1. Researchers implicate genetic locus on chromosome 12 in anorexia nervosa

    May 21, 2017 by Ashley

    From the University of North Carolina Health Care press release:

    A landmark study led by UNC School of Medicine researchers has identified the first genetic locus for anorexia nervosa and has revealed that there may also be metabolic underpinnings to this potentially deadly illness.

    The study, which is the most powerful genetic study of anorexia nervosa conducted to date, included genome-wide analysis of DNA from 3,495 individuals with anorexia nervosa and 10,982 unaffected individuals.

    If particular genetic variations are significantly more frequent in people with a disorder compared to unaffected people, the variations are said to be “associated” with the disorder. Associated genetic variations can serve as powerful pointers to regions of the human genome where disorder-causing problems reside, according to the National Human Genome Research Institute.

    “We identified one genome-wide significant locus for anorexia nervosa on chromosome 12, in a region previously shown to be associated with type 1 diabetes and autoimmune disorders,” said lead investigator, Cynthia Bulik, PhD, FAED, founding director of the UNC Center of Excellence for Eating Disorders and a professor at Karolinska Institutet in Stockholm, Sweden.

    “We also calculated genetic correlations — the extent to which various traits and disorders are caused by the same genes,” said Bulik.

    Anorexia nervosa was significantly genetically correlated with neuroticism and schizophrenia, supporting the idea that anorexia is indeed a psychiatric illness.”

    “But, unexpectedly, we also found strong genetic correlations with various metabolic features including body composition (BMI) and insulin-glucose metabolism. This finding encourages us to look more deeply at how metabolic factors increase the risk for anorexia nervosa,” Bulik said.

    This study was conducted by the Psychiatric Genetics Consortium Eating Disorders Working Group — an international collaboration of researchers at multiple institutions worldwide.

    “In the era of team science, we brought over 220 scientists and clinicians together to achieve this large sample size. Without this collaboration we would never have been able to discover that anorexia has both psychiatric and metabolic roots,” said Gerome Breen, PhD, of King’s College London.

    “Working with large data sets allows us to make discoveries that would never be possible in smaller studies,” said Laramie Duncan, PhD, of Stanford University, who served as lead analyst on the project.

    The researchers are continuing to increase sample sizes and see this as the beginning of genomic discovery in anorexia nervosa. Viewing anorexia nervosa as both a psychiatric and metabolic condition could ignite interest in developing or repurposing medications for its treatment where currently none exist.


  2. Gene mutation may speed up memory loss in Alzheimer’s disease

    May 12, 2017 by Ashley

    From the American Academy of Neurology (AAN) press release:

    A gene mutation may accelerate the loss of memory and thinking skills in people who are at risk for Alzheimer’s disease, according to a study published in the May 3, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. The gene mutation is called the BDNF Val66Met allele, or just the Met allele.

    Brain derived neurotrophic factor (BDNF) is a protein produced by the gene of the same name. It is one of a group of proteins called neurotrophins that help nerve cells grow, specialize and survive. Alleles are parts of genes that work in pairs on the chromosomes to determine a person’s traits.

    “We found that people with Alzheimer’s risk who have this BDNF gene mutation called the Met allele may have a more rapid decline of memory and thinking skills,” said study author Ozioma Okonkwo, PhD, of the University of Wisconsin School of Medicine in Madison, Wisc. “Because this gene can be detected before the symptoms of Alzheimer’s start, and because this presymptomatic phase is thought to be a critical period for treatments that could delay or prevent the disease, it could be a great target for early treatments.”

    For the study, researchers followed 1,023 people with an average age of 55 for up to 13 years who were at risk for Alzheimer’s disease but at the start were still healthy. Participants gave blood samples which were tested for the Met allele gene mutation. Their memory and thinking skills were evaluated at the start of the study and at each study visit, up to five visits. Of that group, 140 were also tested with neuroimaging for beta-amyloid, a sticky protein that can build up into plaques found in the brains of people with Alzheimer’s disease.

    A total of 32 percent of the participants had the Met allele. Researchers found that when compared to people without the gene mutation, those with the mutation lost memory and thinking skills more rapidly. On tests of verbal learning and memory, those with no gene mutation improved by 0.002 units per year, while the scores of people with the mutation declined by 0.021 units per year.

