An observational study in Depressive Disorder, Major, sponsored by Eindhoven University of Technology. Completed at 1 site in Netherlands. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-04-02.
Sponsored by Eindhoven University of Technology · Observational
Background of the study:
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.
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.).
Objective of the study:
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.
Study design:
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.
Study population:
120 patients with major depressive disorder and 60 healthy controls*.
* Inclusion of up to 30 healthy "pilot" participants for technical evaluation. See above.
Primary study parameters/outcome of the study:
Secondary study parameters/outcome of the study (if applicable):
Nature and extent of the burden and risks associated with participation, benefit and group relatedness (if applicable):
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.
Limitation to research to date
Heterogeneous findings of current studies may indicate that MDD has been approached too much as a homogeneous concept, whereas analysing subtypes might be more useful. The literature supports the existence of different MDD subtypes based on biological variables and/or clinical features. Research has distinguished 3 types of MDD based on depressive, symptomatology: a severe melancholic class, a severe atypical class and a class of moderate severity. Both depression severity (moderate vs severe) and the nature of depressive symptoms (melancholic vs atypical) were found to be important differentiators between those subtypes. Other subgroups of relevance may be remission vs. non-remission, early onset vs. late onset depression. The relation with neuroimaging findings is scarce and inconsistent. As depressive symptoms may also strongly fluctuate over time, repeated MRI and clinical data acquisition at different points in time is warranted. There is a relative scarcity of longitudinal MRI studies on MDD. Large representative samples are warranted, addressing multiple factors such as sociodemographic characteristics, clinical history (incl. childhood trauma), co-morbidity and monitoring of treatment, including type and duration. This will elucidate causative mechanisms as well as the role of treatment, which may pave the path towards diagnostic subtyping and treatment navigation. Moreover, brain alterations are usually described on a structural, functional and vascular level and seldom from an integral approach, let alone in a longitudinal design. A multi-modal approach whereby the three levels are considered might thus increase the reproducibility of findings. In addition, there is an urgent need to find biomarkers that are meaningful on the individual patient level. Machine learning is a technique that can be utilized to allow imaging risk markers to be identified at the level of subtypes and ultimately on the individual level, which is crucial for clinical applicability.
Current study
The Neurotrend study will contribute to the existing literature by aiming to predict outcome in MDD using multi-modal imaging with an observational study design. Two scanning sessions with one year in between will be held for patients with MDD and controls, as well as a broad assessment of clinical, cognitive and demographic variables (at baseline and 1-year follow-up). Predicting outcome at the level of subtypes/individuals in a naturalistic clinical setting is a different approach to identify biomarkers than most studies have done so far. For this purpose, machine learning will be used, which is a powerful method to identify biomarkers from the different MRI modalities. For the first time, IVIM and T2*-weighted imaging will be included in the MRI protocol to yield more insight into the microvascularity and microbleeds of the brain. In addition, other novel techniques will be applied to increase the chance of finding meaningful biomarkers. For instance, with respect to the brain alterations on a structural level, high spatial resolutions (using multiband imaging) and better automated segmentation methods will be used to examine the substructures of brain regions with high accuracy as substructural imaging is becoming more popular and could identify more reliable biomarkers. For the brain alterations on a functional level, multiband and multi-echo imaging lead to higher spatial/temporal resolution which will help to reduce the noise and artifacts to which fMRI is very susceptible.
4,845 studies on the registry are indexed under Depressive Disorder; 514 are open to participants now.
This study's enrollment of 83 is below the median of 150 across 653 observational studies indexed under Depressive Disorder.
Browse Depressive Disorder studies →Eindhoven University of Technology is the lead sponsor of 3 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
MMD versus (controls) non-depressed
MDD patients:
Inclusion Criteria:
Satisfy DSM-5 clinical criteria for MDD (acute and subacute duration)
Exclusion Criteria:
More than 3 depressive episodes in the past
60 healthy controls
Inclusion Criteria:
Exclusion Criteria:
Major depressive disorder patients (unipolar)
Device: MRI research
(Control) non-depressed
Device: MRI research
3T MRI protocol of \~1 hour
Basline brain region (subfield) volumes
Volumes are extracted from T1w and T2w scans. Subfield volumes of the hippocampus and amygdala can be extracted from a high-resolution T2w image.
