Originally introduced in 2015, the Act was proposed with the goal of promoting development and speeding approval of new drugs and medical devices, and, in its final form, it offers broad incentives and funding opportunities for many areas of health care research, development, and support.

The law directs increasing the budget for the National Institutes of Health (NIH) and creating an NIH fund to promote innovation in research and support opportunities for young researchers. NIH-funded research plays a crucial role in supporting the approval of many new drugs, so this is a welcome addition for many drug developers and researchers. The bill also commits billions of dollars to research precision medicine, map the human brain, and cure cancer.

A large portion of the Act is devoted to accelerating the drug approval process. The U.S. Food and Drug Administration—the gatekeeper of all drugs and devices in the United States—is now instructed by the Act to consider nontraditional study designs and methods when evaluating approvals of new drugs and indications. While most people, especially those in the health care industry, view the approval of new safe and effective drugs as a laudable goal, the willingness to rely on shorter or smaller clinical trials or observational studies or registries to evaluate safety and effectiveness may prove to be problematic. Such approaches are not as rigorous as randomized, controlled trials, that have been, until now, the gold standard of drug approval data.

The Act also encourages the FDA to rely on biomarkers instead of clinical outcomes to assess effectiveness. However, biomarkers are not always accurate representations or predictors of disease risks and endpoints. The Act does not change FDA approval standards, but it allows the FDA more discretion and leniency in how it approves drugs. Critics argue that the less-than-one-year average approval time does not really need accelerating and the strict research requirements do not need adjusting.

As part of the Act, the FDA can also incentivize hospitals for administering new antimicrobial drugs that have not received confirmatory approval. The Act also incentivizes drugmakers by removing regulatory hurdles that lengthen their approval processes and make them more expensive.

In addition to drug approvals, the Act addresses mental health care in this country: it established provisions for fighting the opioid epidemic, strengthened laws guaranteeing access to mental health care, and provided grants to increase the number of psychologists and psychiatrists. The Act pushes society ahead in our goal of preventing devastating consequences of mental health such as homelessness, incarceration, and suicide.

The Act has, for the most part, good motives, and it includes a little bit for a lot of people. However, it aims to fix problems that may or may not really exist and offers incentives to groups that may or may not benefit from incentives.

Plus, the future of health care in this country is uncertain. The new administration could unwind many of the changes established by the Act and, while the Act provides a framework for authorizing these programs, future Congresses would actually need to vote on and approve the budgets that pay for the provisions in the Act. The benefits and drawbacks of the Act in the real world remain to be seen. Our lawmakers are probably looking in the right direction and trying hard to choose the right path, but just how many obstacles and speed traps we hit along the way will influence just how fast this Act can get us to safe, effective, and accessible health care.

References

21st Century Cures Act. U.S. House of Representatives Committee on Energy and Commerce. https://energycommerce.house.gov/sites/republicans.energycommerce.house.gov/files/documents/114/analysis/20161128%20Cures%20Fact%20Sheet.pdf. Accessed January 23, 2017.

Avorn J, Kesselheim AS. The 21st Century Cures Act—Will it take us back in time? N Engl J Med. 2015;372:2473-2475. PMID: 26039522

Kesselheim AS, Avorn J. The 21st Century Cures Act. N Engl J Med. 2015;373(17):1679-80. PMID: 26488710

Image via tpsdave/Pixabay.

Normally, the brain depends on tau protein to receive nutrients and get rid of waste. When a toxic form of the tau protein clumps together, it forms tangles that are noxious to the brain. These toxic tau proteins may be at least partly responsible for the inflammation that is characteristic of AD, and inflammation may start before the tau tangles form. Now, researchers at the University of Texas speculate that this inflammation may be detectable by examining the retina during routine eye exams. This type of screening would be non-invasive and inexpensive and may eventually allow for early intervention to mitigate brain cell death and cognitive decline.

Authors of the current study, published in Journal of Alzheimer’s Disease, examined brain analyses and retinal samples from human patients with AD, as well as a mouse model of AD. The findings suggest that toxic tau proteins induce inflammation that spreads throughout the brain, initiating the vicious cycle of cell death and more inflammation. Screening of the retina as part of a normal health check-up can detect inflamed tissue earlier in the disease process than other methods of AD screening.

AD has long been known to impact the visual system, and pathophysiological connections have been made between AD and visual disorders, such as certain types of cataract and glaucoma. The eye offers easy access to cerebral functioning, and ocular biomarkers for AD may potentially improve disease diagnosis and management.

AD is the most common form of dementia and its prevalence is growing as the world’s population ages. Patients with AD exhibit profound, progressive declines in cognition, memory, and social functioning. To date, there are no cures and available treatments are only marginally effective at managing some of the symptoms of the disease.

The new findings are far from offering cures or preventions for AD, but the authors hope that, eventually, early detection of inflammation will lead to therapeutic options for reducing inflammation and minimizing neurodegenerative brain damage.

References

Hart NJ, Koronyo Y, Black KL, Koronyo-Hamaoui M. Ocular indicators of Alzheimer’s: exploring disease in the retina. Acta Neuropathol. 2016;132(6):767-787. PMID: 27645291.

Javaid FZ, Brenton J, Guo L, Cordeiro MF. Visual and ocular manifestations of Alzheimer’s disease and their use as biomarkers for diagnosis and progression. Front Neurol. 2016;7:55. PMID: 27148157.

Jun G, Moncaster JA, Koutras C, et al. ?-Catenin is genetically and biologically associated with cortical cataract and future Alzheimer-related structural and functional brain changes. PLoS One. 2012;7(9):e43728. PMID: 22984439.

Kusne Y, Wolf AB, Townley K, et al. Visual system manifestation of Alzheimer’s disease. Acta Ophthalmol. 2016. PMID: 27864881.

Nilson AN, English KC, Gerson JE, et al. Tau oligomers associate with inflammation in the brain and retina of tauopathy mice and in neurodegenerative diseases. J Alzheimers Dis. 2016. PMID: 27716675.

