A poor night’s sleep is enough to put anyone in a bad mood, and although scientists have long suspected a link between mood and sleep, the molecular basis of this connection remained a mystery. Now, new research has found several rare genetic mutations on the same gene that definitively connect the two.
Sleep goes hand-in-hand with mood. People suffering from depression and mania, for example, frequently have altered sleeping patterns, as do those with seasonal affective disorder (SAD). And although no one knows exactly how these changes come about, in SAD sufferers they are influenced by changes in light exposure, the brain’s time-keeping cue.
Although a number of tantalizing leads have linked the circadian clock to mood, there is “no definitive factor that proves causality or indicates the direction of the relationship,” says Michael McCarthy, a neurobiologist at the San Diego Veterans’ Affairs Medical Center and the University of California (UC), San Diego.
To see whether they could establish a link between the circadian clock, sleep, and mood, scientists in the new study looked at the genetics of a family that suffers from SAD and advanced sleep phase. The scientists screened the family for mutations in key genes involved in the circadian clock, and identified two rare variants of the PERIOD3 (PER3) gene in members suffering from SAD and advanced sleep phase.
“We found a genetic change in people who have both seasonal affective disorder and the morning lark trait” says lead researcher Ying-Hui Fu, a neuroscientist at UC San Francisco. When the team tested for these mutations in DNA samples from the general population, they found that they were extremely rare, appearing in less than 1% of samples.
Fu and her team then created mice that carried the novel genetic variants. “PER3’s role in mood regulation has never been demonstrated directly before,” she says. “Our results indicate that PER3 might function in helping us adjust to seasonal changes,” by modifying the body’s internal clock.
“The identification of a mutation in PER3with such a strong effect on mood is remarkable,” McCarthy says. “It suggests an important role for the circadian clock in determining mood.”
The next step will be to investigate how well these results generalize to other people suffering from mood and sleep disorders.