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Mechanism Links Substance Abuse With Vulnerability to Depression

It is well established that a mood disorder can increase an individual’s risk for substance abuse, but there is also evidence that the converse is true; substance abuse can increase a person’s vulnerability to stress-related illnesses. Now, a new study finds that repeated cocaine use increases the severity of depressive-like responses in a mouse model of depression and identifies a mechanism that underlies this cocaine-induced vulnerability.

The research, published by Cell Press in the August 25 issue of the journal Neuron, may guide development of new treatments for mood disorders associated with substance abuse.

“Clinical evidence shows that substance abuse can increase an individual’s risk for a mood disorder,” explains senior study author, Dr. Eric Nestler from Mount Sinai School of Medicine “However, although this is presumably mediated by drug-induced neural adaptations that alter subsequent responses to stress, the mechanisms underlying this phenomenon were largely unexplored.”

Dr. Nestler and colleagues examined whether histone H3 lysine 9 dimethylation (H3K9me2), a prominent type of chromatin modification, might be involved in the effects of repeated cocaine use on vulnerability to depressive-like behaviors. Histones are found in the nucleus where they package the DNA into chromatin, and changing the number of histone methyl groups can alter gene expression. A reduction in H3K9me2 reflects a decrease in the number of histone methyl groups, and previous human and animal studies have found a link between histone methylation and mood disorders.

The researchers found that cocaine increases the susceptibility of mice to stress in a well-established model of depression and that decreased H3K9me2 in the nucleus accumbens, a major reward center in the brain, was a central mechanism linking cocaine with stress vulnerability. Importantly, knockout of an enzyme called G9a that controls H3K9me2 in the nucleus accumbens was sufficient to enhance an animal’s vulnerability to stress, while excess G9a in the same region blocked the ability of cocaine to increase stress susceptibility.

The researchers went on to show that this G9a-mediated resilience to stress was mediated, in part, through repression of the BDNF-TrkB-CREB signaling pathway. This is significant because BDNF-TrkB-CREB signaling is increased in the nucleus accumbens by exposure to stress or cocaine and promotes both depressive and addictive behaviors. “Together, our results provide fundamentally novel insight into how prior exposure to a drug of abuse enhances vulnerability to depression and other stress-related disorders,” concludes Dr. Nestler. “Identifying such common regulatory mechanisms may aid in the development of new therapies for addiction and depression.”

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Driven to Distraction by Bipolar Disorder | Addiction Treatment Strategies


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Driven to Distraction by Bipolar Disorder

If you find it hard to concentrate, controlling mood swings can help. There are also some tips you can use to reduce stress, get more sleep, and stay organized.

Lack of concentration is a common symptom of bipolar disorder. People with bipolar disorder find they are easily distracted or feel lost and confused whether they are at home, at work, or in school.

Being unable to concentrate can be a problem because it makes it hard for people with bipolar disorder to perform tasks such as grocery shopping or preparing meals, or to enjoy activities such as playing a game or watching television. Young people with bipolar disorder may have trouble in school or when studying or reading. The symptom also can put the person with bipolar disorder at risk for injury — accidents happen when people aren’t paying attention.

Distracted by Mood Swings

People with bipolar disorder experience mood swings — they go from episodes of very high energy to extreme lows of depression. When depressed, people often do not concentrate as well. They may have trouble thinking and making decisions. Almost anything can become a distraction when they are down.

The key to improving concentration and avoiding distraction is controlling mood swings. Bipolar disorder is commonly treated with mood-stabilizing medications. It is important that people with bipolar disorder who are on medications take them as prescribed.

At the same time, it is possible that medications can contribute to attention problems. Certain medications have been shown to make it more difficult to concentrate and to learn. People with bipolar disorder should talk to their doctor if they find their medications are making their ability to concentrate worse. Their doctor may be able to adjust the medications to resolve the problem.

Lack of Sleep and Stress Can Affect Concentration

People also can lose their ability to concentrate when they are extremely tired, and people with bipolar disorder can have trouble sleeping, especially if they are in a depressed state. If you want to improve your concentration, try to get enough sleep. To get a good night’s sleep, you should go to bed and wake up the same time every night — weekdays and weekends. Make sure the bedroom is dark, quiet, and a comfortable temperature for sleeping.