Valenti DA. Alzheimer’s disease and glaucoma: imaging the biomarkers of neurodegenerative disease. Int J Alzheimers Dis. 2011. PMID: 21253485.

Image via cocoparisienne / Pixabay.

The new study, published in Nature Communications, used imaging techniques and a method of neural activation called decoded neurofeedback to analyze the brain activity patterns of 17 young-adult participants. The participants engaged in simple perceptual and behavioral exercises that allowed the team of researchers to identify low-confidence and high-confidence brain activity patterns. Next, the participants were given a small monetary reward every time the researchers detected a high-confidence state. The participants also rated their own levels of confidence after the tasks. In the end, the participants unconsciously raised their levels of confidence, in real time, even though they were unaware of the manipulation.

Self-confidence is generally a belief in one’s own abilities. It is a complex internal, emotional state—influenced by myriad factors—that describes how we feel about ourselves. A lack of self-confidence can lead to shyness, social anxiety, lack of assertiveness, communication difficulties, and mental health problems. These factors can, in turn, negatively impact activity levels, relationships, and careers.

To date, self-confidence has been primarily assessed through introspection and self-reports. However, recently, the deeply subjective nature of self-confidence has been examined as an objective quality. Through functional imaging techniques, scientists are beginning to develop neural models for the feelings of confidence, and these new findings have important implications for psychiatry and psychology, as well as understandings of behavior and decision-making.

Self-confidence does not look or feel the same for all people, and, regardless of objective measures of brain activity, it will continue to be an individualized phenomenon, for the most part. The new study does not leave readers with any self-help steps that can be used to improve self-confidence outside of a laboratory setting, but it does support the perspective that self-confidence is flexible and fluid. The finding that self-confidence can be changed by training one’s brain may bring the scientific world one step closer to understanding just how and why certain mental states exist—and, what can be done to change them.

References

Cortese A, Amano K, Koizumi, A, et al. Multivoxel neurofeedback selectively modulates confidence without changing perceptual performance. Nat Commun. 2016;7:13669. PMID: 27976739.

Fleming SM, Maniscalco B, Ko Y, et al. Action-specific disruption of perceptual confidence. Psychol Sci. 26(1):89-98. PMID: 25425059.

Kepecs A, Mainen ZF. A computational framework for the study of confidence in humans and animals. Philos Trans R Soc Lond B Biol Soc. 2012;367(1594):1322-1337. PMID: 22492750.

Kepecs A, Mensh BD. Emotor control: computations underlying bodily resource allocation, emotions, and confidence. Dialogues Clin Neurosci. 2015;17(4):391-401. PMID: 26869840.

The authors evaluated 2 cohorts of people aged 50 years and older from the English Longitudinal Study of Aging. One group contained 9000 people and the other contained approximately 12,500.

When the authors correlated BMI, inflammatory markers, and cognition over a 6-year period, the results in both groups were the same: higher BMI was associated with greater cognitive decline.

Specifically, the higher the BMI at the beginning of the study, the greater increase in levels of inflammatory markers (specifically, C-reactive protein [CRP]) over the next 4 years. The change in CRP predicted greater decline in memory and executive functioning over the following 2 years (a total of 6 years from the start of the study.) Established literature already links inflammation to cognitive decline, but these findings take it a step further by highlighting the role of BMI in systemic inflammation.

Physical activity and body mass are related to cognitive function in adults. BMI is a function of body mass (i.e., weight) and height, and most data reveal an inverse relationship between physical activity and BMI. Likewise, regular exercise has been shown to prevent cognitive decline in adults who are middle aged and older.

The relationship between physical activity and BMI, however, is nuanced because BMI does not account for a person’s amounts of body fat or muscle mass, both of which can skew the calculation. Still, the general trends are intuitive: engage in more physical activity, decrease body weight, lower BMI, and improve cognition.

In the current study, BMI, by way of inflammation, predicted cognitive decline. While no absolute criteria are reported for preventing cognitive decline, the authors provide one more reason – if one is even needed – to maintain an appropriate body weight and levels of physical activity. Changes in cognition related to aging often take years – even decades – to appear, so a healthy BMI at younger ages may prevent cognitive changes years later.

A recent landmark study indicated that healthy lifestyle habits were cumulative in their protective effects against cognitive decline, asserting that exercise and maintaining health body weight were important for 20 years before the onset of cognitive decline.

Healthy BMI is correlated to decreased risks of many diseases and conditions that affect most of the major body’s major organ systems. Now, simply reducing BMI may be a simple, low-cost intervention to decrease the burden of cognitive impairment.

References

Bourassa, K., & Sbarra, D. A. (2016). Body mass and cognitive decline are indirectly associated via inflammation among aging adults. Brain, Behavior, and Immunity. doi:10.1016/j.bbi.2016.09.023

Hemmingsson, E., & Ekelund, U. (2006). Is the association between physical activity and body mass index obesity dependent? International Journal of Obesity. doi:10.1038/sj.ijo.0803458

Memel, M., Bourassa, K., Woolverton, C., & Sbarra, D. A. (2016). Body mass and physical activity uniquely predict change in Cognition for aging adults. Annals of Behavioral Medicine, 50(3), 397–408. doi:10.1007/s12160-015-9768-2

Ronan, L., Alexander-Bloch, A. F., Wagstyl, K., Farooqi, S., Brayne, C., Tyler, L. K., & Fletcher, P. C. (2016). Obesity associated with increased brain age from midlife. Neurobiology of Aging, 47, 63–70. doi:10.1016/j.neurobiolaging.2016.07.010

Szoeke, C., Lehert, P., Henderson, V. W., Dennerstein, L., Desmond, P., & Campbell, S. (2016). Predictive factors for verbal memory performance over decades of Ageing: Data from the women’s healthy Ageing project. The American Journal of Geriatric Psychiatry. doi:10.1016/j.jagp.2016.05.008

Willey, J. Z., Gardener, H., Caunca, M. R., Moon, Y. P., Dong, C., Cheung, Y. K., … Wright, C. B. (2016). Leisure-time physical activity associates with cognitive decline. Neurology, 86(20), 1897–1903. doi:10.1212/wnl.0000000000002582

Image via Wokandapix / Pixabay.

