Tag Archives: #depression

Study Strengthens Argument Postpartum Depression Different To Major Depression (Psychiatry)

Women with postpartum depression experience smell differently to other women, a University of Otago study has found.

Mei Peng image
Dr Mei Peng. © University of Otago

Lead author Dr Mei Peng, of the Department of Food Science, says the findings add further evidence to the growing argument postpartum depression is different to major depression, and requires separate research and medical attention.

“Postpartum depression has been long regarded as a sub-category of major depressive disorder. This condition has a very poor diagnostic rate, with many women suffering from it without being properly diagnosed or treated.

“Recently, the scientific community has been questioning whether postpartum depression should be studied and treated separately from major depression following insights into the different effect each disorder has on neurobiology,” she says.

Pregnancy-related depression is very common, with 6–12 per cent of women being affected during pregnancy, and more than 20 per cent being affected after having a baby. Resolving the status of postpartum depression may have important implications for diagnosis, treatment, policy and research of the disorder.

“Our world-first study helps show the sensory symptoms related to postpartum depression are very different from those of major depression. Specifically, patients with postpartum depression show normal olfactory sensitivity whereas generic depressed patients would show substantially declined olfactory sensitivity.”

The multi-disciplinary study, published in Scientific Reports, assessed the olfactory abilities of 39 depressed mothers, who were pregnant and up to one-year post pregnancy, comparing them against a healthy cohort.

The researchers found no difference between the two groups in terms of their ability to detect smells, but postpartum depressed women experienced different intensity and hedonic perception of some smells.

“These findings imply that postpartum depression is associated with alterations in higher-order olfactory perception, but not early-processing of odours.”

The researchers are currently seeking funding to further study the effects of pregnancy on women’s long-term quality of life.

Publication details:

Olfactory shifts linked to postpartum depression
Mei Peng, Hazel Potterton, JoannaTing Wai Chu and PaulGlue
Scientific Reports

Provided by University of Otago

How Early-life Inflammation Induces Depression in Adolescence (Neuroscience)

Early-life inflammation, such as trauma and viral infections, strongly increases the risk of individual for depression in adulthood, however, the mechanisms are not clear yet.

A team led by Prof. ZHANG Zhi from Division of Life Sciences and Medicine of the University of Science and Technology of China (USTC) of Chinese Academy of Sciences (CAS), collaborating with Prof. XU Lin from CAS, revealed the mechanism by which early-life inflammation induces adolescent depression symptoms. This work has been published in Neuron on July 6th.

Clinically related studies have shown decreased anterior cingulate cortex (ACC) synaptic density and increased inflammation in the brain of depressed patients. Microglial cells are resident immune cells of the brain, and it transforms into reactive states in response to stress challenges. Under the pathological state, activated microglia are the commander of the inflammatory state of the brain tissue, which is closely related to the occurrence and development of depression.

In this work, researchers found that early-life inflammation would lead to the susceptibility of microglial in the ACC to random stress events during adolescent development, and microglia then overengulfed dendritic spines of neurons. This weakened the ability of ACC glutamatergic neuronal (ACCGlu) to fight stress, thus inducing adolescent depression.

To explore the responding and activating model of ACC microglia to stress during mouse development from childhood to adolescence (45 days after birth), researchers established inflammatory model by intraperitoneal administration of lipopolysaccharide (LPS) during the critical time window of mouse brain development (14 days after birth). 6 hours after LPS injection, multiple activation indexes of ACC microglia in mice significantly increased and recovered after 24 hours. Interestingly, during the later development, a series of unpredictable life stress events (such as weaning, caging, noise and fighting) could lead to the re-activation of ACC microglia in LPS mice, being more susceptible than normal mice.

Moreover, before stress, the sharply increase of ACCGlu activity helped mice resist the attack of stress and protect themselves. However, ACC microglia of mice with early-life inflammation were frequently activated by persistent stress in adolescence, and overengulfed the ACCGlu dendritic spines via CX3CR1 signals mediate, consequently reducing the activity of ACCGlu. As a result the body’s ability to cope with stress was impaired, which promoted depression in adolescent mice.

