A Sex-Dependent Association Between Doxycycline Use and Development of Schizophrenia

Witte, Lot de; Laursen, Thomas Munk; Corcoran, Cheryl; Kahn, René S.; Birnbaum, Rebecca; Munk‐Olsen, Trine

doi:10.1093/schbul/sbad008

Cited by 2 publications

(1 citation statement)

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“…This is further substantiated by the current efforts to repurpose several antipsychotic drugs as antibiotics [225]. Conversely, antibiotics such as doxycycline and minocycline exert antipsychotic properties, indicating that postsynaptic DA blockade may not be the only mechanism for alleviating psychotic symptoms [226,227].…”

Section: Antipsychotics As Antibacterialsmentioning

confidence: 99%

Six Decades of Dopamine Hypothesis: Is Aryl Hydrocarbon Receptor the New D2?

Sfera

2023

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In 1957, Arvid Carlsson discovered that dopamine, at the time believed to be nothing more than a norepinephrine precursor, was a brain neurotransmitter in and of itself. By 1963, postsynaptic dopamine blockade had become the cornerstone of psychiatric treatment as it appeared to have deciphered the “chlorpromazine enigma”, a 1950s term, denoting the action mechanism of antipsychotic drugs. The same year, Carlsson and Lindqvist launched the dopamine hypothesis of schizophrenia, ushering in the era of psychopharmacology. At present, six decades later, although watered down by three consecutive revisions, the dopamine model remains in vogue. The latest emendation of this paradigm proposes that “environmental and genetic factors” converge on the dopaminergic pathways, upregulating postsynaptic transmission. Aryl hydrocarbon receptors, expressed by the gut and blood–brain barrier, respond to a variety of endogenous and exogenous ligands, including dopamine, probably participating in interoceptive awareness, a feed-back loop, conveying intestinal barrier status to the insular cortex. The conceptualization of aryl hydrocarbon receptor as a bridge, connecting vagal terminals with the microbiome, may elucidate the aspects of schizophrenia seemingly incongruous with the dopamine hypothesis, such as increased prevalence in urban areas, distance from the equator, autoantibodies, or comorbidity with inflammatory bowel disease and human immunodeficiency 1 virus. In this review article, after a short discussion of schizophrenia outcome studies and insight, we take a closer look at the action mechanism of antipsychotic drugs, attempting to answer the question: do these agents exert their beneficial effects via both dopaminergic and nondopaminergic mechanisms? Finally, we discuss potential new therapies, including transcutaneous vagal stimulation, aryl hydrocarbon receptor ligands, and restoring the homeostasis of the gut barrier.

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Section: Antipsychotics As Antibacterialsmentioning

confidence: 99%