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Timing is everything, to our genes -- ScienceDaily

Using RNA sequencing, the research team tracked gene expression in dozens of different non-human primate tissues every 2 hours for 24 hours. The team found that each tissue contained genes that were expressed at different levels based on the time of day. However, the number of these "rhythmic" genes varied by tissue type, from around 200 in pineal, mesenteric lymph nodes, bone marrow and other tissues to more than 3,000 in prefrontal cortex, thyroid, gluteal muscle and others. In addition, genes that were expressed most often tended to show more rhythmicity, or variability by time. Of the 25,000 genes in the primate genome, nearly 11,000 were expressed in all tissues. Of those (which mostly govern routine cellular functions, such as DNA repair and energy metabolism), 96.6 percent were particularly rhythmic in at least one tissue, varying drastically by when they were sampled.

Brief depression questionnaires could lead to unnecessary antidepressant prescriptions -- ScienceDaily

Of the 545 patients who did not complete brief depression questionnaires during their doctors' office visits, 10.5 percent were diagnosed with depression and 3.8 percent were prescribed antidepressants. Of the 50 patients who completed brief depression questionnaires during their doctors' office visits, 20 percent were diagnosed with depression and 12 percent were prescribed antidepressants.

Insomnia and depression: Japanese hospital workers questionnaire survey : Open Medicine

Chronic insomnia is the one of the factors influencing the development of mental illness. In this survey, we tried to clarify the relationship between chronic insomnia and various factors. Although there is no certainty about other possible independent variables, multiple regression analyses suggested that chronic insomnia is an important factor for depression. Koyama et al. found that subjects who suffered from severe sleeping disorders, not just during depression, tended to have decreased blood flow in the frontal lobe of the brain [2]. When SIGH-D was used to evaluate sleeping disorders, an IS of 3 or higher showed that its severity and the reduced blood flow in the frontal lobe are significantly correlated. Based on this biological finding, preliminary research was conducted with 108 working participants, which included healthy participants and patients with mild to moderate depressive episodes. The result showed that the IS was significantly correlated with the severity of depression, subjective fatigue, sadness, and suicidal thoughts. Thus, an IS evaluation has the possibility of identifying depression based on a questionnaire survey related to direct mood changes [3]. There have been robust findings concerning the biology underlying the close relationship between sleep disorders and depression. For example, Buckley has found that a protracted sleep disorder, not depression, induces hyperactivity of the HPA (hypothalamic-pituitary-adrenal axis) system [14]. Furthermore, exposure to extreme stress causes the excessive secretion of corticotropin releasing hormone (CRH) —a cerebral mechanism for stress adaptation. This release of CRH inhibits the activities of the serotonin pathway in the nervous system that extends from the dorsal raphe nucleus to the prefrontal area via the gamma-aminobutyric acid (GABA) system [15]. It is also known that CRH has a stimulant effect [14]. Therefore, it is inferred that a substantive lack of sleep will lead to a sustained activation of the HPA system once again, thus establishing a vicious cycle. On the other hand, the decline in frontal lobe function due to depression has been established by several earlier studies, including those that used functional brain imaging [15,16,17,18]. The protraction of a sleep disorder activating the HPA system and inhibiting the serotonin nervous system in the frontal lobe is believed to elicit a clinical condition similar to depression. Furthermore, the finding that the hyperactivity of the HPA system increases cortisol secretion, which inhibits the HPA system and damages hippocampal cells, further strengthens the suggested relationship between sleep disorders and depression. This biological finding strengthens the theory that a lack of sleep due to insomnia, exposure to stress, and overwork, leads to depression because of the accumulation of mental fatigue.

On the Couch... with Dick Cavett | Psychology Today

I would spend days reading "The Variety of Religious Experiences" by William James from beginning to end - and not remembering at all what I read. Serani: Oh, I know what that's like. The cognitive fog and slowed thinking. Just terrible. Cavett:  Yeah, I would get three or four sentences into a paragraph and not get it. I'd try again and still couldn't get it. But making the effort to read was better than sitting in my apartment doing nothing or sleeping all day. One day, I'll have to give old William James another try again.