The study, “Early-life inflammation promotes depressive symptoms in adolescence via microglial engulfment of dendritic spines”, Neuron, 2021. DOI: https://doi.org/10.1016/j.neuron.2021.06.012

Featured image: Scheme of how early-life inflammation promotes depressive symptoms in adolescent mice. © CAO Peng et al.

Provided by USTC

Tetanus Toxin Fragment May Treat Depression, Parkinson’s Disease and ALS (Neuroscience)

Depression has been treated traditionally with inhibitors of serotonin reuptake in the central nervous system. These drugs do not come without side effects, such as lack of immediate therapeutic action, the need for daily doses and the danger of becoming addicted to some of these drugs. That is why scientists continue to work on new therapies to treat depression.

In 2019, an international group of researchers co-led by Dr Yousef Tizabe from the Howard University College of Medicine in Washington, D.C., and Professor José Aguilera from the Department of Biochemistry and Molecular Biology and the Institut de Neurociències at the Universitat Autònoma de Barcelona (UAB), observed that a non-toxic derivative of the tetanus neurotoxin (which causes tetanus infections) improved depression symptoms in rat animal models. “One intramuscular dosis of Hc-TeTx made depression symptoms disappear in less than 24 hours, and its effects lasted two weeks”, explains Aguilera. Based on these findings, scientists began to work on discovering the mechanism through which this substance produces these effects.

In a recent study coordinated by Professor Aguilera and conducted in collaboration with the research group led by Dr Thomas Scior of the Benemérita Universidad Autónoma de Puebla (BUAP) in Mexico, researchers demonstrated that Hc-TeTx is capable of inhibiting the transport of serotonin within the central nervous system, by binding to neurotrophin receptors, proteins that induce the survival of neurons. These results, published in the journal Molecules, suggest that the drug may not only serve in treating depression, but also be useful in treating neurodegenerative diseases, such as Parkinson’s disease or amyotrophic lateral sclerosis (ALS).

According to researchers, the advantages of introducing Hc-TeTx as a new drug are evident. A biweekly or monthly dosis would allow medical professionals to control the progress. Since it is a recombinant product, there would be no problems with drug safety, production or high costs. Furthermore, in neurodegenerative cases, Hc-TeTx would stop the development of the pathology and at the same time eliminate any disease-related depressions.

Researchers recently patented the therapeutic use of Hc-TeTx for the treatment of depression, Parkinson’s disease and amyotrophic lateral sclerosis, and are now looking for investors to be able to conduct clinical trials on humans. “This is an important advance in science, and even more so now when in addition to the high incidence in depression and alterations in behaviours, we see mental alterations as a result of COVID-19 and the negative environments of stress, self-isolation or fear”, Aguilera concludes.

Featured image: Mice neuromuscular junction in a tibialis anterior muscle slice. Microscope images obtained for the research. © UAB

Reference: Candalija, A.; Scior, T.; Rackwitz, H.-R.; Ruiz-Castelan, J.E.; Martinez-Laguna, Y.; Aguilera, J. Interaction between a Novel Oligopeptide Fragment of the Human Neurotrophin Receptor TrkB Ectodomain D5 and the C-Terminal Fragment of Tetanus Neurotoxin. Molecules 2021, 26, 3988. https://doi.org/10.3390/molecules26133988

Provided by UAB

Scientists Show How Light Therapy Treats Depression In Mice Model (Psychiatry)

Light activates the circadian clock gene Period1 in a brain region that affects the mood

Light therapy can help improve the mood of people with seasonal affective disorder (SAD) during short winter days, but exactly how this therapy works is not well understood. A new study by Urs Albrecht at the University of Fribourg, published July 8th in the journal PLOS Genetics, finds that light therapy’s beneficial effects come from activating the circadian clock gene Period1 in a part of the brain involved in mood and sleep-wake cycles.