A group of researchers at Baylor College of Medicine evaluated 94 patients aged 18 to 85 years who had been hospitalized for mild, moderate, or severe traumatic brain injury (TBI). Most of the patients (n=92) were Caucasian and more than half (n=56) were male. The research team randomized the patients to receive either 100 mg daily of sertraline (48 patients) or placebo (46 patients) for 24 weeks or until symptoms of a mood disorder occurred.

Overall, sertraline was effective at preventing the onset of depressive symptoms compared to placebo. Sertraline was also well tolerated  and adverse effects in both treatment groups were mild. It is unclear how long the effects of sertraline last in this patient group.

The incidence of TBI is rising and it now is a major cause of death and disability. TBI can occur from injury, stroke, falls, motor vehicle accidents, and violence. People suffering moderate to severe TBI are at risk for depression and loss of life roles. Life satisfaction declines in this population, so prevention of depressive symptoms is imperative for maintaining health and function.

Sertraline, an antidepressant, has been used to treat PTSD but its effects in TBI are still being defined. The results of the study, which were published in JAMA Psychiatry, need to be confirmed with larger sample sizes and in multicenter trials. Further, a question remains if combining sertraline with cognitive behavioral interventions will optimize long-term outcomes.

References

Almeida OP, Hankey GJ, Yeap BB, et al. Prevalence, associated factors, mood and cognitive outcomes of traumatic brain injury in later life. Int J Geriatr Psychiatry. 2015;30(12):1215-1223. PMID: 25703581

Ashman TA, Cantor JB, Gordon WA, et al. A randomized controlled trial of sertraline for the treatment of depression in persons with traumatic brain injury. Arch Phys Med Rehabil. 2009;90(5):733-740. PMID: 19406291

Hien DA, Levin FR, Ruglass LM, et al. Combining seeking safety with sertraline for PTSD and alcohol use disorders: a randomized controlled trial. J Consult Clin Psychol. 2015;83(2):359-369. PMID: 25622199

Jorge RE, Acion L, Burin DI, Robinson RG. Sertraline for preventing mood disorders following traumatic brain injury. JAMA Psychiatry. 2016. Epub ahead of print. doi: 10.1001/jamapsychiatry.2016.2189

Juengst SB, Adams LM, Bogner JA, et al. Trajectories of life satisfaction after traumatic brain injury: influence of life roles, age, cognitive disability, and depressive symptoms. Rehabil Psychol. 2015;60(4):353-364. PMID: 26618215

Schneier FR, Campeas R, Carcamo J, et al. Combined mirtazapine and SSRI treatment of PTSD: a placebo-controlled trial. Depress Anxiety. 2015;32(8):570-579. PMID: 26115513

Image via aloisiocostalatge / Pixabay.

The tests – Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) and ImPACT Pediatric – are the first devices permitted for marketing that assess cognitive function following a potentially concussive injury. Both tests are intended to be used as part of a complete medical evaluation by physicians or other health care personnel trained in assessing signs and symptoms of head injury; the tests are not intended to diagnose concussion or determine possible treatments.

ImPACT is conducted on a desktop or laptop and is designed for patients aged 12 to 59. The more game-like, ImPACT Pediatric, is conducted on a tablet and is designed for patients aged 5 to 11. The tests assess cognitive skills such as word memory, attention span, nonverbal problem solving, and reaction time; the results are compared to an age-matched control database or a patient’s pre-injury scores, if any are available. The manufacturer – ImPACT Applications in Pittsburgh, Pennsylvania – reports that they currently have 17,000 cases in the normative, control database.

In order to gain FDA approval of ImPACT and ImPACT Pediatric, the manufacturer submitted results of more than 250 peer-reviewed device analyses. More than half of these were independent, clinical research studies. Together, the studies resolved that the devices were valid and reliable and able to detect evidence of cognitive dysfunction. The FDA determined that ImPACT and ImPACT Pediatric were safe and effective. Therefore, the results supported the marketing of the devices through a de novo classification process – a regulatory pathway for new, low- to moderate-risk medical devices that are the first of their kind.

Traumatic brain injuries (TBI) account for more than 2 million emergency department visits each year in the United States. More than 50,000 Americans die from TBI annually. Concussion, a subset of mild TBI, is a traumatically induced transient disturbance of brain function that involves a complex pathophysiologic process. As many as 3.8 million concussions occur during competitive and recreational sports in the United States, but approximately half go unreported.

Concussions, especially in sports and the military, are common. However, they are difficult to diagnose, and under-reporting remains a public health burden. Many systems for preventing, assessing, and treating concussions are being investigated and developed, but many questions remain unanswered. Long-term consequences of concussion are still unclear, as well, with pervasive alterations in attention and executive control apparent after a single concussive incident during childhood.

Concussion is a clinical diagnosis that must be made by a health care provider who is familiar with the patient and can recognize and evaluate a concussion. Symptom checklists are objective for evaluating a variety of symptoms related to a head injury, and some standardized assessment tools offer structure for evaluating concussion. Biomarkers are being investigated as potential diagnostic and prognostic tools. Much more research is needed to validate current assessments, and new technologies may provide new insight for diagnosing, evaluating, and managing concussions.

Any mechanism, including the new ImPACT systems, that can raise awareness of concussion and assist in identifying cognitive injury, may offer an important direction for combating concussive injuries in the future.

