PMID- 30539765
OWN - NLM
STAT- MEDLINE
DCOM- 20191029
LR  - 20201209
IS  - 1573-2509 (Electronic)
IS  - 0920-9964 (Linking)
VI  - 202
DP  - 2018 Dec
TI  - Neurobiology of cognitive remediation in schizophrenia: Effects of EAAT2 
      polymorphism.
PG  - 106-110
LID - S0920-9964(18)30401-8 [pii]
LID - 10.1016/j.schres.2018.06.059 [doi]
AB  - Cognitive deficits represent core features of schizophrenia, affecting quality of 
      life and functioning. The excitatory amino acid transporter 2 (EAAT2) is 
      responsible for the majority of glutamate reuptake and its activity is crucial 
      for glutamatergic neurotransmission, prevention of excitotoxic damage and 
      cerebral metabolism. Different studies reported that EAAT2 rs4354668 (-181 T/G) 
      influences cognitive functions and brain structures in patients with 
      schizophrenia. Specifically, the G allele, linked to lower EAAT2 expression, was 
      associated with impaired prefrontal cognitive performance and reduced grey matter 
      volumes. Cognitive remediation therapy (CRT) is one of the best available tool to 
      treat cognitive deficits in schizophrenia, able to induce a neuroplastic 
      modulation of cognitive functions. The present study aims to investigate the 
      effects of rs4354668 on CRT outcome, also considering possible genotype 
      interaction with antipsychotic (AP) treatment, since EAAT2 expression is 
      negatively influenced by clozapine. We examined rs4354668 in 88 clinically 
      stabilized patients with schizophrenia, treated with CRT and assessed at 
      enrolment, at the end of CRT and after 3 months. We observed greater working 
      memory improvements among patients carrying the T/T genotype, regardless of AP 
      treatment. Moreover, we reported a significant interaction between 
      pharmacological treatment and rs4354668 on executive functions, with greater 
      improvements among T/T patients treated with APs other than clozapine. These 
      observations suggest that impaired EAAT2 expression may attenuate CRT outcome. 
      Moreover, our results indicate the possibility that rs4354668 could also 
      differentially influence the response to CRT depending on the AP treatment.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Spangaro, Marco
AU  - Spangaro M
AD  - IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, 
      Milan, Italy. Electronic address: spangaro.marco@hsr.it.
FAU - Bosia, Marta
AU  - Bosia M
AD  - IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, 
      Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
FAU - Bechi, Margherita
AU  - Bechi M
AD  - IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, 
      Milan, Italy.
FAU - Buonocore, Mariachiara
AU  - Buonocore M
AD  - IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, 
      Milan, Italy.
FAU - Cocchi, Federica
AU  - Cocchi F
AD  - IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, 
      Milan, Italy.
FAU - Guglielmino, Carmelo
AU  - Guglielmino C
AD  - IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, 
      Milan, Italy.
FAU - Bianchi, Laura
AU  - Bianchi L
AD  - IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, 
      Milan, Italy.
FAU - Mastromatteo, Antonella
AU  - Mastromatteo A
AD  - IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, 
      Milan, Italy.
FAU - Lorenzi, Cristina
AU  - Lorenzi C
AD  - IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, 
      Milan, Italy.
FAU - Cavallaro, Roberto
AU  - Cavallaro R
AD  - IRCCS San Raffaele Scientific Institute, Department of Clinical Neurosciences, 
      Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
LA  - eng
PT  - Journal Article
DEP - 20180629
PL  - Netherlands
TA  - Schizophr Res
JT  - Schizophrenia research
JID - 8804207
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Glutamate Plasma Membrane Transport Proteins)
RN  - 0 (SLC1A2 protein, human)
SB  - IM
MH  - Adult
MH  - Antipsychotic Agents/*pharmacology
MH  - *Cognitive Dysfunction/etiology/genetics/therapy
MH  - Cognitive Remediation/*methods
MH  - Excitatory Amino Acid Transporter 2
MH  - *Executive Function/drug effects/physiology
MH  - Female
MH  - Glutamate Plasma Membrane Transport Proteins/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Outcome Assessment, Health Care
MH  - Polymorphism, Single Nucleotide
MH  - Retrospective Studies
MH  - *Schizophrenia/complications/genetics/therapy
MH  - Young Adult
OTO - NOTNLM
OT  - Clozapine
OT  - Cognitive deficit
OT  - EAAT2
OT  - Glutamate uptake
OT  - Psychosis
OT  - Rehabilitation
EDAT- 2018/12/13 06:00
MHDA- 2019/10/30 06:00
CRDT- 2018/12/13 06:00
PHST- 2017/10/16 00:00 [received]
PHST- 2018/03/27 00:00 [revised]
PHST- 2018/06/24 00:00 [accepted]
PHST- 2018/12/13 06:00 [entrez]
PHST- 2018/12/13 06:00 [pubmed]
PHST- 2019/10/30 06:00 [medline]
AID - S0920-9964(18)30401-8 [pii]
AID - 10.1016/j.schres.2018.06.059 [doi]
PST - ppublish
SO  - Schizophr Res. 2018 Dec;202:106-110. doi: 10.1016/j.schres.2018.06.059. Epub 2018 
      Jun 29.