Is this peptide a key to happiness?

What makes us happy? Family? Money? Love? How about a peptide?

The neurochemical changes underlying human emotions and social behavior are largely unknown. Now though, for the first time in humans, scientists at UCLA have measured the release of a specific peptide, a neurotransmitter called hypocretin, that greatly increased when subjects were happy but decreased when they were sad.

The finding suggests that boosting hypocretin could elevate both mood and alertness in humans, thus laying the foundation for possible future treatments of psychiatric disorders like depression by targeting measureable abnormalities in brain chemistry.

In addition, the study measured for the first time the release of another peptide, this one called melanin concentrating hormone, or MCH. Researchers found that its release was minimal in waking but greatly increased during sleep, suggesting a key role for this peptide in making humans sleepy.

The study is published in the March 5 online edition of the journal Nature Communications.

"The current findings explain the sleepiness of narcolepsy, as well as the depression that frequently accompanies this disorder," said senior author Jerome Siegel, a professor of psychiatry and director of the Center for Sleep Research at UCLA’s Semel Institute for Neuroscience and Human Behavior. "The findings also suggest that hypocretin deficiency may underlie depression from other causes."

(Image: ALAMY)

Memory Strategy May Help Depressed People Remember the Good Times

New research highlights a memory strategy that may help people who suffer from depression in recalling positive day-to-day experiences. The study is published in Clinical Psychological Science, a journal of the Association for Psychological Science.

Previous research has shown that being able to call up concrete, detailed memories that are positive or self-affirming can help to boost positive mood for people with a history of depression. But it’s this kind of vivid memory for everyday events that seems to be dampened for people who suffer from depression.

Researcher Tim Dalgleish of the Medical Research Council Cognition and Brain Sciences Unit and colleagues hypothesized that a well-known method used to enhance memory — known as the “method-of-loci” strategy — might help depressed patients to recall positive memories with greater ease.

The method-of-loci strategy consists of associating vivid memories with physical objects or locations — buildings you see on your commute to work every day, for instance. To recall the memories, all you have to do is imagine going through your commute.

In the study, depressed patients were asked to come up with 15 positive memories. One group was asked to use the method-of-loci strategy to create associations with their memories, while a control group was asked to use a simple “rehearsal” strategy, grouping memories based on their similarities.

After practicing their techniques, the participants were asked to recall as many of their 15 positive memories as they could.

The two methods were equally effective on the initial memory test conducted in the lab — both groups were able to recall nearly all of the 15 memories.

But the strategies were not equally effective over time.

After a week’s worth of practice at home, the participants received a surprise phone call from the researchers, who asked them to recall the memories one more time.

Participants who used the method-of-loci technique were significantly better at recalling their positive memories when compared to those who used the rehearsal technique.

These data suggest that using the method-of-loci technique to associate vivid, positive memories with physical objects or locations may make it easier for depressed individuals to recall those positive memories, which may help to elevate their mood in the long-term.

This Robotic Mouse Was Designed to Stress Out Real Mice

Lab rats have a new companion, but it’s not friendly. Researchers at Waseda University in Tokyo, Japan, have developed a robotic rat called WR-3 whose job is to induce stress and depression in lab animals, creating models of psychological conditions on which new drugs can be tested.

Animal are used throughout medicine as models to test treatments for human conditions, including mental disorders like depression. Rats and mice get their sense of smell severed to induce something like depression, or are forced to swim for long periods, for instance. Other methods rely on genetic modification and environmental stress, but none is entirely satisfactory in recreating a human-like version of depression for treatment. Hiroyuki Ishii and his team aim to do better with WR-3.

The researchers tested WR-3’s ability to depress two groups of 12 rats, measured by the somewhat crude assumption that a depressed rat moves around less. Rats in group A were constantly harassed by their robot counterpart, while the other rats were attacked intermittently and automatically by WR-3, whenever they moved. Ishii’s team found that the deepest depression was triggered by intermittent attacks on a mature rat that had been constantly harassed in its youth.

The team say they plan to test their new model of depression against more conventional systems, like forced swimming.

The robot has been developed just as new research by Junhee Seok of Stanford University in Palo Alto, California, and colleagues shows that the use of mouse models for human conditions has led researchers trying to find treatments for sepsis, burns and trauma astray at a cost of billions of tax dollars.

Hopkins Researchers Uncover Key to Antidepressant Response

Through a series of investigations in mice and humans, Johns Hopkins researchers have identified a protein that appears to be the target of both antidepressant drugs and electroconvulsive therapy. Results of their experiments explain how these therapies likely work to relieve depression by stimulating stem cells in the brain to grow and mature. In addition, the researchers say, these experiments raise the possibility of predicting individual people’s response to depression therapy, and fine-tuning treatment accordingly. Reports on separate aspects of the research were published in December on the Molecular Psychiatry website, and will also appear in the Feb. 7 issue of Cell Stem Cell.

Imaging Biomarker Predicts Response to Rapid Antidepressant

A telltale boost of activity at the back of the brain while processing emotional information predicted whether depressed patients would respond to an experimental rapid-acting antidepressant, a National Institutes of Health study has found.

