Norell Hadzimichalis, PhD – Brain Blogger Health and Science Blog Covering Brain Topics Wed, 30 May 2018 15:00:03 +0000 en-US hourly 1 The Health Benefits of a Mediterranean Diet Sun, 04 Aug 2013 11:00:57 +0000 The positive health benefits of a Mediterranean diet are well established: The PREDIMED study was launched in 2003 with the aim of assessing the role of a Mediterranean diet for the prevention of cardiovascular disease in asymptomatic patients with high cardiovascular risk. Data stemming from this study clearly implicate the diet in reducing cardiovascular risk via a variety of mechanisms, with participants adhering to the diet reported to have an approximately 30% reduced risk for a cardiovascular event.

The Mediterranean diet consists primarily of plant-based foods including fruit, vegetables, pasta, and rice. It emphasizes replacing butter with “healthier fats”, using herbs and spices for flavor instead of salt, limiting the consumption of red meat, and eating fish and poultry at least twice a week. The PREDIMED study more specifically explored the effects of this type of diet when supplemented with olive oil or tree nuts. Study participants were provided with extra-virgin olive oil and a variety of nuts, in addition to food shopping lists, menus, recipes, dietary training group sessions, and access to a dietician.

Secondarily, the PREDIMED study explored the role of a Mediterranean diet on heart failure, diabetes, cancer, dementia, and other neurodegenerative diseases. Interestingly, research suggests that in addition to a providing cardiovascular protection, this diet may also play a key role in protecting against a variety of brain disorders including age-related cognitive decline and depression.

Data from Elena Martínez-Lapiscina and colleagues further indicate that the supplemented diet results in an increase in cognitive function for patients with cardiovascular risk factors when compared to those patients on a low-fat diet. More specifically, researchers examined cognitive performance as indicated on the Mini-Mental State Examination (MMSE) and the Clock Drawing Test (CDT) after 6.5 years of regulated diet. The results show that those patients consuming Mediterranean-based diets perform better on these tests thus indicating an improvement in cognitive function.

These data are promising and further support a case for a well balanced diet in the protection against disease. They also present an opportunity to narrow down the active compounds in each diet that most notably effect the results and isolate them for further study and/or drug development.


Estruch, R., Ros, E., Salas-Salvadó, J., Covas, M., Corella, D., Arós, F., Gómez-Gracia, E., Ruiz-Gutiérrez, V., Fiol, M., Lapetra, J., Lamuela-Raventos, R., Serra-Majem, L., Pintó, X., Basora, J., Muñoz, M., Sorlí, J., Martínez, J., & Martínez-González, M. (2013). Primary Prevention of Cardiovascular Disease with a Mediterranean Diet New England Journal of Medicine, 368 (14), 1279-1290 DOI: 10.1056/NEJMoa1200303

Martínez-Lapiscina EH, Clavero P, Toledo E, Estruch R, Salas-Salvadó J, San Julián B, Sanchez-Tainta A, Ros E, Valls-Pedret C, & Martinez-Gonzalez MA (2013). Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. Journal of neurology, neurosurgery, and psychiatry PMID: 23670794

Sánchez-Villegas A, Galbete C, Martinez-González MA, Martinez JA, Razquin C, Salas-Salvadó J, Estruch R, Buil-Cosiales P, & Martí A (2011). The effect of the Mediterranean diet on plasma brain-derived neurotrophic factor (BDNF) levels: the PREDIMED-NAVARRA randomized trial. Nutritional neuroscience, 14 (5), 195-201 PMID: 22005283

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Is Thinking Bad For Your Brain? Mon, 29 Jul 2013 11:00:39 +0000 Basic scientific research, old wives’ tales, and common sense all suggest that the best way to promote brain function is to keep your mind active. Intriguingly however, a recent report from Elsa Suberbielle and colleagues published in the journal Nature Neuroscience, seems to suggest just the opposite.

The DNA double helix that encodes the human genome is comprised of approximately 3 billion base pairs that dictate all of our characteristics, ranging from our eye color to our predisposition to heart disease. Disruption of proper base pairing including mutations, insertions, and deletions may lead to a variety of changes in our makeup. Although some of these base pair disruptions are more deleterious that others, double stranded breaks (DSB) in the DNA double helix remains of the most lethal.

