Archive for the ‘Depression’ Category

Pupil dilation in reaction to negative emotional faces predicts risk for depression relapse, according to new research from Binghamton University, State University of New York.

Researchers at Binghamton University, led by PhD student Anastacia Kudinova, aimed to examine whether physiological reactivity to emotional stimuli, assessed via pupil dilation, served as a biological marker of risk for depression recurrence among individuals who are known to be at a higher risk due to having previous history of depression. Participants were 57 women with a history of major depressive disorder (MDD). The researchers recorded the change in pupil dilation in response to angry, happy, sad and neutral faces. The team found that women’s pupillary reactivity to negative (sad or angry faces) but not positive stimuli prospectively predicted MDD recurrence.

“The study focuses on trying to identify certain markers of depression risk using measures that are readily accessible, reliable and less expensive,” said Kudinova. “It is something we can put in any doctor’s office that gives us a quick and easy objective measure of risk.”

Additionally, the researchers found that both high and low reactivity to angry faces predicted risk for MDD recurrence. These findings suggest that disrupted physiological response to negative stimuli indexed via pupillary dilation could serve as a physiological marker of MDD risk, thus presenting clinicians with a convenient and inexpensive method to predict which of the at-risk women are more likely to experience depression recurrence.

“It’s a bit complicated because different patterns of findings were found for pupil reactivity to angry versus sad faces. Specifically, really high or really low pupil dilation to angry faces was associated with increased risk whereas only low dilation to sad faces was associated with risk (high dilation to sad faces was actually protective),” said Brandon Gibb, professor of psychology at Binghamton University and director of the Mood Disorders Institute and Center for Affective Science.

Other contributors to this research include Katie Burkhouse and Mary Woody, both PhD students; Max Owens, assistant professor of psychology at the University of South Florida, St. Petersburg; and Greg Siegle, associate professor of psychiatry at the University of Pittsburgh School of Medicine.
The paper, “Pupillary reactivity to negative stimuli prospectively predicts recurrence of major depressive disorder in women,” was published in Psychophysiology.

https://www.binghamton.edu/mpr/news-releases/news-release.html?id=2448

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by Tori Rodriguez, MA, LPC

Individuals with major depressive disorder (MDD) have double the risk of alcohol use disorders (AUDs) and vice versa, and it has previously been proposed that some people with MDD may use alcohol to self-medicate. Though alcohol can become depressant if used chronically, alcohol initially has an antidepressant effect, though the underlying mechanisms have not been identified. Findings reported in September 2016 in Nature Communications begin to elucidate the basis of this action.

Behavioral and molecular evidence of the rapid antidepressant activity of NMDA receptor (NMDAR) antagonists, which have been found to be effective within 2 hours of administration and remain so for 2 weeks, represents a significant advance in depression treatment. Antidepressant efficacy involves the induction phase and the sustained phase.

The sustained phase of rapid antidepressants requires “both new protein synthesis and an increase in protein stability… for the GABABR shift in function necessary to increase” the activity of mTORC1, a mechanistic target of rapamycin complex 1, the authors explained in their paper. Rapamycin (mTOR) is a “serine/threonine kinase essential for messenger RNA translation” and is required for the sustained impact of rapid antidepressants.

Citing previous findings that ethanol (EtOH) also blocks NMDARs in the hippocampus, scientists at the University of Texas at Austin and Wake Forest University School of Medicine in Winston-Salem, North Carolina, aimed to determine whether EtOH and NMDAR antagonists exert rapid antidepressant effects via the same synaptic pathways in rodents. They hypothesized that EtOH “has lasting antidepressant efficacy, shares the same downstream molecular signaling events as rapid antidepressants, and requires de novo protein synthesis.”

First, they found that acute exposure to EtOH led to antidepressant and anxiolytic behaviors in rodents for up to 24 hours. They then discovered that, like NMDAR antagonists, EtOH alters the expression and signaling of GABABR, increases dendritic calcium, and leads to the synthesis of new GABABRs. This synthesis requires fragile-X mental retardation protein (FMRP), an RNA-binding protein of which precise levels are needed for normal neuronal functioning.

The antidepressant effects and the changes in GABABR expression and dendritic calcium were not observed in in Fmr1-knockout (KO) mice, supporting the concept that FMRP has in important role in regulating protein synthesis after EtOH exposure, and thereby facilitating its antidepressant efficacy.

