New Path Into Bipolar Disorder Comes To Light

New path into bipolar disorder comes to light

Bipolar disorder (BD) is a multifactorial brain disorder in which patients experience radical shifts in mood and undergo periods of depression followed by periods of mania. It has been known for some time that both environmental and genetic factors play important roles in the disease. For instance, exposure to high levels of stress for long periods, especially during childhood, is one factor associated with development of BD.

New research published in Frontiers in Behavioral Neuroscience connects the dots between two genes involved in the brain’s response to environmental stimuli — called EGR3 and BDNF — and may explain the impaired resilience of BD patients to respond to events, including stress. The study not only provides new insights into the biology of BD, but also suggests that EGR3 could be a potential drug target.

Immediate early genes (IEGs) are a class of genes that respond very rapidly to environmental stimuli, including stress. IEGs respond to a stressor by activating other genes that lead to neuronal plasticity — that is, a change in form and function o brain cells in response to changes in the environment. Ultimately, the process of neuronal plasticity gives the brain the ability to learn from and adapt to new experiences.

One type of protein induced by IEGs is the so-called Early Growth Response (EGR) proteins, which translate environmental influence into long-term changes in the brain. These proteins are found throughout the brain and are highly produced in response to environmental changes such as stressful stimuli and sleep deprivation. Without the action played out by these proteins, brain cells and the brain itself cannot appropriately respond to the many stimuli that are constantly received from the environment.

Effective neuronal plasticity also depends on regulatory factors called neurotrophins that promote development and survival of brain cells. Brain-derived neurotrophic factor (BDNF), the neurotrophin mostly found in the brain, has been extensively investigated in BD patients and has been suggested as a hallmark of BD. Indeed, some studies have shown that serum levels of BDNF are reduced in BD patients during periods of depression, hypomania, or mania. Other studies have shown that regardless of mood state, BD patients present reduced levels of BDNF. Overall, changes in BDNF levels seem to be a characteristic found in BD patients that may contribute to the pathophysiology of the disease.

The new study by an international team of researchers from Universidade Federal do Rio Grande do Sul in Brazil, University of Arizona College of Medicine in the United States and McMaster University in Canada connects the dots between these two players to explain the impaired cellular resilience observed in BD that in the grand scheme of things may relate to the impaired resilience presented by BD patients to respond to events, including stress.

In a previous study by the group in 2016, one type of IEG gene known as EGR3, that normally responds to environmental events and stressful stimuli, was found to be repressed in the brain of BD patients. This suggests that when facing a stressor, the EGR3 in BD patients does not respond to the stimulus appropriately. Indeed, BD patients are highly prone to stress and have more difficulties dealing with stress or adapting to it if compared to healthy individuals. The research group is now suggesting that both EGR3 and BDNF may each play a critical role in the impaired cellular resilience seen in BD, and that each of these two genes may affect each other’s expression in the cell.

“We believe that the reduced level of BDNF that has been extensively observed in BD patients is caused by the fact that EGR3 is repressed in the brain of BD patients. The two molecules are interconnected in a regulatory pathway that is disrupted in BD patients,” says Fabio Klamt, leading author of the article.

The authors also add that the fact that EGR3 responds very quickly to environmental stimuli renders the molecule a potential drug target. “It is possible to imagine that EGR3 may be modulated in order to increase its expression and that of BDNF, which may have a positive impact on BD patients,” says Bianca Pfaffenseller, a scientist working at Hospital de Clínicas de Porto Alegre, in Brazil, and the first author of the study.

The idea that mental disorders should be seen as any other chronic disease in which the underlying biology plays an important role has replaced the old descriptions of mental illnesses as the result of bad psychological influences. As Nobel prize laureate Eric Kandel has said, “all mental processes are brain processes and therefore all disorders of mental functioning are biological diseases.” The perspective article authored by Fabio Klamt and colleagues supports this view by offering new insights into the underlying biology of this lifelong and devastating mental disorder affecting millions of people worldwide.

Itsy Bitsy Spider: Fear of spiders and snakes is deeply embedded in us

Snakes and spiders evoke fear and disgust in many people. Even in developed countries lots of people are frightened of these animals although hardly anybody comes into contact with them. Until now, there has been debate about whether this aversion is innate or learnt. Scientists at the Max Planck Institute for Human Cognitive and Brain Sciences (MPI CBS) in Leipzig and the Uppsala University have recently discovered that it is hereditary: Babies as young as six months old feel stressed when seeing these creatures—long before they could have learnt this reaction.

