Antidepressants use associated with birth defects

A new Université de Montréal study in the British Medical Journal reveals that antidepressants prescribed to pregnant women could increase the chance of having a baby with birth defects.

The risk is 6 to 10 %, versus 3 to 5 % in women who do not take the drugs and it is high enough to merit caution in their use, especially since, in most cases, they are only marginally effective, the study says.

“In pregnancy, you’re treating the mother but you’re worried about the unborn child, and the benefit needs to outweigh the risk,” said the study’s senior author, Anick Bérard, a professor at UdeM’s Faculty of Pharmacy[AB1]  and researcher at its affiliated children’s hospital, CHU Sainte-Justine.

A well-known expert in pregnancy and depression, Bérard has previously established links between antidepressants and low birth weight, gestational hypertension, miscarriages and autism. Her new study is among the first to examine the link to birth defects among depressed women.

Every year, about 135,000 Quebec women get pregnant, and of those, about 7 % show some signs of depression, mostly mild to moderate. A much smaller percentage  (less than 1%) suffers from severe depression.

In her study, Bérard looked at 18,487 depressed women in the Quebec Pregnancy Cohort, a  longitudinal, population-based grouping of 289,688 pregnancies recorded between 1998 to 2009. Of the women studied, 3,640 – about 20 per cent – took antidepressants in the first three months.

“We only looked at the first trimester, because this is where all the organ systems are developing,” said Bérard. “At 12 weeks of gestation, the baby is formed.”

Antidepressant use during this critical time-window has the potential to interfere with serotonin intake by the fetus, which can result in malformations.

“Serotonin during early pregnancy is essential for the development of all embryonic cells, and thus any insult that disturbs the serotonin signaling process has the potential to result in a wide variety of malformations,” the study says.

For example, when Celexa (the brand name for citalopram) was taken in the first trimester, the risk of major birth defects jumped from 5 per cent to 8 per cent, Bérard found. In all, 88 cases of malformations were linked to use of the drug.

Similarly, use of Paxil (paroxetine) was associated with an increased risk of heart defects; venlafaxine (Effexor), with lung defects; and tricyclic antidepressants (such as Elavil), with increased eye, ear, face and neck defects.

Depression is on the rise across the globe and is a leading cause of death, according to the World Health Organization. Depression is particularly serious during pregnancy, and doctors – especially psychiatrists, obstetricians and other specialists – are prescribing more antidepressants than ever to expectant mothers.

Over the decade or so that Bérard studied her cohort, the proportion of expectant mothers on antidepressants in Quebec doubled, from 21 users per 1,000 pregnancies in 1998 to 43 per 1,000 in 2009.

Those using the drugs tend to be older, live alone or be on welfare; they also may have other ailments such as diabetes, hypertension and asthma, the new study shows. The women generally don’t have the financial means, leisure time or support to seek other solutions, such as exercising regularly or consulting with a psychotherapist.

“There are a multitude of ways to get mild to moderate depression treated, but you need to have the time and money and also the encouragement to take advantage of them,” Bérard said.

“Given that an increasing number of women are diagnosed with  depression during pregnancy, (the new) results have direct implications on their clinical management,” the study concludes.

“This is even more important given that the effectiveness of antidepressants during pregnancy for the treatment of the majority of cases of depression (mild to moderate depression) have been shown to be marginal.

“Hence, the need for caution with antidepressant use during pregnancy is warranted and alternative non-drug options should be considered.”

Citation: Anick Bérard, Jin-Ping Zhao and Odile Sheehy. “Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec Pregnancy Cohort.” BMJ Open 2017;7:e013372.
DOI: 10.1136/bmjopen-2016-013372
Research funding:  Canadian Institutes of Health Reseach (CIHR), and Fonds de la recherche du Québec – Santé (FRQ-S).
Adapted from press release by Université de Montréal.

Researchers develop in vitro model of brain for research

Harvard University researchers have developed a multiregional brain-on-a-chip that models the connectivity between three distinct regions of the brain. The in vitro model was used to extensively characterize the differences between neurons from different regions of the brain and to mimic the system’s connectivity.  The research was published in the Journal of Neurophysiology.

Image of the in vitro model showing three distinct regions of the brain connected by axons.
Credit: Disease Biophysics Group/Harvard University

“The brain is so much more than individual neurons,” said Ben Maoz, co-first author of the paper and postdoctoral fellow in the Disease Biophysics Group in the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). “It’s about the different types of cells and the connectivity between different regions of the brain. When modeling the brain, you need to be able to recapitulate that connectivity because there are many different diseases that attack those connections.”