Stress also can cause a lack of concentration, and people with bipolar disorder may feel as though they are under a lot of stress.

Here are some tips to help those with bipolar disorder control stress and get organized:

  • Manage your time. Don’t try to do too much. Say no if you can’t do it.
  • Lead a healthy lifestyle. Eat a balanced diet rich in fruits and vegetables and whole grains. Eat only low-fat meats and poultry. Get regular exercise, which can have both mental and physical health benefits. Avoid caffeine.
  • Learn relaxation techniques. These include breathing exercises, yoga, and massage. Remember to balance periods of activity with periods of relaxation.
  • Keep a daily planner. It will help you to remember appointments and commitments.
  • Seek support from family and friends. Spend time talking and listening to each other. Don’t be afraid to ask for help if you need it. Choose a support group you can trust to tell you the truth even if it’s not what you want to hear.
  • Avoid drugs and alcohol. Taking drugs and alcohol may lessen the effectiveness of your bipolar medications and lead to potentially dangerous side effects.
  • Get in a routine. A daily schedule can add structure to your life, and structure can help you cope with stress.

Lack of concentration is a common symptom of bipolar disorder. To control it, seek proper treatment for your mood swings. Also, be sure to get enough sleep and learn to limit stress.

By Beth W. Orenstein
Medically reviewed by Pat F. Bass III, MD, MPH
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Booze a Bad Mix With Poor Impulse Control | Addiction Treatment Strategies


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Booze a Bad Mix With Poor Impulse Control

In a long-running, prospective cohort study among people seeking help for alcohol-related problems, those with poor impulse control had an increased risk of dying, according to Daniel Blonigen, PhD, and colleagues at the Palo Alto Veterans Affairs Medical Center in Palo Alto, Calif.

The effect was independent of the risk associated with alcohol use disorders, Blonigen and colleagues reported online in Alcoholism: Clinical and Experimental Research.

Both impulsivity and alcohol use disorders are known to increase the risk of premature death, the researchers noted, and alcohol use increases impulsive behavior. But there has been no research on how poor impulse control affects mortality risk among people who also have problems with alcohol, they added.

“This is a surprising omission, given that impulsivity is a well-established risk factor for alcohol misuse,” Blonigen and colleagues wrote.

To help clarify the issue, they studied a cohort of 628 people who had sought help for alcohol-related problems and who were followed for 16 years.

The researchers used data on a set of variables collected when participants entered the study and a year later to predict the 15-year probability of death from years one through 16 of the study.

The researchers found:

•Among the 515 participants who remained in the study for the year one assessment, 93 were known to have died in the subsequent 15 years.

•After controlling for age, sex, and marital status, higher impulsivity at baseline was linked to an increased risk of death from years one to 16. A standard deviation increase yielded a hazard ratio (HR) for death of 1.38 with a 95% confidence interval (CI) from 1.10 to 1.74.

•But further adjustment for the severity of alcohol use at baseline accounted for the association, rendering it non-significant.

•However, impulsivity at year one — after treatment for alcohol use disorders — remained a significant predictor for death, with each standard deviation increase yielding an HR of 1.35 with a 95% CI from 1.06 to 1.72.

•That was similar to the risk imposed by alcohol use in the fully adjusted model — an HR of 1.34 with a 95% CI from 1.02 to 1.77.

On the positive side, Blonigen and colleagues reported, a supplemental analysis suggested that a supportive network of peers and friends can moderate the effect of high impulsivity.

The study was not designed to look at why poor impulse control might contribute to an increased risk of death among those with alcohol problems, Blonigen and colleagues noted, but several factors might play a role.

“Impulsivity is linked to a wide range of health-risk behaviors beyond excessive alcohol use,” they noted, including “violent crime, risky driving and sexual practices, (and) illicit drug abuse.”


The researchers cautioned that the study didn’t look closely at other risky activities, such as smoking. Also, they noted, assessment of risk factors was based on self-reporting and impulsivity was measured using a brief 10-item scale.


By Michael Smith, North American Correspondent, MedPage Today

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