How exercise training promotes a sound mind in a sound body -- ScienceDaily

In the earlier study, the researchers were able to show that trained muscles help to clean the blood in a way similar to the kidneys and liver. Through exercise training, the muscles can convert the stress marker kynurenine into kynurenic acid. High levels of kynurenine have been measured in people with depression and mental illness. For this present study, the researchers further examined the function of kynurenic acid. Using mice fed on a fat-rich diet that made them overweight and raised their blood sugar levels, they found that a daily dose of kynurenic acid stopped the mice putting on weight and gave them better glucose tolerance, despite no change in their food intake. The researchers posit the explanation that kynurenic acid activated the cell receptor GPR35, which is found in both fat cells and immune cells. This led in the former to a conversion of white fat into energy-burning brown fat, and in the latter to an enhancement of their anti-inflammatory properties

The Roles of BDNF in the Pathophysiology of Major Depression and in Antidepressant Treatment

Animal studies have demonstrated that stress reduces BDNF expression or activity in the hippocampus and that this reduction can be prevented by treatment with antidepressant drugs. A similar change in BDNF activity occurs in the brain of patients with major depression disorder (MDD). Recently, clinical studies have indicated that serum or plasma BDNF levels are decreased in untreated MDD patients. Antidepressant treatment for at least four weeks can restore the decreased BDNF function up to the normal value. Therefore, MDD is associated with impaired neuronal plasticity. Suicidal behavior can be a consequence of severe impaired neuronal plasticity in the brain. Antidepressant treatment promotes increased BDNF activity as well as several forms of neuronal plasticity, including neurogenesis, synaptogenesis and neuronal maturation. BDNF could also play an important role in the modulation of neuronal networks. Such a neuronal plastic change can positively influence mood or recover depressed mood.

On the Couch... with Dick Cavett | Psychology Today

Cavett: I remember being alone in Montauk by the sea one time, feeling very, very depressed. My late wife was away doing a play in Chicago. It took all that I had to just get the dog to come upstairs and turn on the television. Well, on came an old "Saturday Night Live" episode that I happened to be hosting. I saw myself smiling, cheerful - happy as a clam. I was sparkling. I was funny. And watching that was like a tonic. Had I not watched it, I think I might have stayed in that drowning darkness for more days. Perhaps it can be an area researched more in psychology. You know, seeing yourself in happier times. Maybe there's something to that.

Does dim light make us dumber? -- ScienceDaily

Spending too much time in dimly lit rooms and offices may actually change the brain's structure and hurt one's ability to remember and learn, indicates groundbreaking research by Michigan State University neuroscientists. The researchers studied the brains of Nile grass rats (which, like humans, are diurnal and sleep at night) after exposing them to dim and bright light for four weeks. The rodents exposed to dim light lost about 30 percent of capacity in the hippocampus, a critical brain region for learning and memory, and performed poorly on a spatial task they had trained on previously. The rats exposed to bright light, on the other hand, showed significant improvement on the spatial task. Further, when the rodents that had been exposed to dim light were then exposed to bright light for four weeks (after a month-long break), their brain capacity -- and performance on the task -- recovered fully.

A new path into bipolar disorder comes to light -- ScienceDaily

One type of protein produced by IEGs is the so-called Early Growth Response (EGR) proteins, which translate environmental influence into long-term changes in the brain. These proteins are found throughout the brain and are highly produced in response to environmental changes such as stressful stimuli and sleep deprivation. Without the action played out by these proteins, brain cells and the brain itself cannot appropriately respond to the many stimuli that are constantly received from the environment. Effective neuronal plasticity also depends on neurotrophins, which are regulatory factors that promote development and survival of brain cells. Brain-derived neurotrophic factor (BDNF) is the neurotrophin mostly found in the brain. It has been extensively investigated in BD patients and has been suggested as a hallmark of BD. Indeed, some studies have shown that the levels of BDNF in the serum of BD patients are reduced whenever patients undergo a period of depression, hypomania, or mania. Other studies have shown that regardless of mood state, BD patients present reduced levels of BDNF. Overall, changes in BDNF levels seem to be a characteristic found in BD patients that may contribute to the pathophysiology of the disease.

