Low levels of transthyretin in the CSF of depressed patients.

OBJECTIVE: Transthyretin plays an important role in the transport and distribution 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 with 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 the depressed patients and comparison subjects were compared by analysis of covariance (ANCOVA). The relationship between CSF transthyretin levels and Hamilton Depression Rating Scale scores was determined in a subset of the depressed patients. RESULTS: CSF concentrations of transthyretin were significantly lower in the depressed patients than in the comparison subjects by ANCOVA. Within the depressed group there was no significant overall correlation 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 scores. CONCLUSIONS: Lower CSF transthyretin concentrations in depressed patients may reflect either a stable trait in this population or a state change secondary to depression or other factors. Lower CSF transthyretin concentrations 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.

CSF transthyretin in patients with depression.

Some depressed patients may suffer from restricted central hypothyroidism, which could occur if levels of the thyroid hormone transport protein transthyretin were low. CSF transthyretin was measured in eight inpatients with refractory major depression and nine neurological patients. The depressed patients had significantly lower transthyretin levels than the comparison subjects, suggesting that central hypothyroidism, with normal peripheral thyroid concentrations, could occur in some depressed patients.

The pharmacotherapy of moral or religious scrupulosity.

Moral or religious scrupulosity is a disabling condition which is sometimes seen in patients with obsessive compulsive disorder (OCD). The authors described 10 patients with moral or religious scrupulosity who were treated with fluoxetine or clomipramine. Seven of the 10 patients completed open treatment of at least 8 weeks without requiring adjunctive medication; 5 of those 7 patients were rated as much improved. Among the 3 patients who required adjunctive medication, 1 was rated as much improved. Of the 4 nonresponders at 3 months, 2 responded after longer treatment trials. These results suggest that extreme moral or religious concerns and behaviors might be a form of OCD and that the scrupulosity can be effectively treated with serotonin reuptake blockers.

Pharmacotherapy of four men with paruresis.

Four men with paruresis received trials of atenolol or phenelzine or both. Atenolol was effective in one patient. Three patients had a poor response to phenelzine, and they all experienced troublesome side effects.

Thyroid function in patients maintained on lithium.

To determine the clinical significance of thyroid function abnormalities in patients maintained on lithium, the authors evaluated the relationships of thyroid function tests to clinical response to lithium and side effects from lithium in 20 outpatients meeting DSM-III criteria for major affective disorder. No significant relationships were found between baseline thyroid function tests and clinical response. Thyroxine (T4) and triiodothyronine uptake ratio (T3UR) within the normal range were found to be associated with complaints of lethargy and cognitive impairment. Thirteen subjects were followed prospectively for 6 months with monthly evaluations of affective state, side effects, and occurrence of relapse. Thyroid function tests were repeated at the final visit. Final and mean T3 levels within the normal range were found to be significantly lower in patients who relapsed, and mean T3 level was inversely correlated with affective state as measured by mean scores on the Hamilton Rating Scale for Depression and the Young Mania Rating Scale.

Occult thyroid dysfunction in patients with refractory depression.

Assessment of metabolic rate was useful in evaluating refractory depression in six of 15 women. Five of the six had normal levels of T3 and T4; however, each had an elevated thyrotropin-stimulating hormone level or a low metabolic rate. The depressions responded to medication with thyroid hormone.