Executive attention impairment in first-episode schizophrenia

<p>Abstract</p> <p>Background</p> <p>We compared the attention abilities of a group of first-episode schizophrenia (FES) patients and a group of healthy participants using the Attention Network Test (ANT), a standard procedure that estimates the functional state of three neural networks controlling the efficiency of three different attentional behaviors, i.e., alerting (achieving and maintaining a state of high sensitivity to incoming stimuli), orienting (ability to select information from sensory input), and executive attention (mechanisms for resolving conflict among thoughts, feelings, and actions).</p> <p>Methods</p> <p>We evaluated 22 FES patients from 17 to 29 years of age with a recent history of a single psychotic episode treated only with atypical neuroleptics, and 20 healthy persons matched with FES patients by sex, age, and educational level as the control group. Attention was estimated using the ANT in which participants indicate whether a central horizontal arrow is pointing to the left or the right. The central arrow may be preceded by spatial or temporal cues denoting where and when the arrow will appear, and may be flanked by other arrows (hereafter, flankers) pointing in the same or the opposite direction.</p> <p>Results</p> <p>The efficiency of the alerting, orienting, and executive networks was estimated by measuring how reaction time was influenced by congruency between temporal, spatial, and flanker cues. We found that the control group only demonstrated significantly greater attention efficiency than FES patients in the executive attention network.</p> <p>Conclusions</p> <p>FES patients are impaired in executive attention but not in alerting or orienting attention, suggesting that executive attention deficit may be a primary impairment during the progression of the disease.</p

Effects of acute memantine administration on MATRICS Consensus Cognitive Battery performance in psychosis: Testing an experimental medicine strategy

RATIONALE: Pro-cognitive agents for chronic psychotic disorders (CPDs) might be detected via experimental medicine models, in which neural targets engaged by the drug predict sensitivity to the drug’s pro-cognitive effects. OBJECTIVE: This study aims to use an experimental medicine model to test the hypothesis that “target engagement” predicts pro-cognitive effects of the NMDA antagonist, memantine (MEM), in CPDs. METHODS: MATRICS Consensus Cognitive Battery (MCCB) performance was assessed in CPD (n = 41) and healthy subjects (HS; n = 41) in a double-blind, randomized cross-over design of acute (single dose) MEM (placebo vs. 10 or 20 mg p.o.). Measures of prepulse inhibition (PPI) and mismatch negativity previously reported from this cohort substantiated target engagement. Biomarkers predicting MEM neurocognitive sensitivity were assessed. RESULTS: Testing confirmed MCCB deficits associated with CPD diagnosis, age, and anticholinergic exposure. MEM (20 mg p.o.) reduced MCCB performance in HS. To control for significant test order effects, an “order-corrected MEM effect” (OCME) was calculated. In CPD subjects, greater age, positive MEM effects on PPI, and SNP rs1337697 (within the ionotropic NMDA receptor gene, GRIN3A) predicted greater positive OCME with 20 mg MEM. CONCLUSIONS: An experimental medicine model to assess acute pro-cognitive drug effects in CPD subjects is feasible but not without challenges. A single MEM 20 mg dose had a negative impact on neurocognition among HS. In CPD patients, age, MEM effects on PPI, and rs1337697 predicted sensitivity to the neurocognitive effects of MEM. Any potential clinical utility of these predictive markers for pro-cognitive effects of MEM in subgroups of CPD patients cannot be inferred without a validating clinical trial

Behavioral effects of phencyclidine on nicotine self-administration and reinstatement in the presence or absence of a visual stimulus in rats

RATIONALE: Tobacco use is a serious health problem in the United States and this problem is potentiated in patients with schizophrenia. The reward system is implicated in schizophrenia and may contribute to the high comorbidity between nicotine use and schizophrenia but very little research has been done on the topic. The reward-enhancement effect of nicotine has been shown to be important in nicotine use, but there have been no studies on this effect in animal models of schizophrenia. OBJECTIVES: This study was designed to determine the effects of phencyclidine, used to model negative symptoms of schizophrenia, on self-administration of nicotine with or without a co-occurring sensory reinforcer [i.e., visual stimulus (VS)] in rats. METHODS: Phencyclidine (2.0 mg/kg) was administered before each of 7 nicotine self-administration sessions (0.01 mg/kg/inf) after which rats (n=8–9 per group) were given 7 days of extinction without phencyclidine pretreatment. Reinstatement using phencyclidine (2.0 mg/kg), nicotine (0.2 mg/kg), and yohimbine (1.25 mg/kg, a pharmacological stressor) were tested after extinction to determine if previous exposure to phencyclidine would alter reinstatement of active lever pressing. RESULTS: Phencyclidine initially decreased nicotine self-administration, but only in the groups with a concurrent VS. This decrease in self-administration dissipated after 5 days. During reinstatement, rats that had previously received phencyclidine during self-administration with a VS were more sensitive to stress-induced reinstatement than any other group. CONCLUSIONS: These results show a transitory effect of phencyclidine on nicotine self-administration. Phencyclidine may induce a potential sensitivity to pharmacological stressors contributing to reinstatement of nicotine