The corticosteroid receptor hypothesis of depression.

A working model of depression implicating failure of the coordinated interactions of a distributed network of limbic-cortical pathways is proposed. Resting state patterns of regional glucose metabolism in idiopathic depressed patients, changes in metabolism with antidepressant treatment, and blood flow changes with induced sadness in healthy subjects were used to test and refine this hypothesis. Dorsal neocortical decreases and ventral paralimbic increases characterize both healthy sadness and depressive illness; concurrent inhibition of overactive paralimbic regions and normalization of hypofunctioning dorsal cortical sites characterize disease remission. Normal functioning of the rostral anterior cingulate, with its direct connections to these dorsal and ventral areas, is postulated to be additionally required for the observed reciprocal compensatory changes, since pretreatment metabolism in this region uniquely predicts antidepressant treatment response. This model is offered as an adaptable framework to facilitate continued integration of clinical imaging findings with complementary neuroanatomical, neurochemical, and electrophysiological studies in the investigation of the pathogenesis of affective disorders.

https://neuro.psychiatryonline.org/doi/pdfplus/10.1176/jnp.9.3.471

Limbic-cortical dysregulation: a proposed model of depression.

The Serotonin Signaling System: From Basic Understanding To Drug Development for Functional GI Disorders

Serotonin, tryptophan metabolism and the brain-gut-microbiome axis.

https://www.cell.com/trends/pharmacological-sciences/pdf/0165-6147(94)90315-8.pdf

Current advances and trends in the treatment of depression

Brain serotonin content is dependent on plasma levels of the essential amino acid tryptophan. We investigated the behavioral effects of rapid tryptophan depletion in patients in antidepressant-induced remission. Twenty-one patients who were depressed by DSM-III-R criteria received a 24-hour, 160-mg/d, low-tryptophan diet followed the next morning by a 16-amino acid drink, in a double-blind, placebo-controlled (acute tryptophan depletion and control testing), crossover fashion. Total and free tryptophan levels decreased 87% and 91%, respectively, during acute tryptophan depletion. Fourteen of the 21 remitted depressed patients receiving antidepressants experienced a depressive relapse after the tryptophan-free amino acid drink, with gradual (24 to 48 hours) return to the remitted state on return to regular food intake. Control testing produced no significant behavioral effects. Free plasma tryptophan level was negatively correlated with depression score during acute tryptophan depletion. The therapeutic effects of some antidepressant drugs may be dependent on serotonin availability.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=psych&articleId=495012&pdfFileName=archpsyc_47_5_002.pdf

Harold Landis

Papers

Serotonin Function and the Mechanism of Antidepressant Action: Reversal of Antidepressant-Induced Remission by Rapid Depletion of Plasma Tryptophan

Neuroendocrine and behavioral effects of dietary tryptophan restriction in healthy subjects

Biochemistry and suicidal behavior in depressed patients.

Catecholamine metabolites in human plasma as indices of brain function: Effects of debrisoquin

Cerebrospinal fluid, plasma, and urinary MHPG in children.