Brain mechanisms associated with depressive relapse and associated cognitive impairment following acute tryptophan depletion.
BACKGROUND
Acute tryptophan depletion lowers brain serotonin synthesis and results in a transient, but striking, clinical relapse in recovered depressed patients.


OBJECTIVE
To identify brain regions which change their activity as an acute depressive relapse evolves and to determine how pathological mood might modulate neural activity during a cognitive task.


METHODS
We used H2(15)O positron-emission tomography (PET) to study eight recovered depressed men after tryptophan depletion and after a control procedure. During both PET scan sessions, subjects performed a paced verbal fluency task which alternated with a control verbal repetition task.


RESULTS
Increasing levels of depression after tryptophan depletion were associated with diminished neural activity in the ventral anterior cingulate, orbitofrontal cortex and caudate nucleus regions. In addition, depressive relapse attenuated cognitive task-related activation in the anterior cingulate cortex.


CONCLUSIONS
Our data indicate that changes in neural activity in distinct brain regions mediate the clinical phenomena of depression and depression-related cognitive impairment following acute tryptophan depletion. These changes could be associated with the widespread distribution of serotonin neurons in brain pathways associated with the expression of affect and cognitive performance.
Smith
K A
KA
University Department of Psychiatry, Warneford Hospital, Oxford.
Morris
J S
JS
Friston
K J
KJ
Cowen
P J
PJ
Dolan
R J
RJ
D000328:Adult; D001783:Blood Flow Velocity; D001927:Brain Diseases / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003866:Depressive Disorder / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011581:Psychological Tests; D012008:Recurrence; D012701:Serotonin / Q000378:metabolism; D014055:Tomography, Emission-Computed; D014364:Tryptophan / Q000097:blood / Q000172:deficiency*
D012701:Serotonin; D014364:Tryptophan