Recent quotes:

New study on the placebo effect and antidepressants in children and adolescents -- ScienceDaily

The results of the meta-analysis show that, although antidepressants work significantly better than placebos across the range of disorders, the difference is small and varies according to the type of mental disorder. However, the results also showed that the placebo effect played a significant role in the efficacy of antidepressants. The study also found that patients treated with antidepressants complained of greater side effects than those who received a placebo. The side effects included everything from mild symptoms such as headaches to suicidal behavior. Placebo effect stronger in cases of depression According to the study, the effects of antidepressants and placebos vary according to the type of mental disorder: antidepressants have a greater specific effect in the case of anxiety disorders than depressive disorders. On the other hand, placebos have a stronger effect in depressed patients than in those with an anxiety disorder. Lead authors Dr. Cosima Locher and Helen Koechlin from the Division of Clinical Psychology & Psychotherapy at the University of Basel's Faculty of Psychology see potential here for new treatment concepts. These would make use of factors contributing to the placebo effect, applying them specifically to the treatment of depression.

Lack of sleep could contribute to mental health problems, researchers reveal | Society | The Guardian

After taking into account effects not linked to treatment – as deduced from the no-treatment group – insomnia in the CBT group was found to have fallen by almost half 10 weeks into the study, while both anxiety and depression dropped by a fifth, and paranoia and hallucinations fell by 25% and 30% respectively. “Having insomnia doubles your chances of developing depression and we now know that if you treat the insomnia it reduces depression,” said Freeman.

Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence | The BMJ

Conclusions Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base.

Sexual Consequences of Post-SSRI Syndrome

There are some indications that antidepressant-emergent sexual dysfunctions do not always resolve after discontinuation of the medication and can persist indefinitely in some individuals. Although some or all sexual side effects that start with the use of SSRIs might continue after stopping the medication, other sexual complaints can develop. Decreased capacity to experience sexual pleasure is the most frequent characteristic of this syndrome.

Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration

Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.

Mice Genetically Depleted of Brain Serotonin Do Not Display a Depression-like Behavioral Phenotype - ACS Chemical Neuroscience (ACS Publications)

Reductions in function within the serotonin (5HT) neuronal system have long been proposed as etiological factors in depression. Selective serotonin reuptake inhibitors (SSRIs) are the most common treatment for depression, and their therapeutic effect is generally attributed to their ability to increase the synaptic levels of 5HT. Tryptophan hydroxylase 2 (TPH2) is the initial and rate-limiting enzyme in the biosynthetic pathway of 5HT in the CNS, and losses in its catalytic activity lead to reductions in 5HT production and release. The time differential between the onset of 5HT reuptake inhibition by SSRIs (minutes) and onset of their antidepressant efficacy (weeks to months), when considered with their overall poor therapeutic effectiveness, has cast some doubt on the role of 5HT in depression. Mice lacking the gene for TPH2 are genetically depleted of brain 5HT and were tested for a depression-like behavioral phenotype using a battery of valid tests for affective-like disorders in animals. The behavior of TPH2–/– mice on the sucrose preference test, tail suspension test, and forced swim test and their responses in the unpredictable chronic mild stress and learned helplessness paradigms was the same as wild-type controls. While TPH2–/– mice as a group were not responsive to SSRIs, a subset responded to treatment with SSRIs in the same manner as wild-type controls with significant reductions in immobility time on the tail suspension test, indicative of antidepressant drug effects. The behavioral phenotype of the TPH2–/– mouse questions the role of 5HT in depression. Furthermore, the TPH2–/– mouse may serve as a useful model in the search for new medications that have therapeutic targets for depression that are outside of the 5HT neuronal system.

Increased brain acidity in psychiatric disorders -- ScienceDaily

Researchers at the Institute for Comprehensive Medical Science at Fujita Health University in Japan, along with colleagues from eight other institutions, have identified decreased pH levels in the brains of five different mouse models of mental disorders, including models of schizophrenia, bipolar disorder, and autism spectrum disorder. This decrease in pH likely reflects an underlying pathophysiology in the brain associated with these mental disorders, according to the study published August 4th in the journal Neuropsychopharmacology.

