At-Home Device to Treat Depression: Is This the Future of Mental Health? with Palki Sharma

Very recommendable! At least it is fairly harmless and if it helps some individuals the better! What else might be treatable in this way?

I have blogged here earlier today about this device.

US Food and Drug Administration (FDA) approved the first at-home brain stimulation headset for depression made by a Swedish company

Good news! Apparently, this device has been around for at least two years, but only approved now!

"... delivering gentle electrical currents to regulate mood as an alternative to antidepressants with side effects. ..."

"The U.S. Food and Drug Administration has approved Flow Neuroscience's at-home brain stimulation device to treat depression, offering an alternative to typical antidepressants that can cause side effects with long-term use, the company said on Thursday. ...

Flow's FL-100 delivers a gentle electrical current to the part of the brain that regulates mood and is designed for home use under remote supervision. It is the first such device to be approved in the U.S.

The device is cleared to treat moderate to severe major depressive disorders in adults aged 18 and older, as a standalone treatment or alongside other treatments, who are not considered resistant to medication.

Flow plans to launch the device in the U.S. in the second quarter of 2026 as a prescription-only treatment.

The company's CEO Erin Lee told Reuters the company is targeting a U.S. retail price between $500 and $800. ..."

Friday, December 12, 2025 - Join The Flyover

US FDA approves first at-home device for depression

Source

Severe depression tied to immune system imbalance, not just brain chemistry

Good news! What about lack of sunshine?

"... They found that this immune abnormality affects brain function, and the "Immune Neural Axis" imbalance is the core mechanism of depression, opening up the possibility for the discovery of new biomarkers and the development of new drugs for depression treatment. ...

performed a multi-omics analysis combining blood analysis, single-cell analysis, and patient-derived brain organoids (mini-brains). ..."

From the abstract:

"Major depressive disorder (MDD) with atypical features accompanied by psychotic symptoms represents a severe and under-researched subtype of depression and severe mental illness, characterized by significant personal and social impact.

This study aims to explore novel biomarkers through a precision medicine approach by combining clinical data, white blood cell (WBC) single-cell RNA sequencing (scRNA-seq), plasma proteomics, and brain organoid models to uncover immunological and neurological alterations in patients with this condition. Patients exhibited elevated stress, anxiety, depression, and increased WBC counts, although the difference in WBC count is not significant after adjusting for age.

Plasma proteomic profiling identified an upregulation of proteins implicated in synaptic formation, including Doublecortin-Like Kinase 3 (DCLK3) and Calcyon (CALY), as well as immune-related proteins such as Complement Component 5 (C5).

WBC scRNA-seq revealed significant neutrophil and monocyte transcriptomic alterations, suggesting increased inflammation and immune dysregulation. Patient-derived brain organoids display reduced growth and distinct gene expression patterns compared to controls, particularly under dexamethasone-induced stress conditions.

Combining WBC scRNA-seq, plasma proteomics, and brain organoid models offers a novel framework for understanding the pathophysiology of psychiatric disorders, which is one of the most complex disorders."

Depression tied to immune system imbalance, not just brain chemistry

Depression is Not Only a Disease of the Mind. KAIST Discovers the Immune-Brain Connection​ (original news release)

Exploration of Novel Biomarkers Through a Precision Medicine Approach Using Multi-Omics and Brain Organoids in Patients With Atypical Depression and Psychotic Symptoms (open access)

Figure 2

Differential WBC Single-cell Transcriptomic Profiles in the Patient Group Elevated Inflammatory Gene Expression in Neutrophils and Monocytes

Do transgender and binary adults suffer more from depression than other adults?

Quite possible! 

Were they depressive, because they did not receive gender-affirming hormone therapy? This study does not reveal.

This study also focused only on "moderate-to-severe depressive symptoms". What about other or lesser depressive symptoms?

"Gender-affirming hormone therapy was associated with lower rates of moderate-to-severe depressive symptoms among 3,592 trans and nonbinary people prescribed the treatment compared to those who didn’t receive the treatment, finds a study spanning 48 months of follow-up. JAMA Network Open"

From the key points and abstract:

"Key Points

Question

Is gender-affirming hormone therapy (GAHT) associated with lower rates of moderate to severe depressive symptoms in transgender, nonbinary, and gender diverse (TGD) adults in primary care?