Recent evidence indicates that normal exploration of a new environment causes significant increases in DNA DSBs in mice. In these studies, mice were moved from their home cage to a new larger cage comprised of different litter, odors, stations, and toys. They were allowed to explore the new cage for two hours with other mice that they were familiar with from their home cage. Interestingly, many of the documented breaks in DNA were found in the brain region referred to as the dentate gyrus, which is a critical region for learning and memory.

While, at first glance these data seem to suggest that “normal” thinking is bad for us, commentary from Herrup and colleagues addresses this issue. They report that while the data is scientifically sound, they may need to be viewed from a different perspective. For example, they suggest that the assays used to measure DNA DSBs may in fact be leading to the reported damage and that this idea should be further examined. In addition, is possible that the damage in DNA is functioning as a regulatory mechanism. Perhaps, by allowing some level of DNA damage, a higher degree of neuronal regulation can be achieved. Suberbielle hypothesizes that the formation of the DSBs is a natural process that permits for the remodeling of DNA and changes in gene expression that are necessary for learning, memory, and the effective processing of information.

It may be enticing to initially conclude from this report that thinking is bad for your brain. However, these data should be intended as a springboard for further studies in this area and the genetic regulatory mechanisms that are in place during “normal” brain function.


Herrup, K., Chen, J., & Li, J. (2013). Breaking news: thinking may be bad for DNA Nature Neuroscience, 16 (5), 518-519 DOI: 10.1038/nn.3384

Suberbielle, E., Sanchez, P., Kravitz, A., Wang, X., Ho, K., Eilertson, K., Devidze, N., Kreitzer, A., & Mucke, L. (2013). Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-? Nature Neuroscience, 16 (5), 613-621 DOI: 10.1038/nn.3356

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Multifaceted Causes of Obsessive Compulsive Disorder Sat, 13 Jul 2013 11:00:09 +0000 Obsessive compulsive disorder (OCD) is an anxiety disorder which is characterized by intrusive thoughts (obsessions) that result in worry and repetitive behaviors (compulsions) aimed at alleviating the anxiety. While most of us have run back into the house to check the stove was turned off, people suffering from OCD experience these thoughts more frequently, and to the point that it becomes alienating and all-consuming. But what causes it?

While the exact cause of OCD is not completely elucidated, researchers believe that it results from a combination of genetics and environmental factors. Genetic studies have linked a specific mutation in the serotonin transporter gene to the manifestation of OCD. Additional data from studies on identical twins have corroborated these results.

However, the studies also show that genetics accounts for only 40-65% of the risk for developing OCD, thus indicating that environmental factors also play a role in manifestation of the disease. Reports suggest the potential for a number of different environmental risk factors including strep infections, anxiety, emotional instability, depression, handwriting difficulties, behavioral aggression, and oppositional behaviors.

Differences in the physical structure of the brain are also a prominent factor in patients with OCD. In fact, neuroimaging techniques have revealed structural and volumetric abnormalities in the brains of these patients: People with OCD have a patterned increase in grey matter in the brain in certain areas and a decrease in others.

Other studies have examined the role for a potential chemical imbalance in the brain leading to disease symptoms. From a molecular perspective, data show that in fact neurotransmitter dysregulation does play an important role in the manifestation of OCD symptoms. More specifically, reports indicate that the neurotransmitters serotonin and dopamine are associated with the pathophysiology of OCD. Scientists show that patients with OCD may experience an increase in dopamine in the prefrontal cortex and/or a decrease in serotonin in the basal ganglia.

Currently used medications for managing the disorder including Clomipramine (Anafranil), Zluvoxamine (Luvox), Fluoxetine (Prozac), Paroxetine (Paxil, Pexeva), and Sertraline (Zoloft) specifically focus on regulating these neurotransmitter levels in the brain. Selective serotonin re-uptake inhibitors (SSRIs) decrease symptoms of OCD in two-thirds of adults and children who take them.

While there are a number of available medications for treating OCD symptoms, they come with unique risks. Similar to other psychological disorders, the choice of which mediation to use is often the result of trial and error, and drug interactions must be carefully considered. Furthermore, side effects may include an upset stomach, sleep disturbances, sweating, and a decrease in libido. It is hoped that additional research into the causes and molecular mechanism of OCD will ultimately lead to more effective and safe drugs for treating disease symptoms.