With health care cuts looming, low-cost magnesium a welcome option for treating depression -- ScienceDaily

The researchers at the University of Vermont's Larner College of Medicine conducted an open-label, blocked, randomized cross-over trial involving 126 adults in outpatient primary care clinics. The study participants, who were currently experiencing mild-to-moderate depression, had a mean age of 52, with 38 percent of them male. Participants in the active arm of the study received 248 milligrams of elemental magnesium per day over six weeks, while those in the control arm received no treatment. Depression symptom assessments were conducted on all participants on a bi-weekly basis. The study team found that in 112 participants with analyzable data, consumption of magnesium chloride for six weeks resulted in a clinically significant improvement in measures of depression and anxiety symptoms. In addition, these positive effects were shown quickly, at two weeks, and the supplements were well tolerated and similarly effective regardless of age, sex, or use of antidepressants, among other factors.

Rock climbing envisioned as new treatment for depression -- ScienceDaily

Stelzer explained that bouldering has a number of other important characteristics that make it especially beneficial for the treatment of depression, namely that it helps boost self-efficacy and social interactions -- both of which hold innate benefits for dealing with depression. "You have to be mindful and focused on the moment. It does not leave much room to let your mind wonder on things that may be going on in your life -- you have to focus on not falling," Stelzer said.

Study: Psilocybin Mushrooms Can Help Cancer Anxiety - The Atlantic

In the Johns Hopkins study, half of the 51 participants were given a low dose of psilocybin as control, followed by a high dose five weeks later. (For the other half, the order of the doses was reversed.) The results were remarkable: Six months later, 78 percent of the participants were less depressed than they started, as rated by a clinician, and 83 percent were less anxious. Furthermore, 65 percent had almost fully recovered from depression, and 57 percent from their anxiety, after six months. By comparison, in past studies antidepressants have only helped about 40 percent of cancer patients, performing about as well as a placebo.

Is the dark really making me sad? | Ars Technica

the leading theory is the ‘phase-shift hypothesis’: the idea that shortened days cause the timing of our circadian rhythms to fall out of sync with the actual time of day, because of a delay in the release of melatonin. Levels of this hormone usually rise at night in response to darkness, helping us to feel sleepy, and are suppressed by the bright light of morning. “If someone’s biological clock is running slow and that melatonin rhythm hasn’t fallen, then their clock is telling them to keep on sleeping even though their alarm may be going off and life is demanding that they wake up,” says Kelly Rohan, a professor of psychology at the University of Vermont. Precisely why this should trigger feelings of depression is still unclear. One idea is that this tiredness could then have unhealthy knock-on effects. If you’re having negative thoughts about how tired you are, this could trigger a sad mood, loss of interest in food, and other symptoms that could cascade on top of that. However, recent insights into how birds and small mammals respond to changes in day length have prompted an alternative explanation. According to Daniel Kripke, an emeritus professor of psychiatry at the University of California, San Diego, when melatonin strikes a region of the brain called the hypothalamus, this alters the synthesis of another hormone—active thyroid hormone—that regulates all sorts of behaviours and bodily processes. When dawn comes later in the winter, the end of melatonin secretion drifts later, says Kripke. From animal studies, it appears that high melatonin levels just after the time an animal wakes up strongly suppress the making of active thyroid hormone—and lowering thyroid levels in the brain can cause changes in mood, appetite, and energy. For instance, thyroid hormone is known to influence serotonin, a neurotransmitter that regulates mood. Several studies have shown that levels of brain serotonin in humans are at their lowest in the winter and highest in the summer. In 2016, scientists in Canada discovered that people with severe SAD show greater seasonal changes in a protein that terminates the action of serotonin than others with no or less severe symptoms, suggesting that the condition and the neurotransmitter are linked.

Is the dark really making me sad? | Ars Technica

Seasonality is reported by approximately 10 to 20 percent of people with depression and 15 to 22 percent of those with bipolar disorder. “People often don’t realise that there is a continuum between the winter blues—which is a milder form of feeling down, [sleepier and less energetic]—and when this is combined with a major depression,” says Anna Wirz-Justice, an emeritus professor of psychiatric neurobiology at the Centre for Chronobiology in Basel, Switzerland. Even healthy people who have no seasonal problems seem to experience this low-amplitude change over the year, with worse mood and energy during autumn and winter and an improvement in spring and summer, she says.

data driven future... or not

As Harvard Psychiatrists John Torous and Justin Baker recently wrote in JAMA Psychiatry, “Data science and technology can provide a nearly limitless set of decision-support and self-monitoring tools. However, without individual psychiatrists and the field at large making a concerted push to drive the technology forward…these advances will likely fail to transform our troubled system of care.”

DSM versus neuroscience

Compared with the psychiatric diagnoses listed in the Diagnostic and Statistical Manual of Mental Disorders (D.S.M.), which can be vague and flawed, brain-based research holds out the promise of a precise and truly scientific understanding of mental illness.

