Posts Tagged ‘bipolar’

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, being exposed to high levels of stress for long periods, and especially during childhood, has been associated with the development of BD.

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

One type of protein produced 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 neurotrophins, which are regulatory factors that promote development and survival of brain cells. Brain-derived neurotrophic factor (BDNF) is the neurotrophin mostly found in the brain. It has been extensively investigated in BD patients and has been suggested as a hallmark of BD. Indeed, some studies have shown that the levels of BDNF in the serum of BD patients are reduced whenever patients undergo a period 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.

Now 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 have published an article connecting 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 done by the group in 2016, one type of IEG gene known as EGR3, that normally responds to environmental events and stressful stimuli, was found repressed in the brain of BD patients, suggesting 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. What the research group is now suggesting is 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 entitled “EGR3 immediate early gene and the brain-derived neurotrophic factor in bipolar disorder” and published on February 5th in the journal Frontiers in Behavioral Neuroscience.

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.

This article has been republished from materials provided by Universidade Federal do Rio Grande do Sul. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference
Pfaffenseller, B., Kapczinski, F., Gallitano, A., & Klamt, F. (2018). EGR3 immediate early gene and the brain-derived neurotrophic factor in bipolar disorder. Frontiers in Behavioral Neuroscience, 12, 15.

https://www.technologynetworks.com/genomics/news/potential-drug-target-for-bipolar-identified-297204?utm_campaign=Newsletter_TN_BreakingScienceNews&utm_source=hs_email&utm_medium=email&utm_content=60440362&_hsenc=p2ANqtz-89oHJTQFUqboYjSURU_IOr9bzx6r5zFJCMV1mEAzlZHgi02vXuuEgb5JNs196HT9b7QaknWb1xraugbZ8U_bITr6Kw-A&_hsmi=60440362

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By James Phelps, MD

If light is an antidepressant (true) and antidepressants can make bipolar disorders worse (true), can darkness make bipolar disorders better? Might darkness be anti-manic?

This idea was explored over 2 decades ago, with a stunningly successful case report from the National Institute of Mental Health (NIMH) demonstrating that in at least 1 patient, darkness was indeed a mood stabilizer (1). But the protocol was arduous: 14 hours of enforced darkness every night.

It was so effective, they backed off to 10 hours, from 10 pm to 8 am, which kept the patient well with no medications for over a year. Yet, as clinicians know, patients still resist giving up their electric light, especially their TVs, tablets, and phones.

Hold that thought; and consider a completely separate line of research, which found that all wavelengths of light are not created equal. Blue light is by far the most powerful in setting circadian rhythm.

A new retinal photoreceptor, not a rod or cone, was discovered in 2001; it is sensitive primarily to blue light (2). These receptors connect not to the visual cortex but to the suprachiasmatic nucleus of the hypothalamus, wherein resides the primary biological clock. They are “circadian photoreceptors.”

Now put these 2 lines of research together. At night, when evolutionarily we should have 8 to 14 hours of darkness, one can create “virtual darkness” by blocking just the blue wavelengths of light. This can be done at the source (F.lux for Windows; NightShift for recent Apple products; and lowbluelights.com for no-blue bulbs and nightlights) or by simply donning a pair of amber-colored safety glasses.

The latter are available as fit-over-glasses, # S0360X; or a stylish version for young people with good eyes, # 3S1933X (purchase from Amazon—or, in a fun twist, from your local Airgas welding shop, ~$9). These safety glasses have been shown to preserve melatonin production at night even in a fully lit environment.3 About 50% of patients responded to wearing the amber lenses with reduced sleep latency and improved sleep quality (4).

But now the acid test: if darkness is a mood stabilizer, and if amber lenses produce physiologic darkness, then can the lenses treat acute mania?

This has just been shown quite conclusively(5) (to the extent that a single randomized trial is conclusive; but note this is a replication of another small inpatient study that used real darkness and found similar, though slightly less robust results (6).

In the new study from Norway, patients being admitted with bipolar mania were randomized to wear amber lenses or control clear lenses whenever they were not in real darkness during the 14-hour period from 6 pm to 8 am.

Thus, they replicated the intervention from the NIMH case report, using either real or “virtual darkness” with the amber lenses. The intervention began near admission and continued for 7 days, during which all participants received other treatments, including anti-manic medications, per usual.

Young Mania Rating Scale (YMRS) scores plummeted in the amber lenses group while those of the control group diminished only slightly: starting from a mean YMRS of 25, reductions were 14.1 vs 1.7, respectively.