Researchers from the Disease Biophysics Group at SEAS and the Wyss Institute modeled three regions of the brain most affected by schizophrenia the amygdala, hippocampus and prefrontal cortex. They began by characterizing the cell composition, protein expression, metabolism, and electrical activity of neurons from each region in vitro.

“It’s no surprise that neurons in distinct regions of the brain are different but it is surprising just how different they are,” said Stephanie Dauth, co-first author of the paper and former postdoctoral fellow in the Disease Biophysics Group. “We found that the cell-type ratio, the metabolism, the protein expression and the electrical activity all differ between regions in vitro. This shows that it does make a difference which brain region’s neurons you’re working with.”

Next, the team looked at how these neurons change when they’re communicating with one another. To do that, they cultured cells from each region independently and then let the cells establish connections via guided pathways embedded in the chip.

The researchers then measured cell composition and electrical activity again and found that the cells dramatically changed when they were in contact with neurons from different regions.

“When the cells are communicating with other regions, the cellular composition of the culture changes, the electrophysiology changes, all these inherent properties of the neurons change,” said Maoz. “This shows how important it is to implement different brain regions into in vitro models, especially when studying how neurological diseases impact connected regions of the brain.”

To demonstrate the chip’s efficacy in modeling disease, the team doped different regions of the brain with the drug Phencyclidine hydrochloride commonly known as PCP which simulates schizophrenia. The brain-on-a-chip allowed the researchers for the first time to look at both the drug’s impact on the individual regions as well as its downstream effect on the interconnected regions in vitro.

The brain-on-a-chip could be useful for studying any number of neurological and psychiatric diseases, including drug addiction, post-traumatic stress disorder, and traumatic brain injury.

“To date, the Connectome project has not recognized all of the networks in the brain,” said Parker. “In our studies, we are showing that the extracellular matrix network is an important part of distinguishing different brain regions and that, subsequently, physiological and pathophysiological processes in these brain regions are unique. This advance will not only enable the development of therapeutics, but fundamental insights as to how we think, feel, and survive.”

Citation: Dauth, Stephanie, Ben M. Maoz, Sean P. Sheehy, Matthew A. Hemphill, Tara Murty, Mary Kate Macedonia, Angie M. Greer, Bogdan Budnik, and Kevin Kit Parker. “Neurons derived from different brain regions are inherently different in vitro: A novel multiregional brain-on-a-chip.” Journal of Neurophysiology (2016): jn-00575.
DOI: 10.1152/jn.00575.2016
Research funding: Defense Advanced Research Projects Agency.
Adapted from press release by Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

Stress, cortisol and perceptual learning process

Neuroscientists of the Ruhr University Bochum found that stress has adverse impact on our learning process. Usually when we train our senses, we sharpen them and thereby improve our perceptual performance. However during stressful situations we produce a hormone called cortisol, which completely blocks this important ability. These findings are reported in Journal “Psychoneuroendocrinology” 

Stress by Typographyimages/pixabay

“Previous research has already shown that stress can prevent the retrieval of memories. But now we have discovered that it also has a major effect on our perception and perceptual learning,” explains Dr Hubert Dinse, one of the authors of the study.

In their study, researchers investigated how the sense of touch of 30 study participants could be changed after a training phase. Half of them received a medium dose of the stress hormone cortisol, while the other half received a placebo drug.

To make training comparable across all participants, the researchers employed the well-established approach of passive finger stimulation. Previous studies and several therapy approaches have shown that this method leads to an improved tactile acuity.

Tactile performance was assessed using the so-called “two-point discrimination threshold”. This marker indicates how far apart two stimuli need to be, to be discriminated as two separate sensations the closer they are, the better the sense of touch.

The placebo group improved their tactile acuity, as expected, by about 15 percent. In contrast, the cortisol given to the other group blocked almost all the stimulation-induced improvement. Cognitive psychologist Prof Dr Oliver T. Wolf explains:” Our data show that a single dose of cortisol not only disrupts memory in the hippocampus, but it also has a substantial effect on the plasticity of sensory areas of the brain.”