Dr. Nestler is dean for academic and scientific affairs and director of the Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai. Dr. Hyman is a past director of the National Institute of Mental Health.

Virtually all of today’s treatments are based on serendipitous discoveries made six decades ago.

Study bias

Selective publication of clinical trials on antidepressants also could cause a bias about their perceived effectiveness, according to a study led by researchers at the Portland Veterans Affairs Medical Center (New England Journal of Medicine, 2008). The study examined 74 FDA-registered studies for a dozen antidepressants and found that most studies with negative results were not published in scientific literature or were published in a way that conveyed a positive outcome. The FDA studies showed that half of the drug trials had positive results, but 94 percent of the trials cited in published literature were positive.

ADjusting the body's clock with light to counter depression

Researchers have developed a limited form of sleep deprivation that is euphemistically called wake therapy. It has been shown to have sustained antidepressant benefit in patients with bipolar disorder and major depression. The idea is to get up for the day halfway through the usual sleep period, which shifts the circadian clock to an earlier time. It’s thought that this works by realigning the sleep cycle with other circadian rhythms, like changes in levels of body temperature and the stress hormone cortisol, that are also out of sync with each other in depression. Studies show that it is possible to make wake therapy even more powerful by incorporating two additional interventions: early morning light therapy and what’s called sleep phase advance, in which the patient goes to bed about five to six hours earlier than usual and sleeps for about seven hours. This combination of treatments is called triple chronotherapy, and the typical course involves one night of complete sleep deprivation followed by three nights of phase-advanced sleep and early morning light. In one study of 60 hospitalized patients with bipolar depression who were taking antidepressants or lithium, 70 percent of those who did not have a history of drug resistance improved rapidly with sleep deprivation and early morning light, and 57 percent remained well after nine months. Encouragingly, 44 percent of patients who had failed to respond to at least one trial of anti-depressants also improved.

Cognitive decline after surgery tied to brain's own immune cells: In mouse study, experimental drug blocks post-operative memory loss -- ScienceDaily

Post-operative cognitive dysfunction was previously believed to be caused by deep anesthesia during surgery. But increasing evidence instead links the condition to an inflammatory reaction in the brain, now understood to be a normal response to tissue trauma occurring anywhere in the body -- even surgeries physically distant from the brain, such as hip replacement, may trigger this response. Studies have shown that when this inflammation is excessive or too persistent, as may be the case in the elderly, the normally protective response can negatively impact cognition. "Previous studies on post-operative inflammation in the brain had focused on whether circulating immune cells invade the brain and contribute to cognitive decline," Koliwad said. "Based on our new research, we now know that the brain's own microglia initiate and orchestrate this response, including the infiltration of peripheral immune cells and the resultant memory loss."

The brain's spontaneous activity and its psychopathological symptoms - "Spatiotemporal binding and integration". - PubMed - NCBI

I here suggest to conceive the brain's spontaneous activity in spatiotemporal terms that is, by various mechanisms that are based on its spatial, i.e., functional connectivity, and temporal, i.e., fluctuations in different frequencies, features. I here point out two such spatiotemporal mechanisms, i.e., "spatiotemporal binding and integration". Alterations in the resting state's spatial and temporal features lead to abnormal "spatiotemporal binding and integration" which results in abnormal contents in cognition as in the various psychopathological symptoms. This, together with concrete empirical evidence, is demonstrated in depression and schizophrenia.

Light boosts serotonin

Exposure to bright light is a second possible approach to increasing serotonin without drugs. Bright light is, of course, a standard treatment for seasonal depression, but a few studies also suggest that it is an effective treatment for nonseasonal depression38 and also reduces depressed mood in women with premenstrual dysphoric disorder39 and in pregnant women suffering from depression.40 The evidence relating these effects to serotonin is indirect. In human postmortem brain, serotonin levels are higher in those who died in summer than in those who died in winter.41 A similar conclusion came from a study on healthy volunteers, in which serotonin synthesis was assessed by measurements of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the venous outflow from the brain.42 There was also a positive correlation between serotonin synthesis and the hours of sunlight on the day the measurements were made, independent of season. In rats, serotonin is highest during the light part of the light–dark cycle, and this state is driven by the photic cycle rather than the circadian rhythm.43,44 The existence of a retinoraphe tract may help explain why, in experimental animals, neuronal firing rates, c-fos expression and the serotonin content in the raphe nuclei are responsive to retinal light exposure.44–48 In humans, there is certainly an interaction between bright light and the serotonin system. The mood-lowering effect of acute tryptophan depletion in healthy women is completely blocked by carrying out the study in bright light (3000 lux) instead of dim light.49

Why virtual reality could be a mental health gamechanger | Science | The Guardian

We’ve just completed the first review of every study that has used VR to assess, understand, and treat mental health conditions. The earliest was undertaken almost 25 years ago, at a time when the cost and complexity of the equipment and programming meant that research was confined to a very small number of specialist centres. Since then 285 studies have been published. Most of those have focused on using VR to treat anxiety disorders and particularly phobias, social anxiety, and PTSD. The results have been encouraging — VR is a proven means of delivering rapid, lasting improvements.