    The researchers also found that people with the gene mutation who also had more beta-amyloid had an even steeper rate of decline.

    “When there is no mutation, it is possible the BDNF gene and the protein it produces are better able to be protective, thereby preserving memory and thinking skills,” Okonkwo said. “This is especially interesting because previous studies have shown that exercise can increase levels of BDNF. It is critical for future studies to further investigate the role that the BDNF gene and protein have in beta-amyloid accumulation in the brain.”

    A major strength of the study is that it was one of the largest studies investigating this mutation. A limitation is that the study participants were predominantly white. Also, the number of people with beta-amyloid data was limited.


  3. How neurons and glia cells are created in the developing brain

    May 11, 2017 by Ashley

    From the Institute of Science and Technology Austria press release:

    Neurons and glia are the cells that make up our brain. In the cortex, the brain area that enables us to think, speak and be conscious, neurons and most glia are produced by a type of neural stem cell, called radial glia progenitors (RGPs). It is vital that no errors occur in this process as disruptions can lead to neurodevelopmental disorders such as microcephaly, a condition in which a baby’s head and cortex are significantly smaller than that of other babies. But how is this production of neurons and glia cells controlled? Simon Hippenmeyer and his group at the Institute of Science and Technology Austria (IST Austria), including first author Robert Beattie, as well as colleagues at North Carolina State University and the Fred Hutchinson Cancer Research Center in USA, found that a gene called Lgl1 controls the production of certain neurons in the cortex of mouse embryos, and plays a role in the production of other types of neurons and glia after birth. This is the result of a study published today in Neuron.

    The production of neurons and glia in the developing cortex is tightly regulated. RGPs produce the majority of them. In previous studies, Hippenmeyer and colleagues have shown that the division pattern of RGPs is not random. They have demonstrated that each individual RGP produces a predefined unit of neurons and glia cells in a precisely orchestrated developmental program which ensures that the brain faithfully grows to its normal size.

    In the present Neuron study, the authors asked what mechanisms control the exact output of RGPs. In particular, the researchers investigated the role of the gene Lgl1, which had been predicted to regulate RGP proliferation. The gene’s precise role was previously unknown and Hippenmeyer and colleagues now used a technique called MADM, short for Mosaic Analysis with Double Markers in order to decipher the function of Lgl1 in RGPs at unprecedented single cell resolution.

    Using MADM, Hippenmeyer and colleagues eliminated Lgl1 either in just single RGPs, or in all RGPs. At the same time, individual cells are labelled fluorescently, so that they can be studied under the microscope. The authors show that Lgl1 controls the generation of neurons and glia cells in the developing cortex in two different ways. First, for the generation of neurons in the early embryo the function of Lgl1 is simultaneously required in the entire population of RGPs. If Lgl1 function is absent in all RGPs, but not if absent in just individual RGP cells, dynamic community effects lead to malformation of the cortex resembling ‘Double Cortex Syndrome’, a severe human brain disorder. Second, for the production of glia cells and neurons in the postnatal brain, Lgl1 function is ‘only’ required in the individual stem cell which is just in the process of generating a neuron or glia cell. This type of Lgl1 gene function is called cell-autonomous or intrinsic while the requirement of Lgl1 gene function in the entire community is called non-cell-autonomous. In other words, you require the entire orchestra for a symphony (generate neurons in embryonic cortex) but only an individual soloist for a solo (produce neurons or glia cells in postnatal brain). Simon Hippenmeyer explains how this research will influence the way how the role of genes during development should be analysed in the future: “Our study emphasizes that both intrinsic gene functions and community-based environmental contributions are important for the control of radial glia progenitor cells in the cortex in particular, and for neural stem cells in general. It will thus be important in future genetic loss-of-function experiments to precisely dissect the relative contributions of cell-autonomous, intrinsic, gene functions and the influence of the stem cell niche microenvironment to the overall interpretation of a gene function.”


