Critical receptor involved in response to antidepressants like ketamine

Effective treatment of clinical depression remains a major mental health issue, with roughly 30 percent of patients who do not respond to any of the available treatments. Researchers at the University of Maryland School of Medicine (UMSOM) have discovered a crucial receptor called mGlu2 that is critical to the mechanism of fast-acting antidepressants such as ketamine when used to treat depression.

This discovery into how this type of receptor in the brain works with fast-acting antidepressants is a critical discovery in treating depression, because existing treatments can take weeks before they are effective. A single dose of ketamine that is lower than the amount required to cause anesthesia within 24 hours can alleviates depression in some treatment-resistant patients.

Todd Gould, MD., Associate Professor in the Department of Psychiatry, together with researchers from the National Institutes of Health Intramural Research Program, discovered that this special type of glutamate receptor interacts with ketamine’s mechanism.

Full story at Science Daily

When neurons are out of shape, antidepressants may not work

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for major depressive disorder (MDD), yet scientists still do not understand why the treatment does not work in nearly thirty percent of patients with MDD. Now, Salk Institute researchers have discovered differences in growth patterns of neurons of SSRI-resistant patients. The work, published in Molecular Psychiatry on March 22, 2019, has implications for depression as well as other psychiatric conditions such as bipolar disorder and schizophrenia that likely also involve abnormalities of the serotonin system in the brain.

“With each new study, we move closer to a fuller understanding of the complex neural circuitry underlying neuropsychiatric diseases, including major depression,” says Salk Professor Rusty Gage, the study’s senior author, president of the Institute, and the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease. “This paper, along with another we recently published, not only provides insights into this common treatment, but also suggests that other drugs, such as serotonergic antagonists, could be additional options for some patients.”

Full story at Science Daily

When neurons get the blues

The most commonly prescribed antidepressants, selective serotonin reuptake inhibitors (SSRIs), lift the fog of depression for many people. But for around a third of people with major depressive disorder, SSRIs don’t make much of a difference. Now, researchers from the Salk Institute have pinned down a possible reason why — the neurons in at least some of these patients’ brains may become hyperactive in the presence of the drugs. The study appeared in Molecular Psychiatry on January 30, 2019.

“This is a promising step toward understanding why some patients don’t respond to SSRIs and letting us better personalize treatments for depression,” says Salk Professor Rusty Gage, the study’s senior author, president of the Institute, and the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease.

Depression affects 300 million people around the world, and more than 6 percent of the US population experiences an episode of major depressive disorder (MDD) in any given year. MDD has been linked to an imbalance in serotonin signaling, although the exact mechanism is not well understood.

Full story at Science Daily

PTSD symptoms improve when patient chooses form of treatment

A multiyear clinical trial comparing medication and mental health counseling in the treatment of post-traumatic stress disorder shows that patients who chose their form of treatment — whether drugs or therapy — improved more than those who were simply prescribed one or the other regardless of the patient’s preference.

The study, led by the University of Washington and Case Western Reserve University, was conducted at outpatient clinics in Seattle and Cleveland. It found that both a medication — Sertraline, marketed as Zoloft — and a specific form a therapy known as prolonged exposure were effective in reducing PTSD symptoms during the course of treatment, with improvements maintained at least two years later. But patients who received their choice between the two possible treatments showed greater reduction in symptoms, were more apt to stick to their treatment program and even lost their PTSD diagnosis over time.

The study, published Oct. 19 in the American Journal of Psychiatry, is the first large-scale trial of hundreds of PTSD patients, including veterans and survivors of sexual assault, to measure whether patient preference in the course of treatment impacts the effectiveness of a type of cognitive behavioral therapy and use of selective serotonin reuptake inhibitors, a type of antidepressant often prescribed for PTSD.

Full story at Science Daily

Intervention Shows Promise for Treating Depression in Preschool-Aged Children

Researchers funded by the National Institutes of Health have shown that a therapy-based treatment for disruptive behavioral disorders can be adapted and used as an effective treatment option for early childhood depression. Children as young as 3-years-old can be diagnosed with clinical depression, and although preschool-aged children are sometimes prescribed antidepressants, a psychotherapeutic intervention is greatly needed. The study, funded by the National Institute of Mental Health (NIMH), part of NIH, appears online June 20 in the American Journal of Psychiatry.

