala hyperactivity in MDD and anxiety VS. Breiter et al. 1996; Whalen et al. 1998 Bilateral Amygdala Activation
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
VISUAL CORTEX VISUAL THALAMUS AMYGDALA HEART RATE BLOOD PRESSURE MUSCLE LeDoux. Sci Am. 1994;270:50.
Anxiety Score Attention Retraining Therapy 12 10 8 6 4 2 0 Train to Neutral Train to Angry Altered Response to Stress Training of Attention Eldara, Ricona, & Bar-Haim
NMDA manipulations? Ressler & Davis 2003
Conclusions Clinical Research Longitudinal course Familial aggregation Treatment Basic Science Research Developing better diagnostic markers? Producing novel treatments?
For any questions: To refer patients call: 1-301-496-6643 daniel.pine@nih.gov 301.594.1318