  4. Study links immune system, brain structure and memory

    May 8, 2017 by Ashley

    From the University of Basel press release:

    The body’s immune system performs essential functions, such as defending against bacteria and cancer cells. However, the human brain is separated from immune cells in the bloodstream by the so-called blood-brain barrier. This barrier protects the brain from pathogens and toxins circulating in the blood, while also dividing the immune cells of the human body into those that fulfill their function in the blood and those that work specifically in the brain. Until recently, it was thought that brain function was largely unaffected by the peripheral immune system.

    However, in the past few years, evidence has accumulated to indicate that the blood’s immune system could in fact have an impact on the brain. Scientists from the University of Basel’s Transfaculty Research Platform Molecular and Cognitive Neurosciences (MCN) have now carried out two independent studies that demonstrate that this link between the immune system and brain is more significant than previously believed.

    Search for regulatory patterns

    In the first study, the researchers searched for epigenetic profiles, i.e. regulatory patterns, in the blood of 533 young, healthy people. In their genome-wide search, they identified an epigenetic profile that is strongly correlated with the thickness of the cerebral cortex, in particular in a region of the brain that is important for memory functions. This finding was confirmed in an independent examination of a further 596 people. It also showed that it is specifically those genes that are responsible for the regulation of important immune functions in the blood that explain the link between the epigenetic profile and the properties of the brain.

    Gene variant intensifies traumatic memories

    In the second study, the researchers investigated the genomes of healthy participants who remembered negative images particularly well or particularly poorly. A variant of the TROVE2 gene, whose role in immunological diseases is currently being investigated, was linked to participants’ ability to remember a particularly high number of negative images, while their general memory remained unaffected.

    This gene variant also led to increased activity in specific regions of the brain that are important for the memory of emotional experiences. The researchers also discovered that the gene is linked to the strength of traumatic memories in people who have experienced traumatic events.

    The results of the two studies show that both brain structure and memory are linked to the activity of genes that also perform important immune regulatory functions in the blood. “Although the precise mechanisms behind the links we discovered still need to be clarified, we hope that this will ultimately lead to new treatment possibilities,” says Professor Andreas Papassotiropoulos, Co-Director of the University of Basel’s MCN research platform. The immune system can be precisely affected by certain medications, and such medications could also have a positive effect on impaired brain functions.

    Innovative research methods

    These groundbreaking findings were made possible thanks to cutting edge neuroscientific and genetic methods at the University of Basel’s MCN research platform. Under the leadership of Professor Andreas Papassotiropoulos and Professor Dominique de Quervain, the research platform aims to help us better understand human brain functions and to develop new treatments for psychiatric disorders.


  5. Study suggests social media use attributable to genetic traits

    May 7, 2017 by Ashley

    From the International Communication Association press release:

    It’s easy to think in terms of linking genetics to behavior in simple ways. Are you calm or do you have a temper? Are you creative or analytical? Are you sociable or shy? But can heritable traits actually influence a person to frequently use social media? A recent study by a researcher at the Kent State University found that genetics outweighed environment in social media use using twin study survey data.

    Chance York (Kent State University) will present his findings at the 67th Annual Conference of the International Communication Association in San Diego, CA. Using a behavior genetics framework and twin study data from the 2013 Midlife in the United States (MIDUS III) survey, York examined how both environmental and genetic factors contribute to social media use by applying an analytical model called Defries-Fulker (DF) Regression.

    The data analyzed revealed one- to two-thirds of variance in social media use is attributable to additive genetic traits; unique and shared environmental factors account for the remainder of variance. York also provides an analytical blueprint for using DF regression in future investigations of genetic influence on communication behaviors and media effects.

    Past behavior genetics research using twin study survey data has shown genetic influence on a wide range of communication behaviors. This is the first study to show that genetic traits also affect social media use.

    “This study doesn’t suggest that using DF regression with twin survey data, or the behavioral genetics perspective more generally, can directly assess gene-level influence on specific behaviors. There is no ‘social media gene,'” said York. “The assumption here is that known genetic variation between fraternal and identical twins can be leveraged to study how genetic variation influences patterns of observable behavior. We are still working in a ‘black box’ in that we can’t directly observe how genes impact our neuroanatomy, which in turn impacts cognitive processing, personality, and subsequent media selection and effects. However, this study — and this line of inquiry — is a starting point for studying genetic influence on communication.”