References

Brennan JH, Mitra B, Synnot A, et al. Accelerometers for the assessment of concussion in male athletes: a systematic review and meta-analysis (2016) Sports Medicine. Epub ahead of print. PMID: 27402455

Brett BL, Smyk N, Solomon G, et al. Long-term stability and reliability of baseline cognitive assessments in high school athlete using ImPACT at 1-, 2-, and 3-year test-retest intervals (2016) Archives of Clinical Neuropsychology. Epub ahead of print. PMID: 27538440

Crowe L, Collie A, Hearps S, et al. Cognitive and physical symptoms of concussive injury in children: a detailed longitudinal recovery study (2016) British Journal of Sports Medicine, 50(5):311-6. PMID: 26429808

Faltus J, Huntimer B, Kernozek T, Cole J. Utilization of ImPACT testing to measure injury risk in alpine ski and snowboard athletes (2016) International Journal of Sports Physical Therapy, ;11(4):498-506. PMID: 27525174

Finkbeiner NW, Max JE, Longman S, Debert C. Knowing what we don’t know: long-term psychiatric outcomes following adult concussion in sports. Canadian Journal of Psychiatry. 2016;61(5):270-6. PMID: 27254801

Harmon KG, Drezner JA, Gammons M, et al. American Medical Society for Sports Medicine position statement: concussion in sport (2013) British Journal of Sports Medicine, 47(1):15-26. PMID: 23243113

Kroshus E, Garnett BR, Baugh CM, Calzo JP. Engaging teammates in the promotion of concussion help seeking (2016) Health Education & Behavior, 43(4):442-51. PMID: 27405801

Moore DR, Pindus DM, Raine LB, et al. The persistent influence of concussion on attention, executive control and neuroelectric function in preadolescent children (2016) International Journal of Psychophysiology, 99:85-95. PMID: 26608697

U.S. Food and Drug Administration. FDA allows marketing of first-of-king computerized cognitive tests to help assess cognitive skills after a head injury. News release. August 22, 2016. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm517526.htm.

A new study, published in Translational Psychiatry, reports that GLP-1 receptors may be a target for treating drug abuse. The study was conducted in mice, but it calls attention to previous reports with similar findings.

Dopamine is essential to reward pathways that influence drug abuse and addiction. Endocannabinoids and arachidonic acid, which are also naturally present in the brain, affect the function of dopamine transporters. Activation of GLP-1 receptors reduces arachidonic acid in areas of the brain that are associated with reward; dopamine levels, in turn, reduce. In the current study, the long-lasting GLP-1 receptor agonist, exenatide, abolished cocaine-induced increases in dopamine levels.

GLP-1 is normally found in the gut and influences satiety signaling. In part, GLP-1 agonists, which mimic the activity of naturally-occurring GLP-1, regulate glucose homeostasis in type 2 diabetes by promoting a feeling of fullness. These drugs have been shown to aid in weight loss in patients with type 2 diabetes. These effects might also be due to the reduction in the rewarding effects of food, owing to GLP-1 action in regulating dopamine transporter activity and reducing reward related to food intake.

Both illicit drugs and palatable foods activate reward pathways in the brain. Therefore, pharmacologic modulation of these central nervous system circuits holds promise for reducing unwanted or abusive behaviors. The role of naturally occurring GLP-1 in affecting reward is unknown. The beneficial effects of GLP-1 agonist activity are now believed to extend not just to food, but alcohol and to psychostimulants, such as cocaine and amphetamine.

Several recent studies have highlighted the mechanism by which GLP-1 agonists influence reward-inducing behaviors in the central nervous system. While the place in therapy is not clearly defined, these findings could expand the therapeutic potential of this entire class of drugs.

References

Harasta AE, Power JM, von Jonquieres G, et al. Septal glucagon-like peptide 1 receptor expression determines suppression of cocaine-induced behavior (2015) Neuropsychopharmacology, 40(8):1969-78. PMID: 25669605

Reddy IA, Pino JA, Weikop P, et al. Glucagon-like peptide-1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels (2016) Transl Psychiatry, 6:e809. PMID: 27187231

Richards JE, Anderberg RH, Goteson, et al. Activation of the GLP-1 receptors in the nucleus of the solitary tract reduces food reward behavior and targets the mesolimbic system (2015) PLoS One, 110(3):e0119034. PMID: 25793511

Sirohi S, Schurdak JD, Seeley RJ, et al. Contral peripheral glucagon-like peptide-1 receptor signaling differentially regulate addictive behaviors (2016) Physiol Behav, 161:140-4. PMID: 27072507

Skibicka KP. The central GLP-1: implications for food and drug reward (2013) Front Neurosci 7:181. PMID: 24133407

The large observational study, published in the Journal of Epidemiology and Community Health, reports that a high level of education is associated with an increased risk of brain tumors. The study is based on data from 4.3 million Swedish adults who were monitored between 1993 and 2010. Overall, 5,735 men and 7,101 women developed a brain tumor during the observation period.

Men with at least three years of university-level education had a 19% greater risk of developing gliomas than men with only a compulsory level of education (nine years). Women with the same level of education had a 23% increased risk of gliomas and a 16% increased risk of meningiomas. Marital status and amount of disposable income only slightly affected the risk among men but not among women. Single men had a lower risk of glioma but a higher risk of meningiomas. Occupation also influenced brain tumor risks among men and women: men in professional and management roles had a 20% increased risk of gliomas and a 50% increased risk of acoustic neuromas; women in these roles had a 26% increased risk of gliomas and a 14% increased risk of meningiomas.

Socioeconomic status has been associated with prognosis and outcomes in many types of cancer, as well as the development of breast cancer, childhood leukemia, and Hodgkin’s lymphoma. Socioeconomic status and education level also affect attitudes toward cancer screening and treatment and timeliness of disease presentation. Age, military service record, and insurance coverage have also been associated with cancer risks and outcomes. The reasons behind the associations are unclear, but some risk factors have been hypothesized such as rates of atopy and allergies, cell phone use, and body measurements.

While no firm cause-and-effect conclusions can be drawn from an observational study, the authors of the new study claim that the results are consistent and that examining a large population gives strength to the results. More evidence is needed to confirm if education is, in fact, a true risk factor for developing brain tumors.