Findings

In this cohort study of 3592 TGD patients in primary care at federally qualified community health centers in Boston and New York, 15.3% had moderate-to-severe depressive symptoms assessed using the Patient Health Questionnaire (PHQ). In addition, GAHT was associated with a lower risk of moderate-to-severe depressive symptoms across 48 months of follow-up.

Meaning

The findings of this study suggest that integrated GAHT with primary care and low-barrier GAHT access is associated with lower rates of mental health morbidity in TGD patients.

Abstract

Importance  In the US, transgender, nonbinary, and gender diverse (TGD) adults have high rates of depression. Gender-affirming hormone therapy (GAHT) is associated with improved mental health outcomes, yet existing US studies have short follow ups and lack sample diversity.

Objective

To evaluate the use of GAHT delivered in primary care as an intervention for moderate-to-severe depressive symptoms in diverse TGD adult patients.

Design, Setting, and Participants

LEGACY was an observational cohort study conducted in federally qualified community health centers in Boston and New York that followed up TGD patients (N = 3592) from calendar years 2016 to 2019 (48 months). Participants included individuals aged 18 years or older, gender identity different from sex at birth, a past 12-month medical visit, and signed patient consent form in the electronic health record (EHR).

Exposures

Prescriptions for GAHT obtained from EHR data, using the date of the first and last GAHT prescription in each calendar year of observation (GAHT within the year vs no GAHT during the year).

Main Outcomes and Measures

...

Results

The median age of the 3592 patients was 28 (IQR, 24-36) years. ... In addition, 18.9% were nonbinary, 52.1% lived below the federal poverty level, 34.2% were publicly insured, 4.1% were uninsured, and 5.1% were living with HIV. At baseline, 84.5% of the individuals were prescribed GAHT and 15.3% reported moderate-to-severe depressive symptoms. ...

Conclusions and Relevance

In this longitudinal observational cohort study, GAHT was associated with lower rates of moderate-to-severe depressive symptoms, highlighting the importance of gender-affirming primary care models for TGD patients."

Global Health NOW: Tedros Details Human Costs of U.S. Cuts; Moving Beyond Stigma in Mexico; and The Bureaucrat Bridging Gaps

Gender-Affirming Hormone Therapy and Depressive Symptoms Among Transgender Adults (open access)

Magnetic field applied to both sides of brain shows rapid improvement for depression

Good news!

"The treatment – known as repetitive transcranial magnetic stimulation (TMS) – involves placing an electromagnetic coil against the scalp to relay a high-frequency magnetic field to the brain. ...

“The treatment works faster because, by targeting two areas of the brain implicated in depression, we’re effectively correcting imbalances in two import processes, getting brain regions ‘talking’ to each other correctly.” ..."

From the abstract:

"Background

This study aimed to evaluate a novel rTMS protocol for treatment-resistant depression (TRD), using an EEG 10–20 system guided dual-target accelerated approach of right lateral orbitofrontal cortex (lOFC) inhibition followed by left dorsolateral prefrontal cortex (dlPFC) excitation, along with comparing 20 Hz dlPFC accelerated TMS v. sham.

Methods

Seventy five patients participated in this trial consisting of 20 sessions over 5 consecutive days comparing dual-site (cTBS of right lOFC followed sequentially by 20 Hz rTMS of left dlPFC), active control (sham right lOFC followed by 20 Hz rTMS of left dlPFC) and sham control (sham for both targets). Resting-state fMRI was acquired prior to and following treatment.

Results

Hamilton Rating Scale for Depression (HRSD-24) scores were similarly significantly improved at 4 weeks in both the Dual and Single group relative to Sham. Planned comparisons immediately after treatment highlighted greater HRSD-24 clinical responders (Dual: 47.8% v. Single:18.2% v. Sham:4.3%, χ2 = 13.0, p = 0.002) and in PHQ-9 scores by day 5 in the Dual relative to Sham group. We further showed that accelerated 20 Hz stimulation targeting the left dlPFC (active control) is significantly better than sham at 4 weeks. Dual stimulation decreased lOFC-subcallosal cingulate functional connectivity. Greater baseline lOFC-thalamic connectivity predicted better therapeutic response, while decreased lOFC-thalamic connectivity correlated with better response.

