PER3 Polymorphism Predicts Sleep Structure and Waking Performance

The latest edition of current biology holds an article about the connection of VNTRs on genes and sleep behaviour. (Current Biology 17, 1–6, April 3, 2007)
The genetic background about sleep and waking patterns is largely unknown. This paper writes something about it; not everything is understandable for me, as I have a limited background in biology (actually, no background in biology), but with the use of wikipedia I could draw some conclusions.
Individuals were monitored in their sleep-wake cycles, after which some intensive physiological tests were done. This was done in normal conditions, and in conditions of sleep loss. The persons, selected on basis of their genotype and homozygosity for the PER3 -gene, showed no significant differences in bed time, wake time or sleep duration.

Note: PER3[4/4] means that the person is a homozygote, with 4 repeats of the characteristic amino acid.

In their normal patterns, there was no significant difference in the different stages of sleep (REM sleep, stage 1 sleep, stage 2 sleep, total sleep time), but

"PER3[5/5] subjects fell asleep more readily than PER3[4/4] subjects"

When the PER3[5/5] were kept awake for a long time, the subjects performed worse than PER3[4/4] persons on spatial, reaction-time, and logic tests, especially in the late night and early morning hours:

"Most strikingly, PER3[5/5] homozygotes performed very poorly during the hours after the melatonin midpoint. The decrement in waking performance in the PER3[4/4] homozygotes was far less. These major differences in performance between the two genotypes occurred during the late-night and early-morning hours, a time known from both laboratory and field studies as the nadir of the circadian timing system and during which performance is poorest and sleep propensity at its peak. "

"The PER3 5-repeat allele, which is the less frequent one in most ethnic groups, has been associated with extreme morning preference, while the 4-repeat allele has been linked with DSPS in our previous study."

DSPS is a delayed sleep phase syndrome; people with this syndrome tend to fall asleep late at night, and have difficulty waking up in the morning. Furthermore, for a lot of these persons it doesn't matter at what time they go to bed, because they fall asleep at approximately the same time anyway. DSPS is a syndrome from the bigger family of Circadian rhytm sleep disorders; a well known member from this Circadian rhytm sleep syndrome is the jet lag. This may mean that there's a problem with a part of the brain that produces melatonin, which receives information from the eyes about light and dark.

These results, among others,

" (...) led us to consider it as a candidate for mediating some of the marked individual differences in sleep-wake regulation. These individual differences include the preferred timing of sleep-wake cycles, the structure of sleep, EEG patterns during sleep and wakefulness, and their response to sleep loss and circadian-phase misalignment."
"Our results indicate that the PER3 polymorphism may contribute to the marked individual differences in performance decrement during sleep loss."

All in all, this may signify that there's a relation between day- and nightpeople.

"Conclusions
The effects of the PER3 polymorphism on SWS (slow wave sleep), SWA (slow wave activity), and the decrements of waking performance during the biological night, as observed in this study, are significant and substantial. This implies that this polymorphism may be an important marker for individual differences in sleep and susceptibility to sleep loss and circadianphase misalignment, which are major causes of health problems and accidents in our society."

Of course, there are still a lot of open questions: what happens for example with heterozygotes? Or with a smaller number of VNTRs on the PER3 gene? Is there a connection, or is it just a correlation? I'm not in the position to answer these questions, as I could barely understand the article ;).

From: Viola et al., PER3 Polymorphism Predicts Sleep Structure and Waking Performance, Current Biology (2007), doi:10.1016/j.cub.2007.01.073

Omega-3 Fatty Acids and Mood Disorders

Another interesting article from the American Journal of Psychiatry, titled

"Omega-3 Fatty Acids and Mood Disorders"

Here are the main points; below that there's a summary of the article.


Objective: This article is an overview of epidemiological and treatment studies suggesting that deficits in dietary-based omega-3 polyunsaturated fatty acids may make an etiological contribution to mood disorders and that supplementation with omega-3 fatty acids may provide a therapeutic strategy.