Grape-derived compounds may promote resilience against depression, researchers find: New study used DNA epigenetic mapping to analyze novel inflammatory mechanisms influencing brain circuitry associated with depression -- ScienceDaily

According to the U.S. Centers for Disease Control and Prevention, each year approximately 16 million individuals in the United States have a major depressive episode. Conventional pharmacological treatments are estimated to produce temporary remission in less than 50 percent of patients, and they are often associated with severe adverse effects. Thus, there is an urgent need for a wider spectrum of novel therapeutics. Depression is associated with a multitude of pathological processes, including inflammation of the peripheral immune system, a set of biological structures and processes in the lymph nodes and other tissues that protect against disease and abnormalities involving synapses, the structures that permit neurons to pass an electrical or chemical signal to other neurons. However, currently available antidepressants are largely restricted to targeting the systems that regulate serotonin, dopamine, and other related neurotransmitters, and these treatments do not specifically address inflammation and synaptic maladaptations that are now known to be associated with MDD. Previous research has found that grape-derived polyphenols have some efficacy in modulating aspects of depression, yet the mechanisms of action had largely remained unknown until now. The new study, led by Giulio Maria Pasinetti, PhD, Saunders Professor of Neurology, and a team of investigators from the Center for Integrative Molecular Neuroresilience at the Icahn School of Medicine at Mount Sinai, found that a bioactive dietary polyphenol preparation -- a combination of three grape-derived polyphenol products, including a select Concord grape juice, a select grape seed extract, and trans-resveratrol -- was effective in promoting resilience against stress-induced depression in mice. Specifically, researchers found that DHCA and Mal-gluc can promote resilience in mouse models of depression by modulating inflammation and synaptic plasticity, respectively. DHCA reduces interleukin 6 (IL-6), a pro-inflammatory substance secreted by T cells and macrophages to stimulate immune response, by epigenetically modulating the non-coding sequence of the IL-6 gene. Mal-gluc modulates histone acetylation of the Rac1 gene and allows transcription activators to access the DNA for increased transcription in the brain, which influences the expression of genes responsible for synaptic plasticity. Researchers also demonstrated that DHCA/Mal-gluc treatment was effective in attenuating depression-like phenotypes in a mouse model of increased systemic inflammation induced by transplantation of cells from the bone marrow of stress-susceptible mice.

The Last All-Nighter -

I wish it had ended that easily. In the months that followed, I was exhausted all the time. I slept through appointments and was unable to stay up to meet deadlines. The drug had curbed my appetite, and helped me to drop from a size 8 to a 4. Without it now I was ravenous and neurotic about what I was eating and how I looked. I was sensitive and emotional from the new chemical imbalance, which gaining weight and falling behind at work exacerbated. It was hard to understand that I was experiencing withdrawal, because I was never warned of possible side effects. Without the drug I felt stupid, unable to focus or follow a thought through to completion. I was shy, and unwilling to initiate conversation. The witty, articulate woman I once was seemed to no longer exist. I felt dumb, out of it. I spoke slowly because it took immense effort to gather and express coherent thoughts. I didn’t understand what I was going through, and that made it more difficult to stay healthy. It felt like another phase of the depression I had become so used to. But once I made it through the hardest part, weeks where my body was literally recalibrating itself to function without the stimulant, I felt like my old self again — relaxed, yet motivated to take care of my mind and body; interested in engaging with the world around me. The person I was so eager to shed in lieu of a new, accomplished, adult me, actually ended up being the one most capable of handling the tumult of living in the hectic life of a 20-something starting out in New York.