In previous studies on a cellular level, neuroscientists have demonstrated that cortisol suppresses the strengthening of synaptic connections, and therefore the plasticity of the brain – its ability to learn. The team led by Hubert Dinse therefore suggests, their results could also explain by cortisol-induced suppression of synaptic plasticity.

The results of the study could also affect clinical treatments. Corticosteroids, of which cortisol is one, are often used in the treatment of immunological and neurological diseases. However, the effects on perceptual learning observed in this study may counteract rehabilitation efforts, which rely on just these mechanisms. It is therefore necessary to find out which effects the clinical treatment with these substances has on learning mechanisms in the brain.

Citation: Dinse, Hubert R., J. C. Kattenstroth, M. Lenz, M. Tegenthoff, and O. T. Wolf. “The stress hormone cortisol blocks perceptual learning in humans.” Psychoneuroendocrinology 2017 vol: 77 pp: 63-67.
DOI: 10.1016/j.psyneuen.2016.12.002
Research funding: German Research Foundation (Deutsche Forschungsgemeinschaft, DFG).
Adapted from press release by Ruhr University Bochum.

Research uncovers link between long-term opioid use and preexisting psychiatric and behavioral disease

A wide range of pre-existing psychiatric and behavioral conditions and the use of psychoactive drugs could be important risk factors leading to long-term use of opioid pain medications, reports a study in Journal Pain, the official publication of the International Association for the Study of Pain (IASP).

long term opioid addiction

Using a nationwide insurance database, the researchers identified 10.3 million patients who filed insurance claims for opioid prescriptions between 2004 and 2013. The study looked at whether pre-existing psychiatric and behavioral conditions and use of psychoactive medications were predictors of later opioid use.

“We found that pre-existing psychiatric and behavioral conditions and psychoactive medications were associated with subsequent claims for prescription opioids,” write Patrick D. Quinn, Ph.D., of Indiana University, Bloomington, and colleagues. The association appears stronger for long-term opioid use, and especially for patients with a previous history of substance use disorders.

The results also suggest that some outcomes viewed as harmful outcomes of opioid use substance use disorders, depression, suicidal or self-injuring behavior, and motor vehicle crashes are also predictors of which patients are at risk of long-term use of prescription opioids.

Overall, the results suggested a “modest” increase in any opioid prescriptions for patients with previous psychiatric or behavioral conditions (depression or anxiety disorders, opioid or other substance use disorders, suicide attempts or other self-injury, motor vehicle crashes, and sleep disorders) or use of psychoactive medications.

About 1.7 percent of patients with opioid prescriptions become long-term opioid users (six months or longer). But the risk became substantially higher for patients with mental health conditions or psychoactive medication use. Relative increases in rates of long-term opioid use ranged from 1.5 times for patients taking medications for attention-deficit/hyperactivity disorder, to about 3 times for those with previous substance use disorders other than opioids, to nearly 9 times for those with previous opioid use disorders.

Amid the continuing opioid epidemic, it’s important to understand which patients select (or are selected for) treatment with these pain medications. Previous studies have suggested a pattern of “adverse selection”: patients at greatest risk of harmful outcomes, including those with substance abuse and other psychiatric conditions, may be more likely to be prescribed opioids in higher doses and for longer durations.

Dr. Quinn and coauthors conclude: “Our findings support the ideas that clinical practice has deviated from the ‘careful selection’ under which most clinical trials are conducted and that thorough mental health assessment and intervention should be considered in conjunction with the use of long-term opioid therapy.

Citation: Quinn, Patrick D., Kwan Hur, Zheng Chang, Erin E. Krebs, Matthew J. Bair, Eric L. Scott, Martin E. Rickert, Robert D. Gibbons, Kurt Kroenke, and Brian M. D’onofrio. “Incident and long-term opioid therapy among patients with psychiatric conditions and medications: a national study of commercial health care claims.” Pain 158, no. 1 (2017): 140-148.
DOI: 10.1097/j.pain.0000000000000730
Adapted from press release by Wolters Kluwer publications.

Meditation helps fight major depressive disorder

A breathing-based meditation practice known as Sudarshan Kriya yoga helped alleviate severe depression in people who did not fully respond to antidepressant treatments, reports a study published in the Journal of Clinical Psychiatry from researchers in the Perelman School of Medicine at the University of Pennsylvania. The study bolsters the science behind the use of controlled yogic breathing to help battle depression.