“We have discovered a potential neuroimaging biomarker that may eventually help to personalize treatment selection by revealing brain-based differences between patients,” explained Maura Furey, Ph.D., of NIH’s National Institute of Mental Health (NIMH).

Furey, NIMH’s Carlos Zarate, M.D., and colleagues, reported on their functional magnetic resonance imaging (fMRI) study of a pre-treatment biomarker for the antidepressant response to scopolamine, Jan. 30, 2013, online in JAMA Psychiatry.

Scopolamine, better known as a treatment for motion sickness, has been under study since Furey and colleagues discovered its fast-acting antidepressant properties in 2006. Unlike ketamine, scopolamine works through the brain’s acetylcholine chemical messenger system. The NIMH team’s research has demonstrated that by blocking receptors for acetylcholine on neurons, scopolamine can lift depression in many patients within a few days; conventional antidepressants typically take weeks to work. But not all patients respond, spurring interest in a predictive biomarker.

The acetylcholine system plays a pivotal role in working memory, holding information in mind temporarily, but appears to act by influencing the processing of information rather than through memory. Imaging studies suggest that visual working memory performance can be enhanced by modulating acetylcholine-induced activity in the brain’s visual processing area, called the visual cortex, when processing information that is important to the task. Since working memory performance can predict response to conventional antidepressants and ketamine, Furey and colleagues turned to a working memory task and imaging visual cortex activity as potential tools to identify a biomarker for scopolamine response.

Depressed patients have a well-known tendency to process and remember negative emotional information. The researchers propose that this bias stems from dysregulated acetylcholine systems in some patients. They reasoned that such patients would show aberrant visual cortex activity in response to negative emotional features of a working memory task. They also expected to find that patients with more dysfunctional acetylcholine systems would respond better to scopolamine treatment.

Frontiers publishes systematic review on the effects of yoga on major psychiatric disorders

Yoga has positive effects on mild depression and sleep complaints, even in the absence of drug treatments, and improves symptoms associated with schizophrenia and ADHD in patients on medication, according to a systematic review of the exercise on major clinical psychiatric disorders.

Published in the open-access journal, Frontiers in Psychiatry, on January 25th, 2013, the review of more than one hundred studies focusing on 16 high-quality controlled studies looked at the effects of yoga on depression, schizophrenia, ADHD, sleep complaints, eating disorders and cognition problems.

(Image: Corbis)

Astrocytes Identified as Target for New Depression Therapy

Neuroscience researchers from Tufts University have found that our star-shaped brain cells, called astrocytes, may be responsible for the rapid improvement in mood in depressed patients after acute sleep deprivation. This in vivo study, published in the current issue of Translational Psychiatry, identified how astrocytes regulate a neurotransmitter involved in sleep. The researchers report that the findings may help lead to the development of effective and fast-acting drugs to treat depression, particularly in psychiatric emergencies.

Drugs are widely used to treat depression, but often take weeks to work effectively. Sleep deprivation, however, has been shown to be effective immediately in approximately 60% of patients with major depressive disorders. Although widely-recognized as helpful, it is not always ideal because it can be uncomfortable for patients, and the effects are not long-lasting.

During the 1970s, research verified the effectiveness of acute sleep deprivation for treating depression, particularly deprivation of rapid eye movement sleep, but the underlying brain mechanisms were not known.

Most of what we understand of the brain has come from research on neurons, but another type of largely-ignored cell, called glia, are their partners. Although historically thought of as a support cell for neurons, the Phil Haydon group at Tufts University School of Medicine has shown in animal models that a type of glia, called astrocytes, affect behavior.  

Haydon’s team had established previously that astrocytes regulate responses to sleep deprivation by releasing neurotransmitters that regulate neurons. This regulation of neuronal activity affects the sleep-wake cycle. Specifically, astrocytes act on adenosine receptors on neurons. Adenosine is a chemical known to have sleep-inducing effects.

During our waking hours, adenosine accumulates and increases the urge to sleep, known as sleep pressure. Chemicals, such as caffeine, are adenosine receptor antagonists and promote wakefulness. In contrast, an adenosine receptor agonist creates sleepiness.

“In this study, we administered three doses of an adenosine receptor agonist to mice over the course of a night that caused the equivalent of sleep deprivation. The mice slept as normal, but the sleep did not reduce adenosine levels sufficiently, mimicking the effects of sleep deprivation. After only 12 hours, we observed that mice had decreased depressive-like symptoms and increased levels of adenosine in the brain, and these results were sustained for 48 hours,” said first author Dustin Hines, Ph.D., a post-doctoral fellow in the department of neuroscience at Tufts University School of Medicine (TUSM).

“By manipulating astrocytes we were able to mimic the effects of sleep deprivation on depressive-like symptoms, causing a rapid and sustained improvement in behavior,” continued Hines.

