Posts tagged migraines
Articles and news from the latest research reports.
Most headaches in pregnancy and the postnatal period are benign, but healthcare professionals must be alert to the rarer and more severe causes of headaches, suggests a new review published in The Obstetrician & Gynaecologist (TOG).
The review looks at common causes for headaches during pregnancy and the postnatal period, possible conditions that may be associated with headaches and how healthcare professionals should manage the care of the woman appropriately.
There are 85 different types of headache. Approximately 90% of headaches in pregnancy are migraine or tension-type headaches. However, pregnancy can lead to an increased risk of certain secondary headaches, a headache caused by an underlying health condition, states the review.
The review states that most headaches in pregnancy are benign but in some cases can be more serious. According to the Confidential Enquiries into Maternal Deaths in the United Kingdom 2006 – 2008 report, neurological conditions were the third most common cause of death, considering both direct and indirect causes. The authors of the review therefore emphasise the need for all medical staff to be well trained to take a full history and examination, make a provisional differential diagnosis and know when to seek neurological expertise.
Migraine is a common form of headache; the condition is more common in women, with the highest prevalence rates during the childbearing years. The review states that pregnancy leads to a reduction in the frequency and severity of attacks of migraines without aura, also known as a common migraine. However, women who do experience migraines have a more than two-fold increased risk of pre-eclampsia than those who do not. Women therefore need to be aware to consult a healthcare professional if their headache is different from their usual migraine, highlights the review.
Another condition associated with a headache in pregnancy is idiopathic intracranial hypertension, a build up of high pressure inside the skull, a rare condition but more prevalent in obese women of childbearing age. The condition may present for the first time in pregnancy and pre-existing disease tends to worsen in pregnancy. It can be fatal if it is not treated promptly as a medical emergency.
Pregnancy is also a recognised risk factor for cerebral venous thrombosis (CVT), the presence of a blood clot in the dural venous sinuses, which drain blood from the brain. Caesarean section, systematic infection, vomiting and anaemia increase the risk and headache is the most frequently (80 – 90%) occurring symptom in CVT and often the first symptom reported by patients.
The review also discusses imaging and advises that imaging of the brain should never be withheld because a woman is pregnant and women should be reassured that imaging is safe.
Kirsty Revell, Specialist Registrar, Obstetrics and Gynaecology at the Princess Anne Hospital, Southampton and co-author of the review said:
“Headaches are common in life and in pregnancy. Most headaches are benign, for example migraine or tension headaches, but some headache types can be more serious and an indication that something is seriously wrong.
“It is vital that both GPs and obstetricians are aware of the signs and symptoms associated with these conditions and know when to seek advice from a specialist.”
Jason Waugh, TOG Editor-in-chief added:
“Many women experience headaches during pregnancy and the postpartum period and most are managed by women themselves or within primary care.
“Women presenting with headaches in pregnancy and the postnatal period may be at home, on a maternity ward, in an antenatal clinic, at a tertiary referral centre or in an emergency department. All medical staff should be aware of the symptoms, signs and appropriate response to the rarer and more severe causes of headaches that continue to cause avoidable morbidity and mortality.”
(Image: iStockphoto)
Older migraine sufferers may have more silent brain injury
Older migraine sufferers may be more likely to have silent brain injury, according to research published in the American Heart Association’s journal Stroke.
In a new study, people with a history of migraine headaches had double the odds of ischemic silent brain infarction compared to people who said they didn’t have migraines. Silent brain infarction is a brain injury likely caused by a blood clot interrupting blood flow to brain tissue. Sometimes called “silent strokes,” these injuries are symptomless and are a risk factor for future strokes.
Previous studies indicated migraine could be an important stroke risk factor for younger people.
“I do not believe migraine sufferers should worry, as the risk of ischemic stroke in people with migraine is considered small,” said Teshamae Monteith, M.D., lead author of the study and assistant professor of clinical neurology and chief of the Headache Division at the University of Miami Miller School of Medicine. “However, those with migraine and vascular risk factors may want to pay even greater attention to lifestyle changes that can reduce stroke risk, such as exercising and eating a low-fat diet with plenty of fruits and vegetables.”
High blood pressure, another important stroke risk factor, was more common in those with migraine. But the association between migraine and silent brain infarction was also found in participants with normal blood pressure.