In a randomized, controlled pilot study, led by Anup Sharma, MD, PhD, a Neuropsychiatry research fellow in the department of Psychiatry at Penn, researchers found significant improvement in symptoms of depression and anxiety in medicated patients with major depressive disorder (MDD) who participated in the breathing technique compared to medicated patients who did not partake. After two months, the yoga group cut its mean Hamilton Depression Rating Scale (HDRS) score by several points, while the control group showed no improvements. Hamilton Depression Rating Scale (HDRS) is the most widely used clinician-administered depression assessment that scores mood, interest in activities, energy, suicidal thoughts, and feelings of guilt, among other symptoms.

The meditation technique, which is practiced in both a group setting and at home, includes a series of sequential, rhythm-specific breathing exercises that bring people into a deep, restful, and meditative state: slow and calm breaths alternated with fast and stimulating breaths.

In past studies, the practice has demonstrated a positive response in patients with milder forms of depression, depression due to alcohol dependence, and in patients with major depressive disorder (MDD); however, there are no clinical studies investigating its use for depression in an outpatient setting. Past studies suggest that yoga and other controlled breathing techniques can potentially adjust the nervous system to reduce stress hormones. Overall, the authors also note, well-designed studies that evaluate the benefits of yoga to treat depression are lacking, despite increased interest in the ancient Indian practice. Millions of Americans participate in some form of yoga every year.

In the study, researchers enrolled 25 patients suffering from major depressive disorder (MDD) who were depressed, despite more than eight weeks of antidepressant medication treatment. The medicated patients were randomized to either the breathing intervention group or the “wait list” control group for eight weeks. (The waitlist group was offered the yoga intervention after the study). During the first week, participants completed a six-session program, which featured Sudarshan Kriya yoga in addition to yoga postures, sitting meditation, and stress education. For weeks two through eight, participants attended weekly Sudarshan Kriya yoga follow-up sessions and completed a home practice version of the technique.

Patients in the Sudarshan Kriya yoga group showed a significantly greater improvement in HDRS scores compared to patients in the waitlist group. With a mean baseline, HDRS score of 22.0 (indicating severe depression at the beginning of the study), the group that completed the breathing technique for the full two months improved scores by 10.27 points on average, compared to the waitlist group, which showed no improvements. Patients in the yoga group also showed significant mean reductions in total scores of the self-reported Beck Depression (15.48 point improvement) and Beck Anxiety Inventories (5.19 point improvement), versus the waitlist control group.

Results of the pilot study suggest the feasibility and promise of Sudarshan Kriya as an add-on intervention for major depressive disorder (MDD) patients who have not responded to antidepressants, the authors wrote. “The next step in this research is to conduct a larger study evaluating how this intervention impacts brain structure and function in patients who have major depression,” Sharma said.

Citation: Sharma, Anup, Marna S. Barrett, Andrew J. Cucchiara, Nalaka S. Gooneratne,  and Michael E. Thase. “A Breathing-Based Meditation Intervention for Patients With Major Depressive Disorder Following Inadequate Response to Antidepressants: A Randomized Pilot Study.” The Journal of Clinical Psychiatry 2016.
DOI: 10.4088/JCP.16m10819

Research funding: American Psychiatric Association, Substance Abuse and Mental Health Services Administration Minority Fellowship Program, Indo-American Psychiatric Association, NIH/National Center for Advancing Translational Sciences.
Adapted from press release by University of Pennsylvania Health System.

Increased brain connectivity seen in endurance runners.

University of Arizona researchers discovered that MRI scans of endurance runners’ brains have greater functional connectivity than the brains of more sedentary individuals. Researchers compared brain scans of young adult cross country runners to young adults who don’t engage in regular physical activity. The runners, overall, showed greater functional connectivity or connections between distinct brain regions within several areas of the brain, including the frontal cortex, which is important for cognitive functions such as planning, decision-making and the ability to switch attention between tasks.

Although additional research is needed to determine whether these physical differences in brain connectivity result in differences in cognitive functioning, the current findings, published in the journal Frontiers in Human Neuroscience, help lay the groundwork for researchers to better understand how exercise affects the brain, particularly in young adults.

UA running expert David Raichlen, an associate professor of anthropology, co-designed the study with UA psychology professor Gene Alexander, who studies brain aging and Alzheimer’s disease as a member of the UA’s Evelyn F. McKnight Brain Institute. “One of the things that drove this collaboration was that there has been a recent proliferation of studies, over the last 15 years, that have shown that physical activity and exercise can have a beneficial impact on the brain, but most of that work has been in older adults,” Raichlen said.