References

Borugian MJ, Spinelli JJ, Mezei G, Wilkins R, Abanto Z, & McBride ML (2005). Childhood leukemia and socioeconomic status in Canada. Epidemiology (Cambridge, Mass.), 16 (4), 526-31 PMID: 15951671

Clarke CA, Glaser SL, Keegan TH, & Stroup A (2005). Neighborhood socioeconomic status and Hodgkin’s lymphoma incidence in California. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 14 (6), 1441-7 PMID: 15941953

Kasl RA, Brinson PR, & Chambless LB (2016). Socioeconomic status does not affect prognosis in patients with glioblastoma multiforme. Surgical neurology international, 7 (Suppl 11) PMID: 27217966

Lehrer S, Green S, & Rosenzweig KE (2016). Affluence and Breast Cancer. The breast journal PMID: 27296617

Mezei G, Borugian MJ, Spinelli JJ, Wilkins R, Abanto Z, & McBride ML (2006). Socioeconomic status and childhood solid tumor and lymphoma incidence in Canada. American journal of epidemiology, 164 (2), 170-5 PMID: 16524952

Porter AB, Lachance DH, & Johnson DR (2015). Socioeconomic status and glioblastoma risk: a population-based analysis. Cancer causes & control : CCC, 26 (2), 179-85 PMID: 25421378

Quaife SL, Winstanley K, Robb KA, Simon AE, Ramirez AJ, Forbes LJ, Brain KE, Gavin A, & Wardle J (2015). Socioeconomic inequalities in attitudes towards cancer: an international cancer benchmarking partnership study. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP), 24 (3), 253-60 PMID: 25734238

Image via kaboompics / Pixabay.

A new study, published in Lancet Psychiatry, reports a small trial of psilocybin (a psychedelic substance naturally found in some mushroom species) for treatment-resistant depression. A total of 12 patients with moderate to severe unipolar depression received 2 doses of psilocybin 1 week apart along with psychological support. (A 10-mg dose was given as a test dose and a 25-mg dose was given as the therapeutic dose 7 days later.) The patients had experienced symptoms of depression for an average of nearly 18 years that had not responded to traditional therapies. Symptoms of depression were improved at 1 week and 3 months after psilocybin administration with no unexpected adverse events. Anxiety and anhedonia also improved.

The patients (6 men and 6 women) received each psilocybin dose while resting in a relaxation-inducing treatment room. Two psychiatrists were present in the room during the entire process. The onset of the acute psychedelic effects was between 30 and 60 minutes and the peak was approximately 2 to 3 hours after the dose. The drug was undetectable after 6 hours, and the patients were released at this time. Symptoms were assessed with the 16-item quick inventory of depressive symptoms from 1 week to 3 months after high-dose treatment.

There was no control group in this study, and the patients who participated knew they would be taking the psychedelic. Most of the patients were actively seeking treatment for their depression and 5 of the 12 patients had used psilocybin in the past. All of these factors could have influenced the positive findings.

Overall, the drug was well tolerated, with no serious or unexpected adverse effects; confusion and thought disorders were the most common effects. Some patients experienced nausea and headache. All of the side effects were short-lived and – in the opinion of the participants and researchers – paled in comparison to the long-lived benefits. The single, moderate, but therapeutic, dose of psilocybin had a 3-month antidepressant effect. In fact, the depression symptom scores 1 week after the first low dose of psilocybin were also decreased, suggesting that high-dose therapy may not be required to achieve benefits.

Psilocybin is a serotonin receptor agonist that targets the same pathway that existing antidepressants do, though through a different mechanism. Psilocybin shifts emotional biases away from negative and toward positive stimuli, partly through reductions in activity in the amygdala. Several studies have evaluated the use of the compound for cancer-related stress, end-of-life anxiety, obsessive compulsive disorder, and smoking and alcohol dependence.

Supporters of the new research proclaim the safety and effectiveness of psilocybin and encourage future studies with more rigorous designs. People against the use of psychedelics for medical purposes cite beliefs that psychedelics have negative impacts on mental health. However, no evidence has confirmed this, and some research actually points to decreased psychological distress and suicidal thoughts compared to users of other recreational drugs. Psychedelics, especially psilocybin, also have a low risk of dependence or compulsive use. Overall, psychedelics are considered physiologically safe. Still, any use of once primarily recreational substances in traditional medicine would face massive regulatory, practical, and criminal justice obstacles.

Depression affects nearly 7% of American adolescents and adults. Despite the plethora of drugs available to treat depression, as well as long-standing success with cognitive behavioral therapy, 20% of patients do not respond to treatment and many relapse. There is a need for new, longer-lasting therapies for depression, and psychedelics may be the door (or the looking glass) through which researchers must travel to find effective medications.

References

Baumeister D, Barnes G, Giaroli G, & Tracy D (2014). Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles. Therapeutic advances in psychopharmacology, 4 (4), 156-69 PMID: 25083275

Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, & Nutt DJ (2016). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The lancet. Psychiatry PMID: 27210031

Cowen P (2016). Altered states: psilocybin for treatment-resistant depression. The lancet. Psychiatry PMID: 27210032

Johansen PØ, & Krebs TS (2015). Psychedelics not linked to mental health problems or suicidal behavior: a population study. Journal of psychopharmacology (Oxford, England), 29 (3), 270-9 PMID: 25744618

Kraehenmann R, Preller KH, Scheidegger M, Pokorny T, Bosch OG, Seifritz E, & Vollenweider FX (2015). Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers. Biological psychiatry, 78 (8), 572-81 PMID: 24882567

Kraehenmann R, Schmidt A, Friston K, Preller KH, Seifritz E, & Vollenweider FX (2016). The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity. NeuroImage. Clinical, 11, 53-60 PMID: 26909323

Krebs TS, & Johansen PØ (2013). Psychedelics and mental health: a population study. PloS one, 8 (8) PMID: 23976938

Nichols DE (2016). Psychedelics. Pharmacological reviews, 68 (2), 264-355 PMID: 26841800

Image via Meditations / Pixabay.

A group of researchers at Brown University has been prospectively studying a birth cohort in the New England Family Study. The latest findings from this group, published in the International Journal of Behavioral Medicine, reveal that central obesity and adiposity are inversely related to mindfulness. That is, people who are not mindful are 34% more likely to be obese and are also more likely to have increased abdominal fat. Further, people who were not obese as children but became obese as adults had lower mindfulness scores than people who were not obese in childhood or adulthood.

