Investigating the Effect of the Menstrual Cycle on Social Stress in Early Psychosis Through Ecological Momentary Assessment

Psychosis is a severe mental illness which has major costs both to society and to individuals affected. Relapses of psychosis are incredibly disruptive for patients' lives. For women who have psychosis, the time around their menstrual period carries a particularly high risk for relapse. Patient groups report that the menstrual cycle is an important topic for consideration but it has been relatively overlooked in research to date.

The reasons why the menstrual cycle should affect women with psychosis are not clear but may relate to social stress. Response to stress, particularly in social situations, seems to be important in the development of psychosis. This is the case for people who have recently developed a psychotic illness as well as those who are at higher risk of psychosis. Response to stress also varies across the menstrual cycle, which could explain why psychosis seems to worsen around the time of menstruation.

We will use a newly developed smartphone app, Social Mind to measure daily responses to stress. Smartphone apps offer a convenient way for participants to measure both the menstrual cycle and response to stress. They can also be used to monitor social withdrawal, measured through reduced movement. The app will use phone movement data to passively measure social withdrawal. The app will be used by participants to record their menstrual periods. Women who are either at risk of psychosis or who are experiencing their first episode of psychosis will be asked to complete these measures. For comparison, healthy women will complete the measures as well.

We will analyse whether social stress and withdrawal are affected by the menstrual cycle. We will examine whether relapse of psychosis is more likely at certain times of the cycle and if stress influences it. We will compare differences between women who are experiencing psychosis, those at risk of psychosis and those not affected by mental health problems.

It is hoped by understanding how the menstrual affects response to stress in psychosis, new targets for treatment will be identified. At present, all antipsychotic medications work in a similar way and have troublesome side-effects. Medications that stabilise hormonal fluctuations represent a completely different approach that could work for some women.

The perimenstrual phase of the menstrual cycle carries a higher risk of relapse in women with psychosis. A plausible mechanism for this finding is through response to social stress, known to be abnormal both in psychosis and in those at high risk of developing psychosis. Response to stress varies across the menstrual cycle, likely as a consequence of allopreganolone, a metabolite of progesterone, which is a potent anxiolytic.

We will ask women in the early phase of psychosis (those experiencing their first episode and those at increased risk due to sub-threshold symptoms) to record daily responses to social stress through Social Mind, an app developed with MRC funding, over a follow-up period of one to two years. They will also record when they are experiencing menstrual bleeding through the app. The app will passively measure social withdrawal through GPS data.

We will analyse the effect of the menstrual cycle on response to social stress, social withdrawal and relapse of psychosis. We will model whether the effect of the menstrual cycle in psychosis is mediated through social stress. We will compare these effects between women experiencing their first episode, those at high risk and those without mental health problems. Elucidating the underlying mechanisms between the menstrual cycle and increased psychosis relapse risk could identify novel treatment targets.