  6. Study looks at possible role of genetics in food preferences

    May 2, 2017 by Ashley

    From the Experimental Biology 2017 press release:

    Have you ever wondered why you keep eating certain foods, even if you know they are not good for you? Gene variants that affect the way our brain works may be the reason, according to a new study. The new research could lead to new strategies to empower people to enjoy and stick to their optimal diets.

    Silvia Berciano, a predoctoral fellow at the Universidad Autonoma de Madrid, will present the new findings at the American Society for Nutrition Scientific Sessions and annual meeting during the Experimental Biology 2017 meeting, to be held April 22-26 in Chicago.

    “Most people have a hard time modifying their dietary habits, even if they know it is in their best interest,” said Berciano. “This is because our food preferences and ability to work toward goals or follow plans affect what we eat and our ability to stick with diet changes. Ours is the first study describing how brain genes affect food intake and dietary preferences in a group of healthy people.”

    Although previous research has identified genes involved with behaviors seen in eating disorders such as anorexia or bulimia, little is known about how natural variation in these genes could affect eating behaviors in healthy people. Gene variation is a result of subtle DNA differences among individuals that make each person unique.

    For the new study, the researchers analyzed the genetics of 818 men and women of European ancestry and gathered information about their diet using a questionnaire. The researchers found that the genes they studied did play a significant role in a person’s food choices and dietary habits. For example, higher chocolate intake and a larger waist size was associated with certain forms of the oxytocin receptor gene, and an obesity-associated gene played a role in vegetable and fiber intake. They also observed that certain genes were involved in salt and fat intake.

    The new findings could be used to inform precision-medicine approaches that help minimize a person’s risk for common diseases — such as diabetes, cardiovascular disease and cancer — by tailoring diet-based prevention and therapy to the specific needs of an individual.

    “The knowledge gained through our study will pave the way to better understanding of eating behavior and facilitate the design of personalized dietary advice that will be more amenable to the individual, resulting in better compliance and more successful outcomes,” said Berciano.

    The researchers plan to perform similar investigations in other groups of people with different characteristics and ethnicities to better understand the applicability and potential impact of these findings. They also want to investigate whether the identified genetic variants associated with food intake are linked to increased risks for disease or health problems.


  7. Neurons’ faulty wiring leads to serotonin imbalance, depression-like behavior in mice

    by Ashley

    From the Zuckerman Institute at Columbia University press release:

    Columbia scientists have identified a gene that allows neurons that release serotonin — a neurotransmitter that regulates mood and emotions — to evenly spread their branches throughout the brain. Without this gene, these neuronal branches become entangled, leading to haphazard distribution of serotonin, and signs of depression in mice. These observations shed light on how precise neuronal wiring is critical to overall brain health, while also revealing a promising new area of focus for studying psychiatric disorders associated with serotonin imbalance — such as depression, bipolar disorder, schizophrenia and autism.

    The findings were published in Science.

    “By pinpointing the genes that guide the organization of neurons, we can draw a line between changes to those genes, and the cellular, circuitry and behavioral deficiencies that can occur as a result,” said Tom Maniatis, PhD, a principal investigator at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute, the Isidore S. Edelman Professor and Chair of department of Biochemistry & Molecular Biophysics at Columbia University Medical Center and the studys’ senior author.

    Today’s research is the result of parallel efforts by Dr. Maniatis, his lab and collaborators across Columbia to understand how individual neurons in the brain ‘see’ each other — and how each of their hundreds, or even thousands, of branches wind through the brain without getting tangled up along the way.

    To investigate this problem, Dr. Maniatis and his team focused on a group of genes called clustered protocadherins, or Pcdhs. More than a decade ago, Dr. Maniatis’ lab discovered the human Pcdh gene cluster, and later studies by Maniatis and others revealed that these genes encode a cell surface “barcode” by which individual neurons can distinguish themselves from other neurons.

    Subsequently, collaborative studies with fellow Zuckerman Institute structural biologists Barry Honig, PhD, and Larry Shapiro, PhD, revealed the precise mechanism by which the Pcdh code is assembled at the cell surface, and how this code is “read” when neurons come in contact with each other. This allows neurons to prevent entanglements by recognizing — and steering clear of — their own branches, a process known as self-avoidance.