Time frame: baseline
1-Year brain region (subfield) volumes
Volumes are extracted from T1w and T2w scans. Subfield volumes of the hippocampus and amygdala can be extracted from a high-resolution T2w image.
Time frame: 1 year
Baseline microvascular pseudodiffusion
Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.
Time frame: baseline
Baseline microvascular perfusion fraction
Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.
Time frame: baseline
1-Year microvascular pseudodiffusion
Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.
Time frame: 1 year
1-Year microvascular perfusion fraction
Intravoxel incoherent motion assesses perfusion in the small vessels of the brain.
Time frame: 1 year
Baseline white matter hyperintensity volumes
The FLAIR scan attenuates the CSF signal and therefore, it is excellent in distinguishing white-matter abnormalities surrounding the CSF.
Time frame: baseline
1-Year white matter hyperintensity volumes
The FLAIR scan attenuates the CSF signal and therefore, it is excellent in distinguishing white-matter abnormalities surrounding the CSF.
Time frame: 1 year
Baseline structural connectivity (DTI) fractional anisotropy
This T2\*-weighted scan will measure the anatomical connections between brain areas.
Time frame: baseline
Baseline structural connectivity (DTI) vessel density
This T2\*-weighted scan will measure the anatomical connections between brain areas.
Time frame: baseline
1-Year structural connectivity (DTI) fractional anisotropy
This T2\*-weighted scan will measure the anatomical connections between brain areas.
Time frame: 1 year
1-Year structural connectivity (DTI) vessel density
This T2\*-weighted scan will measure the anatomical connections between brain areas.
Time frame: 1 year
Baseline activity in regions involved in emotion processing
Task-based fMRI will assess activity in, amongst others, the amygdala and anterior cingulate cortex. Activity is expressed in t-values between activity (average measured BOLD signal in region-of-interest) in two conditions/contrasts: Faces versus Rest Faces versus Shapes
Time frame: baseline
1-Year activity in regions involved in emotion processing
Task-based fMRI will assess activity in, amongst others, the amygdala and anterior cingulate cortex. Activity is expressed in t-values between activity (average measured BOLD signal in region-of-interest) in two conditions/contrasts: Faces versus Rest Faces versus Shapes
Time frame: 1 year
Baseline functional connectivity and derivatives thereof
Resting-state fMRI will assess functional connectivity between brain regions and networks. Derivations include e.g. directed or time varying functional connectivity.
Time frame: baseline
1-Year functional connectivity and derivatives thereof
Resting-state fMRI will assess functional connectivity between brain regions and networks. Derivations include e.g. directed or time varying functional connectivity.
Time frame: 1 year
Baseline cerebral blood flow
Arterial spin labeling measures blood flow from which cerebral blood flow can be extracted
Time frame: baseline
1-Year cerebral blood flow
Arterial spin labeling measures blood flow from which cerebral blood flow can be extracted
Time frame: 1 year
Baseline total volume microbleeds (susceptibility-weighted imaging)
This T2\*-weighted scan is used to detect brain microbleeds
Time frame: baseline
Baseline total number of microbleeds (susceptibility-weighted imaging)
This T2\*-weighted scan is used to detect brain microbleeds
Time frame: baseline
1-Year total volume microbleeds (susceptibility-weighted imaging)
This T2\*-weighted scan is used to detect brain microbleeds
Time frame: 1 year
1-Year total number of microbleeds (susceptibility-weighted imaging)
This T2\*-weighted scan is used to detect brain microbleeds
Time frame: 1 year
Baseline depression severity score
Full spectrum of symptoms assessed via the Hamilton Depression Rating Scale (HDRS) 17 questionnaire. 17 items are rated from 0-4 or 0-2. Total scores ranges from 0-51. The HDRS includes questions regarding symptoms such as: depressed mood, feelings of guilt, suicide, anxiety and more.
Time frame: baseline
3-Months depression severity score
Full spectrum of symptoms assessed via the Hamilton Depression Rating Scale (HDRS) 17 questionnaire. 17 items are rated from 0-4 or 0-2. Total scores ranges from 0-51. The HDRS includes questions regarding symptoms such as: depressed mood, feelings of guilt, suicide, anxiety and more.
