Involvement
of dopaminergic mechanisms in the altered reward
processing in major depressive
disorder
Major
depressive disorder (MDD) is associated with
altered brain activity in the prefrontal cortex,
limbic regions, and basal ganglia, and with
abnormalities in the neurotransmitters such as
serotonin, noradrenaline, and dopamine. The link
between these disturbances and the specific
behavioral symptoms of depression remains to be
elucidated. The brain reward system (BRS)
mediates reward behaviors such as pleasure and
motivation. A recent study used
dextroamphetamine in association with functional
magnetic resonance imaging (fMRI) to determine
the neuroanatomical substrates of the altered
BRS responses in MDD.
Twelve unmedicated patients with MDD and twelve
control subjects were studied. All participants
underwent fMRI before and 90 minutes after
taking a 30 mg dose of dextroamphetamine, which
was used as a dopaminergic BRS probe to elicit
measurable rewarding effects. fMRI was performed
during a controlled task with the International
Affective Picture System. The Addiction Research
Center Inventory evaluated the rewarding effects
of dextroamphetamine.
MDD subjects had a 2-fold greater response
to the rewarding effects of dextroamphetamine
comparedto the controls. In addition the degree
of dextroamphetamine reward was associated with
the severity of the anhedonia. Following
dexamphetamine administration MDD subjects
showed a decreased activation in the right
ventrolateral prefrontal cortex, the left and
right caudate and putamen, the left
orbitofrontal cortex, and the supplementary
motor cortex and premotor cortex but an
increased activation of the right and left
temporal poles.
These results suggest that altered dopaminergic
mechanisms in reward processing may be involved
of in MDD. This might help further the
understanding of the neurobiology of anhedonia
in MDD. BRS responses could prove to be useful
for testing new potential anti-anhedonic drugs
for treating MDD. Tremblay
LK, Naranjo CA, Graham SJ, Herrmann N, Mayberg
HS, Hevenor S, Busto UE. Functional
neuroanatomical substrates of altered reward
processing in major depressive disorder revealed
by a dopaminergic probe. Arch Gen Psychiatry
2005, 62:1228-1236.