Discrimination learning, reversal, and set-shifting in first-episode schizophrenia: stability over six years and specific associations with medication type and disorganization syndrome.
BACKGROUND
The intradimensional/extradimensional (IDED) task assesses different forms of learning from feedback. Limited evidence suggests that attentional set-shifting deteriorates over time in schizophrenia. We tested this hypothesis and examined the specificity of learning impairments identified by this task.


METHODS
Two hundred sixty-two first-episode patients and 76 healthy control subjects, matched for age and premorbid IQ, were tested; 104 patients and 25 control subjects were reassessed 1 and 3 years later, and 31 patients were reassessed additionally 6 years later.


RESULTS
Patients showed impaired set-shifting that correlated with current IQ and working memory, but there were no impairments when subgroups were matched on current IQ. In contrast, patients showed marked impairments in rule reversal learning that survived correction for IQ, were present in the context of intact rule abstraction, and correlated with disorganization symptoms. Patients prescribed second-generation antipsychotics were worse on set-shifting compared with first-generation, a finding not explained by demographic data, illness characteristics, or IQ. Patients and control subjects showed stable IDED performance over the first 6 years of illness, although set-shifting was inconsistent over the first year. Those with residual negative symptoms were more likely to fail the set-shifting stage at follow-up.


CONCLUSIONS
First-episode schizophrenia patients can learn and generalize rules but are inflexible when rules change, reflecting reduced responsiveness to negative feedback and difficulty in switching attention. Rule-reversal is a promising target for translational studies, because it is specific, clinically relevant, and might reflect orbitofrontal dysfunction. Set-shifting is related to poor function more generally but might be sensitive to medication effects and valuable for clinical trials.
Leeson
Verity C
VC
UCL Institute of Neurology, London, United Kingdom; Imperial College Faculty of Medicine, London, United Kingdom. v.leeson@ion.ucl.ac.uk
Robbins
Trevor W
TW
Matheson
Elizabeth
E
Hutton
Samuel B
SB
Ron
María A
MA
Barnes
Thomas R E
TR
Joyce
Eileen M
EM
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001288:Attention / Q000502:physiology*; D016022:Case-Control Studies; D004193:Discrimination Learning / Q000502:physiology*; D030141:Feedback, Psychological / Q000502:physiology; D005260:Female; D006801:Humans; D007360:Intelligence; D007859:Learning Disabilities / Q000209:etiology*; D008137:Longitudinal Studies; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D009483:Neuropsychological Tests; D011340:Problem Solving / Q000502:physiology; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy; D012565:Schizophrenic Psychology; D018709:Statistics, Nonparametric; D013997:Time Factors; D055815:Young Adult
D014150:Antipsychotic Agents