Online depression intervention tool found effective in adolescent mothers

Researchers from the University of Louisville found that using an Internet-based depression intervention tool program found effective in improving treatment rates of adolescent depressed mothers. This study is published in journal Archives of Women’s Mental Health.

Roughly half of the 400,000 adolescents 18 and younger who give birth annually in the United States experience depressive symptoms, but less than 25 percent follow referrals for depression evaluation and treatment, according to the study.

Internet-based depression tool consisted of a website with videos of mothers describing their experience with management of postpartum depression. Research study involved more than 200 subjects and findings showed that intervention changed attitudes and helped adolescent depressed mothers to seek mental health and depression treatment.

This research was lead by M. Cynthia Logsdon, Ph.D., W.H.N.P.-B.C., University of Louisville School of Nursing professor who said,

Untreated postpartum depression hinders a mother’s relationship with her child, her functioning at work and school, mothering skills and development. The condition also can harm a baby’s development and attachment to the mother.

Reference: Logsdon, M. Cynthia, John Myers, Jeff Rushton, Jennifer L. Gregg, Allan M. Josephson, Deborah Winders Davis, Kyle Brothers, Kristin Baisch, Anissa Carabello, Krista Vogt, Kayla Jones, and Jennifer Angermeier. “Efficacy of an Internet-based Depression Intervention to Improve Rates of Treatment in Adolescent Mothers.” Archives of Womens Mental Health, 2017. doi:10.1007/s00737-017-0804-z.

Research funding: National Institute of Health.

Adapted from press release by the University of Louisville.

New target receptor for treating depression GPR158

Researchers from the Scripps Research Institute find a new target receptor called GPR158 for treating depression. Their research shows that individuals with high levels of above receptor may be more susceptible to depression following chronic stress.

“The next step in this process is to come up with a drug that can target this receptor,” says Kirill Martemyanov, Ph.D., co-chair of the TSRI Department of Neuroscience and senior author of the new study, which is published in the journal eLife.

“We need to know what is happening in the brain so that we can develop more efficient therapies,” says Cesare Orlandi, Ph.D., the senior research associate at TSRI and co-first author of the study.

The researchers found elevated GPR158 protein in depressed patients, suspected it could play a major role in the disease process. They then conducted an animal study using male and female mice with and without above receptor. Subsequent behavioral tests showed that mice with elevated levels of GPR158 showed signs of depression following chronic stress and suppressing GPR158 protected them from developing depressive behavior and also resilient to stress.

Next, the researchers examined why GPR158 has these effects on depression. The team demonstrated that GPR158 affects key signaling pathways involved in mood regulation in the region of the brain called prefrontal cortex, though the researchers emphasized that the exact mechanisms remain to be established.

Martemyanov explains that GPR158 is a so-called “orphan receptor” (which gets its name because its binding partner/partners are unknown) with a poorly understood biology and mechanism of action. GPR158 appears to work downstream from other important brain systems, such as the GABA, a major player in the brain’s inhibitory control and adrenergic system involved in stress effects.

Laurie Sutton, Ph.D., a research associate at TSRI and co-first author of the study, says this finding matches what doctors have noticed in people who have experienced chronic stress. “There’s always a small population that is resilient they don’t show the depressive phenotype,” says Sutton.

As the search goes on for additional targets for depression, Martemyanov says scientists are increasingly using new tools in genome analysis to identify orphan receptors like GPR158. “Those are the untapped biology of our genomes, with significant potential for development of innovative therapeutics,” he says.

Citation: Sutton, Laurie P., Cesare Orlandi, Chenghui Song, Won Chan Oh, Brian S. Muntean, Keqiang Xie, Alice Filippini, Xiangyang Xie, Rachel Satterfield, Jazmine D W Yaeger, Kenneth J. Renner, Samuel M. Young, Baoji Xu, Hyungbae Kwon, and Kirill A. Martemyanov. “Orphan receptor GPR158 controls stress-induced depression.” ELife 7 (2018). doi:10.7554/elife.33273.

Research funding: National Institutes of Health, University of Iowa, Max Planck Society, Canadian Institutes of Health Research Fellowship.

Adapted from press release by the Scripps Research Institute.

Diets rich in fruits and vegetables associated with lower depression risk

People who eat vegetables, fruit and whole grains may have lower rates of depression over time, according to a preliminary study that will be presented at the American Academy of Neurology’s 70th Annual Meeting.

