Abstract
The monoamine hypothesis of psychopharmacology has been dominating the biological psychiatric research field for decades. Currently psychiatric research has increasingly appreciated psychiatric disorders and suicidal behavior as being highly complex and multi-etiological. In this pathway the gut microbiome and its interrelationship with the brain is gaining traction. The usage of selective serotonin reuptake inhibitors (SSRIs) is increasing in the general population. This is due to their effect on a broad range of psychiatric disorders, and their favorable side effect profile. Still, there are enigmatic aspects about SSRIs, such as the difficulty to predict effect in individual patients, inter-individual differences in side effect, tachyphylaxis (a sudden loss of response to a certain drug), and to date, uncertainties on how they exert their clinical effect. A majority of the serotonin in the human body is produced within the gut, and SSRIs affect enteric neurons. They also exhibit antimicrobial properties that comes with the potential of disrupting microbial hemostasis. We propose that the role of the gut-brain axis and the gut microbiome in relation to psychopharmacology should be more highlighted. With this article, together with similar articles, we would like to provide a hypothetical framework for future studies within this field. We believe that this would have the potential to provide a paradigm shift within the field of psychopharmacology, and result in findings that potentially could contribute to the development of a more personalized and tailored treatment.
Highlights
The connection between the gut and the mind, the so called gut-brain axis [1], is a burgeoning research field that holds promise to further our understanding of the pathophysiological disruptions underlying complex disorders, such as psychiatric disorders and suicidal behavior [1, 2]
Dyspepsia was thought of as the root cause of psychiatric ill health, and even suicide [3]. This reductionistic way of thinking changed its route during the twentieth century, when an opposed reductionistic direction of thinking instead stated that stress and anxiety was the root cause of stomach illnesses, such as peptic ulcers, as well as certain other somatic disorders [3]
Beside from the issues relating to treatmentresistance seen in a high proportion of patients, this might give a further understanding on other enigmatic aspects, e.g., that some patients need higher doses to experience treatment response even though this does not lead to significantly higher serotonin transporter (SERT) bindning, as discussed above [19]
Summary
The connection between the gut and the mind, the so called gut-brain axis [1], is a burgeoning research field that holds promise to further our understanding of the pathophysiological disruptions underlying complex disorders, such as psychiatric disorders and suicidal behavior [1, 2]. Recent hypotheses for mood disorders as well as suicidal behavior have been focusing on several other proposed pathophysiological mechanisms such as neuroinflammation, immune dysregulation, disruptions in neurogenesis, imbalances in neuropeptides and growth factors, and expanding on other types of neurotransmitters [19,20,21,22,23]. In this shift and broadening of perspectives an imbalance in cerebral networks are highlighted, where the monoamine system is appreciated as an integral part in network signaling and modulation [19]. From this perspective disruptions in the monoamine system is thought of as one manifestation among the many heterogeneous disruptions that would form the basis of an underlying pathophysiology [19]
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