Recent quotes:

Getting to the Roots of Pessimism - Neuroscience News

MIT neuroscientists have now pinpointed a brain region that can generate this type of pessimistic mood. In tests in animals, they showed that stimulating this region, known as the caudate nucleus, induced animals to make more negative decisions: They gave far more weight to the anticipated drawback of a situation than its benefit, compared to when the region was not stimulated. This pessimistic decision-making could continue through the day after the original stimulation. The findings could help scientists better understand how some of the crippling effects of depression and anxiety arise, and guide them in developing new treatments. “We feel we were seeing a proxy for anxiety, or depression, or some mix of the two,” says Ann Graybiel, an MIT Institute Professor, a member of MIT’s McGovern Institute for Brain Research, and the senior author of the study, which appears in the Aug. 9 issue of Neuron. “These psychiatric problems are still so very difficult to treat for many individuals suffering from them.”

The Lancet Psychiatry: Exercise linked to improved mental health, but more may not always be better | EurekAlert! Science News

Exercising for 30-60 minutes was associated with the biggest reduction in poor mental health days (associated with around 2.1 fewer days of poor mental health compared with people who did not exercise). Small reductions were still seen for people who exercised more than 90 minutes a day, but exercising for more than three hours a day was associated with worse mental health than not exercising at all. The authors note that people doing extreme amounts of exercise might have obsessive characteristics which could place them at greater risk of poor mental health.

Lack of a Single Molecule May Indicate Severe and Treatment Resistant Depression - Neuroscience News

Naturally produced by the body, LAC performs a number of crucial tasks in the brain. For example, the molecule regulates energy metabolism and interacts with DNA to promote the expression of important genes. Specifically, it acts on a gene that controls levels of the neurotransmitter glutamate–a chemical implicated in almost everything that the brain does. McEwen, the Alfred E. Mirsky Professor, and Nasca, a postdoctoral fellow of the American Foundation for Suicide Prevention, have studied the link between LAC and mood disorders using animal models. In one study, they showed that LAC supplements ameliorate depressive symptoms in mice by reversing brain-cell impairment caused by an excess of glutamate. In a separate rodent study, they observed that LAC treatment reduces depressive behavior and stress-associated neural dysfunction in the medial amygdala, a brain region involved in social interactions. These findings strongly suggest that LAC deficits contribute to a depression-like state in mice, leading the scientists to wonder whether the molecule plays a similar role in humans.

Neural inflammation plays critical role in stress-induced depression -- ScienceDaily

These results show that repeated social defeat stress activates microglia in the medial prefrontal cortex via the innate immune receptors TLR2/4. This triggers the expression of inflammation-related cytokines IL-1? and TNF?, leading to the atrophy and impaired response of neurons in the medial prefrontal cortex, and causing depressive behavior. Professor Furuyashiki says: "These findings demonstrate the importance of neural inflammation caused by the innate immune system for stress-induced depression. This could lead to the development of new antidepressant medication targeting innate immune molecules."

Video: The Underlying Mechanisms of Depression

While it’s likely that there may be more going on with depression than just inflammation by itself, it could be an incredibly useful lens through which to look at promising avenues to potentially treat or prevent it, since controlling systemic inflammation shows promise as being both important for longevity and health in general. Moreover, inflammation can be clinically monitored by well-known biomarkers for systemic inflammation, making it amenable to potentially tracking therapeutic success: the risk of major depression has been shown to increase by 44% for each standard deviation increase in log c-reactive protein.

Suicide is a national epidemic. We need to treat it like one. - The Washington Post

These two treatments are obviously different, but they both point to an entirely new chemical axis in the brain that could be targeted to treat depression: the glutamine/glutamate axis. Commonly abbreviated Glx, these chemicals are suppressed in people with severe depression and post-traumatic stress disorder (PTSD) and do not increase when patients take serotonin-targeting antidepressants. The company I lead is working to develop drugs to raise Glx without the damaging side effects of ketamine or ECT. The science is promising: The FDA recently issued a biomarker letter of support, its first in psychiatry under the 21st Century Cures Act, recognizing that an increased level of Glx correlates with decreased levels of depression and that drugs targeting Glx are linked to a reduction in depression and suicidal ideation.