“This question of what’s occurring in the brain at younger ages hasn’t really been explored in much depth, and it’s important,” he said. “Not only are we interested in what’s going on in the brains of young adults, but we know that there are things that you do across your lifespan that can impact what happens as you age, so it’s important to understand what’s happening in the brain at these younger ages.”

Along with their colleagues, Raichlen and Alexander compared the MRI scans of a group of male cross country runners to the scans of young adult males who hadn’t engaged in any kind of organized athletic activity for at least a year. Participants were roughly the same age — 18 to 25 — with comparable body mass index and educational levels. The scans measured resting state functional connectivity, or what goes on in the brain while participants are awake but at rest, not engaging in any specific task. The findings shed new light on the impact that running, as a particular form of exercise, may have on the brain.

Previous studies have shown that activities that require fine motor control, such as playing a musical instrument, or that require high levels of hand-eye coordination, such as playing golf, can alter brain structure and function. However, fewer studies have looked at the effects of more repetitive athletic activities that don’t require as much precise motor control such as running. Raichlen’s and Alexander’s findings suggest that these types of activities could have a similar effect.

“These activities that people consider repetitive actually involve many complex cognitive functions like planning and decision-making that may have effects on the brain,” Raichlen said.

Since functional connectivity often appears to be altered in aging adults, and particularly in those with Alzheimer’s or other neurodegenerative diseases, it’s an important measure to consider, Alexander said. And what researchers learn from the brains of young adults could have implications for the possible prevention of age-related cognitive decline later on.

“One of the key questions that these results raise is whether what we’re seeing in young adults in terms of the connectivity differences imparts some benefit later in life,” said Alexander, who also is a professor of neuroscience and physiological sciences. “The areas of the brain where we saw more connectivity in runners are also the areas that are impacted as we age, so it really raises the question of whether being active as a young adult could be potentially beneficial and perhaps afford some resilience against the effects of aging and disease.”

Citation: Raichlen, David A., Pradyumna K. Bharadwaj, Megan C. Fitzhugh, Kari A. Haws, Gabrielle-Ann Torre, Theodore P. Trouard, and Gene E. Alexander. “Differences in Resting State Functional Connectivity between Young Adult Endurance Athletes and Healthy Controls.” Frontiers in Human Neuroscience 10 (2016): 610.
DOI: 10.3389/fnhum.2016.00610
Adapted from press release by University of Arizona.

Association between cataracts and depression identified in elderly population

Older adults with cataracts are more likely to have symptoms of depression, reports a study in Optometry and Vision Science, the official journal of the American Academy of Optometry. The link between cataracts and depression is independent of other factors, and appears strongest among older adults with lower education, according to new research by Haifang Wang, MSc, of Soochow University, Suzhou, China, and colleagues.

Age-related cataracts are the leading cause of visual impairment worldwide and are expected to increase as population demographics shift towards advancing age. Depression is also common in older adults.

This large study in Chinese older adults investigated the link between visual impairment and depressive symptoms and provides evidence for an association between cataracts and depression. As part of a community survey study, approximately 4,600 older adults (60 years or older) in one Chinese town completed a depression questionnaire. Participants also underwent a clinical eye examination to rate the presence and severity of cataracts. Cataracts are a very common condition in older adults, with clouding of the lens of the eye causing vision loss.

Excluding those with previous cataract surgery, nearly half (49 percent) of older adults in the study had cataracts in at least one eye. On the depression questionnaire, 8 percent of subjects had depressive symptoms. Symptoms of depression were more common in women than men (11 versus 5 percent), and more common in older age groups.

Older adults with cataracts were more likely to have depressive symptoms, independent of socioeconomic status, lifestyle factors, and visual acuity. On adjusted analysis, symptoms of depression were 33 percent more likely when cataracts were present. Importantly, the odds of depressive symptoms were similar for subjects with cataracts in one eye versus both eyes.

The association between cataracts and depression was even stronger for subjects with no formal education, a 50 percent increase. After all other factors were taken into account, cataracts explained 14 percent of the variation in depression risk.

The researchers note that their study cannot show the direction of the association, vision loss might cause older adults to become isolated and withdrawn, or depression might make them less likely to seek treatment for cataracts.