Mouse study identifies new method for treating depression: Inhibiting brain enzyme alleviates depression, and does it much faster than conventional antidepressants -- ScienceDaily

Palmer and team unraveled a previously underappreciated molecular process that can influence mouse models of depression. Here's how the process works: Cells generate energy. In doing so, they produce a byproduct. That byproduct inhibits neurons and thus influences various behaviors. Typically, the enzyme GLO1 removes this byproduct, but inhibiting GLO1 can also increase the activity of certain neurons in a beneficial way. In mice, Palmer and others have shown that more GLO1 activity makes mice more anxious, but less was known about the system's effect on depression. Palmer and team wondered if they could reduce signs of depression by inhibiting the GLO1 enzyme. The researchers used several different antidepressant tests. They compared responses in three groups of mice: 1) untreated, 2) treated by inhibiting GLO1, either genetically or with an experimental compound, and 3) treated with Prozac, a selective serotonin reuptake inhibitor commonly used to treat depression. The first tests they used were the tail suspension test and the forced swim tests, which are often used to determine whether or not a compound is an antidepressant. In this case, the answer was yes. The other tests -- chronic forced swim test, chronic mild stress paradigm and olfactory bulbectomy -- are well-established measures that can also be used to measure how long it takes for an antidepressant to take effect. In each of these tests, inhibiting the GLO1 enzyme reduced depression-like symptoms in five days, whereas it took 14 days for Prozac to have the same effect. While this new approach to treating depression has so far only been tested in mice and it will take many years of development before a GLO1 inhibitor could be tested in humans, the researchers are excited to find that new, unexplored approaches to treating depression are out there.

Rumination: cause rather than effect of depression?

The metacognitive approach offers promising opportunities for addressing these limitations of treatment by directly targeting rumination and its underlying mechanisms that are seen as essential in the development and maintenance of depression (Wells, 2009).

5 minute bout of walking boosts mood

This may be partly due to the guideline's inclusion of a 10-minute minimum time-bout requirement for PA. Our findings suggest that a shorter, 5-minute bout of PA is adequate to elicit psychological health benefits. This may be encouraging to individuals who perceive “lack of time” as an exercise barrier. Individuals may also perceive this shorter time requirement to be less physically demanding. Notably, the present study demonstrates that mood-related benefits of a 5-minute exercise bout can occur from a self-selected walking pace. A self-selected pace is generalizable, and encouragingly, this may positively influence an individual's confidence in his or her ability to sustain activity and his or her anticipated enjoyment of the activity. Health care providers should consider the positive benefits of a 5-minute bout of exercise when prescribing treatment for patients suffering from mood-related disorders.

Groundbreaking fMRI study finds 4 distinct neurological subtypes of depression - ExtremeTech

We found that, superimposed on this shared pathological core, distinct patterns of abnormal functional connectivity differentiated the four biotypes and were associated with specific clinical-symptom profiles. For example, as compared to controls, reduced connectivity in frontoamygdala networks, which regulate fear-related behavior and reappraisal of negative emotional stimuli, was most severe in biotypes 1 and 4, which were characterized in part by increased anxiety. By contrast, hyperconnectivity in thalamic and frontostriatal networks, which support reward processing, adaptive motor control and action initiation, were especially pronounced in biotypes 3 and 4 and were associated with increased anhedonia and psychomotor retardation. And reduced connectivity in anterior cingulate and orbitofrontal areas supporting motivation and incentive-salience evaluation was most severe in biotypes 1 and 2, which were characterized partly by increased anergia and fatigue.

Physical Exercise and Psychological Well-Being: A Population Study in Finland - ScienceDirect

The results of this cross-sectional study suggest that individuals who exercised at least two to three times a week experienced significantly less depression, anger, cynical distrust, and stress than those exercising less frequently or not at all. Furthermore, regular exercisers perceived their health and fitness to be better than less frequent exercisers did. Finally, those who exercised at least twice a week reported higher levels of sense of coherence and a stronger feeling of social integration than their less frequently exercising counterparts.