Nighttime light has strong effects on the physiology and behavior of mammals. It can reset an animal’s circadian rhythms, and in the form of light therapy, affect mood in humans. Albrecht and his colleagues investigated how nighttime light impacts mood using mice as a model. They exposed mice to a pulse of light at different points during the night and then tested them for depressive behavior. The researchers discovered that light exposure at the end of the dark period–two hours before daytime–had an antidepressant effect on the animals. The pulse of light activated the Period1 gene in a brain region called the lateral habenula, which plays a role in mood. Light at other times, however, had no effect. When they deleted the Period1 gene, the mice no longer experienced the light’s beneficial effects.

The new results provide evidence that turning on Period1 in the lateral habenula is the key to light’s mood-boosting powers. The discovery that mice appeared to be less depressed when exposed to light at the end of the dark period than the beginning is similar to findings in humans. Light therapy is more efficient in the early morning than in the evening for patients with SAD. However, the researchers caution against making too many direct comparisons to humans since mice are nocturnal animals.

The researchers add, “Light perceived in the late part of the night induces expression of the clock gene Per1, which is related to improvement of depression like behavior in mice.”

In your coverage please use this URL to provide access to the freely available article in PLOS Geneticshttp://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009625

Funding: This work was supported by the Velux Foundation (https://veluxstiftung.ch) Projects 995 and 772 to U.A. and the Swiss National Science Foundation (http://www.snf.ch) project number 310030_184667/1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Featured image: Per1 gene expression (yellow color) before (left panel) and after a 15 minute light pulse (right panel) given in the dark at zeitgeber time 22 in the lateral habenula (area visualized by hatched lines). The blue color depicts cell nuclei. The white line bottom left indicates the scale and corresponds to 200 μm © Iwona Olejniczak, 2021, PLOS Genetics, CC-BY 4.0 (https://creativecommons.org/licenses/by/4.0/)

Reference: Olejniczak I, Ripperger JA, Sandrelli F, Schnell A, Mansencal-Strittmatter L, Wendrich K, et al. (2021) Light affects behavioral despair involving the clock gene Period 1. PLoS Genet 17(7): e1009625. https://doi.org/10.1371/journal.pgen.1009625

Provided by PLOS

Anti-inflammatory Effects Of Omega-3 Fatty Acids Could Help Reduce Depression (Psychiatry)

Omega-3 polyunsaturated fatty acids (PUFAs) are metabolised into molecules called lipid mediators and the levels of these in the blood are linked to an improvement in depressive symptoms

The omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in oily fish. Researchers from the National Institute of Health Research (NIHR) Maudsley Biomedical Research Centre assessed the effects of high doses of EPA and DHA in lab-grown neurones and then in patients to help clarify how they reduce inflammation and depression. This novel approach allowed the scientists to identify an important molecular mechanism which can help inform the development of potential new treatments involving omega-3 fatty acids for patients with depression.

Lead author Dr Alessandra Borsini, NIHR Maudsley BRC Senior Postdoctoral Neuroscientist at King’s College London, said: “Using a combination of laboratory and patient research our study has provided exciting new insight into how omega-3 fatty acids bring about anti-inflammatory effects that improve depression. For some time we have known that omega-3 PUFA can induce anti-depressant and anti-inflammatory effects but, without further understanding of how this happens in the human brain, it has been difficult to develop treatments. Our study has helped shine a light on the molecular mechanisms involved in this relationship which can inform the development of potential new treatments for depression using omega-3 PUFA.”

Previous research has shown that people with major depressive disorder have higher levels of inflammation in their bodies than those without the disorder. There are currently no proven anti-inflammatory treatment strategies for depression and, although two important omega-3 PUFAs, EPA and DHA, have been shown to provide anti-inflammatory and antidepressant effects, the precise mechanism by which they do this is unknown.