“These results suggest that optometrists and vision care professionals should think beyond the direct effects of cataracts on visual impairment. We should also consider the broader impact that vision loss may have on mental health and well-being,” comments Michael Twa, OD, Ph.D., FAAO, Editor-in-Chief of Optometry and Vision Science. “As a next step, it would be important to know if the associated depression in older adults is reversible following the restoration of vision after cataract surgery.”

Citation: Wang, Haifang, Hong-Peng Sun, Pei Wang, Yong Xu, and Chen-Wei Pan. “Cataract and Depressive Symptoms among Older Chinese Adults.” Optometry & Vision Science 93, no. 12 (2016): 1479-1484.
DOI: 10.1097/OPX.0000000000000960
Adapted from press release by Wolters Kluwer Health.

Post-traumatic stress disorder treatment with Individual cognitive processing therapy found effective

Individual sessions of cognitive processing therapy (CPT) – a trauma-focused treatment that teaches patients more balanced thinking about traumatic events – were better at reducing the severity of posttraumatic stress disorder (PTSD) in active-duty military members, although group sessions also were effective, according to an article published online by JAMA Psychiatry.

Posttraumatic stress disorder (PTSD) is a serious problem among active-duty military personnel, especially those returning from combat deployment. More data are needed on the efficacy of individual and group therapy treatment for active-duty personnel.

Patricia A. Resick, Ph.D., of the Duke University Medical Center, Durham, N.C., and coauthors conducted a randomized clinical trial of 268 active-duty personnel seeking treatment for posttraumatic stress disorder (PTSD) at Fort Hood, Texas, after being deployed near Iraq or Afghanistan. The participants were nearly all men (91 percent) with an average age of 33.

The participants were assigned to cognitive processing therapy (CPT)  in either 90-minute group sessions (n=133 participants) or 60-minute individual sessions (n=135 participants) twice weekly for six weeks. The 12 sessions (group and individual) were conducted concurrently. Assessment tools were used to measure posttraumatic stress disorder (PTSD) severity, as well as the secondary outcomes of depression and suicidal ideation.

The authors report greater improvement in posttraumatic stress disorder (PTSD) severity when participants received cognitive processing therapy in individual compared with group sessions, although improvements were maintained during the six-month follow-up in both groups, according to the results. Patients assigned to individual cognitive processing therapy had about twice as much improvement.

Depression and suicidal ideation improved equally with both forms of cognitive processing therapy. Still, about 50 percent of the participants, including those receiving individual cognitive processing therapy, still had posttraumatic stress disorder (PTSD) and significant symptoms.

Possible explanations for why patients in individual cognitive processing therapy may have fared better include that those in group received less individual attention and those who missed group cognitive processing therapy sessions missed content that could not be replaced, the authors report. Limitations to the study include patients lost to treatment because of military discontinuation.

Citation: Resick PA, Wachen JS, Dondanville KA, Pruiksma KE, Yarvis JS, Peterson AL, Mintz J, and the STRONG STAR Consortium. Effect of Group vs Individual Cognitive Processing Therapy in Active-Duty Military Seeking Treatment for Posttraumatic Stress DisorderA Randomized Clinical Trial. JAMA Psychiatry. Published online November 23, 2016. doi:10.1001/jamapsychiatry.2016.2729
Adapted from press release by JAMA

Methylphenidate with cognitive behavioral therapy found helpful in traumatic brain injury patients

A combination of the stimulant drug methylphenidate with a process known as cognitive-behavioral rehabilitation is a promising option to help people who suffer from persistent cognitive problems following traumatic brain injury, researchers at Indiana University School of Medicine have reported. The study, believed to be the first to systematically compare the combination therapy to alternative treatments, was published online in the journal Neuropsychopharmacology, a Nature publication.

The researchers, led by Brenna McDonald, PsyD, associate professor of radiology and imaging sciences, and Thomas McAllister, MD, chairman of the Department of Psychiatry, compared the effectiveness of two forms of cognitive therapy with and without the use of methylphenidate, a drug used to treat attention-deficit/hyperactivity disorder and better known by its trade name, Ritalin. “We found that the combination of methylphenidate and Memory and Attention Adaptation Training resulted in significantly better results in attention, episodic and working memory, and executive functioning after traumatic brain injury,” said Dr. McDonald.