Unfortunately, the sample size was smaller than originally intended because of growing public awareness of the effects of blue light and blue light–blocking glasses and consequently the patients knew what effect to expect. Thus, this may be the only such study we’ll ever see, and it took 10 years to replicate the first inpatient study6 of dark therapy.

So I hope that this new Norwegian study will not be dismissed as a pilot. The data are in. Time to move dark therapy into regular practice, as has already been suggested in the latest bipolar-specific psychotherapy, “CBT-IB: A Bipolar-Specific, All-Around Psychotherapy.”

But patients are often hesitant to increase their exposure to darkness: it means giving up things they value, especially television and other electronic entertainment. Blue light blockade can be much more acceptable.

http://www.psychiatrictimes.com/bipolar-disorder/new-zero-risk-treatment-mania/page/0/2?GUID=C523B8FD-3416-4DAC-8E3C-6E28DE36C515&rememberme=1&ts=12082016

by John Haltiwanger

As a musical genre, hip-hop is often denigrated for seemingly condoning misogyny, materialism, violence and crime. But this is an unfair characterization and an overgeneralization.

Yes, there are some rap artists who write songs containing nothing of substance. More often than not, however, hip-hop offers many of us an insightful view into a dark world we’re unfamiliar with: the impoverished inner city.

In this sense, hip-hop has the potential to educate and foster empathy.

To borrow from Jay Z:

I think that hip-hop has done more for racial relations than most cultural icons. Save Martin Luther King, because his dream speech we realized when President Obama got elected.

[Hip-hop] music didn’t only influence kids from urban areas. People listen to this music all around the world, and [they] took to this music.

Once you have people partying, dancing and singing along to the same music, then conversations naturally happen after that.

We all realize that we’re more alike than we’re separate.

Indeed, hip-hop breaches ostensibly impenetrable cultural divides, breeding solidarity among people with disparate backgrounds.

This is precisely why recent albums like Kendrick Lamar’s To Pimp a Butterfly have been widely celebrated and even used by high school teachers to teach lessons about race and oppression.

Beyond enlightening people on race, poverty, the War on Drugs and the inner city, it also appears hip-hop has a hidden benefit as a powerful tool against mental illness.

A study from Cambridge University found that hip-hop is extremely effective in combatting depression, bipolar disorder and addiction.

When you think about the themes hip-hop encompasses, this makes a lot of sense. Many artists rap about overcoming numerous obstacles in the ghetto, from gang violence and poverty to drugs and police brutality.

The overall narrative of hip-hop is one of progress. Artists tell dynamic stories of advancing from deeply oppressive environments to living out their wildest dreams.

Fundamentally, the message of hip-hop is one of hope.

Thus, hip-hop has the effect of “positive visual imagery,” helping people see the light when the whole world feels dark.

In other words, during bipolar episodes or periods of depression, listening to hip-hop can help people visualize or imagine a more positive place and where they’d like to be in the future. In turn, they arrive at a more secure mental state.

The study was conducted by neuroscientist Dr. Becky Inkster and psychiatrist Dr. Akeem Sule.

As Dr. Sule puts it:

Much of hip-hop comes from areas of great socioeconomic deprivation, so it’s inevitable that its lyrics will reflect the issues faced by people brought up in these areas, including poverty, marginalization, crime and drugs.

We can see in the lyrics many of the key risk factors for mental illness, from which it can be difficult to escape.

Hip-hop artists use their skills and talents not only to describe the world they see, but also as a means of breaking free.

We believe that hip-hop, with its rich, visual narrative style, can be used to make therapies that are more effective for specific populations and can help patients with depression to create more positive images of themselves, their situations and their future.

One of the prime examples utilized in the study is that of the Notorious B.I.G.’s “Juicy,” a hip-hop classic.

In the song, Biggie details his rise from deprivation on the harsh streets of Brooklyn to the covers of magazines and a life of affluence. It’s a song about making it against impossible odds.

There are so many other examples like this within the world of hip-hop. From Jay Z’s “On To The Next One” to the more recent Kendrick Lamar track, “i.”

Interestingly enough, not long ago, Lamar stated he penned the song as a form of encouragement and inspiration for prison inmates and suicidal teenagers:

I wrote a record for the homies that’s in the penitentiary right now, and I also wrote a record for these kids that come up to my shows with these slashes on they wrists, saying they don’t want to live no more.

Accordingly, it’s apparent some hip-hop artists are already deliberately attempting to help people with mental illness.

Regardless of the criticism it receives, hip-hop is a form of artistic expression with limitless educative and therapeutic potential.

The rapper Killer Mike has noted there is a commonly held view that hip-hop poses a threat or danger to society, but as he explains:

The kids spending hours per day writing rap songs aren’t a threat to society; they are often trying to escape the threats from society.