“Further understanding of astrocytic signaling and the role of adenosine is important for research and development of anti-depressant drugs. Potentially, new drugs that target this mechanism may provide rapid relief for psychiatric emergencies, as well as long-term alleviation of chronic depressive symptoms,” said Naomi Rosenberg, Ph.D., dean of the Sackler School of Graduate Biomedical Sciences and vice dean for research at Tufts University School of Medicine. “The team’s next step is to further understand the other receptors in this system and see if they, too, can be affected.”

(Image: Paul De Koninck)

Reviewing alcohol’s effects on normal sleep

Sleep is supported by natural cycles of activity in the brain and consists of two basic states: rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. Typically, people begin the sleep cycle with NREM sleep followed by a very short period of REM sleep, then continue with more NREM sleep and more REM sleep, this 90 minute cycle continuing through the night. A review of all known scientific studies on the impact of drinking on nocturnal sleep has clarified that alcohol shortens the time it takes to fall asleep, increases deep sleep, and reduces REM sleep.

Results will be published in the April 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"This review has for the first time consolidated all the available literature on the immediate effects of alcohol on the sleep of healthy individuals," said Irshaad Ebrahim, medical director at The London Sleep Centre as well as corresponding author for the study.

"Certainly a mythology seems to have developed around the impact of alcohol on sleep," added Chris Idzikowski, director of the Edinburgh Sleep Centre. "It is a good time to review the research as the mythology seems to be flourishing more rapidly than the research itself. Also, our understanding of sleep has accelerated in the past 30 years, which has meant that some of the initial interpretations need to be revisited."

Some of the review’s key themes are:

• At all dosages, alcohol causes a reduction in sleep onset latency, a more consolidated first half sleep, and an increase in sleep disruption in the second half of sleep.

  "This review confirms that the immediate and short-term impact of alcohol is to reduce the time it takes to fall asleep," said Ebrahim. "In addition, the higher the dose, the greater the impact on increasing deep sleep. This effect on the first half of sleep may be partly the reason some people with insomnia use alcohol as a sleep aid. However, the effect of consolidating sleep in the first half of the night is offset by having more disrupted sleep in the second half of the night."

• The majority of studies, across alcohol dose, age, and gender, confirm an increase in slow-wave sleep (SWS) in the first half of the night. SWS, often referred to as deep sleep, consists of stages 3 and 4 of NREM. During SWS, the body repairs and regenerates tissues, builds bone and muscle, and appears to strengthen the immune system. Alcohol’s impact on SWS in the first half of the night appears to be more robust than its effect on REM sleep.

  "SWS or deep sleep generally promotes rest and restoration," said Ebrahim. "However, when alcohol increases SWS, this may also increase vulnerability to certain sleep problems such as sleepwalking or sleep apnoea in those who are predisposed."

• Alcohol’s effects on REM sleep in the first half of sleep appear to be dose related. Low and moderate doses show no clear effects on REM sleep in the first half of the night, whereas at high doses, REM sleep reduction in the first part of sleep is significant. Total night REM sleep percent is decreased in the majority of studies at moderate and high doses.

  "Dreams generally occur in the REM stage of sleep," said Ebrahim. "During REM sleep the brain is more active, and may be regarded as ‘defragmenting the drive.’ REM sleep is also important because it can influence memory and serve restorative functions. Conversely, lack of REM sleep can have a detrimental effect on concentration, motor skills, and memory. REM sleep typically accounts for 20 to 25 percent of the sleep period."

• The onset of the first REM sleep period is significantly delayed at all doses and appears to be the most recognizable effect of alcohol on REM sleep, followed by a reduction in total night REM sleep.

"One consequence of a delayed onset of the first REM sleep would be less restful sleep," said Idzikowski. "The first REM episode is often delayed in stressful environments. There is also a linkage with depression."

FDA Approves Magnetic Helmet For Treating Depression

The United States Food and Drug Administration approved a device that treats depression using… magnets. About 14.8 million American adults, or 6.7 percent of the U.S. adult population, are diagnosed with major depression in a given year, and antidepressant medications often don’t help.

The technology, known as deep Transcranial Magnetic Stimulation or TMS, involves placing a helmet filled with electromagnetic coils very close to the scalp and zapping them with pulses of electricity, which causes neurons to fire in very specific areas of the brain.

Magnets, How Do They Work?

First the machine is calibrated by placing it over a part of the brain that causes the subject’s hand to move. Then the coils are aimed at the brain region under treatment. The treatment lasts about 15 to 30 minutes, repeated over several weeks, and is noninvasive—all the person feels is a slight buzzing, and there are no side effects. This makes it a more palatable relative of other treatments that also target the brain directly, such as electroconvulsive therapy (formerly electroshock), or surgically implanted electrodes.

Brainsway, a publicly traded Israeli company, has an exclusive license for the technology from the National Institutes of Health, where its two Israeli scientific cofounders developed it. Their device is already approved in Europe for clinical depression, bipolar disorder, schizophrenia (negative symptoms), Parkinson’s diseases, and PTSD. Clinical trials are under way to test how well brain-zapping electromagnets could work to treat a huge range of ailments including cocaine addiction, Tourette’s syndrome, Alzheimer’s, stroke rehabilitation, multiple sclerosis, even ADHD.

(Credit: theloneliestgod)