We must have all noticed how we can get cranky when we have not had a good night’s sleep. This apparent link has, however, not been fully explained in scientific terms: the biology behind the pattern as to the molecular links has otherwise remained a mystery. Until now. A new study, published in the Proceedings of the National Academy of Sciences, has recently provided unprecedented insight into the subject.
The findings show that a protein called period circadian protein homolog 3 is involved in the link between sleep patterns and mood; it has previously been associated with the regulation of the circadian clock (more commonly known as the body clock, it governs the timing of physiological processes over the day, including sleeping patterns). Previous research has suggested that polymorphism (variant forms of genes) involving the gene coding for the protein, the PERIOD3 (PER3) gene, is associated with sleep disorders.
The researchers had previously found faulty forms of the gene PER3 in three members of a family suffering from a disorder known as familial advanced sleep phase (FASP). The latter is a condition characterised by “persistent early evening sleep onset and early morning awakening“; the affected people feel sleepy in the evening (around 6 to 8 p.m.) and wake up very early (around 3 a.m.). Furthermore, it was found that these 3 people also suffered from seasonal affective disorder
which is characterised by experiencing major depression during winter whose severity decreases in spring and summer. This caused the researchers to determine whether PER3 could be mediating both sleep patterns and mood. This is what they tested in the new study.
For the new experiments, mice were genetically engineered to carry the mutations that disturb the normal synthesis of the key protein: its production was completely blocked in a group of mice, and partly blocked in another group. The sleep patterns of the mice were then observed as they were also subjected to varying seasonal simulations, that is, they were placed in conditions mimicking summer and winter alternately.
The results showed that the mice had disrupted sleep patterns: this effect was more pronounced in mice without PER3 than in those with partial synthesis thereof. Moreover, the disturbed sleep was specially extreme in winter-like conditions (where the mice had only 4 hours of light daily): sleep patterns of mice with a total lack of the protein moved by four hours.
Then, to achieve the main aim of the study which was to determine whether the gene is associated with seasonal affective disorder, the scientists made the mice go through a series of behavioural tests: they dangled the mice by their tails to find out for how long the latter would struggle to ultimately give up (an indication of depression). Their results showed that engineered mice gave up much faster than those which were not modified for the gene. Furthermore, those completely lacking PER3 gave up quicker than those with a partial mutation in the gene; the former also had showed signs of loss of appetite, suggesting that they were not gaining as much pleasure from the sugary water treat as the other mice.
The argument for the apparent depression was further strengthened when the symptoms of the depressive mice were alleviated when anti-depressant imipramine was administered to them: this suggests the mice were indeed experiencing depression or a similar condition.
The researchers conclude that PER3 is responsible, to whatever extent, for generating FASP, and mood disorders like seasonal affective disorder.