Presumably, in Germany most people have never come across a poisonous spider or snake in the wild. Here in this country there are no spiders that pose a threat to humans. Likewise for snakes there are just two species that are indeed poisonous but they are so rare that you hardly ever encounter them. Nevertheless, there are few people that would not shiver at the thought of a spider crawling up their arm, however harmless it may be.

This fear can even develop into anxiety which limits a person’s daily life. Such people are always on edge and cannot enter a room before it is declared “spider free” or cannot venture out into nature for sheer fear that they may encounter a snake. In developed countries one to five per cent of the population are affected by a real phobia of these creatures.

Until now, it was not clear where this widespread aversion or anxiety stems from. While some scientists assume that we learn this fear from our surroundings when we are a child, others suppose that it is innate. The drawback of most previous studies on this topic was that they were conducted with adults or older children—making it hard to distinguish which behaviour was learnt and which was inborn. Such studies with children only tested whether they spot spiders and snakes faster than harmless animals or objects, not whether they show a direct physiological fear reaction.

Scientists at the Max Planck Institute for Human Cognitive and Brain Sciences (MPI CBS) in Leipzig and the Uppsala University, Sweden, recently made a crucial observation: Even in infants a stress reaction is evoked when they see a spider or a snake. And this already at the age of six months, when they are still very immobile and have had little opportunity to learn that these animals can be dangerous.

“When we showed pictures of a snake or a spider to the babies instead of a flower or a fish of the same size and colour, they reacted with significantly bigger pupils”, says Stefanie Hoehl, lead investigator of the underlying study and neuroscientist at MPI CBS and the University of Vienna. “In constant light conditions this change in size of the pupils is an important signal for the activation of the noradrenergic system in the brain, which is responsible for stress reactions. Accordingly, even the youngest babies seem to be stressed by these groups of animals.”

“We conclude that fear of snakes and spiders is of evolutionary origin. Similar to primates, mechanisms in our brains enable us to identify objects as ‘spider’ or 'snake’ and to react to them very fast. This obviously inherited stress reaction in turn predisposes us to learn these animals as dangerous or disgusting. When this accompanies further factors it can develop into a real fear or even phobia. "A strong panicky aversion exhibited by the parents or a genetic predisposition for a hyperactive amygdala, which is important for estimating hazards, can mean that increased attention towards these creatures becomes an anxiety disorder.”

Interestingly, it is known from other studies that babies do not associate pictures of rhinos, bears or other theoretically dangerous animals with fear. “We assume that the reason for this particular reaction upon seeing spiders and snakes is due to the coexistence of these potentially dangerous animals with humans and their ancestors for more than 40 to 60 million years—and therefore much longer than with today’s dangerous mammals. The reaction which is induced by animal groups feared from birth could have been embedded in the brain for an evolutionarily long time.

For modern risks such as knives, syringes or sockets, presumably the same is true. From an evolutionary perspective they have only existed for a short time, and there has been no time to establish reaction mechanisms in the brain from birth. "Parents know just how difficult it is to teach their children about everyday risks such as not poking their fingers into a socket”, Hoehl adds with a smile.

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7 years ago

Geneticists are starting to unravel evolution’s role in mental illness

Psychiatric disorders can be debilitating and often involve a genetic component, yet, evolution hasn’t weeded them out. Now, recent work is beginning to reveal the role of natural selection — offering a peek at how the genetic underpinnings of mental illness has changed over time.

Many psychiatric disorders are polygenic: they can involve hundreds or thousands of genes and DNA mutations. It can be difficult to track how so many genetic regions evolved, and such studies require large genome data sets. But the advent of massive human genome databases is enabling researchers to look for possible connections between mental illnesses and the environmental and societal conditions that might have driven their emergence and development. Others are looking to Neanderthal genetic sequences to help inform the picture of these disorders, as well as cognitive abilities, in humans. Several of these teams presented their findings at the American Society of Human Genetics (ASHG) meeting in Orlando, Florida, in late October.

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ourvioletdeath

7 years ago

(x)

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8 years ago

“remember that time in 7th grade when you-“

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6 years ago

biologists: no macroorganism can survive the endless vacuum of space unprotected for an extended period of time

lichens:

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7 years ago

In a horrible twist of fate, you and your worst enemy are soulmates. Tell the story of how you two reluctantly fall in love.

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6 years ago

The Hand is here! Where is Voigt’s dinner? GUMBY IS HERE ALSO

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7 years ago

Little vases

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ourvioletdeath

7 years ago

Most animals with a well-known white morph (lions, tigers, domestic cats, peacocks) are leucistic, not albinistic. True albinos are much rarer and are usually only bred-for in indoor pets (mice, rats, snakes).

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