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Methamphetamine and the Brain: A Problem of Inhibitory Control. Edythe D. London, Ph.D. David Geffen School of Medicine, UCLA. Mood Disorder anxiety depression. Cognitive Deficits decision-making response inhibition. Inhibitory Control Problems. Drug Abuse.
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Methamphetamine and the Brain: A Problem of Inhibitory Control Edythe D. London, Ph.D. David Geffen School of Medicine, UCLA
MoodDisorder anxiety depression Cognitive Deficits decision-makingresponse inhibition Inhibitory Control Problems Drug Abuse Inhibitory Control Problems (Impulsivity)
HIV Prevalence in LA County heroin injectors at low risk gay male METH users at extreme risk METH-dependent subjects 0 Outpatient clinic, hetero METH-dependent subjects 61 Outpatient clinic, gay/bi Heroin addicts Methadone clinics 10 7 Street heroin addicts 0 20 40 60 80 % HIV Positive LAC HIV Epidemiology (1999-2004);Methamphetamine Use Among Gay and Bisexual Men in LA.http://www.uclaisap.org/documents/final-report_cjr_1-15-04.pdf.
Brain Metabolism During Early Abstinence from Methamphetamine t-values Medial PFC 5 3.5 4 2.5 3 1.5 2 Amygdala 1 0.5 MA > Control Control > MA ED London et al., Arch. Gen. Psychiatry, 2004
t-values 5 4 6 3 2 4 1 2 (+) (-) Mood Disorder in METH Abuse:Related to Glucose Metabolism Depression Anxiety PFC Amygdala ED London et al., Arch. Gen. Psychiatry, 2004
5 4 3 2 1 Loss of Cortical Inhibition of the Amygdala t-values OFC Amygdala 3.5 2.5 1.5 0.5 Control > MA MA > Control Environmental stimuli exaggerated responses ● depression● anxiety● craving ●hostility
Gray Matter Deficits in Cortex PM Thompson et al., J. Neurosci., 2004
Gray Matter Deficit inPrefrontal Cortex PM Thompson et al., J. Neurosci. 2004
Impairment on the Stop-Signal Taskis Related to Methamphetamine Use controlnonsmoker control smoker METH users J. Monterosso et al., Drug Alcohol Depend., 2005
Conscious Emotion Control during fMRI K. Baicy et al., Abstr. Soc. Neurosci, 2006
METH-Dependent Subjects have LowerEmotion Ratings than Healthy Subjects * p = 0.02 vs. “Look” *p = 0.02 vs. control *p = 0.02 vs. control MA Control MA Control
Greater Response of Amygdala inMETH-Dependent Subjects METH-dependent subjects > control LOOK negative > neutral left amygdala, p<0.001 uncorrected, t = 5.68
Greater Activation of PFC in Healthy Subjects During Cognitive Reappraisal Control > METH dependent subjects DECREASE > LOOK p = 0.026, corrected false discovery rate (FDR), t = 4.16
Affect Matching Task Which of the two bottom pictures matches the emotion shown on top?
METH Dependence Blunted Activation: Right Ventrolateral PFC Heightened Activation: Dorsal ACC Pain, Socioemotional threat Emotion integration, Inhibition T T • Dorsal ACC activitycorrelated with: • hostility • interpersonal sensitivity P<.005, 10 voxel extent (n = 12/group) D Payer et al., manuscript in review 2007
Negative Correlation of Activity in Right VLPFC and dACC Problems inhibiting threat response in METH dependence?..... Posterior ACC Right Ventrolateral PFC r = -.516, p < .001
Therapy for Impairments Inhibitory Control Behavioral Therapy Pharmacological Therapy Medications used for Other disorders: ModafinilBupropion Cognitive Behavioral Therapy Attention Process Training
Acknowledgements UCLA Faculty Walter Ling Richard Rawson Tom Newton Sara Simon Timothy Fong Steve Berman John Monterosso Paul Thompson Russell Poldrack Roger Woods Research Fellows Students Jennifer Learn Yun Dong Aaron Lichtman Kate Baicy Doris Payer Grant support: R01 DA 15179 (EDL), R01DA020726 (EDL), Contract 1YO1 DA 50038 (WL, EDL) K01 DA00515-01A1 (JM), MOI RR 00865