Cath, D., Grootheest, D., Willemsen, G., Oppen, P., & Boomsma, D. (2008). Environmental Factors in Obsessive-Compulsive Behavior: Evidence from Discordant and Concordant Monozygotic Twins Behavior Genetics, 38 (2), 108-120 DOI: 10.1007/s10519-007-9185-9

Harsányi A, Csigó K, Demeter G, & Németh A (2007). [New approach to obsessive-compulsive disorder: dopaminergic theories]. Psychiatria Hungarica : A Magyar Pszichiatriai Tarsasag tudomanyos folyoirata, 22 (4), 248-58 PMID: 18167420

Kim CH, Cheon KA, Koo MS, Ryu YH, Lee JD, Chang JW, & Lee HS (2007). Dopamine transporter density in the basal ganglia in obsessive-compulsive disorder, measured with [123I]IPT SPECT before and after treatment with serotonin reuptake inhibitors. Neuropsychobiology, 55 (3-4), 156-62 PMID: 17657168

Ozaki N, Goldman D, Kaye WH, Plotnicov K, Greenberg BD, Lappalainen J, Rudnick G, & Murphy DL (2003). Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. Molecular psychiatry, 8 (11), 933-6 PMID: 14593431

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Caffeine Increases Memory for Humans and Honeybees Mon, 01 Jul 2013 11:00:37 +0000 Consumption of caffeine, in moderation, is reported to have a number of health benefits including increases in alertness, stamina during exercise, pain relief, and memory. Further research indicates that chemically, it functions as an antioxidant and consequently helps to minimize damaging free radicals that are present in a variety of oxidative stress-related disorders including Alzheimer’s Disease and heart disease. Additional data suggest that caffeine may play a role in minimizing depression by increasing the production of dopamine in the brain.

In a recent publication in the journal Science, Dr. Geraldine Wright and colleagues examine the role of caffeine in enhancing memory by exploring an ecological role for low concentrations of caffeine in floral nectar and pollen. They hypothesized that the presence of caffeine may be important in keeping pollinators returning to the plant.

In many cases, pollination is a mutually beneficial process for both pollinators and plants. Hence, from an ecological and evolutionary perspective, plants have evolved to find ways to make their nectar both more memorable and more desirable. In some cases this may involve an increase in nectar strength or quality. In the case of select species’ in the Citrus and Coffea genera however, it seems this has involved the inclusion of caffeine in the nectar.

The researchers trained honeybees to associate a floral scent with a 0.7M sucrose solution containing a variety of different concentrations of caffeine. The data indicate that those honeybees that consumed nectar with low levels of caffeine were 3 times more likely to remember the conditioned scent 24 hours later. Caffeine concentrations greater than 1mM resulted in honeybees being deterred from drinking the sucrose-rich reward solution. The team reported that this is likely due to the bitter taste and toxicity of caffeine at high concentrations.

A deeper exploration into the active molecular pathway in the observed caffeine effect suggests that caffeine increases the excitability of Kenyon cells, a type of cell found in arthropods including honeybees. Functionally, Kenyon cells are similar to human hippocampal neurons in that they play a role in long term memory formation. Indeed, the authors of this paper were able to effectively reverse the caffeine by blocking acetylcholine receptors on the Kenyon cells, thus minimizing their level of activation.

Together, these data corroborate previous reports indicating that low doses of caffeine result in enhanced cognitive performance and memory in humans. They further suggest that this pharmacologic role of caffeine translates to the evolution of various plant species in attracting pollinators via providing a chemical substance to increase long-term memory of honeybees.


Chittka L, & Peng F (2013). Neuroscience. Caffeine boosts bees’ memories. Science (New York, N.Y.), 339 (6124), 1157-9 PMID: 23471393

Wright, G., Baker, D., Palmer, M., Stabler, D., Mustard, J., Power, E., Borland, A., & Stevenson, P. (2013). Caffeine in Floral Nectar Enhances a Pollinator’s Memory of Reward Science, 339 (6124), 1202-1204 DOI: 10.1126/science.1228806

WebMD, New clues on caffeine’s health benefits, (2011, May 6).

