Objective: Transthyretin plays an important role in the transport and distr
ibution of thyroid hormone in the central nervous system (CNS). This study
replicated and extended to patients with nonrefractory depressive illness a
pilot study indicating that patients with refractory major depression have
significantly lower levels of CSF transthyretin than do healthy comparison
subjects. Method: Lumbar punctures were performed in drug-free subjects wi
th DSM-III-R major depression (N=18), DSM-III-R bipolar disorder, depressed
phase (N=1), and healthy comparison subjects (N=24). CSF concentrations of
transthyretin, determined by a quantitative dot-immunobinding assay, of th
e depressed patients and comparison subjects were compared by analysis of c
ovariance (ANCOVA). The relationship between CSF transthyretin levels and H
amilton Depression Rating Scale scores was determined in a subset of the de
pressed patients. Results: CSF concentrations of transthyretin were signifi
cantly lower in the depressed patients than in the comparison subjects by A
NCOVA. Within the depressed group there was no significant overall correlat
ion between CSF transthyretin levels and Hamilton depression scale scores,
but there was a significant inverse correlation in male depressed patients
(N=8) between CSF transthyretin concentrations and Hamilton depression scor
es. Conclusions: Lower CSF transthyretin concentrations in depressed patien
ts may reflect either a stable trait in this population or a state change s
econdary to depression or other factors. Lower CSF transthyretin concentrat
ions may result in altered CNS thyroid hormone homeostasis. Such alteration
could account for certain mood and neurovegetative symptoms of depression
and might contribute to failure of standard antidepressant treatment.