The participants self-reported levels of mindfulness using the 15-point Mindful Attention Awareness Scale. Adiposity was measured using dual-energy X-ray absorptiometry (DXA) scans. The results were adjusted for age, gender, race/ethnicity, birth weight, childhood socioeconomic status, childhood intelligence, and other lifestyle and demographic variables.

Some people practice mindfulness by meditating and learning to intensely focus their thoughts inward. The current study, however, focused more on “dispositional mindfulness” – paying attention to your thoughts and feelings during everyday tasks. Dispositional mindfulness is more of a personality trait than a meditative practice, and the authors think that this trait can be learned and improved.

Being aware of your current feelings and thoughts helps you associate behaviors – like eating, exercising, or smoking, for example – with how you feel (emotionally and physically) after completing the behavior. In this way, mindfulness can help you overcome cravings to eat unhealthy food or smoke a cigarette and override aversions to exercise.

The same group of researchers has linked dispositional mindfulness with healthy diet choices, healthy glucose levels, increased physical activity, a healthy body mass index, and avoiding smoking. Mindfulness has not been associated with healthy blood pressure and cholesterol levels, but these measures of health are not correlated to how you feel in a specific moment, which may influence the findings.

None of these studies can establish a causal link between physical health and mindfulness, but mindfulness may help people cognitively defeat barriers that are preventing them from living their most healthy life. People who are mindful of how they feel are more likely to feel in control of their lives and their choices. Understanding what we do and why we do it is the first step to making better choices.

References

Loucks EB, Britton WB, Howe CJ, Gutman R, Gilman SE, Brewer J, Eaton CB, & Buka SL (2016). Associations of Dispositional Mindfulness with Obesity and Central Adiposity: the New England Family Study. International journal of behavioral medicine, 23 (2), 224-33 PMID: 26481650

Loucks EB, Britton WB, Howe CJ, Eaton CB, & Buka SL (2015). Positive Associations of Dispositional Mindfulness with Cardiovascular Health: the New England Family Study. International journal of behavioral medicine, 22 (4), 540-50 PMID: 25339282

Loucks EB, Gilman SE, Britton WB, Gutman R, Eaton CB, & Buka SL (2016). Associations of Mindfulness with Glucose Regulation and Diabetes. American journal of health behavior, 40 (2), 258-67 PMID: 26931758

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The authors of the current study examined eight years of German data and evaluated associations between PPI use and new diagnoses of dementia. They report that the nearly 3,000 people who were older than 75 and regularly used PPIs had a significantly increased risk of developing dementia compared to people who did not regularly use PPIs. (The same group published a similar report of a longitudinal multicenter study in the European Archives of Psychiatry and Clinical Neuroscience; both studies reported an approximately 1.4-fold increased risk of developing dementia with regular PPI use.) The authors go so far as to posit that avoiding PPIs may prevent dementia.

This observed association between PPIs and dementia is supported by previous pharmacoepidemiological studies and mouse models that indicate that PPI use alters the development and metabolism of beta-amyloid plaques, a key factor in Alzheimer’s, a specific type of dementia. Still, many other factors contribute to the development of dementia, and the authors of the current study adjusted the estimated risks of dementia for several confounding factors: age, sex, other medications, history of stroke, depression, diabetes, and ischemic heart disease. But, they did not adjust for other well-known risks such as family history of dementia, hypertension, and alcohol use. Further, they did not address length of PPI use or dose in the association with dementia.

Data are unclear and associations are far from conclusive evidence of cause-and-effect. In fact, a recent case-control study (also conducted in Germany) reported that PPIs were associated with a decreased risk of dementia. And, several reports of medication use in older adults add to the “which comes first” conundrum of PPIs and dementia. In fact, the reports claim that dementia is associated with an increased risk of inappropriate PPI use.

By 2040, nearly 100 million people worldwide are expected to suffer from dementia. So, an increased understanding of the risks associated with this condition is warranted. However, the current study leaves too many questions unanswered to claim that PPI use should be avoided in the elderly.

Still, the findings may serve as a reminder that many medicines are prescribed incorrectly or inappropriately – especially in the elderly – and health care providers should be diligent to ensure that all medications are used only for the correct indications and at the correct doses, while minimizing risks associated with all medication use.

References

Badiola N, Alcalde V, Pujol A, Münter LM, Multhaup G, Lleó A, Coma M, Soler-López M, & Aloy P (2013). The proton-pump inhibitor lansoprazole enhances amyloid beta production. PloS one, 8 (3) PMID: 23520537

Booker A, Jacob LE, Rapp M, Bohlken J, & Kostev K (2016). Risk factors for dementia diagnosis in German primary care practices. International psychogeriatrics / IPA, 1-7 PMID: 26744954

Dwyer LL, Lau DT, & Shega JW (2015). Medications That Older Adults in Hospice Care in the United States Take, 2007. Journal of the American Geriatrics Society, 63 (11), 2282-9 PMID: 26531894

Gomm W, von Holt K, Thomé F, Broich K, Maier W, Fink A, Doblhammer G, & Haenisch B (2016). Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis. JAMA neurology PMID: 26882076

Haenisch B, von Holt K, Wiese B, Prokein J, Lange C, Ernst A, Brettschneider C, König HH, Werle J, Weyerer S, Luppa M, Riedel-Heller SG, Fuchs A, Pentzek M, Weeg D, Bickel H, Broich K, Jessen F, Maier W, & Scherer M (2015). Risk of dementia in elderly patients with the use of proton pump inhibitors. European archives of psychiatry and clinical neuroscience, 265 (5), 419-28 PMID: 25341874

Hamzat H, Sun H, Ford JC, Macleod J, Soiza RL, & Mangoni AA (2012). Inappropriate prescribing of proton pump inhibitors in older patients: effects of an educational strategy. Drugs & aging, 29 (8), 681-90 PMID: 22775478

Parsons C, Johnston S, Mathie E, Baron N, Machen I, Amador S, & Goodman C (2012). Potentially inappropriate prescribing in older people with dementia in care homes: a retrospective analysis. Drugs & aging, 29 (2), 143-55 PMID: 22204669

Image via Lucky Business / Shutterstock.