These results point to a shared molecular pathway for the antidepressant activity of EtOH and rapid antidepressants, and highlight a mechanism involved in the initial antidepressant action of alcohol. “A shift in GABABR signaling is observed with both rapid antidepressants and acute EtOH treatment, which may provide insight into the molecular basis for the high comorbidity between major depressive disorder and AUD,” the authors concluded.

http://www.psychiatryadvisor.com/addiction/rapid-antidepressant-effect-of-alcohol/article/567335/?DCMP=EMC-PA_Update_RD&cpn=psych_md%2cpsych_all&hmSubId=&NID=1710903786&dl=0&spMailingID=15723696&spUserID=MTQ4MTYyNjcyNzk2S0&spJobID=881842067&spReportId=ODgxODQyMDY3S0

Whole-body hyperthermia is a promising antidepressant modality that works quickly and offers prolonged benefit, according to a study recently published in the online JAMA Psychiatry.

Researchers came to that conclusion after conducting a double-blind study that randomized 30 adults with major depressive disorder to either a single session of active whole-body hyperthermia or a sham treatment that mimicked all aspects of whole-body hyperthermia except its intense heat.

The sham condition was included to strengthen the study design.

“A prior open trial found that a single session of whole-body hyperthermia reduced depressive symptoms,” researchers wrote. “However, the lack of a placebo control raises the possibility that the observed antidepressant effects resulted not from hyperthermia per se, but from nonspecific aspects of the intervention.”

Among participants randomized to sham treatment in the new study, more than 70% believed they had received whole-body hyperthermia, researchers reported, suggesting the placebo was convincing.

When researchers looked at participants’ scores on the Hamilton Depression Rating Scale throughout the 6-week period following the session, they found participants who received active whole-body hyperthermia had significantly reduced scores compared to participants who received sham treatment. Adverse events were mild.

Psych Congress Steering Committee member Charles L. Raison, MD, discussed the findings prior to their publication during a session at last year’s U.S. Psychiatric and Mental Health Congress in San Diego.

“Like ketamine, like scopolamine, and other rapid treatments for depression that are of intense interest in psychiatry, hyperthermia shows the same effect,” he said. “It doesn’t take a week or 2 to work. People feel better very, very quickly, and the effects appear to persist for an extended period of time.”

– Jolynn Tumolo

References

Janssen CW, Lowry CA, Mehl MR, et al. Whole-body hyperthermia for the treatment of major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2016 May 12. [Epub ahead of print].

Lebano L. New data support whole body hyperthermia for rapid treatment of major depression. Psych Congress Network. 2015 Sept. 10.

http://www.psychcongress.com/article/hyperthermia-provides-significant-rapid-relief-depression-study-suggests-27981

ppd

By Natalie Grover

Sage Therapeutics Inc said its drug alleviated symptoms of severe postpartum depression, meeting the main goal of a small mid-stage study and sending the company’s shares soaring.

About one in seven women experience postpartum depression that eventually interferes with her ability to take care of the baby and handle daily tasks, according to the American Psychological Association. There are no specific therapies for PPD. Existing options include standard antidepressants and psychotherapy.

Data on 21 patients showed that the drug, SAGE-547, achieved a statistically significant reduction in symptoms at 60 hours, compared to placebo, on a standard depression scale, Sage said in a news release reporting topline results from the study. (http://bit.ly/29KtPBI)

“This represented a greater than 20 point mean reduction in the depression scores of the SAGE-547 group at the primary endpoint of 60 hours through trial completion with a greater than 12 point difference from placebo. The statistically significant difference in treatment effect began at 24 hours, (p=0.006) with an effect that was maintained at similar magnitude through to the 30-day follow-up (p=0.01),” the company reported.

Typical antidepressants take about four-to-six weeks to take effect, trial investigator Samantha Meltzer-Brody told Reuters. “So the rapid onset of response of this drug is unlike anything else available in the field,” she said.

A woman with PPD can suffer a whirlwind of emotions, including severe anxiety, panic attacks, thoughts of harming herself or the baby, and feelings of worthlessness, shame, guilt or inadequacy.

Cambridge, Massachusetts-based Sage said it had initiated an expansion of the mid-stage study to determine optimal dosing for the injectable drug.

