The primary objective of the proposed study is to examine the neural substrate of cognitive and social-emotional apathy in patients with schizophrenia. Secondary, we intend to explore the concentration of brain metabolites and structural differences…
ID
Source
Brief title
Condition
- Schizophrenia and other psychotic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter will be brain activation (BOLD-response) measured with
functional Magnetic Resonance Imaging (fMRI).
Secondary outcome
Secondary parameters will be metabolic differences using Magnetic Resonance
Spectroscopy (MRS) and white matter pathways using Diffusion Tensor Imaging
(DTI). Furthermore, we will explore local concentration of grey matter, using
Voxel-Based Morphometry (VBM) of a structural MRI scan and fronto-parietal
connectivity and perfusion during a resting-state scan.
Background summary
Apathy is a quantitative reduction of self-generated voluntary and purposeful
behavior. It is a common symptom in several neuropathological disorders, like
schizophrenia. Apathy is very bothersome for the patients and is a strong
predictor of poor outcome. Clinically, a distinction has been made between a
cognitive (CA) and a social-emotional (SEA) form of apathy. These forms both
result in reduced behavioral activation. However, CA and SEA might reflect
different cognitive deficits with different underlying neural substrates. It
has been suggested that CA is due to a lack of self-initiated action and
cognitive control, whereas reduced salience signaling of positive events lies
at the core of SEA. Previous studies have suggested that activation and
connectivity in a dorsal frontostriatal circuit, including the parietal cortex,
may underlie self-initiation. Furthermore, it has been suggested that
activation and connectivity in a ventral frontostriatal network may underlie
positive salience signaling. These circuits might be altered in apathetic
patients with schizophrenia. However, this has never been directly
investigated. In this study, the neural substrates for CA and SEA are examined
in patients with schizophrenia.
Hypotheses: We intend to unravel two possible distinct neural routes for
cognitive and social-emotional apathy, namely a dorsal frontostriatal route,
including the right parietal cortex, for cognitive apathy and a ventral
frontostriatal reward route for social-emotional apathy. In this light we will
examine CA- and SEA-related neural activation and connectivity during tasks and
rest.
Study objective
The primary objective of the proposed study is to examine the neural substrate
of cognitive and social-emotional apathy in patients with schizophrenia.
Secondary, we intend to explore the concentration of brain metabolites and
structural differences between patients with high CA, high SEA, low apathy and
healthy controls.
Study design
The proposed study has an experimental design. Subjects will be presented with
four different fMRI tasks which we expect to robustly activate underlying
circuits for cognitive or social-emotional apathy. The tasks intend to measure
self-initiated realization of intentions, cognitive control, reward
anticipation and affective forecasting. Furthermore 6 interviews will be
administered concerning apathy, depression, and other symptoms of
schizophrenia. Two questionnaires will be filled out by all participants, in
order to assess the experience of pleasure.
Study burden and risks
The study will consist of interviews and questionnaires with a maximum total
duration of 2 hours and 55 minutes, and Magnetic Resonance scans with a maximum
total duration of 2 hours and 10- minutes. Possible participants will first be
interviewed in a screening session of 75 minutes, in order to confirm of rule
out possible diagnoses and establish the level of apathy. In order to reduce
the strain that a long interview and scanning session could entail the
remaining interview and scanning procedures will be divided into two sessions
with a maximum duration of 2 hours and 10 minutes each. These sessions will
preferably take place within one week from each other.
Concerning the MRI scanner, participants will be exposed to a field-strength of
3 Tesla and scanner noise. Thus far, there is no evidence to suggest that
exposing humans to a magnetic field of this strength has a negative influence
on their health. With regard to the noise, earplugs and headphones will be
provided. Subjects will not benefit directly from participating in the study,
however the data collected during this study will enhance understanding of the
neural basis of apathy.
Ant. Deusinglaan 2
Groningen 9713 AW
NL
Ant. Deusinglaan 2
Groningen 9713 AW
NL
Listed location countries
Age
Inclusion criteria
Patients with schizophrenia (N=60)
- At least 18 years of age
- DSM-IV diagnosis of schizophrenia, or schizoaffective disorder
- High levels of cognitive or social-emotional apathy
or
- Absence or low level of apathy
- Patient groups will be matched on age, sex, education, levels of depressive symptoms, levels of D2 dopamine receptor occupancy and handedness
- Written informed consent;Healthy controls (N=20)
- At least 18 years of age
- Matched to patients on age, sex, education, levels of depressive symptoms and handedness
- Written informed consent
Exclusion criteria
Patients with schizophrenia (N=60)
• Presence of a substance dependence disorder
• Presence of a neurological disorder
• Use of medication that can influence task results (e.g. beta-blockers, insulin);Healthy controls (N=20)
• Presence of a neurological or psychiatric disorder, in present or past.
• Use of medication that can influence task results (e.g. psychopharmaca, beta-blockers, insulin)
• High levels of apathy (a score of more than 27 on the AES);All subjects (N=80):
• Visual or hearing problems that cannot be corrected
• Insufficient knowledge of the Dutch language
• Inability to undergo cognitive testing
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL43372.042.13 |