Clinical and neurochemical effect of acute tryptophan depletion in unaffected relatives of patients with bipolar affective disorder.
BACKGROUND
The lowering of mood induced by an acute tryptophan depletion (ATD) has been proposed as a candidate endophenotype for the vulnerability to manic-depressive illness. This study tests this hypothesis in relatives of probands from well-characterized multiplex families affected with bipolar affective disorder (BAD).


METHODS
In a double-blind, crossover design, 20 unaffected relatives (URs) and 19 control subjects received either a 100-g amino acid (AA) drink devoid of tryptophan or a placebo, respectively. Clinical and biochemical effects of ATD were compared between unaffected relatives of BAD probands and age- and sex-matched control subjects.


RESULTS
At 5 hours after AA drink ingestion, relative to the placebo, ATD resulted in 74% and 84% decreases in total plasma tryptophan concentrations in control subjects and relatives of patients with BAD, respectively. Unlike control subjects unaffected relatives experienced a lowering of mood during ATD but not with the placebo. Furthermore, URs tended to show increased impulsivity in the ATD condition. Measurements obtained before ingestion of the AA drink indicated that, relative to control subjects URs exhibited lower serotonin platelet concentrations, lower affinity, and fewer binding sites of the serotonin transporter for imipramine; these differences were unaffected by ATD.


CONCLUSIONS
These results replicate and extend previous findings suggesting that URs of patients with BAD are more susceptible to low tryptophan availability. This finding may bear significance in the purported role of serotonergic mechanisms in the vulnerability to depressive syndrome and/or illness.
Quintin
P
P
Service de Psychiatrie, Hôpital Albert Chenevier et Henri Mondor, AP-HP, Creteil, France.
Benkelfat
C
C
Launay
J M
JM
Arnulf
I
I
Pointereau-Bellenger
A
A
Barbault
S
S
Alvarez
J C
JC
Varoquaux
O
O
Perez-Diaz
F
F
Jouvent
R
R
Leboyer
M
M
D000208:Acute Disease; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007099:Imipramine / Q000627:therapeutic use; D008297:Male; D012701:Serotonin / Q000097:blood; D009435:Synaptic Transmission / Q000502:physiology; D014364:Tryptophan / Q000097:blood / Q000172:deficiency*
D000929:Antidepressive Agents, Tricyclic; D012701:Serotonin; D014364:Tryptophan; D007099:Imipramine