The role of the hypothalamic-pituitary-thyroid (HPT) axis in psychiatric symptoms and disorders has been stressed in many studies. Secretion of thyroid hormones is controlled by this axis. Hypothalamic thyrotropin releasing hormone (TRH) stimulates pituitary thytrotropin-stimulating hormone (TSH) and the latter controls the secretion of thyroid hormones. Serum thyroid hormones regulate the HPT axis by a negative feedback system. The main secretion of the thyroid gland is thyroxine (T4). T4 is converted into triiodothyronine (T3) in various tissues, especially in brain, by enzymes called "deiodinases". Transthyretin, a hormone transporter, transports T4 into the brain (1).
Thyroid hormones play a critical role in the developing and functioning of the brain (2). In this regard, it is suggested that interactions between thyroid hormones and neurotransmitter systems, especially serotonin (5-HT), norepinephrine (NE) and acetyl choline (Ach), probably contribute to the regulation of mood and behaviour (1). T3 enhances the effects of NE, 5-HT and ?-aminobutyric acid, which are thought to be involved in the etiology of some psychiatric conditions (3).
In the literature there are many case reports and studies indicating probable relationships between clinical or subclinical thyroid diseases and psychiatric disorders. So far, many cases have been reported of hypothyrodism or hyperthyroidism associated with psychiatric disorders, including mania, depression, schizophreniform psychosis, paranoid psychosis, cognitive disturbances, delirium and anxiety (4-9). One percent of thyrotoxic patients are suggested to have been first diagnosed with a psychiatric disease (5). Interestingly, it seems that both hyperthyroism and hypothyroidism could lead to mania, anxiety or schizophrenic symptoms. The underlying reason for the co-occurrence of thyroid diseases and psychiatric disorders is not yet known. However, in these cases, combined hormonal and psychotropic interventions may improve symptoms.
Several studies have assessed HPT axis activity in various psychiatric disorders, especially mood disorders and anxiety disorders. Up to 45% of the euthyroid patients with major depression showed blunted TSH response to TRH stimulation (10). Moreover, thyroid hormones accelerate the antidepressant effect of tricyclic antidepressants (11). HPT axis alterations may play an important role in the pathophysiology of bipolar disorder, but this area has received much less attention than major depressive disorder. However, it seems that abnormalities of this axis are not uncommon among bipolar patients, especially among the rapid cycling subgroup. So far, thyroid dysfunctions such as hypothyroidism and exaggerated TSH response to TRH have been found in rapid cycling patients (12,13). In some bipolar patients, latent thyroid dysfunction becomes overt by lithium treatment. Moreover, it has been suggested in a recent study that bipolar disorder itself may cause increased thyroid volumes and decreased thyroid hormones as well as lithium treatment in patients (14).
Few studies have investigated possible thyroid dysfunctions in psychotic patients. In a study, schizophrenic patients showed increased serum T4 levels, which normalized after antipsychotic treatment. Elevated serum T4 levels in schizophrenic patients may suggest an impairment of T4 metabolism in the brain (4).
A few studies of panic disorder have demonstrated evidence of a blunted TSH response to TRH. A previous study showed higher TSH levels in non-medicated patients with severe panic attacks (7). Increased TSH levels seen in patients with panic disorder might be due to reduced intracerebral 5-HT concentrations (15).
Eletroconvulsive therapy (ECT) itself may affect the HPT axis as do psychotropic drugs. In a previous study, elevated TSH levels were found following ECT in depressed patients. This response might contribute to the therapeutic effect of ECT (16).
In conclusion, the HPT axis and thyroid hormones play an important role in the pathophysiology of many psychiatric disorders. However, further well-designed studies are needed to clarify the confusion in this field.