Depression in a dish

The study set out to test the theory that when omega-3 fatty acids are utilised and processed in the body, some of their metabolites (known as lipid mediators) are able to protect the brain from the harmful effects of inflammation. Researchers used a validated in vitro human cell model known as ‘depression in a dish’ that was developed at the NIHR Maudsley Biomedical Research Centre and which uses cells from the hippocampus, a part of the brain fundamental in many cognitive, memory and learning areas thought to be important in depression. Hippocampal cells play an important role in the production of new neurones – neurogenesis.

The study showed that treating human hippocampal cells with EPA or DHA before being exposed to chemical messengers involved in inflammation called cytokines, prevented increased cell death and decreased neurogenesis. Both these impacts had been previously observed in cells exposed to cytokines alone. Further investigation confirmed these effects were mediated by the formation of several key lipid mediators produced by EPA and DHA, namely hydroxyeicosapentaenoic acid (HEPE), hydroxydocosahexaenoic acid (HDHA), epoxyeicosatetraenoic acid (EpETE) and epoxydocosapentaenoic acid (EpDPA), and these were detected for the first time in human hippocampal neurones. Further investigation showed that treatment with an enzyme inhibitor increased the availability of two of these metabolites (EpETE and EpDPA) suggesting a possible way by which future treatments could be optimised.

Professor Anna Nicolaou, professor of Biological Chemistry at the Faculty of Medical and Human Sciences, The University of Manchester, who led the team that measured the lipid mediators using mass spectrometry said: “The lipid mediators that our research identified are broken down in the body relatively quickly, which means they may only be available for a relatively short time. By testing the effect of inhibitors of the enzymes involved in the metabolism of omega-3 PUFA we showed that we can greatly improve how long they can have an effect in the body and ultimately, increase their efficacy. This is very important for the development of new treatments and means that patients could be given higher doses of EPA and DHA together with these enzyme inhibitors to increase the amount of these important compounds in their blood over time.”

Omega-3 metabolites in patients

The study assessed twenty-two patients with major depression who were given either 3 grams of EPA or 1.4 grams of DHA daily for twelve weeks. The lipid metabolites of EPA and DHA were measured in their blood before and after the omega-3 PUFA treatment, along with a score of their depressive symptoms. In both groups of patients, EPA or DHA treatment was associated with an increase in their respective metabolites and a significant improvement in depressive symptoms – an average reduction in symptom scores of 64% and 71% in the EPA and DHA groups respectively. In addition, higher levels of the same metabolites identified in the in vitro experiments were correlated with lower levels of depressive symptoms.

The levels of EPA and DHA used in this study are concentrations that most likely cannot be achieved with dietary consumption of oily fish, a rich source of omega-3 PUFAs, but require therapeutic supplements.

Future Research

The results of the study indicate that the bioactive lipid mediators produced by the breakdown of EPA and DHA in the body could be targeted as a mechanism to reduce depression and inflammation but there is a need to ensure that their effects are prolonged in order for this approach to be successful. Previous research indicates a key enzyme in the omega-3 fatty acid metabolism could be a valid option for drug repurposing and could be used for other inflammation-associated brain disorders, including depression, where at least a sub-group of patients often have chronic levels of inflammation.

Senior author of the paper, Professor Carmine Pariante, NIHR Maudsley BRC Affective Disorders Interface with Medicine Theme Lead said: “There is ever growing interest in the links between the immune system, inflammation and depression but in order to develop new treatments in this area we need to better understand the mechanisms behind these relationships. Our study has provided important insight into how known anti-inflammatory compounds – the omega-3 PUFA – help reduce depression. By identifying and measuring the exact lipid mediators that are involved, identifying the enzyme that prolongs their effects and finding the same lipid mediators in depressed patients treated with omega-3 PUFA and demonstrating improvements in symptoms, we have provided vital information to help shape clinical trials for future therapeutic approaches with omega-3 fatty acids.

“It is important to highlight that our research has not shown that by simply increasing omega-3 fatty acids in our diets or through taking nutritional supplements we can reduce inflammation or depression. The mechanisms behind the associations between depression and omega-3 PUFA are complicated and require further research and clinical trials to fully understand how they work and inform future therapeutic approaches.”