Because Hispanics and African-Americans are at increased stroke risk, researchers from the Northern Manhattan Study (NOMAS) – a collaborative investigation between the University of Miami and Columbia University – studied a multi-ethnic group of older adults (41 percent men, average age 71) in New York City. About 65 percent of participants were Hispanic. Comparing magnetic resonance imaging results between 104 people with a history of migraine and 442 without, they found:
- A doubling of silent brain infarctions in those with migraine even after adjusting for other stroke risk factors;
- No increase in the volume of white-matter hyperintensities (small blood vessel abnormalities) that have been associated with migraine in other studies;
- Migraines with aura — changes in vision or other senses preceding the headache — wasn’t common in participants and wasn’t necessary for the association with silent cerebral infarctions.
“While the lesions appeared to be ischemic, based on their radiographic description, further research is needed to confirm our findings,” Monteith said.
The research raises the question of whether preventive treatment to reduce the severity and number of migraines could reduce the risk of stroke or silent cerebral infarction.
“We still don’t know if treatment for migraines will have an impact on stroke risk reduction, but it may be a good idea to seek treatment from a migraine specialist if your headaches are out of control,” Monteith said.
Migraine Attacks Increase Following Stress
Migraine sufferers who experienced reduced stress from one day to the next are at significantly increased risk of migraine onset on the subsequent day, according to a new study conducted by researchers at the Montefiore Headache Center and Albert Einstein College of Medicine at Yeshiva University. Stress has long been believed to be a common headache trigger. In this study, researchers found that relaxation following heightened stress was an even more significant trigger for migraine attacks. Findings may aid in recommending preventive treatments and behavioral interventions. The study was published online today in Neurology®, the medical journal of the American Academy of Neurology.
Migraine is a chronic condition that affects approximately 38 million Americans. To examine headache triggers, investigators at the Montefiore Headache Center and Einstein conducted a three month electronic daily diary study which captured 2,011 diary records and 110 eligible migraine attacks in 17 participants. The study compared levels of stress and reduction in stress as predictors of headache.
“This study demonstrates a striking association between reduction in perceived stress and the occurrence of migraine headaches,” said study lead author Richard Lipton, M.D., director, Montefiore Headache Center, professor and vice chair of neurology and the Edwin S. Lowe Chair in Neurology, Einstein. “Results were strongest during the first six hours where decline in stress was associated with a nearly five-fold increased risk of migraine onset. The hormone cortisol, which rises during times of stress and reduces pain, may contribute to the triggering of headache during periods of relaxation.”
Data were collected using a custom-programmed electronic diary. Each day participants recorded information about migraine attacks, two types of stress ratings and common migraine triggers, such as hours of sleep, certain foods, drinks and alcohol consumed, and menstrual cycle. They also recorded their mood each day, including feeling happy, sad, relaxed, nervous, lively and bored.
“This study highlights the importance of stress management and healthy lifestyle habits for people who live with migraine,” said Dawn Buse, Ph.D., director, Behavioral Medicine, Montefiore Headache Center, associate professor, Clinical Neurology, Einstein, and study co-author. “It is important for people to be aware of rising stress levels and attempt to relax during periods of stress rather than allowing a major build up to occur. This could include exercising or attending a yoga class or may be as simple as taking a walk or focusing on one’s breath for a few minutes.”
Researchers may have discovered a plan to disable Meniere’s disease
Researchers at University of Colorado School of Medicine may have figured out what causes Meniere’s disease and how to attack it. According to Carol Foster, MD, from the department of otolaryngology and Robert Breeze, MD, a neurosurgeon, there is a strong association between Meniere’s disease and conditions involving temporary low blood flow in the brain such as migraine headaches.
Meniere’s affects approximately 3 to 5 million people in the United States. It is a disabling disorder resulting in repeated violent attacks of dizziness, ringing in the ear and hearing loss that can last for hours and can ultimately cause permanent deafness in the affected ear. Up until now, the cause of the attacks has been unknown, with no theory fully explaining the many symptoms and signs of the disorder.
"If our hypothesis is confirmed, treatment of vascular risk factors may allow control of symptoms and result in a decreased need for surgeries that destroy the balance function in order to control the spell" said Foster. "If attacks are controlled, the previously inevitable progression to severe hearing loss may be preventable in some cases."
