Research news in brief

Gene mutation explains night-owl behaviour

US and Turkish research published in Cell has found a gene mutation which may explain why some people stay up late and have trouble getting up in the morning. A mutation in a gene called CRY1 alters the human circadian clock, which dictates rhythmic behaviour such as sleep–wake cycles. Carriers of the gene variant experienced nighttime sleep delays of 2–2.5 hours compared with non-carriers, the researchers found. Night owls are often diagnosed at sleep clinics with delayed sleep phase disorder (DSPD). This study is the first to implicate a gene mutation in the development of DSPD, which affects up to 10% of the public, according to clinical studies. People with DSPD often struggle to fall asleep at night, and sometimes sleep comes so late that it fractures into a series of long naps. DSPD and other sleep disorders are associated with anxiety, depression, cardiovascular disease and diabetes. People with DSPD also have trouble conforming to societal expectations and morning work schedules. Not all cases of DSPD are attributable to this gene mutation. However, the researchers found it in 1 in 75 of individuals of non-Finnish, European ancestry in a gene database search. By studying the skin cells of people with DSPD, they discovered a mutation in CRY1, which helps drive the circadian clock. Normally, the clock begins its cycle by building up proteins, called activators, in a cell. These activators produce their own inhibitors that, over time, cause the activators to lose their potency. When all the activators in the cell have been silenced, inhibitors are no longer produced and eventually degrade. Once they’ve all gone, the potency of the activators surges and the cycle begins again. The CRY1 protein is one of the clock’s inhibitors. The mutation the researchers found is a single-point mutation in the CRY1 gene, meaning that just one letter in its genetic instructions is incorrect. Yet this change causes a chunk of the gene’s resulting protein to be missing. That alteration causes the inhibitor to be overly active, prolonging the time that the activators are suppressed and stretching the daily cycle by half an hour or more. The circadian clock responds to external environmental cues, so it is possible for people to manage the effects of the mutation on sleep. The researchers reported that one carrier in the study maintained a sleep routine through self-enforced regular sleep and wake times and exposure to bright light during the day.

Gut bacteria adapted to human breast milk

An international study involving a research from the University of Western Australia, published in Cell Chemical Biology, has found that breast milk provides vital nutrients not only to infants, but also to beneficial microbes that inhabit the gastrointestinal tract. A bacterial species called Bifidobacterium longum has successfully adapted to the unique niche of the infant gut by producing an enzyme called LnbX, which enables this microbe to grow on a sugar that is abundant only in human milk. Human milk sugars are known to selectively promote the growth of beneficial gut microbes such as bifidobacteria, which prevent diarrhoea and pathogenic infection in infants. One major component of human milk is a sugar called lacto-N-tetraose, which is virtually absent in the milk of other mammals. Bifidobacteria produce enzymes that break down this sugar, strongly suggesting that a symbiotic relationship recently evolved between these microorganisms and humans. In previous studies, the researchers had characterised LnbB and isolated LnbX – enzymes that degrade lacto-N-tetraose in Bifidobacterium bifidum and Bifidobacterium longum, respectively. In the new study, the researchers set out to build on those findings by determining the x-ray crystal structure of the catalytic domain of LnbX. The crystal structure, in combination with mutation and pharmacological experiments, revealed that LnbX has a distinct structure and catalytic mechanism from LnbB and, therefore, belongs to a novel family of glycoside hydrolase enzymes called GH136. “Even though B. longum and B. bifidum belong to the same genus and inhabit the same environment, they use different enzymes to break down lacto-N-tetraose, taking advantage of the varied structures of this unique human milk sugar,” the researchers said. “The findings suggest that different strains and species of beneficial bifidobacteria have independently evolved distinct molecular tools to digest the same human milk sugar, explaining their ability to co-exist and thrive in the gastrointestinal tract of breast milk-fed infants.”

PTSD symptoms common in remote, pregnant Indigenous women

Around 40% of rural and remote Indigenous women experience post-traumatic stress disorder (PTSD) symptoms, according to a NSW study published in the Australian and New Zealand Journal of Obstetrics and Gynaecology. The authors surveyed 150 pregnant Indigenous women about stressful life events they’d experienced and their impacts. They found that around 40% had PTSD symptoms, much higher levels than those of European victims of crisis – including after terrorism attacks. PTSD is the one established mental health condition associated with premature delivery, and the international rate of PTSD in non-Indigenous pregnant women had been previously established at approximately 1–4% in pregnant women who had not been exposed to childhood sexual abuse. The researchers from the University of Newcastle and the University of Sydney, said that there may be negative impacts on both mother and baby, and urged more research, as well as responses by government, health and community groups to deal with the high rates. One hundred and fifty rural and remote Indigenous women were invited to complete a survey during each trimester of their pregnancy. The survey measures were the stressful life events and the Impact of Events Scale. Approximately 40% of this group exhibited PTSD symptoms during their pregnancy with a mean score of 33.38 (standard deviation [SD] = 14.37) compared with the study of European victims of crisis, including terrorism attacks (20.6, SD = 18.5). “Most striking was the number of the cohort who experienced at least one death of a family member/close friend (49.6%), overcrowding at home (35.9%) and an inability to gain employment (33%). While many participants were exposed to mental illness (29.4%), a limitation of the stressful life events survey is that it does not define if this is related to their own personal mental illness or a personal contact.” The impact of PTSD on premature birth rates was concerning, the authors wrote. “Indigenous infants are born prematurely at double the rate of non-Indigenous infants … In addition, the arrival of a premature infant is a further risk factor for the development of PTSD. The impact on an infant being cared for by a mother struggling with PTSD includes the development of infant regulatory difficulties and socio-emotional problems evident as early as the first year of life. By the second year of life, infant mental health issues are evident with increased internalising and externalising behaviours.”

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