Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm.
OBJECTIVE
Dysfunctional attitudes are negatively biased assumptions and beliefs regarding oneself, the world, and the future. In healthy subjects, increasing serotonin (5-HT) agonism with a single dose of d-fenfluramine lowered dysfunctional attitudes. To investigate whether the converse, a low level of 5-HT agonism, could account for the higher levels of dysfunctional attitudes observed in patients with major depression or with self-injurious behavior, cortex 5-HT(2) receptor binding potential and dysfunctional attitudes were measured in patients with major depressive disorder, patients with a history of self-injurious behavior, and healthy comparison subjects (5-HT(2) receptor density increases during 5-HT depletion).


METHODS
Twenty-nine healthy subjects were recruited to evaluate the effect of d-fenfluramine or of clonidine (control condition) on dysfunctional attitudes. Dysfunctional attitudes were assessed with the Dysfunctional Attitude Scale 1 hour before and 1 hour after drug administration. In a second experiment, dysfunctional attitudes and 5-HT(2) binding potential were measured in 22 patients with a major depressive episode secondary to major depressive disorder, 18 patients with a history of self-injurious behavior occurring outside of a depressive episode, and another 29 age-matched healthy subjects. Cortex 5-HT(2) binding potential was measured with [(18)F]setoperone positron emission tomography.


RESULTS
In the first experiment, dysfunctional attitudes decreased after administration of d-fenfluramine. In the second experiment, in the depressed group, dysfunctional attitudes were positively associated with cortex 5-HT(2) binding potential, especially in Brodmann's area 9 (after adjustment for age). Depressed subjects with extremely dysfunctional attitudes had higher 5-HT(2) binding potential, compared to healthy subjects, particularly in Brodmann's area 9.


CONCLUSIONS
Low levels of 5-HT agonism in the brain cortex may explain the severely pessimistic, dysfunctional attitudes associated with major depression.
Meyer
Jeffrey H
JH
Vivian M. Rakoff PET Imaging Centre, Clarke Division, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St., Toronto, ON, M5T 1R8, Canada. jmeyer@camhpet.on.ca
McMain
Shelley
S
Kennedy
Sidney H
SH
Korman
Lorne
L
Brown
Gregory M
GM
DaSilva
Jean N
JN
Wilson
Alan A
AA
Blak
Thomas
T
Eynan-Harvey
Rahel
R
Goulding
Verdell S
VS
Houle
Sylvain
S
Links
Paul
P
D000293:Adolescent; D000328:Adult; D001290:Attitude; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D003000:Clonidine / Q000494:pharmacology; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology; D006801:Humans; D008297:Male; D010555:Personality Inventory; D011744:Pyrimidinones; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D016728:Self-Injurious Behavior / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D014055:Tomography, Emission-Computed
D011744:Pyrimidinones; D011985:Receptors, Serotonin; D005277:Fenfluramine; C045359:setoperone; D003000:Clonidine