Foster explains that these attacks can be caused by a combination of two factors: 1) a malformation of the inner ear, endolymphatic hydrops (the inner ear dilated with fluid) and 2) risk factors for vascular disease in the brain, such as migraine, sleep apnea, smoking and atherosclerosis.
The researchers propose that a fluid buildup in part of the inner ear, which is strongly associated with Meniere attacks, indicates the presence of a pressure-regulation problem that acts to cause mild, intermittent decreases of blood flow within the ear. When this is combined with vascular diseases that also lower blood flow to the brain and ear, sudden loss of blood flow similar to transient ischemic attacks (or mini strokes) in the brain can be generated in the inner ear sensory tissues. In young people who have hydrops without vascular disorders, no attacks occur because blood flow continues in spite of these fluctuations. However, in people with vascular diseases, these fluctuations are sufficient to rob the ear of blood flow and the nutrients the blood provides. When the tissues that sense hearing and motion are starved of blood, they stop sending signals to the brain, which sets off the vertigo, tinnitus and hearing loss in the disorder.
Restoration of blood flow does not resolve the problem. Scientists believe it triggers a damaging after-effect called the ischemia-reperfusion pathway in the excitable tissues of the ear that silences the ear for several hours, resulting in the prolonged severe vertigo and hearing loss that is characteristic of the disorder. Although most of the tissues recover, each spell results in small areas of damage that over time results in permanent loss of both hearing and balance function in the ear.
Since the first linkage of endolymphatic hydrops and Meniere’s disease in 1938, a variety of mechanisms have been proposed to explain the attacks and the progressive deafness, but no answer has explained all aspects of the disorder, and no treatment based on these theories has proven capable of controlling the progression of the disease. This new theory, if proven, would provide many new avenues of treatment for this previously poorly-controlled disorder.
(Source: eurekalert.org)
It’s shocking: Ultra-focused electric current helps brain curb pain
Imagine significantly reducing a persistent migraine or fibromyalgia by a visit to a doctor who delivers low doses of electricity to the brain.
Alex DaSilva, assistant professor of prosthodontics at the University of Michigan, and colleagues are optimizing the next generation for such a technique, called high-definition transcranial direct current stimulation, or HD-tDCS.
The researchers have published several studies with the conventional tDCS, which also treats pain by “shocking” the brain with low doses of electrical current delivered noninvasively through electrodes placed on the scalp. The current modulates targeted areas of the brain, and one of the mechanisms is by activating the release of opioid-like painkillers.
HD-tDCS delivers an even more precisely focused current to the targeted areas of the brain. Preliminary reports have shown better pain relief in patients and a longer and more pronounced effect on the brain, said DaSilva, who heads the Headache and Orofacial Pain Effort Laboratory at the U-M School of Dentistry.
The increased precision of HD-tDCS means researchers can custom-place the electrodes to the skull. In this way, they can modulate specific areas in the brain to treat a wider range of conditions, such as neuropathic pain and stroke. Other uses include neurophysiological studies and cognitive and behavioral assessments.
One 20-minute session of HD-tDCS significantly reduced overall pain perception in fibromyalgia patients as described in one of the studies.
Researchers control the current by a portable device, which they hope physicians can eventually use in the clinic as a noninvasive treatment for chronic pain patients.
"We are working hard to make the technology available for clinical use at U-M," DaSilva said. "Our lab is getting a good number of emails from chronic pain patients looking for treatment."
The conventional technology is already available for many companies, and the HD-tDCS is being patented by the company of one of the developers.
To allow broad access and further investigation of the HD-tDCS technology by other researchers, DaSilva and colleagues released a scientific video demonstrating the step-by-step guideline of the research protocol: www.jove.com/embed/directions/50309?key=uahsva6y
Depression twice as likely in migraine sufferers
The prevalence of depression among those with migraine is approximately twice as high as for those without the disease (men: 8.4% vs. 3.4%; women 12.4% vs. 5.7%), according to a new study published by University of Toronto researchers.
In a paper published online this week in the journal Depression Research and Treatment, investigators reported that younger migraine sufferers were particularly at risk for depression. Women with migraines who were younger than 30 had six times the odds of depression in comparison to sufferers who were aged 65 and over, said lead author, Professor Esme Fuller-Thomson, Sandra Rotman Endowed Chair at the University of Toronto’s Factor-Inwentash Faculty of Social Work. Unmarried individuals and migraine sufferers who had difficulties with daily activities also had high odds of depression.