A team of NIH-funded scientists in Massachusetts examined the genomes of 65,000 people (about 29,000 of whom had schizophrenia), 700 postmortem brains, and genetically engineered mice to examine genetic risks related to schizophrenia. The gene they discovered, called complement component 4, or C4, is one of more than 100 chromosomal sites that are already known to be associated with schizophrenia. Most of the already-identified genes are related to neurodevelopment, neuroplasticity, immunology, and neuroendocrinology.

C4 has known roles in immunity, but it was interesting to schizophrenia researchers because it is highly variable among individuals: people have different numbers of copies of the C4 gene and distinct DNA sequences that can make the gene work differently in different people. Note that this is not normally how most genes work, which made the C4 gene a puzzling subject to investigate.

The C4 protein produced by the gene supports connections between neurons in the brain (synapses). When the brain is maturing, the C4 protein prunes synapses that are no longer needed, thus optimizing the brain’s performance. In humans, most of this pruning and streamlining of the brain’s synapses occurs during the late teenage years or early adulthood. Not so coincidentally, this is the same time as the onset of most cases of schizophrenia.

The gene is expressed primarily in two main forms: C4A and C4B. The more C4A that is present in the brain, the greater the risk for schizophrenia. Essentially, the more C4, the more pruning, and the more lost synapses.

Schizophrenia is characterized by hallucinations, delusions, dysfunctional thought processes, and agitated body movements. Current treatments, including antipsychotic medications, only treat the symptoms of the disease and not the underlying cause. To date, genetic and environmental factors have been suspected of increasing the risk of schizophrenia, including psychosocial stress, cannabis use, and living in urban areas.

Schizophrenia affects about 1% of the US population and 21 million people worldwide. It is believed to be almost entirely heritable, but the specific genetic activities related to its development and the precise pathogenesis of this complex disease have been largely unknown until now. The discovery of the relationship between C4 and brain maturation changes the focus of schizophrenia research, potentially leading to early detection, novel treatments to counteract excessive C4 activity, and even prevention in those at risk of the disease.

References

Hosák L, & Hosakova J (2015). The complex etiology of schizophrenia – general state of the art. Neuro endocrinology letters, 36 (7), 631-637 PMID: 26859583

Hubbard L, Tansey KE, Rai D, Jones P, Ripke S, Chambert KD, Moran JL, McCarroll SA, Linden DE, Owen MJ, O’Donovan MC, Walters JT, & Zammit S (2015). Evidence of Common Genetic Overlap Between Schizophrenia and Cognition. Schizophrenia bulletin PMID: 26678674

Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, Tooley K, Presumey J, Baum M, Van Doren V, Genovese G, Rose SA, Handsaker RE, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Daly MJ, Carroll MC, Stevens B, & McCarroll SA (2016). Schizophrenia risk from complex variation of complement component 4. Nature, 530 (7589), 177-83 PMID: 26814963

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A new brain imaging study, published in Biological Psychology, reports that there are distinct brain differences in children known to be at risk of depression compared to children not an increased risk.

Researchers from Harvard Medical School and the Massachusetts Institute of Technology scanned the brains of 27 children aged 8 to 14 years who were considered high-risk for depression because of their family histories. They also scanned the brains of 16 children with no known family history of depression. The team used functional magnetic resonance imaging (fMRI) to measure the communication and connections between regions of the brain and identified patterns in children at risk for depression. Specifically, there was a strong connection between the subgenual anterior cingulate cortex and the default mode network (the regions that are active when the mind is unfocused). This same connection has been observed in adults with depression.

The researchers also found active connections between the amygdala (which is important in processing emotions) and the inferior frontal gyrus (which is involved in processing language). They identified lower than normal connections in the frontal and parietal cortex (which are important for thinking and decision-making).

Several of the areas identified in the current study have been related to depression in previous studies, though it was unclear if the differences in activity levels and connections caused depression or if the differences were the result of it. The new findings suggest that the changes in brain activity come before the onset of depression, which may allow for the screening of people without depression to identify who is likely to develop depression later in life and who is not. Ultimately, such screening and identification could lead to early treatment and intervention. This information may also help to understand why some people who are at risk for depression avoid the disorder altogether.

Early intervention is important for depression because, once a person suffers with its first symptoms, he or she is more likely to experience them again. If someone can avoid the onset of symptoms, his or her life – and mental health – may take an entirely different path. Effective treatment for depression, which often includes medication and psychotherapy, is important for avoiding serious complications of depression such as poor school and work performance, decreased social functioning, recurrent episodes of depression, and suicide.

While the exact mechanisms of depression are still unclear, this study highlights the fact that functional and structural features of the brain do play a part in its development. Social, educational, and family context and experience also certainly play a role in mental health and depression. The more aware we are of risk factors for and early signs of depression, the more hope we can offer to those likely to face the illness.

References

Chai XJ, Hirshfeld-Becker D, Biederman J, Uchida M, Doehrmann O, Leonard JA, Salvatore J, Kenworthy T, Brown A, Kagan E, de Los Angeles C, Whitfield-Gabrieli S, & Gabrieli JD (2015). Functional and structural brain correlates of risk for major depression in children with familial depression. NeuroImage. Clinical, 8, 398-407 PMID: 26106565

Lewis CP, Nakonezny PA, Ameis SH, Vande Voort JL, Husain MM, Emslie GJ, Daskalakis ZJ, & Croarkin PE (2016). Cortical inhibitory and excitatory correlates of depression severity in children and adolescents. Journal of affective disorders, 190, 566-75 PMID: 26580570

Luby JL, Belden AC, Jackson JJ, Lessov-Schlaggar CN, Harms MP, Tillman R, Botteron K, Whalen D, & Barch DM (2016). Early Childhood Depression and Alterations in the Trajectory of Gray Matter Maturation in Middle Childhood and Early Adolescence. JAMA psychiatry, 73 (1), 31-8 PMID: 26676835

Image via Olimpik / Shutterstock.