Depression, antidepressants, and the shrinking hippocampus

Both the tragic components and the intellectual challenge of depression have deepened in the last decade with a series of high-visibility reports that indicate prolonged, major depression is associated with atrophy within the central nervous system. A report in this issue of PNAS by Czéh et al. (1) adds support to a possible route for reversing these morphological changes. Such atrophy is centered in a brain region called the hippocampus. This structure plays a critical role in learning and memory, and the magnitude of the hippocampal volume loss (nearly 20% in some reports; refs. 2–4) helps explain some well-documented cognitive deficits that accompany major depression. These were careful and well-controlled studies, in that the atrophy was demonstrable after controlling for total cerebral volume and could be dissociated from variables such as history of antidepressant treatment, electroconvulsive therapy, or alcohol use. Moreover, more prolonged depressions were associated with more severe atrophy. These findings of hippocampal atrophy raise immediate questions. First, is it permanent? Tentatively, this appears to be the case, as the atrophy persisted for up to decades after the depressions were in remission. In addition, the extent of atrophy did not lessen with increasing duration of remission (2–4).

Feel anxious? Have trouble sleeping? You may be traveling for business too often -- ScienceDaily

People who travel for business two weeks or more a month report more symptoms of anxiety and depression and are more likely to smoke, be sedentary and report trouble sleeping than those who travel one to six nights a month, according to a latest study conducted by researchers at Columbia University's Mailman School of Public Health and City University of New York. Among those who consume alcohol, extensive business travel is associated with symptoms of alcohol dependence. Poor behavioral and mental health outcomes significantly increased as the number of nights away from home for business travel rose. This is one of the first studies to report the effects of business travel on non-infectious disease health risks. The results are published online in the Journal of Occupational and Environmental Medicine.

Swimming rats

More troubling, these screens occasionally became imposters for disease models in the academic literature as well as in industry, despite scant corroborative evidence. In the widely used forced-swim and tail-suspension tests, for example, a compound is considered to be an antidepressant when, compared with a control, it causes a rat or mouse to continue swimming or actively struggling longer. Forced-swim and tail-suspension tests do not even model the therapeutic action of antidepressants, because in these rodent screens, a single dose of antidepressant is active, whereas in depressed patients, antidepressant drugs require weeks of administration to exert a therapeutic effect.

Withdrawing -- and what helped

Maybe dealing with life’s distresses has its own chemistry. I know I hated every second of it. I don’t know if the medication helped. But I do know that I’m very glad I’m off.

Chemical imbalance boosts negative viewsof mentally ill

“The results of the current study suggest that we may actually treat people more harshly when their problem is described in disease terms,” Mehta wrote. “We say we are being kind, but our actions suggest otherwise.” The problem, it appears, is that the biomedical narrative about an illness like schizophrenia carries with it the subtle assumption that a brain made ill through biomedical or genetic abnormalities is more thoroughly broken and permanently abnormal than one made ill though life events. “Viewing those with mental disorders as diseased sets them apart and may lead to our perceiving them as physically distinct. Biochemical aberrations make them almost a different species.”

Analysis shows wearable data could help identify mental health conditions in diabetic populations | MobiHealthNews

Kumar said that individuals with mental health illnesses (MHI) are also at a higher risk for developing diabetes than those without. This is because MHI is associated with unhealthy eating habits, less physical activity and a potential increase in weight.  The analysis, which was complied by using data from general Achievement use, found that diabetes patients that self-reported symptoms of MHI walk on average 1,469 steps less per day than those without MHI symptoms. The mean daily steps taken by diabetes patients with no MHI symptoms was 7,032, compared to patients with MHI symptoms who walked 5,663 steps a day.  Participants with MHI symptoms had a lower frequency of days with high activity levels and more frequent days with lower activity levels than their counterparts without MHI symptoms. There was little difference in sleep between the two groups; patients with MHI symptoms slept an average of 6.48 hours and those with MHI symptoms slept an average of 6.72 hours.  The analysis looked at survey results from 1,330 participants with diabetes. Three hundred and thirty-six or 25.3 percent reported having some MHI in the last year. Of that 77 percent reported having anxiety symptoms and 23.7 percent reported having some form of depression.