Data drawn from a representative sample of more than 67,000 Canadians, the 2005 Canadian Community Health Survey, were used to examine gender-specific associations between migraine and depression. More than 6,000 respondents reported that they had been diagnosed by a health professional with migraines. Consistent with prior research, the prevalence of migraines was much higher in women than men, with one in every seven women, compared to one in every 16 men, reporting that they had migraines.
The study also investigated the relationship between migraine and suicidal ideation. For both men and women, those with migraines were much more likely to have “ever seriously considered suicide or taking (their) own life” than were those without migraines (men: 15.6% versus 7.9%; women: 17.6% versus 9.1%). Migraineurs under age 30 had four times the odds of lifetime suicidal ideation in comparison to migraineurs aged 65 and over. Other factors associated with suicidal ideation among those with migraines included unmarried status, lower household income and greater activity limitations.
Co-author and former graduate student Meghan Schrumm commented “We are not sure why younger migraineurs have such a high likelihood of depression and suicidal ideation. It may be that younger people with migraines have not yet managed to find adequate treatment or develop coping mechanisms to minimize pain and the impact of this chronic illness on the rest of their lives. The much lower prevalence of depression and suicidal ideation among older migraineurs suggests a promising area for future research.”
Dr. Fuller-Thomson adds that this study “draws further attention to the need for routine screening and targeted interventions for depression and suicidality, particularly among the most vulnerable migraineurs: Individuals who are young, unmarried and those with activity limitations.”
(Image: Shutterstock)
Migraine May Permanently Change Brain Structure
Migraine may have long-lasting effects on the brain’s structure, according to a study published in the August 28, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“Traditionally, migraine has been considered a benign disorder without long-term consequences for the brain,” said study author Messoud Ashina, MD, PhD, with the University of Copenhagen in Denmark. “Our review and meta-analysis study suggests that the disorder may permanently alter brain structure in multiple ways.”
The study found that migraine raised the risk of brain lesions, white matter abnormalities and altered brain volume compared to people without the disorder. The association was even stronger in those with migraine with aura.
For the meta-analysis, researchers reviewed six population-based studies and 13 clinic-based studies to see whether people who experienced migraine or migraine with aura had an increased risk of brain lesions, silent abnormalities or brain volume changes on MRI brain scans compared to those without the conditions.
The results showed that migraine with aura increased the risk of white matter brain lesions by 68 percent and migraine with no aura increased the risk by 34 percent, compared to those without migraine. The risk for infarct-like abnormalities increased by 44 percent for those with migraine with aura compared to those without aura. Brain volume changes were more common in people with migraine and migraine with aura than those with no migraines.
“Migraine affects about 10 to 15 percent of the general population and can cause a substantial personal, occupational and social burden,” said Ashina. “We hope that through more study, we can clarify the association of brain structure changes to attack frequency and length of the disease. We also want to find out how these lesions may influence brain function.”
(Image: Getty images)
Drug blocks light sensors in eye that may trigger migraine attacks
New compound by Salk scientists offers a way to treat migraine and potentially other disorders of the central nervous system
For many migraine sufferers, bright lights are a surefire way to exacerbate their headaches. And for some night-shift workers, just a stroll through a brightly lit parking lot during the morning commute home can be enough to throw off their body’s daily rhythms and make daytime sleep nearly impossible. But a new molecule that selectively blocks specialized light-sensitive receptors in the eyes could help both these groups of people, without affecting normal vision according to a study published August 25, 2013 in Nature Chemical Biology.
"It took almost ten years to find and test a molecule that fit all the properties and acted in vivo as we wanted," says senior study author Satchidananda Panda, an associate professor in Salk’s Regulatory Biology Laboratory.
Scientists have known for nearly a century that humans and animals can sense light even when they can’t see. Before they’ve opened their eyes, and even before cells that allow vision have matured, newborn mice still scurry away from bright lights, and set their sleep-wake cycles based on the patterns of light and dark throughout the day. The same is true of many blind people-though they can’t see what’s in front of them, their bodies still follow daily circadian rhythms, and the pupils of their eyes constrict in response to light.