    In the two papers published in Science, Dr. Maniatis and his team examined the function of Pcdhs in the wiring of olfactory sensory neurons (which impart a sense of smell), and serotonergic neurons (which produce and release serotonin). The olfactory sensory neuron (OSN) study revealed that the diversity of Pcdhs, working together, produced the necessary combinations of cell-coating molecules to provide each neuron its unique identity. In the absence of diversity, OSNs fail to wire properly in the brain, and the mice fail to distinguish between different odors.

    The serotonergic neuron study revealed another important function of Pcdhs.

    “The main job of these neurons is to distribute serotonin uniformly throughout the brain, which is responsible for maintaining mood balance,” said Dr. Maniatis, who is also director of Columbia’s Precision Medicine Initiative. “To do this, the neurons lay their branches out in a precise, evenly-spaced pattern — a process called axonal tiling. However, the exact mechanism that allows them to do this remained elusive.”

    In a series of experiments in mice, Dr. Maniatis’ team pinpointed a single gene within the Pcdh cluster, called Pcdh-alpha-c2, that was responsible for the ability of serotonergic neurons to assemble into a tiled pattern throughout the brain, and thus evenly distribute serotonin.

    “We were surprised to find that, unlike other neurons that displays distinct barcodes of diverse Pcdhs, all serotonergic neurons display a single functional recognition protein,” said Dr. Maniatis. “Thus, serotonergic axonal branches can recognize and repel one another, leading to their even spacing.”

    “We found that deleting the Pcdh-alpha-c2 caused serotonergic neuron branches to become tangled and clumped together,” Dr. Maniatis continued. “Serotonin was released, but it wasn’t distributed evenly throughout the brain.”

    Silencing Pcdh-alpha-c2 also resulted in striking behavioral changes. Compared to normal, healthy mice, Pcdh-alpha-c2-deficient mice showed behavioral despair (reduced desire to escape) and enhanced fear memory (increased freezing when frightened) — both classic signs indicative of depression.

    “Serotonin imbalance has long been linked to a variety of psychiatric disorders, including depression, bipolar disorder and schizophrenia, but most studies focus on problems with the production or uptake of serotonin, not on problems with the brain’s wiring itself,” said Dr. Maniatis. “Wiring anomalies are clearly a new place to look.”

    Today’s results may also inform studies of autism. After an exhaustive genetic analysis of autistic individuals and their families by an international consortium of investigators, several hundred genes have been identified that are associated with the disorder, as documented by the Simons Foundation Autism Research Initiative (SFARI) human gene module. Among these genes is the Pcdh gene cluster — including Pcdh-alpha-c2.

    “For this pair of studies published today, we focused on two types of neurons that are well understood and have been deeply explored, but this is only the starting point,” said Dr. Maniatis. “If we are to truly understand how the brain is wired both in health and in disease, then the rest of the brain is where we have to go next.”


  8. Gene mutation helps explain night owl behavior

    April 11, 2017 by Ashley

    From the Cell Press press release:

    Some people stay up late and have trouble getting up in the morning because their internal clock is genetically programmed to run slowly, according to a study published April 6 in Cell. A mutation in a gene called CRY1 alters the human circadian clock, which dictates rhythmic behavior such as sleep/wake cycles. Carriers of the gene variant experienced nighttime sleep delays of 2-2.5 hours compared to non-carriers.

    “Carriers of the mutation have longer days than the planet gives them, so they are essentially playing catch-up for their entire lives,” says first author Alina Patke, a research associate in the lab of principal investigator Michael Young, Richard and Jeanne Fisher Professor and Head of the Laboratory of Genetics at The Rockefeller University.

    Night owls are often diagnosed at sleep clinics with delayed sleep phase disorder (DSPD). This study is the first to implicate a gene mutation in the development of DSPD, which affects up to 10% of the public, according to clinical studies.