Antidepressants and the Placebo Effect

Many patients in clinical trials realize that they have been given the real drug, rather than the placebo, most likely because of the drug’s side effects. What effect is this likely to have in a clinical trial? We do not have to guess at the answer to this question. Bret Rutherford and his colleagues at Columbia University have provided the answer. They examined the response to antidepressants in studies that did not have a placebo group with those in studies where they did have a placebo group (Rutherford, Sneed, & Roose, 2009). The main difference between these studies is that in the first case, the patients were certain they were getting an active antidepressant, where as in the placebo-controlled trials, they knew that they might be given a placebo. Knowing for sure that they were getting an active drug boosted the effectiveness of the drug significantly. This supports the hypothesis that the relatively small difference between drug and placebo in antidepressant trials are at least in part due to “breaking blind” and discerning that one is in the drug group, because of the side effects produced by the drug.

Antidepressants and the Placebo Effect

The most commonly prescribed antidepressants are SSRIs, drugs that are supposed to selectively target the neurotransmitter serotonin. But there is another antidepressant that has a very different mode of action. It is called tianeptine, and it has been approved for prescription as an antidepressant by the French drug regulatory agency. Tianeptine is an SSRE, a selective serotonin reuptake enhancer. Instead of increasing the amount of serotonin in the brain, it is supposed to decrease it. If the theory that depression is caused by a deficiency of serotonin were correct, we would expect to make depression worse. But it doesn’t. In clinical trials comparing the effects of tianeptine to those of SSRIs and tricyclic antidepressants, 63% of patients show significant improvement (defined as a 50% reduction in symptoms), the same response rate that is found for SSRIs, NDRIs, and tricyclics, in this type of trial (Wagstaff, Ormrod, & Spencer, 2001). It simply does not matter what is in the medication – it might increase serotonin, decrease it, or have no effect on serotonin at all. The effect on depression is the same.

Antidepressants and the Placebo Effect

Yet this 11% figure may overestimate the number of people who benefit from antidepressants. Antidepressants are also prescribed to people who do not qualify for the diagnosis of major depression. My neighbor’s pet dog died; his physician prescribed an antidepressant. A friend in the US was diagnosed with lumbar muscle spasms and was prescribed an antidepressant. I have lost count of the number of people who have told me they were prescribed antidepressants when complaining of insomnia – even though insomnia is a frequently reported side effect of antidepressants. About 20% of patients suffering from insomnia in the United States are given antidepressants as a treatment by their primary care physicians (Simon & VonKorff, 1997), despite the fact that “the popularity of antidepressants in the treatment of insomnia is not supported by a large amount of convincing data, but rather by opinions and beliefs of the prescribing physicians” (Wiegand, 2008, p. 2411).

Antidepressants and the Placebo Effect

More important, in both analyses, the mean difference between drug and placebo was less than two points on the HAM-D. The HAM-D is a 17-item scale on which people can score from 0 to 53 points, depending on how depressed they are. A six-point difference can be obtained just by changes in sleep patterns, with no change in any other symptom of depression. So the 1.8 difference that we found between drug and placebo was very small indeed – small enough to be clinically insignificant. But you don’t have to take my word for how small this difference is. The National Institute for Health and Care Excellence (NICE), which drafts treatment guidelines for the National Health Service in the United Kingdom, has established a three-point difference between drug and placebo on the HAM-D as a criterion of clinical significance (NICE, 2004). Thus, when published and unpublished data are combined, they fail to show a clinically significant advantage for antidepressant medication over inert placebo.

Star Neuroscientist Tom Insel Leaves the Google-Spawned Verily for ... a Startup? | WIRED

“I spent 13 years at NIMH really pushing on the neuroscience and genetics of mental disorders, and when I look back on that I realize that while I think I succeeded at getting lots of really cool papers published by cool scientists at fairly large costs—I think $20 billion—I don’t think we moved the needle in reducing suicide, reducing hospitalizations, improving recovery for the tens of millions of people who have mental illness,” Insel says. “I hold myself accountable for that.”

Antidepressants associated with significantly elevated risk of death, researchers find

Antidepressants block the absorption of serotonin in these organs as well, and the researchers warn that antidepressants could increase the risk of death by preventing multiple organs from functioning properly. The researchers reviewed studies involving hundreds of thousands of people and found that antidepressant users had a 33% higher chance of death than non-users. Antidepressant users also had a 14% higher risk of cardiovascular events, such as strokes and heart attacks. The findings were published today in the journal Psychotherapy and Psychosomatics.