More than ten years ago, Panda’s lab group discovered that melanopsin, a receptor found in neurons connecting the eyes and brain, is responsible for sensing light independently of normal vision. Since then, researchers have determined that the receptor is vital for maintaining sleep cycles and other circadian rhythms in those with healthy vision, constricting the pupil of the eye in bright light, and potentially exacerbating the light-sensitivity associated with migraine headaches. While melanopsin senses light for these non-vision purposes in the body, closely related receptors-rhodopsin and cone opsins-provide vision-forming information to the brain.
Panda figured that if he could find a compound that blocked melanopsin, but not rhodopsin or cone opsins, it could pave the way toward treating migraines or circadian rhythm imbalances. Scientists already know of one class of compounds, retinoids, which interact with opsins, but they’re non-specific and so bind to melanopsin, rhodopsin, cone opsins, and a whole handful of other receptors in the body, causing widespread side effects. Panda wanted something more specific. So for ten years, his lab group, in collaboration with scientists at the pharmaceutical company Lundbeck, has attempted to find chemical compounds that specifically shut off melanopsin in animals.
In their latest search, Panda and his collaborators turned to the Lundbeck library of diverse compounds. In hundreds of 384-well plates, a team led by Ken Jones at Lundbeck tested whether each chemical from the library turned off melanopsin by measuring the calcium levels after the plate was exposed to light. When melanopsin is functioning, calcium levels increase after light exposure indicating that light has been sensed and a signal is being generated. Several compounds from the chemical library stopped this calcium increase from happening, suggesting that they were blocking the function of melanopsin.
None of these compounds looked like retinoids, so it was an exciting breakthrough, Panda says. The chemicals, dubbed opsinamides, also showed no interaction with rhodopsin or other opsins. “We wanted to make sure they were specific to melanopsin,” says Panda. To find out whether the opsinamides would have a physiological response in addition to binding to melanopsin in bench experiments, Megumi Hatori and Ludovic Mure from Panda’s Salk lab group next looked at whether the drug affected the pupillary constriction in mice. Normally, in extremely bright light, the pupil of the eye shrinks to its smallest size. But when the mice were treated with one of the opsinamides, their pupils didn’t shrink as usual. Most importantly, the drug had no detectable effect in mice lacking melanopsin, further showing its specificity for melanopsin. Finally, newborn mice treated with the compound no longer avoided bright lights. The results, Panda says, show that the drug is stopping melanopsin from signaling the brain when the eyes are exposed to bright light.
"So far, everything known about melanopsin has been discovered using knock-out mice that completely lack the receptor," says Panda. "So this offers a new way to study the protein." Kenneth Jones, the former project head at Lundbeck, notes that "the two compounds require further optimization in anticipation of clinical testing but are extraordinarily useful for research purposes and as leads in the discovery process." Co-author Jeffrey Sprouse has co-founded a start-up company, Cyanaptic, to do just that.
Once more effective compounds are developed, Panda expects that they could eventually have utility in a variety of clinical settings. “There are many people who would like to work when they have migraine pain exacerbated by light,” he says. “If these drugs could stop the light-sensitivity associated with the headaches, it would enable them to be much more productive.”
Moreover, Panda says, the drugs could help shift-workers set their sleep schedules without exposure to sunlight interfering with their circadian rhythms. His lab group doesn’t yet have results on how the drugs affect circadian rhythms, but based on the known mechanisms of melanopsin, Panda says that it is likely the new opsinamides alter sleep.
Migraine is Associated with Variations in Structure of Brain Arteries
The network of arteries supplying blood flow to the brain is more likely to be incomplete in people who suffer migraine, a new study by researchers in the Perelman School of Medicine at the University of Pennsylvania reports. Variations in arterial anatomy lead to asymmetries in cerebral blood flow that might contribute to the process triggering migraines.
The arterial supply of blood to the brain is protected by a series of connections between the major arteries, termed the “circle of Willis” after the English physician who first described it in the 17th century. People with migraine, particularly migraine with aura, are more likely to be missing components of the circle of Willis.
Migraine affects an estimated 28 million Americans, causing significant disability. Experts once believed that migraine was caused by dilation of blood vessels in the head, while more recently it has been attributed to abnormal neuronal signals. In this study, appearing in PLOS ONE, researchers suggest that blood vessels play a different role than previously suspected: structural alterations of the blood supply to the brain may increase susceptibility to changes in cerebral blood flow, contributing to the abnormal neuronal activity that starts migraine.
