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(So does running) Ketamine reverses neural changes underlying depression-related behaviors in mice: Study sheds light on the neural mechanisms underlying remission of depression -- ScienceDaily

Researchers took high-resolution images of dendritic spines in the prefrontal cortex of mice before and after they experienced a stressor. Dendritic spines are protrusions in the part of neurons that receive communication input from other neurons. The researchers found that mice displaying behaviors related to depression had increased elimination of, and decreased formation of, dendritic spines in their prefrontal cortex compared with mice not exposed to a stressor. This finding replicates prior studies linking the emergence of behaviors related to depression in mice with dendritic spine loss. In addition to the effects on dendritic spines, stress reduced the functional connectivity and simultaneous activity of neurons in the prefrontal cortex of mice. This reduction in connectivity and activity was associated with behaviors related to depression in response to stressors. Liston's group then found that ketamine treatment rapidly restored functional connectivity and ensemble activity of neurons and eliminated behaviors related to depression

Gut Bacteria Linked to Depression Identified – Neuroscience News

Mireia Valles-Colomer (VIB-KU Leuven): ‘Many neuroactive compounds are produced in the human gut. We wanted to see which gut microbes could participate in producing, degrading, or modifying these molecules. Our toolbox not only allows to identify the different bacteria that could play a role in mental health conditions, but also the mechanisms potentially involved in this interaction with the host. For example, we found that the ability of microorganisms to produce DOPAC, a metabolite of the human neurotransmitter dopamine, was associated with better mental quality of life.’

The cumulative effect of reporting and citation biases on the apparent efficacy of treatments: the case of depression

Figure 1 demonstrates the cumulative impact of reporting and citation biases. Of 105 antidepressant trials, 53 (50%) trials were considered positive by the FDA and 52 (50%) were considered negative or questionable (Fig. 1a). While all but one of the positive trials (98%) were published, only 25 (48%) of the negative trials were published. Hence, 77 trials were published, of which 25 (32%) were negative (Fig. 1b). Ten negative trials, however, became ‘positive’ in the published literature, by omitting unfavorable outcomes or switching the status of the primary and secondary outcomes (Fig. 1c). Without access to the FDA reviews, it would not have been possible to conclude that these trials, when analyzed according to protocol, were not positive. Among the remaining 15 (19%) negative trials, five were published with spin in the abstract (i.e. concluding that the treatment was effective). For instance, one article reported non-significant results for the primary outcome (p = 0.10), yet concluded that the trial ‘demonstrates an antidepressant effect for fluoxetine that is significantly more marked than the effect produced by placebo’ (Rickels et al., 1986). Five additional articles contained mild spin (e.g. suggesting the treatment is at least numerically better than placebo). One article lacked an abstract, but the discussion section concluded that there was a ‘trend for efficacy’. Hence, only four (5%) of 77 published trials unambiguously reported that the treatment was not more effective than placebo in that particular trial (Fig. 1d). Compounding the problem, positive trials were cited three times as frequently as negative trials (92 v. 32 citations in Web of Science, January 2016, p < 0.001, see online Supplementary material for further details) (Fig. 1e). Among negative trials, those with (mild) spin in the abstract received an average of 36 citations, while those with a clearly negative abstract received 25 citations. While this might suggest a synergistic effect between spin and citation biases, where negatively presented negative studies receive especially few citations (de Vries et al., 2016), this difference was not statistically significant (p = 0.50), likely due to the small sample size. Altogether, these results show that the effects of different biases accumulate to hide non-significant results from view.

You Can't Cure Depression By Working Out - Tonic

Our two proven treatment paths for psychiatric illnesses are medication and therapy. People have messed around with the possibility of a third (electroconvulsive therapy, heat therapy) but we don't currently have one, no matter how many people say running eases their nerves better than medication.

SSRIs a 'Double-Edged Sword' in Major Depression?

Investigators led by Igor Branchi, PhD, Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy, explored the hypothesis that SSRIs may not "affect mood per se but [may amplify] the influence of living conditions on mood."

How does helping people affect your brain? Study shows neurobiological effects of giving social support -- ScienceDaily

"Humans thrive off social connections and benefit when they act in the service of others' well-being," according to the authors. A previous study by Dr. Inagaki, also published in Psychosomatic Medicine, found that giving social support has positive effects on brain areas involved in stress and reward responses. That study suggested that providing support -- not just receiving it -- may be an important contributor to the physical and mental health benefits of social support.

In test with rats, cannabidiol showed sustained effects against depression for seven days -- ScienceDaily

"The forced swim test is used to measure the effect of antidepressant drugs because all known antidepressants shorten the duration of immobility and hence lengthen swim time. A reduction in immobility time in this test is interpreted as 'antidepressant-like' behavior." The researchers found that cannabidiol induced acute and sustained antidepressant-like effects in mice submitted to the forced swim test. "However, to make sure this result isn't due to the increase in movement caused by a psychostimulant effect leading the animals to swim more vigorously, for example, we performed a separate test to control for locomotor activity," Joca explained. "To do this we used the open-field test, which consists of putting the animal in a novel arena and letting it explore the new environment freely while its locomotor and exploratory activity is recorded. A drug is said to have potential antidepressant effects if it reduces immobility time and increases swim time in the forced swim test without increasing locomotor activity in the open-field test, showing that the effects observed in the forced swim test aren't secondary to nonspecific alterations in locomotor activity."