The new study, published in Alzheimer’s and Dementia, evaluated nearly three decades of data from a Swedish study of twins. By comparing the lives and medical histories of more than 1,000 fraternal and identical twins, the authors were able to uncover a link between anxiety and dementia. The study participants completed tests, questionnaires, and screenings every three years throughout the study.

Overall, anxiety symptoms were significantly associated with an increased risk of dementia. The association between anxiety and dementia was stronger among fraternal twins than among identical twins, which calls to question genetic components of both anxiety and dementia.

Many studies have reported connections between dementia and other psychological conditions, including depression and neuroticism. The link observed in the current study was independent of other psychological variables. Anxiety, in general, is not as well studied as other mental health conditions – especially in older adults – because it can be viewed as a personality trait rather than a psychological condition.

In the current twin study, the authors note that the participants who had anxiety and later developed dementia experienced more than usual symptoms of anxiety; these participants were fidgety and chronically stressed. A limitation of the findings is that the levels of anxiety were self-reported by the twins, and not all signs or symptoms of anxiety may have met the diagnostic criteria for an anxiety disorder.

Why might anxiety increase dementia?

Anxiety may increase the risk of dementia by stressing the circuits in the brain that are regulated by the amygdala, the hippocampus, and the prefrontal cortex. Chronic stress can lead to structural degeneration and impaired functioning of the brain, which, over time, can lead to dementia, among other conditions. Current investigations hope to determine if pharmacological or non-pharmacological interventions can reverse these stress-induced brain changes. It was unclear in the twin study if treatment for anxiety mitigated the risk of developing dementia.

Like most mental health conditions and diseases, dementia is likely caused by a combination of genetic and environmental factors. We cannot yet predict who will get dementia and who will not, nor can we treat dementia effectively. But, the more links and associations we identify about risk factors and causes of this devastating condition, the brighter the future of psychological health care looks for older adults.

References

Leuner B, & Shors TJ (2013). Stress, anxiety, and dendritic spines: what are the connections? Neuroscience, 251, 108-19 PMID: 22522470

Mah L, Szabuniewicz C, & Fiocco AJ (2016). Can anxiety damage the brain? Current opinion in psychiatry, 29 (1), 56-63 PMID: 26651008

Petkus AJ, Reynolds CA, Wetherell JL, Kremen WS, Pedersen NL, & Gatz M (2015). Anxiety is associated with increased risk of dementia in older Swedish twins. Alzheimer’s & dementia : the journal of the Alzheimer’s Association PMID: 26549599

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Each year, nearly 800,000 people in the United States experience stroke, which is a disruption in the flow of blood to the brain, either due to a hemorrhage (a burst blood vessel) or a clot that blocks blood flow through a vessel. If people survive a stroke, they may experience paralysis, speech, and language problems, behavior changes, and cognitive impairment such as memory loss.

A new study, published in the journal Stroke – a publication of the American Heart Association – reports that multilingual people experienced better outcomes after stroke than people who spoke only one language.

The authors evaluated data from 608 stroke patients from India who were part of a stroke registry. Approximately half of the patients were bilingual, which was defined as speaking at least two languages. The multi- and single-language groups were the same in terms of age and other risk factors for stroke outcomes. Outcomes were assessed using standard cognitive screening tools and dementia rating scales; the assessments were completed within 3 to 24 months of the stroke.

In this study, approximately 40% of bilingual patients had normal cognitive function after stroke, but only 20% of single-language patients had the same. Plus, bilingual patients had better memory and attention following stroke compared to their single-language counterparts. There was no difference in the rates of aphasia (a communication disorder characterized by difficulty reading, writing, and speaking)between bilingual and single-language groups.

In addition to benefiting stroke outcomes, bilingualism has been associated with delayed onset of cognitive decline in other studies. However, the actual benefits of speaking several languages is still debated owing to inconsistencies in study design and measurement of cognitive abilities. The findings of the current study, in particular, may not be widely applicable. People from the region in which the study was conducted speak as many as four languages and commonly switch among them during the day. Cognitive benefits of multilingualism may not be as pronounced in regions in which the need to function in more than one language is not as great.

While bilingualism helped patients fare better in this study, it is likely that any mentally challenging task could offer similar protective benefits for cognition. Switching languages requires executive function similar to playing a musical instrument or completing Sudoku puzzles. Any intellectually stimulating task that is pursued over time may be able to offer similar cognitive benefits and prevent impairment due to normal aging or stroke.

References

Alladi S, Bak TH, Mekala S, Rajan A, Chaudhuri JR, Mioshi E, Krovvidi R, Surampudi B, Duggirala V, & Kaul S (2015). Impact of Bilingualism on Cognitive Outcome After Stroke. Stroke; a journal of cerebral circulation PMID: 26585392

Hope TM, Parker Jones ‘, Grogan A, Crinion J, Rae J, Ruffle L, Leff AP, Seghier ML, Price CJ, & Green DW (2015). Comparing language outcomes in monolingual and bilingual stroke patients. Brain : a journal of neurology, 138 (Pt 4), 1070-83 PMID: 25688076

Perani D, & Abutalebi J (2015). Bilingualism, dementia, cognitive and neural reserve. Current opinion in neurology, 28 (6), 618-25 PMID: 26544028

von Bastian CC, Souza AS, & Gade M (2015). No Evidence for Bilingual Cognitive Advantages: A Test of Four Hypotheses. Journal of experimental psychology. General PMID: 26523426

Zahodne LB, Schofield PW, Farrell MT, Stern Y, & Manly JJ (2014). Bilingualism does not alter cognitive decline or dementia risk among Spanish-speaking immigrants. Neuropsychology, 28 (2), 238-46 PMID: 24188113

Image via oneinchpunch / Shutterstock.