"People with migraine actually have differences in the structure of their blood vessels - this is something you are born with," said the study’s lead author, Brett Cucchiara, MD, Associate Professor of Neurology. "These differences seem to be associated with changes in blood flow in the brain, and it’s possible that these changes may trigger migraine, which may explain why some people, for instance, notice that dehydration triggers their headaches."
In a study of 170 people from three groups - a control group with no headaches, those who had migraine with aura, and those who had migraine without aura - the team found that an incomplete circle of Willis was more common in people with migraine with aura (73 percent) and migraine without aura (67 percent), compared to a headache-free control group (51 percent). The team used magnetic resonance angiography to examine blood vessel structure and a noninvasive magnetic resonance imaging method pioneered at the University of Pennsylvania, called Arterial spin labeling (ASL), to measure changes in cerebral blood flow.
"Abnormalities in both the circle of Willis and blood flow were most prominent in the back of the brain, where the visual cortex is located. This may help explain why the most common migraine auras consist of visual symptoms such as seeing distortions, spots, or wavy lines,” said the study’s senior author, John Detre, MD, Professor of Neurology and Radiology.
Both migraine and incomplete circle of Willis are common, and the observed association is likely one of many factors that contribute to migraine in any individual. The researchers suggest that at some point diagnostic tests of circle of Willis integrity and function could help pinpoint this contributing factor in an individual patient. Treatment strategies might then be personalized and tested in specific subgroups.
Getting to grips with migraine
Researchers identify some of the biological roots of migraine from large-scale genome study
In the largest study of migraines, researchers have found 5 genetic regions that for the first time have been linked to the onset of migraine. This study opens new doors to understanding the cause and biological triggers that underlie migraine attacks.
The team identified 12 genetic regions associated with migraine susceptibility. Eight of these regions were found in or near genes known to play a role in controlling brain circuitries and two of the regions were associated with genes that are responsible for maintaining healthy brain tissue. The regulation of these pathways may be important to the genetic susceptibility of migraines.
Migraine is a debilitating disorder that affects approximately 14% of adults. Migraine has recently been recognised as the seventh disabler in the Global Burden of Disease Survey 2010 and has been estimated to be the most costly neurological disorder. It is an extremely difficult disorder to study because no biomarkers between or during attacks have been identified so far.
"This study has greatly advanced our biological insight about the cause of migraine," says Dr Aarno Palotie, from the Wellcome Trust Sanger Institute. "Migraine and epilepsy are particularly difficult neural conditions to study; between episodes the patient is basically healthy so it’s extremely difficult to uncover biochemical clues.
"We have proven that this is the most effective approach to study this type of neurological disorder and understand the biology that lies at the heart of it."
The team uncovered the underlying susceptibilities by comparing the results from 29 different genomic studies, including over 100,000 samples from both migraine patients and control samples.
They found that some of the regions of susceptibility lay close to a network of genes that are sensitive to oxidative stress, a biochemical process that results in the dysfunction of cells.
The team expects many of the genes at genetic regions associated with migraine are interconnected and could potentially be disrupting the internal regulation of tissue and cells in the brain, resulting in some of the symptoms of migraine.
"We would not have made discoveries by studying smaller groups of individuals," says Dr Gisela Terwindt, co-author from Leiden University Medical Centre. "This large scale method of studying over 100,000 samples of healthy and affected people means we can tease out the genes that are important suspects and follow them up in the lab."
The team identified an additional 134 genetic regions that are possibly associated to migraine susceptibility with weaker statistical evidence. Whether these regions underlie migraine susceptibility or not still needs to be elucidated. Other similar studies show that these statistically weaker culprits can play an equal part in the underlying biology of a disease or disorder.
"The molecular mechanisms of migraine are poorly understood. The sequence variants uncovered through this meta-analysis could become a foothold for further studies to better understanding the pathophysiology of migraine" says Dr Kári Stefánsson, President of deCODE genetics.
"This approach is the most efficient way of revealing the underlying biology of these neural disorders," says Dr Mark Daly, from the Massachusetts General Hospital and the Broad Institute of MIT and Harvard. "Effective studies that give us biological or biochemical results and insights are essential if we are to fully get to grips with this debilitating condition.
"Pursuing these studies in even larger samples and with denser maps of biological markers will increase our power to determine the roots and triggers of this disabling disorder."