Conclusions

Our novel accelerated dual TMS protocol shows rapid clinically relevant antidepressant efficacy which may be related to state-modulation. This study has implications for community-based accessible TMS without neuronavigation and rapid onset targeting suicidal ideation and accelerated discharge from hospital."

Magnetic field applied to both sides of brain shows rapid improvement for depression | University of Cambridge "A type of therapy that involves applying a magnetic field to both sides of the brain has been shown to be effective at rapidly treating depression in patients for whom standard treatments have been ineffective."

A novel dual-site OFC-dlPFC accelerated repetitive transcranial magnetic stimulation for depression: a pilot randomized controlled study (open access)

Figure 1. Coil position and study procedure.

New, permanent brain wiring found that predicts depression in adults and children as young as 9 years old

Good news! Could this be a breakthrough?

"Although depression comes and goes, people who are prone to it retain distinct brain-wiring networks throughout their lives. An analysis of more than 180 functional magnetic resonance images showed that compared with healthy controls, people with major depression have larger ‘salience networks’ that integrate sensory information and emotion. These networks become more active during a depressive episode but persist even after the depression lifts. Researchers found the large networks in children as young as nine years old who had not yet been depressed but who went on to develop the disease as teenagers, suggesting this trait causes depression rather than being a result of it."

"The symptoms of depression might come and go, but new evidence suggests that the pattern of brain wiring behind it remains the same for life. The largest imaging study of its kind has found that a certain brain network involved in directing attention to stimuli is nearly twice as big in people with depression as it is in the rest of the population — and that it remains that way when a person no longer feels depressed. ...

To test this, the team turned to the ABCD Study, which aims to track brain development in nearly 12,000 children between the ages of 9 and young adulthood. They identified 57 children who did not have depression before the age of 13 but who developed the disorder as adolescents. At ages at young as nine years, these children already had expanded salience networks compared with their peers.  ..."

From the abstract:

"Decades of neuroimaging studies have shown modest differences in brain structure and connectivity in depression, hindering mechanistic insights or the identification of risk factors for disease onset. Furthermore, whereas depression is episodic, few longitudinal neuroimaging studies exist, limiting understanding of mechanisms that drive mood-state transitions. The emerging field of precision functional mapping has used densely sampled longitudinal neuroimaging data to show behaviourally meaningful differences in brain network topography and connectivity between and in healthy individuals, but this approach has not been applied in depression. Here, using precision functional mapping and several samples of deeply sampled individuals, we found that the frontostriatal salience network is expanded nearly twofold in the cortex of most individuals with depression. This effect was replicable in several samples and caused primarily by network border shifts, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was stable over time, unaffected by mood state and detectable in children before the onset of depression later in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in frontostriatal circuits that tracked fluctuations in specific symptoms and predicted future anhedonia symptoms. Together, these findings identify a trait-like brain network topology that may confer risk for depression and mood-state-dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time."

Nature Briefing: Translational Research

Found: a brain-wiring pattern linked to depression "The disease has a consistent mark in the brain even when symptoms are absent."

Frontostriatal salience network expansion in individuals in depression (open access)

The human brain contains distinct networks of different sizes, but the salience network – shown here in black – is consistently larger in people with major depressive disorder (two right columns).

Fig. 1: Frontostriatal salience network is expanded nearly twofold in the cortex of highly sampled individuals with depression.

Tweaked psychedelic toad toxin alleviates anxiety in mice

Sometimes the cure is worse than the disease comes to mind! (just kidding) 😊 A toast the toad!

"Psychedelic substances have gained attention in recent years as treatments for depression and other central nervous system disorders. Now, researchers have made an analog of 5-MeO-DMT that appears to relieve anxiety and depression in mice without causing hallucinations."

"To deter predators, the Colorado river toad (Incilius alvarius) exudes the toxin 5-MeO-DMT from glands within its skin. While the substance puts off predators, people who consume 5-MeO-DMT can have a psychedelic experience. ..."

Tweaked psychedelic toad toxin alleviates anxiety in mice Analog of the psychoactive compound 5-MeO-DMT doesn’t induce hallucinations in the rodents

Ketamine produces wide variety of responses in the brain, researchers find

Good news!

"Since Yale researchers first observed the ability of the anesthetic ketamine to dramatically improve symptoms in many patients with treatment-resistant depression more than two decades ago, the drug has provided a powerful new therapeutic option for mental health professionals.