Time frame: 3 months
6-Months depression severity score
Full spectrum of symptoms assessed via the Hamilton Depression Rating Scale (HDRS) 17 questionnaire. 17 items are rated from 0-4 or 0-2. Total scores ranges from 0-51. The HDRS includes questions regarding symptoms such as: depressed mood, feelings of guilt, suicide, anxiety and more.
Time frame: 6 months
9-Months depression severity score
Full spectrum of symptoms assessed via the Hamilton Depression Rating Scale (HDRS) 17 questionnaire. 17 items are rated from 0-4 or 0-2. Total scores ranges from 0-51. The HDRS includes questions regarding symptoms such as: depressed mood, feelings of guilt, suicide, anxiety and more.
Time frame: 9 months
1-Year depression severity score
Full spectrum of symptoms assessed via the Hamilton Depression Rating Scale (HDRS) 17 questionnaire. 17 items are rated from 0-4 or 0-2. Total scores ranges from 0-51. The HDRS includes questions regarding symptoms such as: depressed mood, feelings of guilt, suicide, anxiety and more.
Time frame: 1 year
Baseline depression severity score
Full spectrum of symptoms assessed via the Hamilton Depression Rating Scale (HDRS) 17 questionnaire. 17 items are rated from 0-4 or 0-2. Total scores ranges from 0-51. The HDRS includes questions regarding symptoms such as: depressed mood, feelings of guilt, suicide, anxiety and more.
Time frame: At baseline
Sleep score
As assessed from the insomnia severity index questionnaire. 7 items are scored from 0-4. Range scores: 0-28. Higher score ---\> More insomnia-related symptoms.
Time frame: At baseline and after 1 year
Anxiety score
As assessed from the State-Trait Anxiety Inventory Dutch Y 1 (STAI-DY1) questionnaire. 20 items are scored from 1-5. Range scores: 20-100. Higher score --\> More anxiety-related symptoms
Time frame: At baseline and after 1 year
Neuroticism score
As assessed from the Neuroticism, Extraversion, Openness to Experiences Five-Factor Inventory (NEO-FFI) questionnaire. 60 items can be scored from 1-5. Range scores: 60-300. Higher scores ---\> more symptoms related to neuroticism.
Time frame: At baseline and after 1 year
Childhood trauma score
As assessed from the Childhood trauma questionnaire (Dutch: JTV) - long version. 28 items can be scored from 1-5. Range scores: 28-140. Higher score --\> More traumatic experience during childhood.
Time frame: At baseline and after 1 year
Psychosis score
As assessed from the Community Assessment of Psychic Experience (CAPE) questionnaire. 42 items range from 0-3. If an item is scored from 1-3, a more detailed question should be filled in ranging from 0-3. Range scores: 0-252 (42 \* (3 \* 2)). Higher scores --\> more psychotic symptoms.
Time frame: At baseline and after 1 year
Comorbidities
As assessed from the MINI neuropsychiatric interview. No scores/scale. Labels indicate different comorbidities that might be crucial for biological subtype identification.
Time frame: At baseline and after 1 year
Medication and treatment
Custom questionnaire to assess type and dose of medication and types of treatments received. No scores and no scale.
Time frame: Every 3 months for MDD - At baseline and 1 year follow-up for healthy controls
Psychomotor speed and reaction time
As assessed by an eye-tracker camera and custom task in Tobii software Subjects have to focus on a white block appearing multiple times on a black background. It is an indication of medication influence on cognition. No scale; faster reaction times indicate higher performance.
Time frame: At baseline and after 1 year
Attention and processing speed
As assessed by FEPSY software. Includes visual reaction times and pattern recognition tasks. No scale; faster reaction times indicate higher performance.
Time frame: At baseline and after 1 year
Long and short-term verbal memory
As assessed by the RVALT (15 words memory and recall test). Each repetition a score from 1-15 can be achieved; higher scores indicate higher performance.
Time frame: At baseline and after 1 year
Plan to share: Undecided — No plan available yet
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Eindhoven University of Technology