The biology of addiction risk looks like addiction
Research suggests that people at increased risk for developing addiction share many of the same neurobiological signatures of people who have already developed addiction. This similarity is to be expected, as individuals with family members who have struggled with addiction are over-represented in the population of addicted people.
However, a generation of animal research supports the hypothesis that the addiction process changes the brain in ways that converge with the distinctive neurobiology of the heritable risk for addiction. In other words, the more one uses addictive substances, the more one's brain acquires the profile of someone who has inherited a risk for addiction.
One such change is a reduction in striatal dopamine release. Dopamine is a key brain chemical messenger involved in reward-related behaviors. Disturbances in dopamine signaling appear to contribute to reward processing that biases people to seek drug-like rewards and to develop drug-taking habits.
In the current issue of Biological Psychiatry, researchers at McGill University (Montreal, Quebec) report that individuals at high risk for addiction show the same reduced dopamine response often observed in addicted individuals, identifying a new link between addiction risk and addiction in humans.
Marco Leyton and his colleagues recruited young adults, aged 18 to 25, who were classified into three groups: 1) a high-risk group of occasional stimulant users with an extensive family history of substance abuse; 2) a comparison group of occasional stimulant users with no family history; and 3) a second comparison group of individuals with no history of stimulant use and no known risk factors for addiction. Volunteers underwent a positron emission tomography (PET) scan involving the administration of amphetamine, which enabled the researchers to measure their dopamine response.
The authors found that the high-risk group of non-dependent young adults with extensive family histories of addiction displayed markedly reduced dopamine responses in comparison with both stimulant-naïve subjects and non-dependent users with no family history.
"This interesting new parallel between addiction risk and addiction may help to focus our attention on reward-related processes that contribute to the development of addiction, perhaps informing prevention strategies," said John Krystal, Editor of Biological Psychiatry.
Leyton, a Professor at McGill University, said, "Young adults at risk of addictions have a strikingly disturbed brain dopamine reward system response when they are administered amphetamine. Past drug use seemed to aggravate the dopamine response also but this was not a sufficient explanation. Instead, the disturbance may be a heritable biological marker that could identify those at highest risk."
This finding suggests that there are common brain mechanisms that promote the use of addictive substances in vulnerable people and in people who have long-standing habitual substance use.
Better understanding this biology may help to advance our understanding of how people develop addiction problems, as well as providing hints related to biological mechanisms that might be targeted for prevention and treatment.
Among patients with TBI, maintaining higher
EPO doesn't improve neurological outcomes
In patients with a traumatic brain injury (TBI), neither the administration of the hormone erythropoietin (EPO) or maintaining a higher hemoglobin concentration through blood transfusion resulted in improved neurological outcome at six months, according to a study in JAMA. Transfusing at higher hemoglobin concentrations was associated with a higher risk of adverse events.
Patients with severe TBI commonly develop anemia. For patients with neurological injury, anemia is a potential cause of secondary injury, which may worsen neurological outcomes. Treatment of anemia may include transfusions of packed red blood cells or administration of erythropoietin. There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold (if the hemoglobin concentration drops below a certain level, a transfusion is performed) after a TBI, according to background information in the article.
Claudia Robertson, MD, of the Baylor College of Medicine (Houston), and colleagues conducted a randomized clinical trial that included 200 patients (erythropoietin, n = 102; placebo, n = 98) with a closed head injury at neurosurgical intensive care units in two U.S. level I trauma centers between May 2006 and August 2012. Patients were enrolled within 6 hours of injury and had to be unable to follow commands after initial stabilization. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL.
In the placebo group, 34 patients (38.2%) recovered to a favorable outcome (defined as good recovery and moderate disability, as measured by a functional assessment inventory) compared with 17 patients (48.6%) in the erythropoietin 1 group (first dosing regimen) and 17 patients (29.8%) in the erythropoietin 2 group (second dosing regimen). Thirty-seven patients (42.5%) assigned to the transfusion threshold of 7 g/dL recovered to a favorable outcome compared with 31 patients (33 %) assigned to the transfusion threshold of 10 g/dL.
There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (21.8%) vs (8.1%) for the threshold of 7 g/dL.