However, only 65% of patients treated with ketamine respond to therapy and a new Yale-led study published April 17 in the journal eLife helps explain why.

Using functional magnetic resonance imaging (fMRI), researchers found that ketamine produces a variety of different response patterns in the brains of individuals, an observation that challenges the widely held assumption that treatments for mental health conditions produce the same effect in all people. ...
the different ways that ketamine affects the brain can be related to patterns of gene expression, a finding that might one day help predict who is most likely to respond to ketamine treatment. ...
In fact, they found that ketamine produced many more individually distinct “functional connectivity signatures” than has been observed in studies on the effects of psilocybin and LSD, the researchers report. ..."

From the abstract:

"Background:

Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine’s molecular mechanisms connect to its neural and behavioral effects.

Methods:

We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets.

Results:

We found that:

(i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability;

(ii) ketamine’s data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and

(iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level.

Conclusions:

These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry."

Ketamine produces wide variety of responses in the brain, researchers find | YaleNews A new Yale-led study explains why only 65% of patients treated with ketamine respond to therapy.

Ketamine induces multiple individually distinct whole-brain functional connectivity signatures (open access)

Figure 6 with 4 supplements. Individual variation in ketamine-induced neuro-behavioral changes.

The time has come for over-the-counter antidepressants

Food for thought!

"Anyone can now walk into a pharmacy in the United States and buy oral contraceptives over the counter without a prescription, thanks to the FDA’s approval of norgestrel (Opill). This change reflects the drug’s safety and the public health imperative to ensure wider access to birth control. But another safe class of medicine that addresses a massive public health need remains unavailable except by prescription: the antidepressants known as selective serotonin reuptake inhibitors (SSRIs).

These medications, which have been used in the U.S. for three decades, have repeatedly been shown to be safe and effective for treating major depression and anxiety disorders. ..."

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The time has come for over-the-counter antidepressants

Key language markers of depression on social media depend on race | PNAS. Really!

To use machine learning & language models to detect or measure depression in individuals is probably a good idea!

Unfortunately, like so many other superficial studies, this study did not take any socioeconomic or sociocultural circumstances into account only black and white skin color. Akin to pseudoscience!

However, I do surmise that depression could be differently expressed,  because e.g. the music preferences between white and black Americans are also different. Just an empirical observation.

From the abstract:

"Depression has robust natural language correlates and can increasingly be measured in language using predictive models. However, despite evidence that language use varies as a function of individual demographic features (e.g., age, gender), previous work has not systematically examined whether and how depression’s association with language varies by race. We examine how race moderates the relationship between language features (i.e., first-person pronouns and negative emotions) from social media posts and self-reported depression, in a matched sample of Black and White English speakers in the United States. Our findings reveal moderating effects of race: While depression severity predicts I-usage in White individuals, it does not in Black individuals. White individuals use more belongingness and self-deprecation-related negative emotions. Machine learning models trained on similar amounts of data to predict depression severity performed poorly when tested on Black individuals, even when they were trained exclusively using the language of Black individuals. In contrast, analogous models tested on White individuals performed relatively well. Our study reveals surprising race-based differences in the expression of depression in natural language and highlights the need to understand these effects better, especially before language-based models for detecting psychological phenomena are integrated into clinical practice."

Key language markers of depression on social media depend on race | PNAS (open access)

'I was trapped': Harris County Judge Lina Hidalgo talks decision to seek treatment for depression

Bravo! I think, we have to thank her for acknowledging her mental health issue and having her depression treated while in office.

Hopefully, she has set an example for other high level government officials to come forward and be treated or resign.

You only wish the senile, demented and corrupt 46th President would do the same!

"In one of her first interviews since returning to office, Harris County Judge Lina Hidalgo discussed seeking treatment for depression and why she feels it's important to talk about mental health."

Lina Hidalgo talks decision to seek treatment for depression Hidalgo discussed her decision to seek treatment for depression and why she feels it's important to talk about mental health.

Lina Hidalgo takes leave of absence as Harris County judge to receive treatment for depression. Will other politicians emulate?

Let's congratulate this lady and young, up and coming Texas politician born in Bogota, Colombia! Hopefully, she sets an example for other politicians that health comes first! I wish her a speedy and full recovery!