    People with DSPD often struggle to fall asleep at night, and sometimes sleep comes so late that it fractures into a series of long naps. DSPD and other sleep disorders are associated with anxiety, depression, cardiovascular disease, and diabetes. People with DSPD also have trouble conforming to societal expectations and morning work schedules.

    “It’s as if these people have perpetual jet lag, moving eastward every day,” says Young. “In the morning, they’re not ready for the next day to arrive.”

    Patke is a night owl and usually works late into the night. She, however, does not carry the CRY1 variant. Not all cases of DSPD are attributable to this gene mutation. However, Young and Patke found it in 1 in 75 of individuals of non-Finnish, European ancestry in a gene database search. “Our variant has an effect on a large fraction of the population,” she says.

    Young, who has studied the genes involved in the circadian clock of the fruit fly, connected with clinical researchers at the Weill Cornell Medical College to understand the molecular underpinnings of human sleep disorders. By studying the skin cells of people with DSPD, he and Patke discovered a mutation in CRY1, which helps drive the circadian clock.

    The circadian clock is a fundamental element of life on Earth and has remained more or less the same, genetically, throughout the evolution of animals. “It’s basically the same clock from flies to humans,” Young says.

    Normally the clock begins its cycle by building up proteins, call activators, in a cell. These activators produce their own inhibitors that, over time, cause the activators to lose their potency. When all the activators in the cell have been silenced, inhibitors are no longer produced and eventually degrade. Once they’ve all gone, the potency of the activators surges, and the cycle begins again.

    The CRY1 protein is one of the clock’s inhibitors. The mutation Young and Patke found is a single-point mutation in the CRY1 gene, meaning just one letter in its genetic instructions is incorrect. Yet this change causes a chunk of the gene’s resulting protein to be missing. That alteration causes the inhibitor to be overly active, prolonging the time that the activators are suppressed and stretching the daily cycle by half an hour or more.

    In addition to their initial study of a multigenerational family in the U.S., Young and Patke collaborated with clinical researchers at Bilkent University to analyze the sleep patterns of six families of Turkish individuals, 39 carriers of the CRY1 variant and 31 non-carriers. The carriers had delayed sleep onset times and some had fractured, irregular sleep patterns. The mid-point of sleep for non-carriers was about 4 a. m. But for carriers, the mid-point was shifted to 6-8 a.m.

    Because the mutation does not disable the protein, it can have an effect on individuals whether they carry one or two copies of the gene. Of the 39 Turkish carriers studied, 8 had inherited the mutation from both parents, and 31 had inherited only one copy of the mutation.

    The circadian clock responds to external environmental cues, so it is possible for people to manage the effects of the mutation on sleep. For instance, one carrier in the study reported maintaining a sleep routine through self-enforced regular sleep and wake times and exposure to bright light during the day. “An external cycle and good sleep hygiene can help force a slow-running clock to accommodate a 24-hour day,” says Patke. “We just have to work harder at it.”


  9. Study reverses thinking on genetic links to stress, depression

    April 7, 2017 by Ashley

    From the Washington University School of Medicine:

    New research findings often garner great attention. But when other scientists follow up and fail to replicate the findings? Not so much.

    In fact, a recent study published in PLOS One indicates that only about half of scientific discoveries will be replicated and stand the test of time. So perhaps it shouldn’t come as a surprise that new research led by Washington University School of Medicine in St. Louis shows that an influential 2003 study about the interaction of genes, environment and depression may have missed the mark.

    Since its publication in Science, that original paper has been cited by other researchers more than 4,000 times, and some 100 other studies have been published about links between a serotonin-related gene, stressful life events and depression risk. It indicated that people with a particular variant of the serotonin transporter gene were not as well-equipped to deal with stressful life events and, when encountering significant stress, were more likely to develop depression.

    Such conclusions were widely accepted, mainly because antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs) help relieve depression for a significant percentage of clinically depressed individuals, so many researchers thought it logical that differences in a gene affecting serotonin might be linked to depression risk.

    But in this new study, the Washington University researchers looked again at data from the many studies that delved into the issue since the original publication in 2003, analyzing information from more than 40,000 people, and found that the previously reported connection between the serotonin gene, depression and stress wasn’t evident. The new results are published April 4 in the journal Molecular Psychiatry.

