Hersenactiviteit Onderliggend aan Predictief voor Suicide

Rationale: Suicide is an urgent societal problem, with alarming numbers that steadily increase in the Netherlands. However, the exact social, psychological and brain mechanisms underlying the risk of suicidal behavior remain largely unknown. It has been proposed that suicidal ideation may result from altered social-emotional processing, e.g. difficulties in cognitive control of emotion, in the face of adversity. This would lead to a “psychological
pain” that can fuel hopelessness. Another important ingredient of hopelessness is a lack of flexibility to envision positive future scenarios. Feeling trapped in this desperate situation, suicide can be seen as the only solution. To come to the suicidal act some facilitating factors come into play, which we hypothesize to include reduced ability to take the perspective of others (which may reduce empathy in weighing the emotional consequences for close
others). However, the exact nature of this process has not yet been elucidated. In this study,
we will for the first time, examine several key cognitive-emotional processes in relation to
suicidal behavior using brain imaging: emotion regulation, envisioning future positive events
and inferring on emotions of others. In addition, neural markers may identify those patients at
high risk of future suicidality (suicide attempts and/or ideation) and can contribute to the
development of more personalized treatment options by shedding light on the processes
involved. Moreover, it is not yet known whether and to which extent such (neural) mechanisms "normalize" with time and treatment (i.e. are more similar to healthy comparison subjects). Most of the time participants receive a treatment with elements of cognitive behavior therapy (CBT) to reduce suicidal thoughts and behavior.

Objective: The objectives of this study are threefold. First, we aim to understand the underlying neural mechanisms of suicidality. Therefore, we will investigate brain activation during resting state and three psychological processes that have been suggested to be of relevance to suicidality, but have not been studied yet using brain imaging: emotion
regulation, positive imagery of future change and inferring on emotions of others. Second, to
identify who is at risk for relapse of suicidal behavior despite adequate application of standard treatment protocol, we will investigate whether brain activation could serve as a marker for future suicidality, including both suicidal ideations and attempts. Third, to understand and target the underlying mechanisms, it is essential to know which mechanisms can be altered and are influenced by the current state of suicidality.

Study design: The current study has an experimental design. We will employ a longitudinal fMRI study in which we will follow a group of recent suicide attempters, patients with comparable psychopathology and a group of healthy participants for one year. The tasks during fMRI scanning intend to measure emotion regulation, affective forecasting and inferring emotions of others. Furthermore, several interviews and questionnaires will be
administered.

Study population: The study population will consists of 46 patients with a recent suicide
attempt (less than two weeks ago), 24 patient controls and 24 healthy controls. The patient
controls and healthy controls will be matched on age, sex, handedness and level of
education. In addition, the patient controls will be matched on psychiatric diagnosis.

Main study parameters/endpoints: The main study parameter is brain activation/connectivity measured with functional magnetic resonance imaging (fMRI) during different types of emotional processing tasks and resting state. For the second objective, the
main study endpoint will be the association between brain activation at first measurement and suicidal ideation/attempts at follow-up. For the third objective, the main endpoint will be change in brain activation at follow-up (second MRI scan) as compared to the first measurement.

- brain activation and connectivity during emotion regulation, thinking about future events, inferring on emotions of others and rest are different in patients with a recent suicide attempt compared to patient controls and healthy controls

- brain activation and connectivity during these processes is predictive for suicidal behavior in the year following the attempt.

- brain activation and connectivity during these processes change with a change in suicidality in the following year during which treatment according to current clinical guidelines was administered.

baseline, 1 month, 3 months, 6 months and 12 months

treatment as usual (according to current guidelines)