THE PREVALENCE OF AFFECTIVE-DISORDER AND IN PARTICULAR OF A RAPID-CYCLING OF BIPOLAR DISORDER IN PATIENTS WITH ABNORMAL THYROID-FUNCTION TESTS

OBJECTIVE Cognitive and affective functioning is sensitive to changes in thyroid hormones. We have sought to determine: (1) the prevalence o f thyroid function abnormalities in a psychiatric population on admiss ion (as compared to the prevalence in a normal population), and (2) wh ether such thyroid function abnormalities are associated with the occu rrence or development of cognitive and affective disorders. DESIGN Ser um was collected 2-3 weeks after hospitalization in 3 major clinics fr om 3756 psychiatric patients in 1987-1990, stored, and assayed in 1993 for the presence of antibodies against the TSH-receptor and thyropero xidase (TPO-Ab) and for TSH levels. The psychiatric cohort was matched with a control population of healthy individuals living in the same a rea (n = 1877). The prevalence study was followed by a case-control st udy involving patients from one clinic that had routinely assigned a D SM-IIIR classification to its patients. Cases were those admissions wi th thyroid abnormalities and three subgroups of cases were randomly fo rmed demonstrating either TSH less than 0.4 mU/l (n = 44) or over 4.0 mU/l (n = 44), or TPO-Ab positivity (n = 50). Cases were compared to r andom controls from the same psychiatric population, viz patients with out thyroid abnormalities (n = 83). Comparison was with respect to the ir psychiatric follow-up diagnosis (the investigator was blinded to th e thyroid test results). RESULTS Prevalence study. The percentage of p atients positive for TSH-receptor-Ab was 0.26 (9/3504), for TPO-Ab was 10.0 (331/3316) and outside the TSH range of 0.4-4.0 mU/l was 10.0 (( 332/3316): 5.9% (198/3316) > 4.0 mU/l and 4.1% (134/3316) < 0.4 mU/l). Abnormal total thyroxine levels were found in only 9.8% of subjects w ith abnormal TSH, indicating the predominantly subclinical character o f the thyroid alteration. In comparison, the healthy area controls ove r 55 years of age showed the same prevalence of positive TPO-antibodie s and TSH under 0.4 mU/l, but a higher prevalence of TSH over 4.0 mU/l . Case-control study. In the case control analysis differences could n ot be noticed with regard to prevalences of dementia, schizophrenia or other psychiatric illnesses apart from the prevalence of affective di sorders which were more prevalent in TPO-Ab positive patients and pati ents with a low serum TSH. Since prior use of lithium, carbamezapine, carbimazole and/or thyroxine could be a factor of importance in this a ssociation, analyses were also carried out excluding patients with suc h prior drug use. In these analyses affective disorders were still mor e prevalent in patients with a low serum TSH (particularly in males, 4 0% in cases vs 9% in controls, P < 0.05). The most significant associa tion was however between TPO-antibody positivity (and in particular wi th high titre and/or with TSH > 4.0 mU/l) and a subgroup of the affect ive disorders, viz with a rapid cycling of bipolar disorder (18% in ca ses vs 0% in controls, P < 0.001). CONCLUSION Though causal relations cannot be determined from this cross-sectional study, this admission s urvey found early forms of autoimmune thyroid disease, sometimes chara cterized only by TPO-Abs, highly significantly associated with rapid c ycles of a bipolar disorder. It also found a weak association between subclinical hyperthyroidism (low serum TSH without TPO-Ab positivity) and affective disorder.