Painting a Nuanced Picture of Brain System Regulation Moods and Movements - Neuroscience News

In a series of behavioral tests, the scientists also showed that serotonin neurons from the two groups can respond differently to stimuli. For example, neurons in both groups fired in response to mice receiving rewards like sips of sugar water but they showed opposite responses to punishments like mild foot shocks. “We now understand why some scientists thought serotonin neurons are activated by punishment, while others thought it was inhibited by punishment. Both are correct – it just depends on which subtype you’re looking at,” Luo said.

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.

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

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.

Ketamine Acts Fast to Treat Depression and Its Effects Last, But How? - Neuroscience News

Ketamine produces rapid and robust antidepressant effects in depressed patients within hours of administration, often when traditional antidepressant compounds have failed to alleviate symptoms. We hypothesized that ketamine would translocate Gαs from lipid rafts to non-raft microdomains, similarly to other antidepressants but with a distinct, abbreviated treatment duration. C6 glioma cells were treated with 10 µM ketamine for 15 min, which translocated Gαs from lipid raft domains to non-raft domains. Other NMDA antagonist did not translocate Gαs from lipid raft to non-raft domains. The ketamine-induced Gαs plasma membrane redistribution allows increased functional coupling of Gαs and adenylyl cyclase to increase intracellular cyclic adenosine monophosphate (cAMP). Moreover, increased intracellular cAMP increased phosphorylation of cAMP response element-binding protein (CREB), which, in turn, increased BDNF expression. The ketamine-induced increase in intracellular cAMP persisted after knocking out the NMDA receptor indicating an NMDA receptor-independent effect. Furthermore, 10 µM of the ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) also induced Gαs redistribution and increased cAMP. These results reveal a novel antidepressant mechanism mediated by acute ketamine treatment that may contribute to ketamine’s powerful antidepressant effect. They also suggest that the translocation of Gαs from lipid rafts is a reliable hallmark of antidepressant action that might be exploited for diagnosis or drug development.

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).

Lessons learned from placebo groups in antidepressant trials

The analysis of ‘nocebo effects’, e.g. adverse effects in placebo groups of antidepressant trials also confirms the impact of expectations: nocebo symptoms reflected the typical side-effect patterns expected in the drug group, with higher symptoms rates in the placebo groups of tricyclic antidepressant trials compared with placebo groups of trials testing selective serotonin reuptake inhibitors.

Antidepressants and bladder medicines linked to dementia in landmark study -- ScienceDaily

"We studied patients with a new dementia diagnosis and looked at what anticholinergic medication they were prescribed between four and 20 years prior to being diagnosed. "We found that people who had been diagnosed with dementia were up to 30 per cent more likely to have been prescribed specific classes of anticholinergic medications. And the association with dementia increases with greater exposure to these types of medication. "What we don't know for sure is whether the medication is the cause. It could be that these medications are being prescribed for very early symptoms indicating the onset of dementia.

Antidepressant withdrawal

About half (54%) met their goal of completely discontinuing one or more medications; 46% reported another outcome (use was reduced, use increased, or use stayed the same). Concerns about medications’ effects (for example, long-term effects and side effects) prompted the decision to discontinue for 74% of respondents. They used various strategies to cope with withdrawal symptoms, which 54% rated as severe. Self-education and contact with friends and with others who had discontinued or reduced medications were most frequently cited as helpful. Although more than half rated the initial medication decision with prescribers as largely collaborative, only 45% rated prescribers as helpful during discontinuation. Of respondents who completely discontinued, 82% were satisfied with their decision.

Men and women have opposite genetic alterations in depression: A study examines the sex-specific molecular changes in major depressive disorder -- ScienceDaily

Most of the genes that had altered expression were changed in only men or only women. However, genes that were altered in both men and women were changed in opposite directions. Women had increased expression of genes affecting synapse function, whereas men had decreased expression of the same genes. Women had decreases in genes affecting immune function, whereas men had increased expression of these genes. Additionally, the researchers applied their methods to data from a different set of subjects and replicated the opposing changes.

Psychiatric Medications Kill More Americans than Heroin

According to data from the MEPS (Medical Expenditure Panel Survey) database, the number of prescriptions for psychiatric medications (i. e. sedatives, antidepressants, psychostimulants, and antipsychotics) increased 117% between 1999 and 2013, from 197,247,557 prescriptions in 1999 to 427,837,506 prescriptions in 2013. Meanwhile, death rates from psychiatric medication overdose climbed a whopping 240% over the same time period, from 1.31 deaths per 100,000 in 1999 to 4.46 deaths per 100,000 in 2013 (we are excluding the CDC death rate data from 2014 since the MEPS 2014 data has not yet been published).

2008 -- long term use of antidepressants

More than 60% of Americans taking antidepressant medication have taken it for 2 years or longer, with 14% having taken the medication for 10 years or more.

Heart attack patients prescribed antidepressants have worse one-year survival -- ScienceDaily

After adjusting for baseline characteristics the researchers found that the rates of stroke and subsequent heart attacks were similar between the two groups, but patients prescribed antidepressants had significantly worse survival. The rate of all-cause mortality at one-year after discharge was 7.4% in patients prescribed antidepressants compared to 3.4% for those not prescribed antidepressants (p<0.001). Antidepressant prescription was an independent predictor for mortality, and increased the odds by 66% (odds ratio: 1.66; 95% confidence interval: 1.16 to 2.39).