"Among patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of at least 10 g/dL resulted in improved neurological outcome at 6 months. These findings do not support either approach in patients with traumatic brain injury," the authors conclude.
For older adults, lack of sleep leads to faster brain ageing
Researchers at Duke-NUS Graduate Medical School Singapore (Duke-NUS) have found evidence that the less older adults sleep, the faster their brains age. These findings, relevant in the context of Singapore's rapidly ageing society, pave the way for future work on sleep loss and its contribution to cognitive decline, including dementia.
Past research has examined the impact of sleep duration on cognitive functions in older adults. Though faster brain ventricle enlargement is a marker for cognitive decline and the development of neurodegenerative diseases such as Alzheimer's, the effects of sleep on this marker have never been measured.
The Duke-NUS study examined the data of 66 older Chinese adults, from the Singapore-Longitudinal Aging Brain Study. Participants underwent structural MRI brain scans measuring brain volume and neuropsychological assessments testing cognitive function every two years. Additionally, their sleep duration was recorded through a questionnaire. Those who slept fewer hours showed evidence of faster ventricle enlargement and decline in cognitive performance.
"Our findings relate short sleep to a marker of brain aging," said June Lo, the lead author and a Duke-NUS Research Fellow. "Work done elsewhere suggests that seven hours a day for adults seems to be the sweet spot for optimal performance on computer-based cognitive tests. In coming years we hope to determine what's good for cardio-metabolic and long term brain health too," added Professor Michael Chee, senior author and Director of the Center for Cognitive Neuroscience at Duke-NUS.
The study is published in the July 1 issue of the journal SLEEP.
Running, combined with visual
experience, restores brain function
In a new study by UC San Francisco scientists, running, when accompanied by visual stimuli, restored brain function to normal levels in mice that had been deprived of visual experience in early life.
In addition to suggesting a novel therapeutic strategy for humans with blindness in one eye caused by a congenital cataract, droopy eyelid, or misaligned eye, the new research – the latest in a series of UCSF studies exploring effects of locomotion on brain function – suggests that the adult brain may be far more capable of rewiring and repairing itself than previously thought.
In 2010, Michael Stryker, the W.F. Ganong Professor of Physiology, and postdoctoral fellow Cris Niell, now at the University of Oregon, made the surprising discovery that neurons in the visual area of the mouse brain fired much more robustly whenever the mice walked or ran.
Earlier this year, postdoctoral fellow Yu Fu, Stryker, and a number of colleagues built on these findings, identifying and describing the neural circuit responsible for this locomotion-induced "high-gain state" in the visual cortex of the mouse brain.
Neither of these studies made clear, however, whether this circuit might have broader functional or clinical significance.
It has been known since the 1960s that visual areas of the brain do not develop normally if deprived of visual input during a "critical period" of brain development early in life. For example, in humans, if amblyopia ("lazy eye") or other major eye problems are not surgically corrected in infancy, vision will never be normal in the affected eye – if such individuals lose sight in their "good" eye in later life, they are blind.
In the new research, published June 26 in the online journal eLife, Stryker and UCSF postdoctoral fellow Megumi Kaneko, closed one eyelid of mouse pups at about 20 days after birth, and that eye was kept closed until the mice reached about five months of age.
As expected, the mice in which one eye had been closed during the critical developmental period showed sharply reduced neural activity in the part of the brain responsible for vision in that eye.
As in the previous UCSF experiments in this area, some mice were allowed to run freely on Styrofoam balls suspended on a cushion of air while recordings were made from their brains.
Little improvement was seen in the mice that had been deprived of visual input either when they were simply allowed to run or when they received visual training with the deprived eye not accompanied by walking or running.
But when the mice were exposed to the visual stimuli while they were running or walking, the results were dramatic: within a week the brain responses to those stimuli from the deprived eye were nearly identical to those from the normal eye, indicating that the circuits in the visual area of the brain representing the deprived eye had undergone a rapid reorganization, known in neuroscience as "plasticity."
Interestingly, this recovery was stimulus-specific: if the brain activity of the mice was tested using a stimulus other than that they had seen while running, little or no recovery of function was apparent.