The study was a collaboration between researchers from King’s College London, The University of Manchester and China Medical University.

The paper Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis was published today (Wednesday 16 June) in Molecular Psychiatry.

The paper will be available after the embargo lifts on: https://www.nature.com/articles/s41380-021-01160-8

Reference: Borsini, A., Nicolaou, A., Camacho-Muñoz, D. et al. Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis. Mol Psychiatry (2021). https://doi.org/10.1038/s41380-021-01160-8

Provided by Kings College London

UIC Research Identifies Potential Pathways To Treating Alcohol Use Disorder, Depression (Psychiatry)

A discovery from researchers at the University of Illinois Chicago may lead to new treatments for individuals who suffer from alcohol use disorder and depression. 

The study, “Transcriptomics identifies STAT3 as a key regulator of hippocampal gene expression and anhedonia during withdrawal from chronic alcohol exposure,” is published in the journal Translational Psychiatry by researchers at UIC’s Center for Alcohol Research in Epigenetics. 

Amy Lasek
Amy Lasek, associate professor of psychiatry and anatomy and cell biology at the UIC College of Medicine. © UIC

“During withdrawal from long-term alcohol use, people often suffer from depression, which may cause them to start drinking again as a way to self-medicate. If we can treat that aspect, we hope we can prevent people from relapsing,” said Amy Lasek, UIC associate professor of psychiatry and anatomy and cell biology at the College of Medicine, and an author of the study. 

Withdrawal from chronic alcohol drinking can often result in depression. For this study, researchers removed postmortem hippocampus samples of rats in alcohol withdrawal. The hippocampus is a brain region that plays a role in depression and cognitive function. Researchers conducted RNA sequencing of all the RNA transcripts in the hippocampus and looked for those that were changed during withdrawal from alcohol. 

One of the RNA transcripts that was changed makes a protein called STAT3. STAT3 is a transcription factor that controls the expression of many different genes, including immune response genes. Notably, several known STAT3-regulated genes were also increased in the hippocampus during withdrawal from alcohol, indicating that STAT3 might be a “master regulator” of several genes in the hippocampus during withdrawal.  

The rats were treated during withdrawal with a compound that blocks STAT3 activity. The rats’ withdrawal-induced anhedonia, or inability to feel pleasure, was alleviated. 

Additionally, researchers looked at the same genes in human postmortem hippocampus samples of individuals who had a medical diagnosis of alcohol use disorder, alcoholism. They found that STAT3 and its target genes were elevated in the postmortem hippocampus of human subjects who died without alcohol in their systems — in withdrawal or abstinent from alcohol — when compared to samples from control subjects who did not have alcohol use disorder. These results were strikingly similar to the results found in the rat study.  

“The human and rat studies are similar, which might mean that our rat results can potentially be applied to humans. We haven’t done any treatments of people with alcohol use disorder, but we can see from the rat data that if we block STAT3 during withdrawal we can alleviate depression,” Lasek said. 

Some genes regulated by STAT3 are involved in the innate immune response in the brain. There is a known connection between hyperactive immune response and major depressive disorder, Lasek said. 

“We know that chronic alcohol use can induce an immune response in the brain. By inhibiting STAT3, we think that we are dampening that hyperactive immune response by blocking the ability of STAT3 to increase the expression of these immune-response genes during withdrawal, Lasek said.  

Lasek said inflammation in the brain is currently a hot research topic and further research may determine if dampening the brain’s inflammatory response could treat psychiatric disorders.

Antidepressants currently available are not effective in reducing alcohol drinking. And other drugs available to treat alcohol use disorder are not universally effective. Further study for a better understanding of how STAT3 works could hopefully lead to more effective interventions for alcohol use disorder and related depression, Lasek said. 