She admits to a usually stigmatizing health issue! Bravo! Kudos!

Contrast this with the senile, demented and corrupt 46th President! He should have resigned a long time ago!

Harris County Judge Lina Hidalgo receiving treatment for depression

Postpartum Depression’s New Treatment

Good news! Hopefully, other forms of depression can be better treated soon!

"The FDA’s approval late last week of the first pill targeting postpartum depression is a breakthrough in alleviating the widespread—yet under-treated—condition ...

The drug zuranolone, branded as Zurzuvae, is geared towards people with severe pregnancy-related depression and can relieve symptoms in just 3 days. It has previously been available only via IV.

The pills’ accessibility and speed are “extremely important” in the early days of parent-infant bonding ...

Under-treated: 

1 in 7 women experience depression after childbirth—but only half receive treatment ...

How the pills work: 

Taken 1X a day for 14 days, the drug mimics progesterone, a hormone that can plummet after childbirth.

A new study found that among 196 women with postpartum depression, 57% taking daily zuranolone showed “significant improvements” in symptoms after 2 weeks, which continued for 45 days."

Global Health NOW: Postpartum Depression’s New Treatment; Redefining Chronic Fatigue; and Solving Japan’s Recluse Problem

How psychedelic compounds stimulate neuronal growth

Are we finally beginning to better understand the processes of addiction, depression and the like!

"Psychedelics belong to a group of compounds called psychoplastogens, which can promote neuronal growth and restore atrophied connections in the brain. This ability makes the molecules promising as potential treatments for neuropsychiatric diseases such as chronic depression and addiction. In a new study, scientists have untangled the mechanism of how these compounds trigger the rewiring of the brain, providing a better understanding of why these compounds differ from other neurochemicals that share the same binding targets ...

Classic psychedelics such as psilocybin and LSD bind to the 5-hydroxytryptamine 2A (5-HT2A) receptor, an important G-protein-coupled receptor (GPCR) that’s involved in cellular signaling. But so does serotonin, the ubiquitous, mood-dictating neurotransmitter. The lingering mystery is why serotonin doesn’t stimulate the same neuroplasticity effects that psychedelic compounds do.

The new study has found the answer. “The location of the 5-HT2A receptor is critical for determining the kinds of signaling pathways that a ligand can induce,” ...

For a GPCR, the 5-HT2A receptor is weird. Most GPCR proteins reside on the cellular surface to relay signals between the cell and its environment. But in neurons, the majority of 5-HT2A receptors populate the inside of the cell. ... team discovered that psychoplastogens need to reach the receptors within neurons to spark intracellular signaling. Merely hitting the receptors on the outside won’t count.

“The fact that psychedelics may interact with intracellular receptors—that’s really interesting,” ... “a major advance.”

Serotonin—unlike N,N-dimethyltryptamine (DMT),which is found in ayahuasca brew, for example—is a polar molecule, so it can’t easily cross the lipid bilayer of the cell membrane to get inside. On the other hand, greasy compounds can access the intracellular space ...

However, if serotonin is able to enter the cell, it too can kick-start the same signaling events that would lead to neuronal growth. After [team] forced neurons to take up serotonin, the researchers observed them sprouting more branches and more protrusions as a result. The researchers also genetically engineered mice to express a serotonin transporter and saw antidepressant-like behavior, unlike control mice that did not produce the same protein.

The paper is a landmark study, because it opens up new questions about this particular plasticity mechanism, ... “What are the pathways activated by the serotonin 2A receptor located intracellularly? What are the pathways responsible for these medical effects?” ..."

"The mechanism underlying psychedelic action

Psychedelic compounds promote cortical structural and functional neuroplasticity through the activation of serotonin 2A receptors. However, the mechanisms by which receptor activation leads to changes in neuronal growth are still poorly defined. Vargas et al. found that activation of intracellular serotonin 2A receptors is responsible for the plasticity-promoting and antidepressant-like properties of psychedelic compounds, but serotonin may not be the natural ligand for those intracellular receptors ..."