Image via Klagyivik Viktor / Shutterstock.

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Electronic Devices Are Unlikely To Cause Cancer Tue, 25 Jun 2013 11:00:29 +0000 Technology has taken over our lives. From the moment we wake and begin checking emails to the moment we go to bed, computers, tablets, smart phones, and television screens consume our world. While in many ways these devices are enriching our lives, are they also taking a negative toll on our bodies and minds?

Some of the potentially negative short-term effects of use (and specifically overuse) of electronic devices are more apparent than others. The use of electronic devices while driving has been indisputably associated with an increased risk of car accidents. From a physical standpoint, turning up the volume on MP3 players, particularly when using ear buds, has been shown to form the foundation for hearing problems.

In addition, prolonged use of electronic devices has been linked to a more sedentary lifestyle and hence an increased risk for cardiac disease. Academically, children are suffering by relying on abbreviations and slang to get their messages across, even in cases of formal writing. In fact, a study by the Kaiser Family Foundation indicates that children aged six and under spend an average of two hours per day using screen-based media. These numbers only increase as a child ages.

The data on more long-term health benefits, however, are less clearly defined. An extensive literature review of data published between 2000 and 2010 explored the effects of cell phones on human health. Interestingly, the data were inconclusive with regards to documented negative health effects including cancer. Further review explored the potential link between cancer and other electronic devices, yielding similar results.

An additional report published in the International Journal of Epidemiology corroborated these studies and specifically indicated that there is no increase in risk for either glioma or meningioma as a result of using mobile devices.

From a molecular perspective, this inability to conclusively document linkage between electronic devices and cancer may be explained by the low-frequency radiation emitted by these devices. These low-frequency waves are not strong enough to break the molecular bonds needed to cause mutations in DNA, and hence cause cancer. In fact, cell phones emit less than 0.001 kilojoule per mole of energy. This is far less than the great than 4800 kilojoules per mole of energy known to cause mutations in DNA and related carcinogenic effects.

While these early studies do seem encouraging at lessening the fear of dying from the overuse of electronic devices, additional longitudinal studies are still warranted to explore other potentially deleterious effects of overuse of electronic devices. Either way, we should probably remember to “unplug ourselves” every once in awhile and explore more social, emotional, and physical aspects of human life.


The Henry J. Kaiser Family Foundation, Electronic media in the lives of infants, toddlers and preschoolers, (Fall, 2003).

Moussa MM (2011). Review on health effects related to mobile phones. Part II: results and conclusions. The Journal of the Egyptian Public Health Association, 86 (5-6), 79-89 PMID: 22173110

INTERPHONE Study Group (2010). Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international case-control study. International journal of epidemiology, 39 (3), 675-94 PMID: 20483835

eSkeptic, Do cell phones cause cancer? (2010, 9 June).

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The Overlooked Role of Universities in the Drug Discovery Process Tue, 04 Jun 2013 11:00:35 +0000 Drug discovery is the process by which novel therapeutic candidates are discovered and ultimately developed into human-grade medications. These candidates may include compounds ranging from modified or unmodified natural products or extracts and small molecules to biologics. Forbes reports that the average cost of drug development for a major pharmaceutical company is between $4 billion and $11 billion, which is a great deal higher than the more commonly reported $1 billion, as it accounts for failure rates. And in fact, failure rates are an important part of the drug discovery process.

Estimates show there is a 1 in 30 chance for the identification of an initial drug target to result in a product launch. Furthermore, reports indicate that it can take more than 12 years from the initial molecular target discovery to progress through preclinical studies and ultimately to US Food and Drug Administration (FDA) regulated human clinical trials. Costs accrue throughout this lengthy process for various items including personnel, research materials, collaborations, patent filings, clinical trials, and regulatory applications.

Many people tend to associate the development of drugs with the large pharmaceutical companies that sell them including Johnson & Johnson, Pfizer, and Merck & Co., to name a few. However, in most cases the critical initial discovery role of the smaller organization is overlooked.

A recent agreement between Eisai, one of the largest pharmaceutical companies based on revenue, and Johns Hopkins University Brain Science Institute (JHUBSi) represents the current push in university-private sector collaboration for drug discovery. In this arrangement, JHUBSi is tasked with taking the lead in identifying novel compounds to potentially treat neurological disorders and Eisai will have the option to further develop and commercialize these leads through a licensing agreement. The university stands to benefit financially from the potential receipt of up front payments, royalties, and negotiated milestone payments once a licensing agreement is reached.