Method: Relevant published studies are detailed and considered.

Results: Several epidemiological studies suggest covariation between seafood consumption and rates of mood disorders. Biological marker studies indicate deficits in omega-3 fatty acids in people with depressive disorders, while several treatment studies indicate therapeutic benefits from omega-3 supplementation. A similar contribution of omega-3 fatty acids to coronary artery disease may explain the well-described links between coronary artery disease and depression.

Conclusions: Deficits in omega-3 fatty acids have been identified as a contributing factor to mood disorders and offer a potential rational treatment approach. This review identifies a number of hypotheses and studies for consideration. In particular, the authors argue for studies clarifying the efficacy of omega-3 supplementation for unipolar and bipolar depressive disorders, both as individual and augmentation treatment strategies, and for studies pursuing which omega-3 fatty acid, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), is likely to provide the greatest benefit.
(Am J Psychiatry 163:6, June 2006)

I learned a few things from this paper: first, the omega-3 fatty acids can be either marine-based or from plants.
The rapid growth in population has been associated with a change in diet, resulting in a decrease in omega-3 while the uptake of omega-6 (e.g. from vegetable oils) has increased. Some authors suggest that there's a connection between the depression-rate and other neurological disorders and the increase of the omega-6 fatty acids; there's a possible link between fish consumption and mood disorders. Both Iceland and Japan, which both have high consumption rates of fish, have low rates of "seasonal affective disorders". As the consumption rate of fish declines (and the consumption of 'Western' food rises), the rates of seasonal affective disorders increases, even when they receive more winter sunlight. Furthermore, the "likelihood of having depressive symptoms was significantly higher among infrequent fish consumers than among frequent consumers." Some research also opposes these findings, but there's a general tendency to support the previously mentioned claims. Other research state that this is especially so with women. But in short, 5 out of 6 researches find that there's a correlation between fish consumption (omega-3 intake) and mood disorders.
During pregnancy the fetus accumulates more DHA (primary component of omega-3) than the intake of the mother, and after the birth the depletion of the omega-3 acids continues by breast-feeding. This contributes to the risk for depression around the time of birth. So feed your wife some fish during pregnancy (finally a reason to be happy someone eats dead animals);

• it's safe
  
• it may have "additional benefits for the infant’s neurodevelopment"
  

Then there's a lot of biological mumbo-jumbo, which I don't fully understand, but which still support the previous claims. Some possible mechanisms are presented, to continue to the treatment studies. Bipolar/depressed/borderline patients which took omega-3 had in general greater symptom reduction. On the other hand, there are some experiments which don't reproduce this effect, but again, in general, the results support the previous idea.

Interesting stuff.

Spatial memory and depression

In my first post I already mentioned that this blag is mostly for myself, and that I'd add notes for myself about things I like or want to remember. This is such a piece.
In the American Journal of Psychiatry I found an interesting article titled:

Performance on a Virtual Reality Spatial Memory Navigation Task in Depressed Patients

The title doesn't leave much for the imagination on what it's about, but the findings are interesting nonetheless:

Method: Performance on a novel virtual reality navigation task and a traditional measure of spatial memory was assessed in 30 depressed patients (unipolar and bipolar) and 19 normal comparison subjects.

Results: Depressed patients performed significantly worse than comparison subjects on the virtual reality task, as assessed by the number of locations found in the virtual town. Betweengroup differences were not detected on the traditional measure. The navigation task showed high test-retest reliability.

Conclusions: Depressed patients performed worse than healthy subjects on a novel spatial memory task. Virtual reality navigation may provide a consistent, sensitive measure of cognitive deficits in patients with affective disorders, representing a mechanism to study a putative endophenotype for hippocampal function.
(Am J Psychiatry 2007; 164:516–519, link )

Well, there you go. I think this was interesting, and I want to remember it.
(The only question I have that the article didn't answer is, if there existed a correlation between the familiarity with the game and the people who were depressed. I.e. whether the depressed people could be more familiar with the game)