Association of Depressive Symptoms and Heart Rate Variability in Vietnam War–Era Twins: A Longitudinal Twin Difference Study | JAMA Psychiatry | JAMA Network

The association between depression and autonomic dysregulation, indexed by HRV, is bidirectional, with stronger evidence suggesting that autonomic function affects depression risk rather than vice versa.

The immune system and the pathogenesis of depression

During chronic infections and other chronic medical conditions associated with intense immune activation, the sickness behaviour syndrome can develop into a depressive episode. Studies have found that certain cancer and hepatitis c therapies, which often involve the use of cytokines, have been associated with the development of flu-like depressive symptoms. The causal role of the cytokines has been established by the fact that the depressive symptoms appear almost immediately after cytokine administration and disappear shortly after cytokine treatment is terminated.

The immune system and the pathogenesis of depression

There is bidirectional communication between the HPA axis and the immune system. Cytokines activate the HPA axis and thus lead to the release of cortisol, the stress hormone, which ordinarily suppresses the immune response. Cortisol also inhibits its own release and thus the body is able to maintain a stable immune response through a tightly regulated feedback inhibition system. This regulation mechanism seems to be dysfunctional in depressive disorders and is thought to occur because of cytokine mediated receptor resistance to cortisol, thus impairing feedback inhibition. This essentially means that cytokines make cortisol unable to act on the receptors that would inhibit its release. Long story short — the HPA axis is hyperactive because of cytokines, leading to a chronic stress response because cytokines impair the body’s ability to regulate it — thus leading to depressive symptoms.

Antidepressants don't work, or depression doesn't exist (as a meaningful category)

The real truth isn't found within the published paper but rather within a busy table on page 142 of the online appendix. It is here where the authors report what we want: the actual difference between drugs and placebo, before and after treatment, on the depression rating scales. Here we see that the Cohen's d standardized mean difference effect sizes range from a low of 0.19 to a high of 0.62 with amitriptyline. Thus, amitriptyline exceeds the clinically meaningful threshold of 0.50, with a traditional meta-analytic method. No other drug does so, with the closest second place being fluvoxamine, with a Cohen's d value of 0.44. Looking at all of the agents, 10 drugs have Cohen's d values less than 0.30, which is very small and clinically meaningless, whereas four have effect sizes from 0.30 to 0.34. Thus, 74% (14/19) of antidepressants clearly have little or no clinically important benefit in this analysis (for some reason, no data are provided in this table with two of the drugs). Four drugs have effect sizes of 0.37-0.44, and as noted, one agent exceeds the 0.50 threshold (amitriptyline). Perhaps a clearer conclusion than anything else is the well-proven fact that the tricyclic antidepressants are more effective than newer agents (there were no monoamine oxidase inhibitors in this meta-analysis).

Rare mutation of gene carried by Quebec family gives insight into how the brain is wired: Brain scans could further understanding of psychiatric disorders, brain's reward system -- ScienceDaily

By scanning the brain of 20 family members who share an altered copy of DCC, the researchers found less connectivity between the areas where dopamine neurons originate (the substantia nigra and ventral tegmental area) and their target sites, such as the striatum and frontal cortex. One of these target sites -- the striatum -- was also smaller. "It's very interesting because we were able to show that this DCC gene alteration induces similar changes to the brain in both mice and humans," says Cecilia Flores. Because the brain systems affected by the gene influence responses to rewards, it was not surprising to see that the family members with the DCC mutation also have lower impulsivity traits and are less likely to smoke cigarettes. Indeed, an increasing number of studies, including those by Professor Flores' team, link DCC to psychiatric conditions. "Because the gene affects the brain's dopamine pathways, which are implicated in schizophrenia, addiction and depression, our study potentially helps us understand how these disorders arise.

