Abstract
Melatonin is a nocturnally secreted hormone believed to play a major role in circadian regulation. Patients with bipolar affective disorder (BPAD) have super sensitivity to the melatonin suppressing effects of light compared to matched controls [1], [2]. This super sensitivity also occurs in BPAD probands offspring [3] suggesting this phenomenon has a genetic diathesis and represents a potential trait marker of illness. This case study reports on a pair of monozygotic twins discordant for both BPAD disorder and melatonin sensitivity to light.
The female twins were aged 22 at testing and monozygosity established through DNA testing. Twin A had a 4-year history of BPAD-1 confirmed by clinical interview (JO) and the Composite International Diagnostic Interview (CIDI-auto). At the time of testing, Twin A had been euthymic for more than 6months and was maintained on lithium carbonate (750 mg/day) and sodium valproate (2000 mg/day). Twin B had no psychiatric history. Both twins attended the Department of Psychiatry, Austin Health on four testing nights. Serial blood samples were collected at regular intervals between 20.00 hours and 02.30 hours on each night and assayed for melatonin levels by specific radioimmunoassay. At 21.00 hours, the twins were seated in a darkened room and on the baseline night they remained in this environment through the night. On the next three nights a light-box was used to create light at intensities of 200, 500 and 1000 lux at eye level between 24.00 hours and 01.00 hours. Changes in plasma melatonin levels across the baseline night were analysed by an area under the melatonin concentration– time curve. Melatonin suppression by light was calculated by contrasting the change between 23.45–24.00 hours and 00.45–01.00 hours.
The results of the baseline night indicated that both twins had a normal melatonin rhythm with rising plasma melatonin levels between 21.00 hours and 01.30 hours. However, Twin A had about a third less overall melatonin secretion than her unaffected twin (1280 pg.h/mL vs 3413 pg.h/mL). The suppression of melatonin between midnight and 01.00 hours for the twins A versus B was 43% versus 17%, 58% versus 40% and 74% versus 59% at 200, 500 and 1000 lux, respectively. A paired samples t-test showed that Twin A had significantly greater melatonin suppression by light, t(1,3) =3.436; p=0.041.
The current study shows decreased melatonin production and an increased sensitivity to light in a twin with BPAD compared to her unaffected monozygotic twin.
Medications are unlikely to account for differences in sensitivity as recent research indicates that both lithium and valproate decrease sensitivity to light in healthy controls [4], [5]. Evidence from a larger twin study in our laboratory indicates that normalmonozygotic twins are highly concordant on light sensitivity [Hallam, KT: unpublished data]. However, in this case study the affected twin shows sensitivity similar to patients with BPAD in previous studies [1], [2] while her unaffected twin was similar to a control subject. Despite a growing body of evidence indicating a genetic pre-disposition to BPAD the biochemical abnormalities underlying the illness are still unknown. The present results support the notion that abnormalities in circadian systems are a factor in the pathogenesis and symptommatology of BPAD.