Evidence suggests brain serotonin (5HT) and behavioral alterations persist after recovery (REC) from bulimia nervosa (BN) and anorexia nervosa (AN). PET imaging, using radioligand technologies, has the potential of direct characterization of dynamic relationships between neurotransmission and human behavior. III and REC (>1 year normal menses; no binge/purging; healthy, stable weight) AN, BN, and BN-AN women (18 to 45 years old) will be studied to distinguish state and trait, and will be compared to healthy women.
In Aim 1 [11C]WAY100635 binding will assess 5HT(1A) receptors alterations that may be common to AN and BN. Studies suggest REC AN and BN have a 30 to 60% increase in binding of [11C]WAY100635 in the raphe nucleus (pre-synaptic 5HT(1A) autoreceptors) and cingulate-temporal regions (postsynaptic 5HT(1A) receptors), with binding in these latter regions positively correlated with anxiety. We hypothesize increased postsynaptic 5HT(1A) receptor activity is related to anxious, harm avoidant behaviors and is a susceptibility for developing an ED.
Aims 2 to 4 will investigate vulnerabilities that may distinguish AN and BN subtypes.
In Aim 2 [18F]altanserin binding will assess postsynaptic 5HT(2A) receptors. Data show diminished [18F]altanserin binding in orbital frontal regions in REC BN and in cingulate-temporal regions in REC AN. [18F]altanserin binding may reflect regional brain differences in modulation of impulse control, or motivation and integration of cognition and mood that may distinguish ED subgroups.
In Aim 3 [11C]raclopride binding will assess the dopamine D2 postsynaptic receptor as altered dopamine activity in AN women may contribute to increased motor activity and altered reward and novelty seeking.
In Aim 4 [11C]McN5652 binding will assess the 5HT transporter (5HT t ), as data raise a possibility that altered 5HT t activity may occur in BN.
Aim 5 will seek to replicate and extend data suggesting that 5HT activity in REC BN and AN may be dissociated from normal age- related relationships which may offer insights into developmental mechanisms. Understanding potential biologic vulnerabilities in AN and BN may contribute to developing new treatment interventions for these often chronic and deadly disorders as well as shed light on 5HT activity and behavior. This is a competing renewal of MH42984.
Showing the most recent 10 out of 77 publications