Early birds less prone to depression: Largest study yet links chronotype to mental health -- ScienceDaily

In 2009, all the participants included in the study were free of depression. When asked about their sleep patterns, 37 percent described themselves as early types, 53 percent described themselves as intermediate types, and 10 percent described themselves as evening types. The women were followed for four years to see who developed depression. Depression risk factors like body weight, physical activity, chronic disease, sleep duration, or night shift work were also assessed. The researchers found that late chronotypes, or night owls, are less likely to be married, more likely to live alone and be smokers, and more likely to have erratic sleep patterns. After accounting for these factors, they found that early risers still had a 12 -- 27 percent lower risk of being depressed than intermediate types. Late types had a 6 percent higher risk than intermediate types ( this modest increase was not statistically significant.) "This tells us that there might be an effect of chronotype on depression risk that is not driven by environmental and lifestyle factors," said Vetter.

A bad night's sleep linked to suicidal thoughts the following day in people with depression

The researchers found that short sleep duration and poor sleep quality both predicted higher severity of suicidal ideation on the following day, even after controlling for anxiety and depression symptom severity. “However, suicidal thoughts did not predict sleep problems the following night,” Littlewood noted.

Probiotic Shot May Alleviate Brain Stress | GEN

“Given the evidence for reduced immunoregulation and chronic low-grade inflammation in anxiety and trauma-related disorders, microbial interventions that increase Treg, promote immunoregulation, and increase anti-inflammatory signaling may have value in the prevention or treatment of these disorders,” the authors suggest. M. vaccae has previously been shown to increase induction of Treg production and anti-inflammatory cytokines. A previous study by CU Boulder scientists showed that mice given injections of a heat-killed M. vaccae preparation and then placed in housing with an aggressive male exhibited less anxiety-like behavior and were less likely to suffer colitis or peripheral inflammation than control animals. These findings suggest that immunoregulatory and anti-inflammatory treatments can “buffer against the proinflammatory effects of stress,” the researchers point out.  What hasn’t been studied before is whether M. vaccae has a direct impact on stress-induced neuroinflammation.

Insel and "digital phenotype"

His company is working on using the technique to pre-screen for depression, post-traumatic stress disorder, schizophrenia and bipolar disorder. Their initial studies were able to link the digital features from participants' phones to how well they did on neural cognitive tests.

Chronobiological therapy for mood disorders: Expert Review of Neurotherapeutics: Vol 11, No 7

Alteration of the sleep–wake cycle and of the sleep structure are core symptoms of a major depressive episode, and occur both in course of bipolar disorder and of major depressive disorder. Many other circadian rhythms, such as the daily profiles of body temperature, cortisol, thyrotropin, prolactin, growth hormone, melatonin and excretion of various metabolites in the urine, are disrupted in depressed patients, both unipolar and bipolar individuals. These disrupted rhythms seem to return to normality with patient recovery. Research on circadian rhythms and sleep have led to the definition of nonpharmacological therapies of mood disorder that can be used in everyday practice. These strategies, named chronotherapeutics, are based on controlled exposures to environmental stimuli that act on biological rhythms, and demonstrate good efficacy in the treatment of illness episodes.

Reddit Has a Really Surprising Effect on Users' Mental Health, Study Shows

Using three other subreddits - r/happy, r/bodybuilding, and r/loseit - as their control group, the researchers determined that contributors to the mental health subreddits appeared to have trouble clearly communicating initially. However, over time, those users showed "statistically significant improvement" in both their lexical diversity and readability. "I started to notice that as they come in more, and they participate more, they're more calmed down, and they're articulating a little bit better," study author Albert Park told Healthcare Analytics News.

Reduced hippocampal volume observed in currently but not previously depressed older adults

By analyzing MRI brain scans, Calati and her colleagues observed hippocampal volume reduction in currently depressed participants compared to the healthy control group. But they found no significant difference between those with a history of past, but not current, depression and the healthy controls. “When we compared the three groups, we found left posterior hippocampal volume reduction in currently depressed individuals when compared to healthy subjects. This reduction was not present when we compared past depressed subjects to healthy controls,” Calati explained.

