biological correlates of cognitive remediation in schizophrenia
TRANSCRIPT
BIOLOGICAL CORRELATES OF COGNITIVE REMEDIATION
IN SCHIZOPHRENIA
Barcelona Clinic Schizophrenia Unit Hospital Clinic of Barcelona
University of Barcelona
IDIBAPS CIBERSAM
Rafael Penadés, Ph.D.
Overview
• Neuroimaging of cognitive remediation
• Biomarkers of cognitive recovery: BDNF
• Conclusions
Neuroimaging in Schizophrenia
BrainMapping
HYPOFRONTALITY
Functional Mapping
NETWORKSDMN
ConnectomicsStructural Abnormalities
BRAIN MORPHOLOGY
PEG,CAT SPECT, PET MRI, fMRI, MEG
Regions of Interest
Whole Brain Analysis
CONNECTIVITY
Development of Image Analysis
TractographyGraph analysisRestingNeuroactivation
Multimodal studies
Penadés et al. (2017)
Neuroimaging Cognitive remediation
HYPOFRONTALITY NETWORKS
BRAIN MORPHOLOGY AND
VOLUME CONNECTIVITY
Wykes (1998)Wexler (2000)Penadés (2000)Penadés (2002)
Wykes (2002)Haut (2010)Rowland (2010)Edwards (2010)Bor (2011)Subramaniam (2012)Hooker (2012; 2013)
Penadés (2013) Subramaniam (2014)
Vianin (2014)
Eack (2010)
Penadés et al. (2017)
• CRT improves activation• Reduction of Hypofrontality• Individual differences
HYPOFRONTALITY
Wykes (1998)Wexler (2000)Penadés (2000)Penadés (2002)
Penadés (2000)
Wexler (2000)
Wykes et al (2002)N = 18
CRT (n = 6) Occupational Therapy (n = 6) Healthy Control (n = 6)
HYPOFRONTALITY
• Frontal activation improvement is related with improvement in working memory tasks• Specificity of the CRT
Wykes (2002)
HYPOFRONTALITY
Wykes (2002)Haut (2010)Rowland (2010)Bor (2011)Subramaniam (2012)Hooker (2012; 2013)Vianin (2014)Subramaniam (2014)
• Increased activity in: • Prefrontal cortex
• Lateral• Medial• Dorsolateral
• Parietal• Insula, caudate, thalamus
Bor (2011)
Haut (2010)
Meyer-Lindenberg et al. (2001)
PACIENTS >CONTROLS CONTROLS > PACIENTS
NETWORKS
NETWORKS
Reduction of the non-specific activation of CEN
Improvement of the deactivation of the DMN
Reduced activation is probably due to better efficiency of the networks
Penadés (2013)
BRAIN MORPHOLOGY AND
VOLUME
Penadés (2013) DTIIncrease of the white matter integrity in the genus of the corpus callosum
Eack (2010) VBMGreater preservation of grey matter volume over 2 years in the left hippocampus, parahippocampal gyrus, and fusiform gyrus
Greater grey matter increases in the left amygdala
Cortical Thickness and Memory Improvement after CRT
• LEFT:• Superior frontal• Caudal middle frontal• Precuneus• Paracentral Gyrus
• RIGHT:• Superior frontal• Caudal Middle frontal• Pars opercularis
• Greater baseline CTh in frontal and temporal lobes is related with more improvement in memory after CRT
Penadés et al. (2016)
Biomarkers for cognition
BDNF as a Biomarker of Treatment
Key modulator of synaptic transmission and plasticity
Brain-Derived Neurotrophic Factor (BDNF)Mediates hippocampal
long-term potentiation
Bai Lu et al. 2003
BDNF and cognition
Cognitive Remediation and BDNF
Vinogradov et al. (2009)
RCT (NCT 02341131)
• N = 70 patients with Schizophrenia • N = 15 healthy controls
• Primary Outcome: • Serum BDNF: Baseline, week-4, week-16
• Secondary Outcomes:• Cognitive function
• Experimental conditions:• CRT vs AC
Baseline cognition
Cognitive Outcomes
CRT and serum BDNF
Penadés et al (In preparation)
CRT and BDNF polymorphism Val66Met-rs6265
p = 0.006
Penadés et al (In preparation)
Conclusions• No significant effect of CRT on serum BDNF levels
• Cognitive and functional improvement after CRT were not correlated with changes in BDNF levels
• Genetic polymorphisms of BDNF gene could be playing a mediating role in CRT response
• Val/Val improved more than Met carriers although difference was not statistically significant
• The status of the BDNF as a biomarker of cognitive recovery is still premature
General Conclusions
• Cognitive remediation improves brain activation• Changes involve mainly prefrontal and thalamic regions • Improvement in the efficiency of Brain Networks have also been
described• Structural changes have been described both in grey and in white
matter• Findings are not linked to a particular remediation approach• No peripheral biomarkers for CRT have been stablished yet
Thanks for the kind attention!