Sage is also evaluating the drug for use in super refractory status epilepticus (SRSE), a life-threatening seizure disorder, as well as essential tremor.

http://www.psychcongress.com/article/drug-postpartum-depression-succeeds-mid-stage-study-27946

An immersive virtual reality therapy could help people with depression to be less critical and more compassionate towards themselves, reducing depressive symptoms, finds a new study from UCL (University College London) and ICREA-University of Barcelona.

The therapy, previously tested by healthy volunteers, was used by 15 depression patients aged 23-61. Nine reported reduced depressive symptoms a month after the therapy, of whom four experienced a clinically significant drop in depression severity. The study is published in the British Journal of Psychiatry Open and was funded by the Medical Research Council.

Patients in the study wore a virtual reality headset to see from the perspective of a life-size ‘avatar’ or virtual body. Seeing this virtual body in a mirror moving in the same way as their own body typically produces the illusion that this is their own body. This is called ’embodiment’.

While embodied in an adult avatar, participants were trained to express compassion towards a distressed virtual child. As they talked to the child it appeared to gradually stop crying and respond positively to the compassion. After a few minutes the patients were embodied in the virtual child and saw the adult avatar deliver their own compassionate words and gestures to them. This brief 8-minute scenario was repeated three times at weekly intervals, and patients were followed up a month later.

“People who struggle with anxiety and depression can be excessively self-critical when things go wrong in their lives,” explains study lead Professor Chris Brewin (UCL Clinical, Educational & Health Psychology). “In this study, by comforting the child and then hearing their own words back, patients are indirectly giving themselves compassion. The aim was to teach patients to be more compassionate towards themselves and less self-critical, and we saw promising results. A month after the study, several patients described how their experience had changed their response to real-life situations in which they would previously have been self-critical.”

The study offers a promising proof-of-concept, but as a small trial without a control group it cannot show whether the intervention is responsible for the clinical improvement in patients.

“We now hope to develop the technique further to conduct a larger controlled trial, so that we can confidently determine any clinical benefit,” says co-author Professor Mel Slater (ICREA-University of Barcelona and UCL Computer Science). “If a substantial benefit is seen, then this therapy could have huge potential. The recent marketing of low-cost home virtual reality systems means that methods such as this could potentially be part of every home and be used on a widespread basis.”

Publication: Embodying self-compassion within virtual reality and its effects on patients with depression. Falconer, CJ et al. British Journal of Psychiatry Open (February, 2016)

New research published in the Canadian Medical Association Journal shows that even mild concussions sustained in ordinary community settings might be more detrimental than anyone anticipated; the long-term risk of suicide increases threefold in adults if they have experienced even one concussion. That risk increases by a third if the concussion is sustained on a weekend instead of a weekday—suggesting recreational concussions are riskier long-term than those sustained on the job.

“The typical patient I see is a middle-aged adult, not an elite athlete,” says Donald Redelmeier, a senior scientist at the University of Toronto and one of the study’s lead authors. “And the usual circumstances for acquiring a concussion are not while playing football; it is when driving in traffic and getting into a crash, when missing a step and falling down a staircase, when getting overly ambitious about home repairs—the everyday activities of life.”

Redelmeier and his team wanted to examine the risks of the concussions acquired under those circumstances. They identified nearly a quarter of a million adults in Ontario who were diagnosed with a mild concussion over a timespan of 20 years—severe cases that resulted in hospital admission were excluded from the study—and tracked them for subsequent mortality due to suicide. It turned out that more than 660 suicides occurred among these patients, equivalent to 31 deaths per 100,000 patients annually—three times the population norm. On average, suicide occurred almost six years after the concussion. This risk was found to be independent of demographics or previous psychiatric conditions, and it increased with additional concussions.

For weekend concussions, the later suicide risk increased to four times the norm. Redelmeier and his fellow researchers had wondered whether the risk would differ between occupational and recreational concussions. They did not have information about how the concussions happened, so they used day of the week as a proxy. Although they do not know why weekend risk is indeed higher, they suspect it may be because on weekends medical staff may not be as available or accessible or people may not seek immediate care.

Although the underlying causes of the connection between concussion and suicide are not yet known, Redelmeier says that there were at least three potential explanations. A concussion may be a marker but not necessarily a mechanism of subsequent troubles—or, in other words, people who sustain concussions may already have baseline life imbalances that increase their risks for depression and suicide. “But we also looked at the subgroup of patients who had no past psychiatric history, no past problems, and we still found a significant increase in risk. So I don’t think that’s the entire story,” he notes. One of the more likely explanations, he says, is that concussion causes brain injury such as inflammation (as has been found in some studies) from which the patient may never fully recover. Indeed, a study conducted in 2014 found that sustaining a head injury leads to a greater risk of mental illness later in life. The other possibility is that some patients may not give themselves enough time to get better before returning to an ordinary schedule, leading to strain, frustration and disappointment—which, in turn, may result in depression and ultimately even suicide.