    “Our goal was to get everyone who had gathered data about this relationship to come together and take another look, with each research team using the same tools to analyze data the same way,” said the study’s first author, Robert C. Culverhouse, PhD, an assistant professor of medicine and of biostatistics. “We all ran exactly the same statistical analyses, and after combining all the results, we found no evidence that this gene alters the impact stress has on depression.”

    Over the years, dozens of research groups had studied DNA and life experiences involving stress and depression in the more than 40,000 people revisited in this study. Some previous research indicated that those with the gene variant were more likely to develop depression when stressed, while others didn’t see a connection. So for almost two decades, scientists have debated the issue, and thousands of hours of research have been conducted. By getting all these groups to work together to reanalyze the data, this study should put the questions to rest, according to the researchers.

    “The idea that differences in the serotonin gene could make people more prone to depression when stressed was a very reasonable hypothesis,” said senior investigator Laura Jean Bierut, MD, the Alumni Endowed Professor of Psychiatry at Washington University. “But when all of the groups came together and looked at the data the same way, we came to a consensus. We still know that stress is related to depression, and we know that genetics is related to depression, but we now know that this particular gene is not.”

    Culverhouse noted that finally, when it comes to this gene and its connection to stress and depression, the scientific method has done its job.

    “Experts have been arguing about this for years,” he said. “But ultimately the question has to be not what the experts think but what the evidence tells us. We’re convinced the evidence finally has given us an answer: This serotonin gene does not have a substantial impact on depression, either directly or by modifying the relationship between stress and depression.”

    With this serotonin gene variant removed from the field of potential risk factors for depression, Culverhouse and Bierut said researchers now can focus on other gene-environment interactions that could influence the onset of depression.


  10. A new blue gene: NKPD1 variant increases depression risk

    April 6, 2017 by Ashley

    From the Elsevier press release:

    A study of people from an isolated village in the Netherlands reveals a link between rare variants in the gene NKPD1 and depressive symptoms. The findings are published in the current issue of Biological Psychiatry. The study, led by co-first authors Najaf Amin, PhD, of Erasmus University Medical Center in the Netherlands and Nadezhda Belonogova of the Russian Academy of Sciences in Novosibirsk, Russia, helps researchers understand the molecular pathology of the disease, which could eventually improve how depression is diagnosed and treated.

    Genetics play a strong role in risk for depression, but the identification of specific genes contributing to the disorder has eluded researchers. “By sequencing all of the DNA that codes for mRNA and ultimately, proteins, Dr. Amin and colleagues found a single gene that may account for as much as 4% of the heritable risk for depression,” said Doctor John Krystal, Editor of Biological Psychiatry.

    To identify the gene, the researchers assessed data from the Erasmus Rucphen Family study, which was composed of a collection of families and their descendents living in social isolation until the past few decades. In a population like this, genetic isolation leads to an amplification of rarely occurring variants with little other genetic variation, providing a more powerful cohort for the discovery of rare variants. Nearly 2,000 people who had been assessed for depressive symptoms were included in the analysis.

    Using whole-exome sequencing to examine portions of DNA containing genetic code to produce proteins, Amin and colleagues found that several variants of NKPD1 were associated with higher depressive symptom scores. The association between depressive symptoms and NKPD1 were also replicated in an independent sample of people from the general population, although the replication sample highlighted different variants within NKPD1.

    “The involvement of NKPD1 in the synthesis of sphingolipids and eventually of ceramides is interesting,” said Dr. Amin, referring to the predicted role of NKPD1 in the body. Altered sphingolipid levels in blood have been associated with depression and have been proposed as a therapeutic target for major depressive disorder.

    “We are the first to show a possible genetic connection in this respect,” said Dr. Amin, adding that this implies that such a therapy might be beneficial for patients carrying risk variants in the NKPD1 gene.

    As with other psychiatric disorders, depression lacks genetic or biochemical markers to aid diagnosis and treatment of the disorder. According to Dr. Amin, moving depression treatment into the era of precision and personalized medicine will require a transition to objective and unbiased measurements where patients are stratified based on the molecular pathology of the disease. “NKPD1 may be one such molecular mechanism,” she said.