In addition to Lasek, the paper’s authors are Hu Chen, Kana Hamada, Eleonora Gatta, Ying Chen, Huaibo Zhang, Jenny Drnevich, Harish Krishnan, Mark Maienschein-Cline, Dennis Grayson, and Subhash Pandey, all of UIC, and Wei-Yang Chen of the University of Washington, Seattle. 

This work was funded by grants from the National Institute on Alcohol Abuse and Alcoholism (P50 AA022538 to A.W.L., S.C.P., and D.R.G.; U01 AA020912 to A. W.L.; and T32 AA026577 to K.H.) and the National Center for Advancing Translational Science (UL1 TR002003 to M.M.C.). S.C.P. is also supported by the senior research career scientist award from the Department of Veterans Affairs.  

Provided by UIC

Low Doses Of “Laughing Gas” Could Be Fast Acting, Highly Effective Treatment For Severe Depression (Psychiatry)

A new study at the University of Chicago Medicine and Washington University found that a single inhalation session with 25% nitrous oxide gas was nearly as effective as 50% nitrous oxide at rapidly relieving symptoms of treatment-resistant depression, with fewer adverse side effects. The study, published June 9 in Science Translational Medicine, also found that the effects lasted much longer than previously suspected, with some participants experiencing improvements for upwards of two weeks.

These results bolster the evidence that non-traditional treatments may be a viable option for patients whose depression is not responsive to typical antidepressant medications. It may also provide a rapidly effective treatment option for patients in crisis.

Often called “laughing gas,” nitrous oxide is frequently used as an anesthetic that provides short-term pain relief in dentistry and surgery.

In a prior study, the investigators tested the effects of a one-hour inhalation session with 50% nitrous oxide gas in 20 patients, finding that it led to rapid improvements in patient’s depressive symptoms that lasted for at least 24 hours when compared to placebo. However, several patients experienced negative side effects, including nausea, vomiting and headaches.

“This investigation was motivated by observations from research on ketamine and depression,” said Peter Nagele, MD, Chair of Anesthesia and Critical Care at UChicago Medicine. “Like nitrous oxide, ketamine is an anesthetic, and there has been promising work using ketamine at a sub-anesthetic dose for treating depression. We wondered if our past concentration of 50% had been too high. Maybe by lowering the dose, we could find the ‘Goldilocks spot’ that would maximize clinical benefit and minimize negative side effects.”

In the new study, the investigators repeated a similar protocol with 20 patients, this time adding an additional inhalation session with 25% nitrous oxide. They found that even with only half the concentration of nitrous oxide, the treatment was nearly as effective as 50% nitrous oxide, but this time with just one quarter of the negative side effects.

Furthermore, the investigators looked at patients’ clinical depression scores after treatment over a longer time course; while the last study only evaluated depression symptoms up to 24 hours after treatment, this new study conducted additional evaluations over two weeks. To their surprise, after just a single administration, some patients’ improvements in their depression symptoms lasted for the entire evaluation period.

“The reduction in side effects was unexpected and quite drastic, but even more excitingly, the effects after a single administration lasted for a whole two weeks,” said Nagele. “This has never been shown before. It’s a very cool finding.”

These results indicate promise for nitrous oxide as a rapid and effective treatment for those suffering from severe depression that fails to respond to other treatments, such as SSRIs, a common type of antidepressant medication.

“A significant percentage — we think around 15% — of people who suffer from depression don’t respond to standard antidepressant treatment,” said Charles Conway, MD, Professor of Psychiatry and Director of the Treatment Resistant Depression and Neurostimulation Clinic at Washington University School of Medicine. “These ‘treatment-resistant depression’ patients often suffer for years, even decades, with life-debilitating depression. We don’t really know why standard treatments don’t work for them, though we suspect that they may have different brain network disruptions than non-resistant depressed patients. Identifying novel treatments, such as nitrous oxide, that target alternative pathways is critical to treating these individuals.”

Despite its “laughing gas” reputation, patients who receive such a low dosage actually fall asleep.

“They’re not getting high or euphoric, they get sedated,” Nagele said.