Lea Alhilali, a physician and researcher at the Barrow Neurological Institute who did not participate in this study, uses diffusion tensor imaging (an MRI technique) to measure the integrity of white matter in the brain. Her team has found similarities between white matter degeneration patterns in patients with concussion-related depression and noninjured patients with major depressive disorder—particularly in the nucleus accumbens, or the “reward center” of the brain. “It can be difficult to tease out what’s related to an injury and what’s related to the circumstances surrounding the trauma,” Alhilali says. “There could be PTSD, loss of job, orthopedic injuries that can all influence depression. But I do believe there’s probably an organic brain injury.”

Alhilali points to recent studies on chronic traumatic encephalopathy (CTE), a progressive degenerative brain disease associated with repeated head traumas. Often linked to dementia, depression, loss of impulse control and suicide, CTE was recently diagnosed in 87 of 91 deceased NFL players. Why, then, she says, should we not suspect that concussion causes other brain damage as well?

This new study may only represent the tip of the iceberg. “We’re only looking at the most extreme outcomes, at taking your own life,” Redelmeier says. “But for every person who dies from suicide, there are many others who attempt suicide, and hundreds more who think about it and thousands more who suffer from depression.”

More research needs to be done; this study was unable to take into account the exact circumstances under which the concussions were sustained. Redelmeier’s research examined only the records of adults who sought medical attention, it did not include more severe head injuries that required hospitalization or extensive emergency care. To that extent, his findings may have underestimated the magnitude of the absolute risks at hand.

Yet many people are not aware of these risks.

Redelmeier is adamant that people should take concussions seriously. “We need to do more research about prevention and recovery,” he says. “But let me at least articulate three things to do: One, give yourself permission to get some rest. Two, when you start to feel better, don’t try to come back with a vengeance. And three, even after you’re feeling better, after you’ve rested properly, don’t forget about it entirely. If you had an allergic reaction to penicillin 15 years ago, you’d want to mention that to your doctor and have it as a permanent part of your medical record. So, too, if you’ve had a concussion 15 years ago.”

http://www.scientificamerican.com/article/a-single-concussion-may-triple-the-long-term-risk-of-suicide1/

by Tori Rodriguez, MA, LPC

As the search continues for effective drug treatments for dementia, patients and caregivers may find some measure of relief from a common, non-pharmaceutical source. Researchers have found that music-related memory appears to be exempt from the extent of memory impairment generally associated with dementia, and several studies report promising results for several different types of musical experiences across a variety of settings and formats.

“We can say that perception of music can be intact, even when explicit judgments and overt recognition have been lost,” Manuela Kerer, PhD, told Psychiatry Advisor. “We are convinced that there is a specialized memory system for music, which is distinct from other domains, like verbal or visual memory, and may be very resilient against Alzheimer’s disease.”

Kerer is a full-time musical composer with a doctoral degree in psychology who co-authored a study on the topic while working at the University of Innsbruck in Austria. She and her colleagues investigated explicit memory for music among ten patients with early-state Alzheimer’s disease (AD) and ten patients with mild cognitive impairment (MCI), and compared their performance to that of 23 healthy participants. Not surprisingly, the patient group demonstrated worse performance on tasks involving verbal memory, but they did significantly better than controls on the music-perceptional tasks of detecting distorted tunes and judging timbre.

“The temporal brain structures necessary for verbal musical memory were mildly affected in our clinical patients, therefore attention might have shifted to the discrimination tasks which led to better results in this area,” she said. “Our results enhance the notion of an explicit memory for music that can be distinguished from other types of explicit memory — that means that memory for music could be spared in this patient group.”

Other findings suggest that music might even improve certain aspects of memory among people with dementia. In a randomized controlled trial published in last month in the Journal of Alzheimer’s Disease, music coaching interventions improved multiple outcomes for both patients with dementia and their caregivers. The researchers divided 89 pairs of patients with dementia and their caregivers into three groups: two groups were assigned to caregiver-led interventions that involved either singing or listening to music, while a third group received standard care. Before and after the 10-week intervention, and six months after the intervention, participants were assessed on measures of mood, quality of life and neuropsychological functioning.

