Op-Ed The New Study on Serotonin and Depression Isn’t About Antidepressants

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The New Study on Serotonin and Depression Isn’t About Antidepressants​

Shayla Love
Vice
22 Jul 2022

Excerpt:
In the original TV ad for the antidepressant Zoloft, a gray cloud hovers over a sad blob, rain falling on the blob’s dejected expression. “You know when you feel the weight of sadness,” a voiceover says.


The commercial lists the symptoms of depression, and explains that “while the cause is unknown, depression may be related to an imbalance of natural chemicals between nerve cells in the brain. Zoloft works to correct this imbalance. You shouldn’t have to feel this way anymore.”

The chemical the ad is referring to is serotonin, a neurotransmitter that does many things in the brain and has long been theorized to have something to do with the symptoms of depression. The slightly more complex version of the story that ad is alluding to goes that depression is caused by a “chemical imbalance,” or low or abnormal levels of serotonin, and that taking an antidepressant, or selective serotonin reuptake inhibitor (SSRI), by changing serotonin levels in the brain, makes a person feel better.

In the face of this story, it’s easy to understand how a new paper in Nature Molecular Psychiatry this week seemed like a bombshell. In a systematic review of studies on serotonin levels in people with depression, it found no evidence that depressed people had lower serotonin levels or abnormal serotonin activity compared to non-depressed people.
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Dopamine System Dysregulation in Major Depressive Disorders - PMC

Anhedonia is considered a core feature of major depressive disorder, and the dopamine system plays a pivotal role in the hedonic deficits described in this disorder. Dopaminergic activity is complex and under the regulation of multiple brain ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
"MDD is a complex disorder, comprised of many symptoms, each symptom likely involving unique neuronal circuits. To study and treat MDD in the most efficient manner, the DSM, based on clusters of clinical symptoms, is unfortunately limited. The National Institute of Mental Health has launched the Research Domain Criteria approach to create a research classification system based on biologically determined variables, such as genetics, imaging, cognitive science, behavior, or neural circuits. Indeed, it is hypothesized that symptoms, more than diagnostic categories, are linked to specific circuit disruptions, and therefore understanding their biological foundations will facilitate the treatment of disorders that include such symptoms. "

It's quite obvious for us nowadays, it seems that 50 years ago it wasn't so clear... oh well...

Glutamate and GABA Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine - PMC

In patients with major depressive disorder (MDD) or bipolar disorder (BD), abnormalities in excitatory and/or inhibitory neurotransmission and neuronal plasticity may lead to aberrant functional connectivity patterns within large brain networks. ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

"In patients with major depressive disorder (MDD) or bipolar disorder (BD), abnormalities in excitatory and/or inhibitory neurotransmission and neuronal plasticity may lead to aberrant functional connectivity patterns within large brain networks. Network dysfunction in association with altered brain levels of glutamate (Glu) and gamma-aminobutyric acid (GABA) have been identified in both animal and human studies of depression."


Glutamate and depression: Reflecting a deepening knowledge of the gut and brain effects of a ubiquitous molecule - PMC

The versatility of glutamate as the brain’s foremost excitatory neurotransmitter and modulator of neurotransmission and function is considered common knowledge. Years of research have continued to uncover glutamate’s effects and roles in several ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
Super interesting paper:
"This review examines current understanding of the roles of endogenous and exogenous sources of glutamate and the glutamatergic system in the aetiology, progression and management of depression. It also examines the relationships that link the gut-brain axis, depression and glutamate (Figure (Figure1);1); as it emphasizes how the gut-brain axis could impact depression pathogenesis and management via changes in glutamate homeostasis. Finally, we consider what the likely future of glutamate-based therapies and glutamate-based therapeutic manipulations in depression are, and if with them, we are now on the final chapter of understanding the neurochemical milieu of depressive disorder."


Early life stress and glutamate neurotransmission in major depressive disorder - PMC

Early life stress (ELS) and glutamate neurotransmission have been implicated in the pathophysiology of major depressive disorder (MDD). In non-human primates, ELS was positively correlated with cortical Glx (i.e., glutamate + glutamine). However, ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
Low n- but interesting article...
 
After 4 months of treatment, 41% of the participants achieved remission, defined as no longer meeting the criteria for major depressive disorder
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Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder​

Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder - PMC

To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to standard antidepressant medication (sertraline) and greater reductions in ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
 
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