psychiatric and physical comorbidities and their impact on the course of bipolar disorder a prospective naturalistic 4year followup study objectives the aim of the present study was to increase the available evidence on how physical and psychiatric comorbidities influence the longterm outcome in bipolar i and ii disordermethods we examined the prevalence of comorbid physical metabolic cardiovascular thyroid and neurological diseases and psychiatric neurotic stressrelated somatoform and personality disorders and their impact on the risk of relapse in bipolar disorder a total of 284 consecutively admitted patients with icd10 bipolar i n161 and ii n123 disorder were followed up naturalistically over a period of 4 yearsresults globally 220 patients had metabolic 188 cardiovascular 188 thyroid and 76 neurological diseases 155 had neurotic stressrelated and somatoform disorders 120 had personality disorders and 529 had nicotine dependence we did not find any effect of comorbid metabolic cardiovascular or neurological diseases or psychiatric disorders on the relapse risk however the presence of thyroid diseases and especially hypothyroidism was associated with an increased risk of manic relapse in bipolar disorder i thyroid disease hazard ratio hr27 p003 hypothyroidism hr37 p001 among patients with hypothyroidism higher blood levels of baseline thyroidstimulating hormone btsh were also associated with an increased risk of manic relapse hr107 per milliinternational units per liter p011 whereas blood levels of free triiodothyronine ft3 or free thyroxine ft4 were not found to have an influenceconclusions our data underline the negative longterm impact of thyroid diseases and especially hypothyroidism with high blood levels of btsh on bipolar disorder with more manic episodes and the importance of its detection and treatment