How to Motivate Yourself to Exercise When You Have Depression | Mind | US News

But for people with depression – a condition in which low motivation to do regular daily activities (say, taking a shower, getting dressed or going to work) is a prominent symptom – finding motivation to exercise can feel like a fool's errand. Indeed, in a study of 245 patients at a Michigan mental health outpatient clinic, 80 percent of patients wanted to exercise more, but most said their mood limited their ability to do so. "All people experience procrastination on tasks that feel like they're going to take a lot of effort – that's universal," says Rachel Hershenberg, an assistant professor of psychiatry and behavioral sciences at Emory University in Atlanta. "That urge to avoid – that's what gets magnified in depression."

How social isolation transforms the brain: A particular neural chemical is overproduced during long-term social isolation, causing increased aggression and fear -- ScienceDaily

Confirming and extending previous observations, the researchers showed that prolonged social isolation leads to a broad array of behavioral changes in mice. These include increased aggressiveness towards unfamiliar mice, persistent fear, and hypersensitivity to threatening stimuli. For example, when encountering a threatening stimulus, mice that have been socially isolated remain frozen in place long after the threat has passed, whereas normal mice stop freezing soon after the threat is removed. These effects are seen when mice are subjected to two weeks of social isolation, but not to short-term social isolation -- 24 hours -- suggesting that the observed changes in aggression and fear responses require chronic isolation.

Association of Efficacy of Resistance Exercise Training With Depressive Symptoms: Meta-analysis and Meta-regression Analysis of Randomized Clinical Trials | Depressive Disorders | JAMA Psychiatry | JAMA Network

Resistance exercise training significantly reduced depressive symptoms among adults regardless of health status, total prescribed volume of RET, or significant improvements in strength. Better-quality randomized clinical trials blinding both allocation and assessment and comparing RET with other empirically supported treatments for depressive symptoms are needed.

Association of Depressive Symptoms and Heart Rate Variability in Vietnam War–Era Twins: A Longitudinal Twin Difference Study | Cardiology | JAMA Psychiatry | JAMA Network

The association between depression and autonomic dysregulation, indexed by HRV, is bidirectional, with stronger evidence suggesting that autonomic function affects depression risk rather than vice versa. The opposite causal pathway from depression to lower HRV is mostly driven by antidepressant use. These findings highlight an important role of autonomic nervous system in the risk of depression and contribute new understanding of the mechanisms underlying the comorbidity of depression and cardiovascular disease.

Tick tock: Study links body clock to mood disorders | AFP.com

or the new study, an international team led by University of Glasgow psychologist Laura Lyall analysed data -- taken from the UK Biobank, one of the most complete long-term health surveys ever done -- on 91,105 people aged 37 to 73. The volunteers wore accelerometers that measured patterns of rest and activity and had this record compared to their mental history, also taken from the UK Biobank. Individuals with a history of disrupting their body's natural rhythm -- working night shifts, for example, or suffering repeated jetlag -- also tended to have a higher lifetime risk of mood disorders, feelings of unhappiness, and cognitive problems, the researchers found.

Surprising Finding About ‘Shock Therapy’ for Depression Suggests More Patients Should Try It Sooner - Neuroscience News

Ross notes that the team had not expected ECT to come out as cost-effective for third-line use – they had expected this to be true for fifth- to sixth-line treatment. The findings suggest that if patients and physicians decide to try a third, fourth or fifth antidepressant or psychotherapy course, or combinations of medicine and therapy before they opt for ECT, the latter would will still be most cost-effective the sooner they decide to try it.

How parents cause children's friendships to end -- ScienceDaily

Results from the study found clear support for their hypothesis that negative features of parenting, such as depression and psychological control, increase the risk that best friendships would end. For children with clinically depressed parents, the risk of best friendship dissolution increased by up to 104 percent. There was a similar, although not quite as dramatic, increase in the risk of best friendship dissolution for children with psychologically controlling parents.

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial - The Lancet

In patients with treatment-resistant depression, iTBS was non-inferior to 10 Hz rTMS for the treatment of depression. Both treatments had low numbers of dropouts and similar side-effects, safety, and tolerability profiles. By use of iTBS, the number of patients treated per day with current rTMS devices can be increased several times without compromising clinical effectiveness.