Research found that people whose diets adhered more closely to the Dietary Approaches to Stop Hypertension (DASH) diet were less likely to develop depression than people who did not. DASH diet consists of fruit, vegetables, whole grains and fat-free or low fat dairy products. This diet limits intake of foods that contain sugar and saturated fats. Previous research have shown health benefits such as lowering high blood pressure and bad cholesterol (LDL), along with lowering body weight.

“Depression is common in older adults and more frequent in people with memory problems, vascular risk factors such as high blood pressure or high cholesterol, or people who have had a stroke,” said study author Laurel Cherian, MD, of Rush University Medical Center in Chicago and a member of the American Academy of Neurology. “Making a lifestyle change such as changing your diet is often preferred over taking medications, so we wanted to see if diet could be an effective way to reduce the risk of depression.”

For the study, 964 participants with an average age of 81 were evaluated yearly for an average of six-and-a-half years. They were monitored for symptoms of depression and also filled out questionnaires about how often they ate various foods, and the researchers looked at how closely the participants’ diets followed diets such as the Dietary Approaches to Stop Hypertension (DASH) diet, Mediterranean diet and the traditional Western diet.

Participants were divided into three groups based on how closely they adhered to the diets. People in the two groups that followed the Dietary Approaches to Stop Hypertension (DASH) diet most closely were less likely to develop depression than people in the group that did not follow the diet closely.  On the other hand, the more closely people followed a Western diet, a diet that is high in saturated fats and red meats and low in fruits and vegetables the more likely they were to develop depression.

Cherian noted that the study does not prove that the Dietary Approaches to Stop Hypertension (DASH) diet leads to a reduced risk of depression; it only shows an association.

“Future studies are now needed to confirm these results and to determine the best nutritional components of the Dietary Approaches to Stop Hypertension (DASH) diet to prevent depression later in life and to best help people keep their brains healthy,” said Cherian.

Adapted from press release by the American Academy of Neurology.

People with depression found to have low arginine levels

Researchers from the University of Eastern Finland have shown that people suffering from major depressive disorder have reduced arginine levels. One of the role of arginine in body is to produce nitric oxide, which in turn have role in vascular regulation and is a nervous system and immune defence mediator. The global arginine bioavailability ratio (GABR) is an indicator of the body’s arginine levels, and the ratio has previously been used to measure the body’s capacity to produce nitric oxide. Previous research shows that educed arginine bioavailability is also known to be an independent risk factor of cardiovascular diseases.

Current research published in Journal of Affective Disorders shows that people suffering from major depressive disorders have reduced arginine bioavailability.

“It is possible that depression-induced inflammatory responses lead to reduced arginine levels. This may result in insufficient production of nitric oxide for the needs of the nervous system and circulation. However, we don’t know yet what exactly causes reduced arginine bioavailability in people with depression,” says Doctoral Student Toni Ali-Sisto, the lead author of the study.

The study carried out by the University of Eastern Finland and Kuopio University Hospital involved 99 adults with diagnosed major depressive disorder and 253 non-depressed controls. The concentrations of three amino acids, namely arginine, citrulline and ornithine, were analysed from their fasting glucose samples, and this data was used to calculate their GABRs. Symmetric and asymmetric dimethylarginine concentrations were also measured, as they both play a role in the production of nitric oxide. The findings were then compared between the depressed and the non-depressed controls. The study also analysed whether these concentrations changed in people with depression during a follow-up of eight months, and whether remission of depression had an effect on the concentrations.

“Although our study shows that people with depression have reduced arginine bioavailability, this doesn’t mean that taking an arginine supplement would protect against depression. That’s an area for further research,” Ali-Sisto says.

People with depression had weaker arginine bioavailability than their non-depressed controls. The study did not find significant differences in the symmetric and asymmetric dimethylarginine concentrations. The use of anti-depressants or anti-psychotics did not affect the concentrations, either.

Contrary to the researchers’ expectations, there were no clear differences in the concentrations measured from people who had recovered from depression and people who remained depressed.

“Arginine bioavailability was slightly higher in people who had recovered from depression than in people who remained depressed. However, a more extensive set of data and a longer follow-up period are necessary for estimating arginine’s role in depression recovery.”