While it remains challenging to get non-traditional treatments for depression accepted in the mainstream, researchers hope that these results, and other similar studies, will open the minds of reluctant physicians toward the unique properties of these drugs.

“These have just been pilot studies,” said Nagele. “But we need acceptance by the larger medical community for this to become a treatment that’s actually available to patients in the real world. Most psychiatrists are not familiar with nitrous oxide or how to administer it, so we’ll have to show the community how to deliver this treatment safely and effectively. I think there will be a lot of interest in getting this into clinical practice.”

With broader public acceptance, Nagele hopes that these results can open doors for those patients who are struggling to find adequate therapies for their depression.

“There is a huge unmet need,” he said. “There are millions of depressed patients who don’t have good treatment options, especially those who are dealing with suicidality. If we develop effective, rapid treatments that can really help someone navigate their suicidal thinking and come out on the other side — that’s a very gratifying line of research.”

The study, “A Phase 2 Trial of Inhaled Nitrous Oxide for Treatment-Resistant Major Depression,” was supported by and Independent NARSAD Investigator Grant from the Brain and Behavior Research Foundation. Additional authors include Frank Brown, Nisha Jain, and Robert Gibbons of UChicago and Ben J. Palanca, Britt Gott, Linda Barnes, Thomas Nguyen, Willa Xiong, Naji C. Salloum, Gemma D. Espejo, Christina N. Lessov-Schlagger, Wayland W.L. Cheng, Helga Komen, Branden Yee, Jacob D. Bolzenius, Alvin Janski and Charles F. Zorumski of Washington University School of Medicine.

Provided by University of Chicago Medicine

Want To Reduce Your Depression Risk? Wake Up An Hour Earlier (Psychiatry)

Waking up just one hour earlier could reduce a person’s risk of major depression by 23%, suggests a sweeping new genetic study published May 26 in the journal JAMA Psychiatry.

The study of 840,000 people, by researchers at University of Colorado Boulder and the Broad Institute of MIT and Harvard, represents some of the strongest evidence yet that chronotype—a person’s propensity to sleep at a certain time —influences depression risk.

It’s also among the first studies to quantify just how much, or little, change is required to influence mental health.

As people emerge, post-pandemic, from working and attending school remotely— a trend that has led many to shift to a later sleep schedule—the findings have important implications.

“We have known for some time that there is a relationship between sleep timing and mood, but a question we often hear from clinicians is: How much earlier do we need to shift people to see a benefit?” said senior author Celine Vetter, assistant professor of integrative physiology at CU Boulder. “We found that even one-hour earlier sleep timing is associated with significantly lower risk of depression.”

Previous observational studies have shown that night owls are as much as twice as likely to suffer from depression as early risers, regardless of how long they sleep. But because mood disorders themselves can disrupt sleep patterns, researchers have had a hard time deciphering what causes what.

Other studies have had small sample sizes, relied on questionnaires from a single time point, or didn’t account for environmental factors which can influence both sleep timing and mood, potentially confounding results.

In 2018, Vetter published a large, long term study of 32,000 nurses showing that “early risers” were up to 27% less likely to develop depression over the course of four years, but that begged the question: What does it mean to be an early riser?

How your genes influence when you wake up

To get a clearer sense of whether shifting sleep time earlier is truly protective, and how much shift is required, lead author Iyas Daghlas turned to data from the DNA testing company 23 and Me and the biomedical database UK Biobank. Daghlas then used a method called “Mendelian randomization” that leverages genetic associations to help decipher cause and effect.

“Our genetics are set at birth so some of the biases that affect other kinds of epidemiological research tend not to affect genetic studies,” said Daghlas, who graduated in May from Harvard Medical School.

More than 340 common genetic variants, including variants in the so-called “clock gene” PER2, are known to influence a person’s chronotype, and genetics collectively explains 12-42% of our sleep timing preference.