The researchers adapted Parent-Child Interaction Therapy (PCIT), which has been shown to be an effective way to treat disruptive behavioral disorders in young children. In standard PCIT treatment, parents are taught techniques for successfully interacting with their children. They then practice these techniques in controlled situations while being coached by a clinician.

Full story at NIMH

Postpartum depression risk, duration and recurrence

Postpartum affective disorder (AD), including postpartum depression (PPD), affects more than one in two hundred women with no history of prior psychiatric episodes, and raises the risk of later affective disorder for those women, according to a new study published in PLOS Medicine by Marie-Louise Rasmussen from Statens Serum Institut, Denmark, and colleagues.

PPD is estimated to affect more than 5 percent of all women following childbirth, making it the most common postnatal complication of childbearing. In the new study, researchers analyzed data from the Danish national registries on 457,317 women who had a first child (and subsequent births) between 1996 and 2013 and had no prior psychiatric hospital contacts or use of antidepressants. Postpartum AD was defined as an antidepressant prescription fill or hospital contact for depression within six months after birth.

Full story at Science Daily

Using antidepressants during pregnancy may affect your child’s mental health

The use of antidepressants has been on the rise for many years. Between 2 and 8% of pregnant women are on antidepressants. Now researchers from the National Centre for Register-based Research at Aarhus BSS show that there is an increased risk involved in using antidepressants during pregnancy.

The researchers, headed by Xiaoqin Liu, have applied register-based research to the study of 905,383 children born between 1998 and 2012 with the aim of exploring the possible adverse effects of the mother’s use of antidepressants during her pregnancy.

They found that out of the 905,383 children in total, 32,400 developed a psychiatric disorder later in life. Some of these children were born to mothers who were on antidepressants during their pregnancy, while other children had not been exposed to medication.

Full story at Science Daily

Novel mode of antidepressant action may help patients unresponsive to SSRIs

Antidepressants treat symptoms of depression by increasing levels of brain signaling molecules (neurotransmitters) such as serotonin, as with the most widely used type of antidepressant, selective serotonin reuptake inhibitors (SSRIs). However, many of the 350 million people worldwide thought to be affected with depression do not respond to SSRI treatment.

Now, researchers in the Department of Neuroscience and Cell Biology at Osaka University have found that an activator of the serotonin type 3 receptor (5HT3R) produces antidepressant effects in mice and increases nerve cell growth in the part of the brain responsible for memory and spatial navigation (the hippocampus). They also showed that it functions using a different mechanism than the commonly used SSRI fluoxetine, and therefore may be suitable for patients with depression who do not respond favorably to current medication.

Full story of antidepressant action helping patients to SSRIs at Science Daily

Antidepressants Induce Resilience and Reverse Susceptibility

When they work, antidepressant medications may take weeks or months to alleviate symptoms of depression. Progress in developing new and more effective antidepressant treatments has been limited, though a new study published in Biological Psychiatry offers new insights into how antidepressants work.

Using a mouse model of depression, researchers found that a therapeutic response to antidepressant medication may stem from changes in gene expression that induce resilience and reverse vulnerability to exhibiting depression-like responses to stress. The study, led by Dr. Eric Nestler of the Icahn School of Medicine at Mount Sinai in New York, teases apart the mechanisms of two different antidepressant drugs- the conventional tricyclic antidepressant imipramine and fast-acting ketamine.

Full story of antidepressants can induce resilience at Science Daily

Enzyme research provides a new picture of depression

Despite the fact that more than four percent of the world’s population suffer from depression, and even though approximately 1,500 individuals commit suicide each year in Sweden, the understanding of the pathophysiology of depression remains unclear and only a few new discoveries of mechanisms behind it have been made in recent years. New approved pharmacological interventions are mainly absent, despite intensive research on the subject.

Researchers at Karolinska Institutet have characterized the role of the enzyme CYP2C19 in depression and functional and morphological changes in the brain. The enzyme is responsible for the metabolism of many neuroactive compounds, including antidepressants, and is located in the fetal brain and adult liver.

Full story of enzyme research in depression at Science Daily