Citation: Ali-Sisto, Toni, Tommi Tolmunen, Heimo Viinamäki, Pekka Mäntyselkä, Minna Valkonen-Korhonen, Heli Koivumaa-Honkanen, Kirsi Honkalampi, Anu Ruusunen, Jatin Nandania, Vidya Velagapudi, and Soili M. Lehto. “Global arginine bioavailability ratio is decreased in patients with major depressive disorder.” Journal of Affective Disorders 229 (2018): 145-51. doi:10.1016/j.jad.2017.12.030.

Adapted from press release by the University of Finland.

Role of diet and gut microbiome in the major depressive disorder

An international group of researchers headed by André Carvalho has published in Psychotherapy and Psychosomatic a paper that provides new data and prospects for the links between the intestinal flora and several disorders, notably depression.

Persistent low-grade immune-inflammatory processes, oxidative and nitrosative stress and hypothalamic-pituitary-adrenal axis activation are integral to the pathophysiology of the major depressive disorder. The microbiome, intestinal compositional changes, and resultant bacterial translocation add a new element to the bidirectional interactions of the gut-brain axis. New evidence implicates these pathways in the onset of the major depressive disorder. In addition, abnormalities in the gut-brain axis are associated with several chronic non-communicable disorders, which frequently co-occur in individuals with depression, including but not limited to irritable bowel syndrome, chronic fatigue syndrome, obesity, and type 2 diabetes mellitus.

The composition of the gut microbiota is influenced by several genetic and environmental factors (e.g. diet). Several lines of evidence indicate that gut-microbiota-diet interactions play a significant pathophysiological role in depression and related medical comorbidities. Gut dysbiosis and the leaky gut may influence several pathways implicated in the biology of major depressive disorder, including but not limited to immune activation, oxidative and nitrosative stress, and neuroplasticity cascades. However, methodological inconsistencies and limitations limit comparisons across studies.

Authors conclude that intestinal dysbiosis and the leaky gut may constitute a key pathophysiological link between depression and its medical comorbidities. This emerging literature opens relevant preventative and therapeutic perspectives.

Citation: Slyepchenko, Anastasiya, Michael Maes, Felice N. Jacka, Cristiano A. Köhler, Tatiana Barichello, Roger S. Mcintyre, Michael Berk, Iria Grande, Jane A. Foster, Eduard Vieta, and André F. Carvalho. “Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities.” Psychotherapy and Psychosomatics 86, no. 1 (2016): 31-46. doi:10.1159/000448957.
Adapted from press release by Karger medical and scientific publishers.

Review of literature shows that Acupuncture improves medical treatment for depression and chronic pain

Health specialists at the University of York have found that acupuncture treatment can boost the effectiveness of standard medical care, lessening the severity of chronic pain and depression.

In a report published in the National Institute for Health Research (NIHR) Journals Library, the researchers showed that there is significant evidence to demonstrate that acupuncture provides more than a placebo effect.

Professor of Acupuncture Research, Hugh MacPherson, working with a team of scientists from the UK and US, brought together the results of 29 high-quality clinical trials focused on patients treated with acupuncture and standard medical care.

In the majority of these trials, patients with chronic pain treated with acupuncture and standard medical care were tested against those who were provided with standard medical care alone, such as anti-inflammatory drugs and physiotherapy. The trials involved approximately 18,000 patients diagnosed with chronic pain of the neck, lower back, head, and knee.

The report shows that the addition of acupuncture compared to standard medical care alone significantly reduced the number of headaches and migraine attacks and reduced the severity of neck and lower back pain. It also showed that acupuncture reduced the pain and disability of osteoarthritis, which led to patients being less reliant on anti-inflammatory tablets to control pain.

The study also concluded that acupuncture is cost-effective, with the value for money being rated as less than the threshold of £20,000 cost per quality of life year – a metric for cost-effectiveness used by the National Institute for Health and Care Excellence (NICE).

Professor MacPherson, from the University of York’s Department of Health Sciences, said: “There has been an increase in practitioners using acupuncture as an intervention. Approximately four million acupuncture treatments are provided a year in the UK, but the evidence to show how clinically effective this form of treatment is has been limited.

“There has been a question mark for many years over whether policy and decision makers should or should not provide wider access to acupuncture. Our aim was to bring together data from high-quality clinical trials and provide a robust evidence base that will help reduce this uncertainty and support commissioners and health professionals in making informed decisions backed up with research.”

The team also conducted a new clinical trial for depression, where acupuncture or counseling was provided and compared to the effectiveness of medication, such as antidepressants.