From the absract:

"Decreased dendritic spine density in the cortex is a hallmark of several neuropsychiatric diseases, and the ability to promote cortical neuron growth has been hypothesized to underlie the rapid and sustained therapeutic effects of psychedelics. Activation of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) is essential for psychedelic-induced cortical plasticity, but it is currently unclear why some 5-HT2AR agonists promote neuroplasticity, whereas others do not. We used molecular and genetic tools to demonstrate that intracellular 5-HT2ARs mediate the plasticity-promoting properties of psychedelics; these results explain why serotonin does not engage similar plasticity mechanisms. This work emphasizes the role of location bias in 5-HT2AR signaling, identifies intracellular 5-HT2ARs as a therapeutic target, and raises the intriguing possibility that serotonin might not be the endogenous ligand for intracellular 5-HT2ARs in the cortex."

How psychedelic compounds stimulate neuronal growth

Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors (no public access)

5-HT2A receptors (colored) usually reside inside neurons, unlike most other signalling proteins that usually sit on the cell surface.

Psilocybin Relieves Some (but not all) Treatment-Resistant Depression Cases: Largest trial to date

As far as severe depressions are concerned, treatment progress seems to be excruciatingly slow! Suicidal ideation or behavior or self-injury are among the largest risks for these individuals.

Should we allow individuals suffering from severe, essentially otherwise untreatable or treatment-resistant depression to experiment with psychoactive substances under medical supervision? Why not?

Did they not use placebos for this study? It appears so!

The positive effects were wearing off after 12 weeks. That sounds like a very good result.

I have a hunch that perhaps longer treatment at low dosages maybe more promising in the long term? E.g. the study chose 3 weeks as the "primary end point" for evaluation, which seems to be too short a period.

"For years, some researchers have looked to psychedelic drugs, including psilocybin (the active ingredient in so-called magic mushrooms), as a potential treatment for some psychiatric conditions. The largest trial to date of psilocybin for depression, published today (November 3) in the New England Journal of Medicine, finds that a dose of synthetic psilocybin combined with counseling did alleviate symptoms for some patients. But for some participants who did respond, the effects wore off within 12 weeks of the treatment. ...

The Phase 2 clinical trial, funded in part by the mental health care startup Compass Pathways, which makes the synthetic psilocybin used in the study, included 233 patients for whom at least two depression medications had not worked. The participants were randomly assigned to receive psilocybin at one of three dosing levels: 25 mg, 10 mg, or 1 mg (used as a control). ..."

From the abstract:

"BACKGROUND

Psilocybin is being studied for use in treatment-resistant depression.

METHODS

In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery–Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits).

RESULTS

A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were −12.0 for 25 mg, −7.9 for 10 mg, and −5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P<0.001) and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P=0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups.

CONCLUSIONS

In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. ..."

Psilocybin Relieves Some Treatment-Resistant Depression Cases: Trial | The Scientist Magazine® The research has caveats, including side effects and a lack of durability in the benefits of a single dose.

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression (no public access)

Research suggests depression may not be due to a chemical imbalance in the brain

If this research is confirmed, then it means for decades tens of millions patients were quite possibly prescribed the wrong medication and have been treated the wrong way over long periods. There are currently 8.3 million people in the UK alone taking antidepressants. That is depressing! 

Distinct Microbiome and Metabolites Linked with Depression

Amazing stuff! Do you have the guts? The microbiome is one of the wonders of human life!

"... Over the past decade, researchers have linked disturbances within this complicated microbial society to a variety of diseases. Major depressive disorder (MDD) is one such condition, but the studies have been small and the findings imprecise. A study published December 2 in Science Advances changes all that with its vivid description of a distinct microbiome associated with major depressive disorder, as well as the profile of molecules these organisms produce. The researchers were able to use this microbial “fingerprint” to distinguish between individuals with MDD and healthy controls, solely on the composition of a few microbes and compounds in their fecal matter. ..."

"... Here, using whole-genome shotgun metagenomic and untargeted metabolomic methods, we identified 3 bacteriophages, 47 bacterial species, and 50 fecal metabolites showing notable differences in abundance between MDD patients and healthy controls (HCs). ...
Furthermore, we identified a combinatorial marker panel that robustly discriminated MDD from HC individuals in both the discovery and validation sets."

Distinct Microbiome and Metabolites Linked with Depression | The Scientist Magazine® The gastrointestinal tracts of people with major depressive disorder harbor a signature composition of viruses, bacteria, and their metabolic products, according to the most comprehensive genomic and metabolomic analysis in depression to date.

Here is a link to the respective research paper:

Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders