May 28, 2010

A Look Into The Future: Could Bone Marrow Transplant Cure OCD?

Previous research has found that mice, which are missing the Hox genes, a group of core developmental genes, groom themselves compulsively to the point of removing their own hair and leaving self-inflicted sores. Additionally, a more recent study has discovered a link between the Hoxb8 gene and behaviors similar to those found in people with obsessive compulsive spectrum disorder (OCD) and that these mice can be cured with a bone marrow transplant.
“It turns out that the Hoxb8 gene in question plays an important role in the development of immune cells known as microglia, which reside in the brain. Studies in which the researchers labeled Hoxb8 cells found that they show up in the brain exclusively in bone marrow-derived microglia. When they transplanted healthy bone marrow from control mice into the mutant animals, normal microglia made it to the animals' brains in about four weeks' time and many of the animals then stopped their incessant grooming, allowing their hair to grow back in, within three months of the procedure.”
Microglia is a type of glial cell that acts as the first and main form of active immune defense in the central nervous system. During the process of blood cellular formation, some hematopoietic stem cells, which are any cells within the bone marrow whose function is to produce blood cells, give rise to microglia. According to Mario Capecchi of Howard Hughes Medical Institute and University of Utah School of Medicine, hox genes are heavily involved in hematopoietic stem cells, which are critical for the proper number and placement of embryonic segment structures, such as legs, antennae, and eyes.

Capecchi explains that “the classic job of microglia, which outnumber neurons in the brain, is to scan the brain for problems […] When they find that something is wrong -- maybe a pathogen has invaded or there has been a stroke -- they change their shape to infiltrate the area and "clean up the mess." Amazingly, microglia can scan the whole brain in only an hour.

These cells maneuver around the brain and make stops at active neuronal synapses monitoring brain activity. From this research, Capecchi believes that microglia may also regulate neural activity and when it is unable to, as in the case of Hoxb8 mutants, pathologies like OCD-like behaviors may result. The exact way in which microglia controls brain activity is not yet known; however these findings suggest that the immune system may have a larger role in mental health disorders. Capecchi states:
"we have provided strong support for the hypothesis that the excessive pathological grooming behavior exhibited by Hoxb8 mutant mice is caused by a defect in microglia. That a behavioral deficit could be corrected by bone marrow transplantation is indeed surprising. The therapeutic implications of our study on amelioration of neurological behavioral deficits in humans have not escaped us."
Capecchi explains that a connection exists between the immune system and disorders such as depression, autism, Alzheimer's, OCD and schizophrenia, but it has never been entirely clear. This study should lead to more exciting discoveries in how microglia can affect neural activity and behavior. Perhaps our vast knowledge of the immune system could lead to more discoveries and treatments for mental illness.

Compulsive Behavior in Mice Cured by Bone Marrow Transplant
Microglia

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May 1, 2010

Older Adults May Have Higher Risks Associated With Drinking

Contrary to popular belief, risks associated with alcohol consumption do not only strike the young. “A new study by researchers at the David Geffen School of Medicine at UCLA has found that more than a third of drinkers 60 years old and older consume amounts of alcohol that are excessive or that are potentially harmful in combination with certain diseases they may have or medications they may be taking.”

Researchers studied data from 3,308 older patients from primary care clinics in and around Santa Barbara, California. However, the sample used is more likely to be white, married, well-educated with high income. In addition, findings are based on self-reports, which also weakens the validity of this study.

Despite a clear lack of generalizability and reliability, researchers have found that the risk associated with drinking in older adults who already have certain illnesses or take medications while consuming alcohol are just as numerous as those at risk from alcohol consumption alone.

The Comorbidity Alcohol Risk Evaluation Tool (CARET) was used to assess drinking habits among these older adults. Results determined whether they were considered to be at risk if they fell into any of the following categories:
  • more than 2 drinks consumed on most days of the week

  • one to two drinks consumed on most days in combination with other illnesses like gout, hepatitis or nausea

  • one to two drinks consumed on most days in combination with medications, such as antidepressants or sedatives
The specific findings include:
  • 34.7 percent (1,147) of older adults were at risk due to drinking alone or to drinking in combination with comorbidities or medications, and 19.5 percent fell into multiple risk categories.

  • Of those at risk, 56.1 percent fell into at least two risk categories, and 31 percent fell into all three.

  • Participants who had not graduated from high school had 2.5 times the odds of at-risk drinking as those who had completed graduate school.

  • Respondents with annual household incomes between $80,000 and $100,000 had 1.5 times the odds of being at-risk as those with incomes under $30,000.

  • Respondents who were 80 or older had half the odds of at-risk drinking as those between the ages of 60 and 64.

  • Asians had less than half the odds of at-risk drinking as Caucasians.
Results must be taken with a grain of salt when applying them to the general population as a 62-year-old married white male with a high annual household income cannot compare to an 85-year-old widowed Asian female with a low an annual income. The study also makes no mention of drinking habits prior to older age.

Regardless of the various inconsistencies, results do suggest that Physicians may need to pay more attention to the drinking habits of certain older adults and any possible interactions that may exist between alcohol consumption and other illnesses or medications since this study has shown that as many as one in three older adults in this study’s sample that continue to drink into older adulthood are more at risk.

High Rates of at-Risk Drinking Among Elderly Adults, Study Finds

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