The observed change in current feelings of depression is appreciable. According to Spielberger's norms for state depression scores,
[24] the mean scores of participants in this study went from being largely ‘neutral depressive’ in the placebo condition to being ‘mild depressive’ following the consumption of gluten.
[24] However, Spielberger's norms are based on clinical populations whereas patients in the current study had not been diagnosed as clinically depressed. That said, this observed change over a 3-day intervention is plausible. Personality and mood states are widely accepted as being transitory and rapidly changing, often from moment to moment.
[29] If such a change is indeed a gluten-specific effect, the mechanisms involved require elucidation.
One explanation might be alterations in cortisol secretion as circulating concentrations of cortisol are greater with negative affect (i.e. aversive moods such as anxiety, hostility and depression). However, the degree to which this association is due to stable individual differences (i.e. traits) or transient differences in affect (i.e. states) remains unclear.
[30] There is currently no evidence that gluten ingestion can stimulate cortisol secretion, but this link has been seldom studied.
[31] In the current study, cortisol concentrations during each dietary period were measured in saliva, a technique that has been shown to provide a feasible, accurate and practical alternative to blood determinations.
[32, 33] These were similar across all dietary treatments, indicating that state depression may not be as closely associated with cortisol secretion compared to trait depression, as previously described.
[30]
A second potential mechanism is via alteration of brain serotonin (5-hydroxy-tryptophan, 5-HT). Decreased brain 5-HT concentration has been long suggested as a cause of depression.[34] The synthesis of 5-HT in the brain is dependent on the availability of its amino acid precursor, tryptophan. Interestingly, recent work has identified a link between protein ingestion, tryptophan production and concentrations of 5-HT in the brain.[35] In this study, rats consuming food supplemented with food-grade wheat for 2 h had modest reductions in concentration of tryptophan in the brain suggesting that 5-HT pathways are remarkably sensitive to various proteins present in food.[35] Whether carbohydrate-depleted gluten results in reductions of tryptophan concentration in the human brain requires further exploration. Nonetheless, serotonergic dysfunction due to impaired availability of tryptophan has been shown to play a role in various psychological conditions including depression.[36-39]
A third explanation involves the so-called gluten ‘exorphins’. These opioid peptides derived from partially digested food proteins including gluten can modulate intestinal function,[31] and can cross the blood–brain barrier and interfere with pain-inhibitory systems, emotionality and memory processes by modulating other hormonal or neurotransmitter systems via the opioid receptors as well as endogenous opioid peptides in the central nervous system (CNS).[40] Such a possibility could be investigated by, for example, the concomitant use of naloxone to block opioid receptors.
A fourth possibility might involve gluten-mediated changes in gut microbiota. Several studies have reported intestinal dysbiosis in patients with coeliac disease.[41] Interestingly, some of the alterations in gut microbiota are restored after adherence to a GFD.[41] This suggests that these changes are secondary consequences of the disease and perhaps directly related to the consumption of gluten. Evidence supporting an important influence of gut microbiota on emotional behaviour and underlying brain mechanisms is well established in adult rodents[42-44] and is emerging in humans. A recent study has provided first evidence that probiotics can modulate the activity of brain regions involved in processing emotion and sensation in adult women.[45] Whether 3 days is sufficient to induce changes in microbiota is uncertain, but this hypothesis requires further investigation in the NCGS population.
… importantly no difference was observed in anxiety or salivary cortisol levels across the three dietary challenges and depression was only associated with the ingestion of gluten.
In conclusion, the findings of gluten-specific acute changes in current feelings of depression, with no effects on trait indicates, provide a clue that the improvement reported by participants may be in the perception of their general well-being rather than in gastrointestinal symptoms. Such an association requires a larger and more detailed examination.