Interestingly, of the 252 new drugs approved by the FDA from 1998 to 2007, approximately 24% originated from University or biotechnology company research and were subsequently transferred to a pharmaceutical or biotechnology company to further the research and develop a product that could be marketed. These data verify the fundamental role for university research and suggest that technology transfer is an essential component to the development of therapeutics.

In fact, university research has resulted, in part, in the development of many well-known therapeutics including insulin as a treatment for diabetes, various tuberculosis antibiotics, Allegra, and multiple chemotherapeutic agents such as Cisplatin. University research has contributed to the development of other areas of technology transfer and product commercialization, including in the development of various vaccines, medical devices such as the ultrasound and the pacemaker, and everyday items such as the seat belt and Google.

While the role of large pharmaceutical companies is integral in the development of novel drugs, it is important to also note that universities and biotechnology companies play an important, and often overlooked role as well. Industry-academia collaborations may represent the future of drug development and it is predicted that in years to come, we will see more than 24% of novel drugs originating from technologies developed by universities and biotechnology companies.


Bains, W., Drug Discovery World, (Fall 2004). Failure rates in drug discovery and development: will we ever get any better?

Herper, M., Forbes, (October 2012). The Truly Staggering Cost Of Inventing New Drugs.

Kneller, R. (2010). The importance of new companies for drug discovery: origins of a decade of new drugs Nature Reviews Drug Discovery, 9 (11), 867-882 DOI: 10.1038/nrd3251

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Laughter is the Best Medicine, Really Wed, 20 Mar 2013 11:00:07 +0000 Hunter Doherty Adams, better known as Patch Adams, is both a physician and a clown who incorporates humor and joy as a form of alternative medicine for patients. While at face value these methods may seem to work simply as a means of distracting patients from their disease condition, is there also a molecular basis to this method of “treatment”?

Data indicate that there is significant biophysical and biochemical truth supporting this method, so much so that scientists continue to examine the relevant biochemical pathways active during laughter in an attempt to identify drug targets and develop novel drugs. When we laugh multiple areas of our brain including the frontal and occipital lobes become activated. On a biophysical level our blood pressure is lowered and our abdominal, diaphragm, respiratory, facial, leg, and back muscles are all actively engaged. Buchowski and colleagues at Vanderbilt University have determined that 10-15 minutes of laughter burns approximately 50 calories. This physical activity also results in an increase in movement of lymphatic fluids which facilitates the immune system in more effectively clearing cellular waste. Furthermore, it results in an increase in blood oxygen content and circulation which may help to inhibit the growth of parasites, bacteria, and cancer cells.

At the biochemical level, research has focused on examining the changes in hormone levels in response to laughter. Berk and colleagues at Loma Linda University School of Medicine report a reversal in serum levels of various hormones that play key roles in the stress hormone response cascade including cortisol, dopac, epinephrine, and growth hormone. Additional data from Stanford University indicate that humor activates the mesolimbic reward pathway in the brain, the same area of the brain that is implicated by cocaine and other addicting substances or rewarding activities.

While the data are broad and in some cases descriptive, the message is clear. The multifaceted and seemingly endless positive health effects of laughter make it, truly, the best medicine.  With that being said, I encourage everyone to redirect their attention to one of my favorite free medications:


Buchowski MS, Majchrzak KM, Blomquist K, Chen KY, Byrne DW, & Bachorowski JA (2007). Energy expenditure of genuine laughter. International journal of obesity (2005), 31 (1), 131-7 PMID: 16652129

Berk LS, Tan SA, Fry WF, Napier BJ, Lee JW, Hubbard RW, Lewis JE, & Eby WC (1989). Neuroendocrine and stress hormone changes during mirthful laughter. The American journal of the medical sciences, 298 (6), 390-6 PMID: 2556917

Mobbs D, Greicius MD, Abdel-Azim E, Menon V, & Reiss AL (2003). Humor modulates the mesolimbic reward centers. Neuron, 40 (5), 1041-8 PMID: 14659102

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