Harvard Mental Health Letter

Thyroid deficiency and mental health

At least 13 million Americans suffer from thyroid disorders, and in more than 80% of cases, the problem is an underactive thyroid gland — hypothyroidism. The condition is more common in women, and the rate rises with age, reaching 20% in women over 65. The interest for mental health is that thyroid deficiency may be associated with cognitive and emotional disturbances, and thyroid hormones may be useful in the treatment of depression.

Sitting at the base of the neck, the thyroid gland produces hormones that regulate basal metabolic rate, the speed at which our bodies burn food for energy. The thyroid gets its directions from the hypothalamus, at the base of the brain, by way of the pituitary gland. On a signal from the hypothalamus, the pituitary sends thyroid-stimulating hormone (TSH) into the bloodstream. It travels to the thyroid gland and causes the release of thyroxine (T4), which is partly converted into triiodothyronine (T3). Through a feedback mechanism, the hypothalamus determines when levels of T4 and T3 are low and alerts the pituitary to supply more TSH.

In a person with hypothyroidism, the thyroid gland does not fully respond to TSH, so levels of T3 and T4 remain low while TSH accumulates in the blood. The most common cause is an autoimmune disease, Hashimoto's thyroiditis, but the symptoms can also result from an infection, from cancer, or from treatment of an overactive thyroid (hyperthyroidism) with surgery, radiation, or medications.

Clinical hypothyroidism is identified by an abnormally high level of TSH and abnormally low levels of thyroid hormones. It is treated with a synthetic form of thyroxine, taken in a pill. Subclinical thyroid deficiency, which has few or no symptoms, is defined as abnormally high TSH with normal thyroid hormone levels. Experts disagree on whether and when it requires treatment.

The symptoms of hypothyroidism are variable and sometimes hard to pin down. They may include fatigue, sluggishness, cold intolerance, weight gain, constipation, muscle or joint pain, thin and brittle hair or fingernails, reduced sexual drive, high blood pressure, high cholesterol, and a slow heart rate. Patients may also have problems with concentration and memory.

Some of these symptoms also occur in depression or other psychiatric disorders, and there may be links between hypothyroidism and depression, although the evidence is conflicting and doubtful.

Researchers at the University of Iowa found that among nearly 7,000 healthy young adults, men with TSH and T4 levels suggesting subclinical hypothyroidism were more likely to be depressed. In a Dutch study, depressed patients who were not taking antidepressants had higher blood levels of TSH than controls matched for age and sex. German researchers comparing psychiatric patients with and without thyroid conditions found a correlation between subclinical thyroid deficiency and mild depression. Thyroid abnormalities were not associated with any other psychiatric symptoms in this study. Another German study found an association between mood deterioration and clinical hypothyroidism. In a study of adolescent girls who had recently been sexually abused, lower levels of T4 were associated with post-traumatic stress disorder and depressive symptoms.

In an Italian study, 36 women with mild hypothyroidism performed poorly on neuropsychological tests and psychological rating scales. After six months of standard treatment with thyroxine, their mood and verbal fluency improved. Belgian researchers compared controls with patients before and after removal of the thyroid gland for cancer. After the operation, patients were more anxious and depressed than controls and had more problems with attention and executive function. Dutch researchers found that high levels of TSH were correlated with memory deficits in people in their 50s and 60s, but the difference vanished when depressive symptoms were taken into account.

But findings have been inconsistent, especially in studies with larger numbers of participants. In one such survey, Canadian researchers found that the only psychiatric disorder associated with thyroid disease was social anxiety disorder (social phobia). In a study of more than 300 people over age 60 who came to internal medicine and psychiatry clinics, some of them for depression and others for symptoms suggesting abnormal thyroid activity, researchers found a high rate of depression among those with subclinical hypothyroidism but not those with clinical hypothyroidism. A large Norwegian survey found no relationship between TSH levels and anxiety or depression.

So the influence of thyroid deficiency on mental health remains uncertain. Findings may conflict because studies have selected patients and evaluated depressive symptoms and thyroid function by different standards.

There's better evidence that thyroid medication may be helpful for depressed patients, even those with normal thyroid function. German researchers found that high doses of thyroxine improved the symptoms of 17 depressed patients who had not responded to antidepressant drugs. Half of them recovered, and only one failed to improve. These results have been replicated with T3.

More than a hundred Israeli patients with major depression were divided into two groups and given either an antidepressant alone or an antidepressant and thyroxine. The combination was nearly three times more likely to produce a response within six weeks.

Canadian researchers found that added thyroxine helped patients with major depression who did not respond to selective serotonin reuptake inhibitors.

Researchers at Massachusetts General Hospital in Boston administered either thyroxine or the mood stabilizer lithium to 142 patients whose depression had not improved despite earlier treatment. About 25% of those taking thyroxine improved, compared with 16% of those taking lithium.

Examining all the findings so far, an expert panel has concluded that there is not enough evidence to associate TSH levels with psychiatric symptoms or to recommend thyroxine treatment for depressed patients. But there may be just enough evidence to explore these possibilities further — and to recommend tests of thyroid function in seriously depressed patients.

References

Abraham G, et al. "T3 Augmentation of SSRI-Resistant Depression," Journal of Affective Disorders (April 2006): Vol. 91, Nos. 2–3, pp. 211–15.

Constant EL, et al. "Anxiety and Depression, Attention, and Executive Functions in Hypothyroidism," Journal of the International Neuropsychological Society (September 2005): Vol. 11, No. 5, pp. 535–44.

Engum A, et al. "Thyroid Autoimmunity, Depression and Anxiety; Are There Any Connections? An Epidemiological Study of a Large Population," Journal of Psychosomatic Research (November 2005): Vol. 59, No. 5, pp. 263–68.

Geracioti TD. "Identifying Hypothyroidism's Psychiatric Presentations," Current Psychiatry Online (November 2006): Vol. 5, No. 11. www.currentpsychiatry.com.

Nierenberg AA, et al. "A Comparison of Lithium and T3 Augmentation Following Two Failed Medication Treatments for Depression: A STAR*D Report," American Journal of Psychiatry (September 2006): Vol. 163, No. 9, pp. 1519–30.

Patten SB, et al. "Self-Reported Thyroid Disease and Mental Disorder Prevalence in the General Population," General Hospital Psychiatry (November–December 2006): Vol. 28, No. 6, pp. 503–08.

For more references, please see www.health.harvard.edu/mentalextra.