In the Memory and Attention Adaptation Training intervention – also used to assist patients with cognitive issues following breast cancer chemotherapy – therapists work with patients to help them develop behaviors and strategies to improve performance in memory and other cognitive tasks. In this study, this “metacognitive” approach was compared with Attention Builders Training, which Dr. McDonald likened to more of a “drill and practice” approach.

The 71 participants who completed the six-week trial were adults who had experienced a traumatic brain injury of at least mild severity – a blow to the head with some alteration of consciousness – at least four months previously, and who either complained of having cognitive problems, or who had been identified with cognitive problems in testing. The participants were divided into four groups: the two cognitive therapy approaches with the drug therapy, and the two approaches with placebo. After six weeks, the researchers found that participants in the combination metacognitive-Ritalin group improved significantly better in word list learning, nonverbal learning and measures of attention-related and executive function.

However, Dr. McDonald cautioned that due to the relatively small number of participants in the each of the four arms of the trial – 17 to 19 people each – the results of the trial should be considered preliminary. Nonetheless, she said, the work breaks new ground in providing evidence for the combination therapy.

Citation: “Methylphenidate and Memory and Attention Adaptation Training for Persistent Cognitive Symptoms after Traumatic Brain Injury: A Randomized, Placebo-Controlled Trial”. Brenna C McDonald, Laura A Flashman, David B Arciniegas, Robert J Ferguson, Li Xing, Jaroslaw Harezlak, Gwen C Sprehn, Flora M Hammond, Arthur C Maerlender, Carrie L Kruck, Karen L Gillock, Kim Frey, Rachel N Wall, Andrew J Saykin and Thomas W McAllister. Neuropsychopharmacology
2016
DOI: http://dx.doi.org/10.1038/npp.2016.261
Research funding: National Institutes of Health
Adapted from press release by Indiana University

Research on Zebrafish show that probiotic bacteria help reduce stress and anxiety

Researchers at the University of Missouri, using a zebrafish model, determined that a common probiotic sold in supplements and yogurt can decrease stress-related behavior and anxiety. Studying how gut bacteria affect behavior in zebrafish could lead to a better understanding of how probiotics may affect the central nervous system in humans. Their results recently were published in Scientific Reports a journal of Nature.

“Zebrafish are an emerging model species for neurobehavioral studies and their use is well-established in drug-screening,” said Aaron Ericsson, director of the MU Metagenomics Center and a research assistant professor in the Department of Veterinary Pathobiology. “Our study has shown that simple probiotics that we normally use to keep our digestive tract in sync, could be beneficial to reducing our stress levels as well.”

In a series of studies, researchers tested how zebrafish behaved after doses of Lactobacillus plantarum, a common bacteria found in yogurt and probiotic supplements. In the first study, scientists added the bacteria to certain tanks housing zebrafish; other tanks of zebrafish received no probiotics. Then, the researchers introduced environmental stressors to both groups, such as draining small amounts of water from the tank and overcrowding.

“Each day we introduced a different stressor — tests that are validated by other researchers and cause higher anxiety among zebrafish,” said Elizabeth Bryda, professor of veterinary pathobiology in the MU College of Veterinary Medicine. “These are common environmental stress patterns, such as isolation stress and temperature change, so it made the tests relevant to humans as well.”

By analyzing the gene pathways of both groups of fish, the research team found that zebrafish that were given the probiotic supplements showed a reduction in the metabolic pathways associated with stress. “By measuring the genes associated with stress and anxiety, our tests were able to predict how this common probiotic is able to benefit behavioral responses in these fish,” said Daniel Davis, assistant director of the MU Animal Modeling Core.

To test their theory further, the researchers measured the movements of fish in their tanks using sophisticated computer measuring and imaging tools. Previous studies of fish behavior have found that fish that are stressed tend to spend more time at the bottom of their tanks. Once the fish were administered probiotics, they tended to spend more time toward the top of the tanks — the change in behavior indicating they were less stressed or less anxious.

Citation: Davis, Daniel J., Holly M. Doerr, Agata K. Grzelak, Susheel B. Busi, Eldin Jasarevic, Aaron C. Ericsson, and Elizabeth C. Bryda. “Lactobacillus plantarum attenuates anxiety-related behavior and protects against stress-induced dysbiosis in adult zebrafish.” Scientific Reports 6 (2016).
DOI: http://dx.doi.org/10.1038/srep33726
Research funding: Missouri-Columbia College of Veterinary Medicine
Adapted from press release by the University of Missouri-Columbia.