What are the Developmental Trajectories for Gray and White Matter? NIMH scanned children every 2 years for 8-10 years (N=1000 scans; ages 4-22) Analysis in collaboration with UCLA (P. Thompson), MNI (A. Evans)

Thompson/Sowell 2003 (N=45) Von Economo 1929

Cortical Thinning During Brain Development: Primary Cortices -> Association Cortices 13 children scanned with MRI every 2 years for 8 years What is the dynamic trajectory of cortical thinning? Gogtay/ Thompson PNAS 2004

Time-Lapse Map of Brain Development (PNAS, 2004)

Childhood Onset Schizophrenia (COS; N=94) Onset before age 13; Unmodified DSM IIIR/IV criteria Premorbid IQ >70; No Primary Neurological Disorder Severe, treatment refractory Rare (~ 1 in 30,000 – 50,000) Continuous with adult onset schizophrenia but somewhat less confounded (e.g., substance abuse)

Derailment of Teenage Brain Development 1 Derailment of Teenage Brain Development 1. Teens with Schizophrenia show a progressively spreading wave of gray matter loss (Thompson PNAS 2001) 2. Worse SANS, SAPS, and CGAS scores at follow-up correlate with greater loss at follow-up 3. Follows trajectory of normal brain maturation but exaggerated (up to 5% loss/year; worst in frontal cortex)

P. Thompson et al., PNAS 2001

P. Thompson et al., PNAS 2001

P. Thompson et al., PNAS 2001

Bipolar Brain Development (Ratio Maps) 9 Bipolar v. 12 Controls; 3 scans each, Age, sex and scan interval matched. Gogtay et al. JCPP in Press COS Brain Development 12 COS v. 12 Controls; 3 scans each Age, sex and scan interval matched. Thompson et al. PNAS 2001

P. Thompson et al., Nature Neurosci. 2001

P. Thompson et al., Nature, 2000

P. Thompson et al., Nature, 2000

Mean Annualized Growth Rate Maps NIMH HEALTHY CONTROLS N=12 (6 male / 6 female), AGE: 13.5±0.7 yrs. at baseline NIMH CHILDHOOD-ONSET SCHIZOPHRENIA (COS) N=12 (6 male / 6 female), AGE: 13.9±0.8 yrs. at baseline % Growth Rate shown in RED % Loss Rate shown in BLUE Thompson/ Rapoport 2007 -2% -1% 0% +1% +2%