In a study of 755 patients with depression in the North of England, researchers showed that both acupuncture and counseling significantly reduced the severity of depressions and that these benefits were largely sustained for up to 12 months after treatment.

Professor MacPherson said: “The front-line treatment for depression in primary care usually involves antidepressants; however, they do not work well for more than half of patients.

“In the largest study of its kind, we have now provided a solid evidence base to show that not only can acupuncture and counseling bring patients out of an episode of depression, but it can keep the condition at bay for up to a year on average.”

The benefits of acupuncture are partially associated with placebo effects, which has contributed to the uncertainty around acupuncture’s clinical effectiveness. Professor MacPherson states, however, that this new research provides definitive evidence that when acupuncture is used to treat chronic pain, the reductions in pain are substantially more than those measured from sham (placebo) acupuncture.

Used only in clinical trials for research purposes, sham acupuncture involves inserting needles at the ‘wrong’ locations or using non-inserted needles (fake needles) at the correct locations. That ‘true’ acupuncture has significantly more effect in reducing pain than sham acupuncture, provides evidence that acupuncture is not simply a placebo effect.

Professor MacPherson added: “Our new data provides a significant step forward in treating chronic pain and managing depression because patients and health professionals can now make decisions on acupuncture with more confidence. Not only is it more cost effective, but it reduces pain levels and improves mood levels, which could reduce over-reliance on drugs that can sometimes result in unwanted side effects.”

Citation: MacPherson H, Vickers A, Bland M, Torgerson D, Corbett M, Spackman E, et al. Acupuncture for chronic pain and depression in primary care: a programme of research. Programme Grants Appl Res 2017;5(3)
DOI: 10.3310/pgfar05030
Adapted from press release by University of York.

Antidepressants use associated with birth defects

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

long term opioid addiction

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

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

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

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

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

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

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

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

Meditation helps fight major depressive disorder

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

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

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

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

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

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

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

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

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

Research categorizes depression in to 4 subtypes based on fMRI scans

Patients with depression can be categorized into four unique subtypes defined by distinct patterns of abnormal connectivity in the brain, according to new research from Weill Cornell Medicine.

In a collaborative study published in Nature Medicine, Dr. Conor Liston, an assistant professor of neuroscience in the Feil Family Brain and Mind Institute and an assistant professor of psychiatry at Weill Cornell Medicine, has identified biomarkers in depression by analyzing more than 1,100 functional magnetic resonance imaging (fMRI) brain scans of patients with clinical depression and of healthy controls, gathered from across the country. These biomarkers may help doctors to better diagnose depression subtypes and determine which patients would most likely benefit from a targeted neuro-stimulation therapy called transcranial magnetic stimulation that uses magnetic fields to create electrical impulses in the brain.

“The four subtypes of depression that we discovered vary in terms of their clinical symptoms but, more importantly, they differ in their responses to treatment,” Dr. Liston said. “We can now predict with high accuracy whether or not a patient will respond to transcranial magnetic stimulation therapy, which is significant because it takes five weeks to know if this type of treatment works.”

Approximately 10 percent of Americans are diagnosed with clinical depression each year, and it is by some estimates the leading cause of disability in many developed countries.

Historically, efforts to characterize depression involved looking at groups of symptoms that tend to co-occur and then testing neurophysiological links. And while past pioneering studies have defined different forms of depression, the association between the various types and the underlying biology has been inconsistent. Further, diagnostic biomarkers have yet to prove useful in distinguishing depressed patients from healthy controls or in reliably predicting treatment response among individuals.

Researchers from Weill Cornell Medicine and seven other institutions derived the biomarkers by assigning statistical weights to abnormal connections in the brain and then predicting the probability that they belonged to one subtype versus another. The study found that distinct patterns of abnormal functional connectivity in the brain differentiated the four biotypes and were linked with specific symptoms. For example, reduced connectivity in the part of the brain that regulates fear-related behavior and reappraisal of negative emotional stimuli was most severe in biotypes one and four, which exhibited increased anxiety.

Going forward, Dr. Liston will seek to replicate and confirm the results of this research and discover if it is broadly applicable to studying the biology of depression and other forms of mental illness.

“Subtyping is a major problem in psychiatry,” Dr. Liston said. “It’s not just an issue for depression, and it would be really valuable to have objective biological tests that can help diagnose subtypes of other mental illnesses, such as psychotic disorders, autism and substance abuse syndromes.”

Neuroimaging categorizes 4 depression subtypes