The researchers assessed deidentified genetic data on these variants from up to 850,000 individuals, including data from 85,000 who had worn wearable sleep trackers for 7 days and 250,000 who had filled out sleep-preference questionnaires. This gave them a more granular picture, down to the hour, of how variants in genes influence when we sleep and wake up.

In the largest of these samples, about a third of surveyed subjects self-identified as morning larks, 9% were night owls and the rest were in the middle. Overall, the average sleep mid-point was 3 a.m., meaning they went to bed at 11 p.m. and got up at 6 a.m.

With this information in hand, the researchers turned to a different sample which included genetic information along with anonymized medical and prescription records and surveys about diagnoses of major depressive disorder.

Using novel statistical techniques, they asked: Do those with genetic variants which predispose them to be early risers also have lower risk of depression?

The answer is a firm yes.

Each one-hour earlier sleep midpoint (halfway between bedtime and wake time) corresponded with a 23% lower risk of major depressive disorder.

Put another way, if someone who normally goes to bed at 1 a.m. goes to bed at midnight instead and sleeps the same duration, they could cut their risk by 23%; if they go to bed at 11 p.m., they could cut it by about 40%.

It’s unclear from the study whether those who are already early risers could benefit from getting up even earlier. But for those in the intermediate range or evening range, shifting to an earlier bedtime would likely be helpful.

Light days, dark nights key

What could explain this effect?

Some research suggests that getting greater light exposure during the day, which early-risers tend to get, results in a cascade of hormonal impacts that can influence mood.

Others note that having a biological clock, or circadian rhythm, that trends differently than most peoples’ can in itself be depressing.

“We live in a society that is designed for morning people, and evening people often feel as if they are in a constant state of misalignment with that societal clock,” said Daghlas.

He stresses that a large randomized clinical trial is necessary to determine definitively whether going to bed early can reduce depression. “But this study definitely shifts the weight of evidence toward supporting a causal effect of sleep timing on depression.”

For those wanting to shift themselves to an earlier sleep schedule, Vetter offers this advice:

“Keep your days bright and your nights dark,” she says. “Have your morning coffee on the porch. Walk or ride your bike to work if you can, and dim those electronics in the evening.”

Reference: Daghlas I, Lane JM, Saxena R, Vetter C. Genetically Proxied Diurnal Preference, Sleep Timing, and Risk of Major Depressive Disorder. JAMA Psychiatry. 2021 May 26. doi: 10.1001/jamapsychiatry.2021.0959. Epub ahead of print. PMID: 34037671.

Provided by University of Colorado Boulder

Combination of Psychotherapy and Pharmacotherapy More Effective in Treating Depression (Psychiatry)

Psychologic treatment of depression compared with pharmacotherapy and combined treatment in primary care: A network meta-analysis

Most patients with depression are treated in primary care, however, relatively few clinical trials for treating depression have focused on primary care. Researchers at the Vrije University Amsterdam examined the effects of the two major approaches to treating depression: psychotherapy and pharmacotherapy, as well as combined treatment and care-as-usual. The study integrated the results of 58 randomized controlled trials with a total of 9,301 patients. Results concluded that both psychotherapy and pharmacotherapy were significantly more effective than care-as-usual or waitlist control. However, they found no significant difference between psychotherapy and pharmacotherapy as stand-alone treatments. Combined treatment, particularly in studies that included cognitive behavioral therapy, was better than either pharmacotherapy or psychotherapy alone. Treatment in primary care should be organized to accommodate any of these treatments in response to patients’ preferences and values, the authors write.

Reference: Pim Cuijpers, Matthijs Oud, Eirini Karyotaki, Hisashi Noma, Soledad Quero, Andrea Cipriani, Bruce Arroll and Toshi A. Furukawa, “Psychologic Treatment of Depression Compared With Pharmacotherapy and Combined Treatment in Primary Care: A Network Meta-Analysis”, The Annals of Family Medicine May 2021, 19 (3) 262-270; DOI: https://doi.org/10.1370/afm.2676 https://www.annfammed.org/content/19/3/262

Provided by American Academy of Family Physicians