Neurological MRI-based biomarkers for treatment navigation in depression

Major depressive disorder is a severe neuropsychiatric condition that affects
approximately 15% to 18% of people worldwide during their lifetime (Malhi &
Mann, 2018). Selection of the optimal treatment is difficult. Usually, a
depressive episode is treated first-line with psychotherapy, pharmacotherapy or
both in different combinations. When these treatments are ineffective, other
treatment options are considered, including more invasive treatments such as
electroconvulsive therapy, transcranial magnetic stimulation, or deep brain
stimulation. Despite the numerous treatment options, two thirds of MDD patients
remain symptomatic after treatment and approximately one third will not achieve
remission after finishing four consecutive treatments. (Holtzheimer & Mayberg,
2011; Malhi & Mann, 2018). Several scientific studies indicate that brain
imaging can help in choosing the right treatment for patients with depression
(Drysdale et al., 2017; Mayberg, 2003; Mayberg et al., 1999). However, these
studies have not taken advantage of the latest development in MRI acquisition
techniques (Cohen, Nencka, Lebel, & Wang, 2017; Le Bihan, 2019).

A certain correlation (functional / structural, vascular or a mix of both) is
expected between clinical data (obtained from psychometric tests such as the
HDRS and psychiatric evaluations) and MRI parameters (functional activity,
structural connectivity, anatomical variations, perfusion / diffusion etc.).

Identification of MRI-based biomarkers to predict clinical outcome of major
depressive disorder in comparison with healthy controls. Outcome is defined by
level of depressive and cognitive symptomatology and related comorbidity.

An independent treating physician will inform a potentially eligible patient
and ask whether he/she is interested in voluntary participation in the study.
If he/she is interested, the independent treating physician will refer the
patient to one of the clinicians from the GGz who is also involved in the
Neurotrend study for further steps such as providing the information letter /
informed consent and scheduling an intake interview at least one week after
receiving all necessary information. Healthy controls will be recruited through
public advertisement and via the website www.neurotrend.nl. Pilot subjects will
be recruited from the Eindhoven University community and via the website
www.neurotrend.nl. Both groups, healthy controls and pilot subjects, will have
at least one week to consider and decide on participation.

One week later an intake session will take place in which the inclusion and
exclusion criteria will be checked. During this session, patients can also ask
questions about the study and the informed consent will be signed if the
participant is willing to participate voluntarily in the study. Subsequently at
the end of the intake session, a starting (baseline) date will be planned for
this participant .

The actual participation starts at baseline. In total, 120 depressed patients
and 60 healthy controls will participate in the study. Each participant visits
Kempenhaeghe twice, whereby each session, is dedicated to complete
questionnaires and cognitive tests, such as memory tasks and eye tracking. In
the last hour, the participant will be scanned (MRI). Two weeks before each
visit, the participant has to fill in some questionnaires that have been sent
to the participant.

The participant burden is low and is divided into an intake session and two
research sessions. The MRI scan is non-invasive, and subjects can indicate that
they want to stop the scan at any time during the scan by squeezing a type of
balloon that will lie next to the subject in the case that they feel
uncomfortable or for any other reason. Subjects with MRI contraindications
(e.g. claustrophobia, pregnancy or implants not suitable for MRI) are already
excluded in advance and will therefore not participate in the study at all.
Mostly, the subjects will lie still during the scan, except for one affective
task in which they will be asked to match different emotional faces for about 5
minutes.The cognitive tests will only consist of memory, reaction speed,
attention, and processing speed tasks which in total, do not last more than 30
minutes. The risks of the MRI scanner (CE-marked) are minimal.