Aims and Hypothesis We propose a medical hypothesis on pathophysiology of psychogenic polydipsia in psychiatric patients.

Background Compulsive behaviours, which aim to reduce distress, are common in severe psychosis, autistic spectrum disorders and many neuropsychiatric disorders. Repetitive and dysfunctional acts that characterise compulsivity can include excessive fluid consumption, usually referred to as psychogenic polydipsia in the psychiatric literature.

The pathophysiology of psychogenic polydipsia is not well understood, but some researchers hypothesise that it has phenomenological similarities with obsessive- compulsive disorder, and both are neurobiologically related. It is believed that one of the mechanisms of compulsive behaviour involves serotonergic dysfunction.

Tryptophan is an essential amino acid and a precursor to the neurotransmitter serotonin.

Normally, most of the dietary tryptophan is used in the kynurenine pathway, but a small portion is converted into serotonin, and some are utilised by gut microbiota. Dysbiosis in the gut microbiome and alteration in tryptophan metabolites levels can induce behavioural abnormalities and imitate some psychiatric symptoms. Changes in gut microbiota composition can activate tryptophan metabolism via the kynurenine pathway and microbial pathway resulting in the overproduction of its metabolites, consequently, reducing the tryptophan availability to serotonin synthesis. Additionally, depletion of dietary tryptophan has been linked with abnormal serotonin metabolism and alteration of gut microbial diversity leading to depression, aggressive behaviour, antisocial personality disorder and compulsive water drinking.

Methods A systematic literature review searching databases, the key words included psychogenic polydipsia, tryptophan metabolism, compulsive behaviours, microbiome in psychiatric patients.

Results Number of hypotheses have been suggested for the mechanism of psychogenic polydipsia, including involvement of the hypothalamic-pituitary-adrenal (HPA) axis and being compulsive-obsessive in nature. However, gut microbiome and its function have not been suggested previously.

Gut microbes can affect the brain in various ways. It has been reported that they can produce neurotransmitters that are directly involved in psychiatric disorders. Microbes can cause inflammation and disfunction of nervous system and produce tryptophan metabolites which contributes to immune response, intestinal homeostasis, gut barrier and permeability.

It has been reported that they are involved in activation of the HPA axis stimulating over drinking behaviour as well as affecting serotonergic system.

The main key points and analysis from literature review will be outlined to support the hypothesis.

Conclusions The literature suggests that gut microbiota, tryptophan and its metabolites play an important role in gut-brain communication and it could be involved in the pathophysiology of psychogenic polydipsia. Changing the gut microbial composition could modulate/regulate tryptophan metabolites and alter behaviour.