The concept of schizophrenia is coming to an end – here's why

I expect to see the end of the concept of schizophrenia soon … the syndrome is already beginning to breakdown, for example, into those cases caused by copy number [genetic] variations, drug abuse, social adversity, etc. Presumably this process will accelerate, and the term schizophrenia will be confined to history, like “dropsy”.

Smartphone addiction creates imbalance in brain, study suggests -- ScienceDaily

The study involved 19 young people (mean age 15.5, 9 males) diagnosed with internet or smartphone addiction and 19 gender- and age-matched healthy controls. Twelve of the addicted youth received nine weeks of cognitive behavioral therapy, modified from a cognitive therapy program for gaming addiction, as part of the study. Researchers used standardized internet and smartphone addiction tests to measure the severity of internet addiction. Questions focused on the extent to which internet and smartphone use affects daily routines, social life, productivity, sleeping patterns and feelings. "The higher the score, the more severe the addiction," Dr. Seo said. Dr. Seo reported that the addicted teenagers had significantly higher scores in depression, anxiety, insomnia severity and impulsivity. The researchers performed MRS exams on the addicted youth prior to and following behavioral therapy and a single MRS study on the control patients to measure levels of gamma aminobutyric acid, or GABA, a neurotransmitter in the brain that inhibits or slows down brain signals, and glutamate-glutamine (Glx), a neurotransmitter that causes neurons to become more electrically excited. Previous studies have found GABA to be involved in vision and motor control and the regulation of various brain functions, including anxiety. The results of the MRS revealed that, compared to the healthy controls, the ratio of GABA to Glx was significantly increased in the anterior cingulate cortex of smartphone- and internet-addicted youth prior to therapy. Dr. Seo said the ratios of GABA to creatine and GABA to glutamate were significantly correlated to clinical scales of internet and smartphone addictions, depression and anxiety.

Frontiers | Metacognitive Therapy for Depression in Adults: A Waiting List Randomized Controlled Trial with Six Months Follow-Up | Psychology

A new treatment approach to depression that has produced encouraging results is metacognitive therapy (MCT; Wells, 2009). This approach is based on the metacognitive model where psychological disorder results from an inflexible and maladaptive response pattern to cognitive events labeled the Cognitive Attentional Syndrome (CAS; Wells, 2000; Wells and Matthews, 1994, 1996). The CAS consists of persistent worry and rumination, threat monitoring and ineffective coping strategies that contribute to the maintenance of emotional disorder. Rumination in depression is seen as a coping strategy which follows an initial negative thought labeled a ‘trigger thought’. The depressed individual engages in rumination consisting of repeatedly analyzing negative feelings, past failures and mistakes. Depression is therefore understood as an extension of low mood resulting from a problem of overthinking (e.g., worry and rumination) and withdrawal of active coping. (e.g., social withdrawal and reduction in activity). According to the metacognitive model of depression, rumination and worry is maintained by metacognitions and not by changes in mood or events. Further, this response to triggers extends negative thinking, leads to reduced attentional flexibility and involves a failure to exercise appropriate control over negative affective experiences (Wells, 2009). According to the metacognitive model metacognitive beliefs control, monitor and appraise the CAS (Wells, 2009). There are both positive and negative metacognitive beliefs. Positive metacognitions are concerned with the benefits of worry and rumination, while negative metacognitions are concerned with the uncontrollability and danger of thoughts. Positive metacognitions related to depression may be exemplified by statements like: “Analyzing the causes of my sadness will give me an answer to the problem”, and “Thinking the worst will make me snap out of it”. Such positive metacognitive beliefs lead to repeated and/or prolonged engagement in ruminative thinking. Negative metacognitions are activated as the rumination process leads to distress and/or as a result of what the individual learns about depression. Examples of negative metacognitions are: “I can’t control my thinking”, “My thoughts are caused by my defective brain”, “Sleeping more will sort out my mind”. and “Thinking like this means I could have a mental breakdown”. Negative metacognitions lead to more distress and to unhelpful behaviors that reduce effective coping.