Results showed that the singing intervention improved working memory among patients with mild dementia and helped to preserve executive function and orientation among younger patients, and it also improved the well-being of caregivers. The listening intervention was found to have a positive impact on general cognition, working memory and quality of life, particularly among patients in institutional care with moderate dementia not caused by AD. Both interventions led to reductions in depression.

The findings suggest that “music has the power to improve mood and stimulate cognitive functions in dementia, most likely by engaging limbic and medial prefrontal brain regions, which are often preserved in the early stages of the illness,” study co-author Teppo Särkämö, PhD, a researcher at the University of Helsinki, Finland, told Psychiatry Advisor. “The results indicate that when used regularly, caregiver-implemented musical activities can be an important and easily applicable way to maintain the emotional and cognitive well-being of persons with dementia and also to reduce the psychological burden of family caregivers.”

Singing has also been shown to increase learning and retention of new verbal material in patients with AD, according to research published this year in the Journal of Clinical & Experimental Neuropsychology, and findings published in 2013 show that listening to familiar music improves the verbal narration of autobiographical memories in such patients. Another study found that a music intervention delivered in a group format reduced depression and delayed the deterioration of cognitive functions, especially short-term recall, in patients with mild and moderate dementia. Group-based music therapy appears to also decrease agitation among patients in all stages of dementia, as described in a systematic review published in 2014 in Nursing Times.

n addition to the effects of singing and listening to music on patients who already have dementia, playing a musical instrument may also offer some protection against the condition, according to a population-based twin study reported in 2014 in the International Journal of Alzheimer’s Disease. Researchers at the University of Southern California found that older adults who played an instrument were 64% less likely than their non-musician twin to develop dementia or cognitive impairment.

“Playing an instrument is a unique activity in that it requires a wide array of brain regions and cognitive functions to work together simultaneously, throughout both the right and left hemispheres,” co-author Alison Balbag, PhD, told Psychiatry Advisor. While the study did not examine causal mechanisms, “playing an instrument may be a very effective and efficient way to engage the brain, possibly granting older musicians better maintained cognitive reserve and possibly providing compensatory abilities to mitigate age-related cognitive declines.”

She notes that clinicians might consider suggesting that patients incorporate music-making into their lives as a preventive activity, or encouraging them to keep it up if they already play an instrument.
Further research, particularly neuroimaging studies, is needed to elucidate the mechanisms behind the effects of music on dementia, but in the meantime it could be a helpful supplement to patients’ treatment plans. “Music has considerable potential and it should be introduced much more in rehabilitation and neuropsychological assessment,” Kerer said.

http://www.psychiatryadvisor.com/alzheimers-disease-and-dementia/neurocognitive-neurodegenerative-memory-musical-alzheimers/article/452120/3/

References

Kerer M, Marksteiner J, Hinterhuber H, et al. Explicit (semantic) memory for music in patients with mild cognitive impairment and early-stage Alzheimer’s disease. Experimental Aging Research; 2013; 39(5):536-64.

Särkämö T, Laitinen S, Numminen A, et al. Clinical and Demographic Factors Associated with the Cognitive and Emotional Efficacy of Regular Musical Activities in Dementia. Journal of Alzheimer’s Disease; 2015; published online ahead of print.

Palisson J, Roussel-Baclet C, Maillet D, et al. Music enhances verbal episodic memory in Alzheimer’s disease. Journal of Clinical & Experimental Neuropsychology; 2015; 37(5):503-17.

El Haj M, Sylvain Clément, Luciano Fasotti, Philippe Allain. Effects of music on autobiographical verbal narration in Alzheimer’s disease. Journal of Neurolinguistics; 2013; 26(6): 691–700.

Chu H, Yang CY, Lin Y, et al. The impact of group music therapy on depression and cognition in elderly persons with dementia: a randomized controlled study. Biological Research for Nursing; 2014; 16(2):209-17.

Craig J. Music therapy to reduce agitation in dementia. Nursing Times; 2014; 110(32-33):12-5.
Balbag MA, Pedersen NL, Gatz M. Playing a Musical Instrument as a Protective Factor against Dementia and Cognitive Impairment: A Population-Based Twin Study. International Journal of Alzheimer’s Disease; 2014; 2014: 836748.