Narrative Review of Molecular Basis of Depression/Antidepressant Treatments (including ECT)
Out on PubMed, from researchers in Brescia and Novedrate, Italy, is this review article:
Despite the extensive research conducted in recent decades, the molecular mechanisms underlying major depressive disorder (MDD) and relative evidence-based treatments remain unclear. Various hypotheses have been successively proposed, involving different biological systems. This narrative review aims to critically illustrate the main pathogenic hypotheses of MDD, ranging from the historical ones based on the monoaminergic and neurotrophic theories, through the subsequent neurodevelopmental, glutamatergic, GABAergic, inflammatory/immune and endocrine explanations, until the most recent evidence postulating a role for fatty acids and the gut microbiota. Moreover, the molecular effects of established both pharmacological and non-pharmacological approaches for MDD are also reviewed. Overall, the existing literature indicates that the molecular mechanisms described in the context of these different hypotheses, rather than representing alternative ones to each other, are likely to contribute together, often with reciprocal interactions, to the development of MDD and to the effectiveness of treatments, and points at the need for further research efforts in this field.
Keywords: antidepressant drugs; brain-derived neurotrophic factor; electroconvulsive therapy; inflammation; major depressive disorder; monoamines; neurotrophins; non-pharmacological treatments; serotonin.
The pdf is here.
The below comment is from Max Fink:
ReplyDeleteNeuroscience of AD and ECT
This extensive review in Genes exemplifies the adage, "to a man with a hammer, everything is a nail." For more than 70 years, biochemists, geneticists, neuroscientists have each developed a laboratory test, measured rat tissues after dosing with a chemical used by clinicians to treat "major depressions" or "therapy resistant depressions". Finding brain and tissue changes, the jump is made to a hypothesis that the chemicals used by psychiatrists must have a specific action on these systems.
In 1970s, Bernard Carroll identified a specific depressive illness, melancholia, marked by abnormal functions of the human brain HPA axis. In one study, melancholic patients were shown to have abnormal cortisol functions. Successfully treated by ECT, they were dischaged. Two returned depressed with abnormal cortisol functions; re-treatment reversed the cortisol dysfunction and the melancholia again. Cortisol abnormality became a basis for a specified form of emotionl illness, eminently relieved by inducing seizures.
Lessons? Studying MDD and TRD cases are doomed to failure since each offers a DSM mishmash of depressions, anxieties, character disorders and occasional melancholia. Identifying melancholia by HAMD criteria and cortisol abnormalities, treating by effective seizures, provides understanding of a neuroendocrine basis for an identifiable illness and mechanism for treatment.
Are rats and mice in neuroscience studies depressed or melancholic? How do we know?
Max Fink
See Blog notes April 28, 2020; and,
Taylor MA, Fink M. Melancholia: A Clinician's Guide to Diagnosis and Treatment. Cambridge U Press, 2006.