Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia. Of those affected, 70–84% are reported to be treatment resistant from the outset. This raises the possibility that the neurobiological mechanisms of treatment resistance emerge before the onset of psychosis and have a neurodevelopmental origin. Neuropsychological investigations can offer important insights into the nature, origin and pathophysiology of treatment-resistant schizophrenia (TRS), but methodological limitations in a still emergent field of research have obscured the neuropsychological discriminability of TRS. We report on the first systematic review and meta-analysis to investigate neuropsychological differences between TRS patients and treatment-responsive controls across 17 published studies (1864 participants). Five meta-analyses were performed in relation to (1) executive function, (2) general cognitive function, (3) attention, working memory and processing speed, (4) verbal memory and learning, and (5) visual−spatial memory and learning. Small-to-moderate effect sizes emerged for all domains. Similarly to previous comparisons between unselected, drug-naïve and first-episode schizophrenia samples v. healthy controls in the literature, the largest effect size was observed in verbal memory and learning [dl = −0.53; 95% confidence interval (CI) −0.29 to −0.76; z = 4.42; p < 0.001]. A sub-analysis of language-related functions, extracted from across the primary domains, yielded a comparable effect size (dl = −0.53, 95% CI −0.82 to −0.23; z = 3.45; p < 0.001). Manipulating our sampling strategy to include or exclude samples selected for clozapine response did not affect the pattern of findings. Our findings are discussed in relation to possible aetiological contributions to TRS.

There is evidence in the literature that cognitive functions in schizophrenia (SC) may be improved by atypical neuroleptics (NLPs) in contrast to typical medication, but there is still controversy regarding this apparent superiority of atypical drugs. In this study, we assessed the differential effects of risperidone and haloperidol on verbal memory, attention, and psychiatric symptoms in SC. The performance of 28 SC participants, randomly assigned to risperidone (2–6 mg/day) or haloperidol (2–40 mg/day), was compared with that of healthy controls. The California Verbal Learning Test (CVLT), the d2 Cancellation Test, and the Positive and Negative Symptoms Scale were administered at baseline and 3, 6, and 12 months. Relative to controls, all SC participants showed markedly impaired verbal memory and processing speed at each assessment period. There was no differential effect between the two NLPs on CVLT and d2 performance. However, risperidone was more effective than haloperidol in reducing psychiatric symptoms. Improvement in symptom severity was not associated with improvement in neurocognitive performance on these specific tests. Neither conventional nor atypical neuroleptic medications improved neurocognitive functioning over a 12-month follow-up, suggesting that psychopathological improvement under risperidone is independent of cognitive function. (JINS, 2008, 14, 110–118.)

Recent models of impaired awareness in brain injury draw a distinction between metacognitive knowledge of difficulties and online awareness of errors (emergent and anticipatory). We examined performance of 31 Traumatic Brain Injury (TBI) participants and 31 healthy controls using a three-strand approach to assessing awareness. Metacognitive knowledge was assessed with an awareness interview and discrepancy scores on three questionnaires—Patient Competency Rating Scale, Frontal Systems Behavioral Scale and the Cognitive Failures Questionnaire. Online Emergent Awareness was assessed using an online error-monitoring task while participants performed tasks of sustained attention. Online anticipatory awareness was examined using prediction performance on two cognitive tasks. Results indicated that the TBI Low Self-Awareness (SA) group and High SA group did not differ in terms of severity, chronicity or standard neuropsychological tasks but those with Low SA were more likely to exhibit disinhibition, interpersonal problems and more difficulties in total competency. Sustained attention abilities were associated with both types of online awareness (emergent and anticipatory). There was a strong relationship between online emergent and online anticipatory awareness. Metacognitive knowledge did not correlate with the other two measures. This study highlights the necessity in adopting a multidimensional approach to assessing the multifaceted phenomenon of awareness of deficits. (JINS, 2007, 13, 38–49.)

The degree of neuropsychological dysfunction across multiple domains was examined in individuals suffering from chronic fatigue syndrome (CFS). In this descriptive study, a similar series of neuropsychological tests was administered to a group of CFS patients and healthy participants. More specifically, CFS patients (n = 141) who met the 1994 Case Definition criteria were compared to 76 healthy control participants on tests of memory, attention (concentration), speed of information processing, motor speed, and executive functioning. On the 18 measures administered, CFS patients scored 1 standard deviation below the healthy mean on nine measures and scored 2 standard deviations below the healthy mean on four of the measures. Moreover, results indicated that CFS patients were more likely than healthy controls to fail (1.6 SD below the healthy mean) at least one test in each of the following domains: attention, speed of information processing, and motor speed, but not on measures of memory and executive functioning. Finally, CFS patients demonstrated a greater total number of tests failed across domains. (JINS, 2004, 10, 278–285.)

This meta-analysis summarizes the broad spectrum of neuropsychological research on HIV disease across a sample of 41 primary studies and an aggregate of 8,616 participants for 10 major neuropsychological ability areas. Analyses of the course of cognitive decline within and across Centers for Disease Control classifications reveals statistically significant cognitive deficits from asymptomatic HIV to AIDS. Effect sizes (Cohen, 1988) were calculated to reflect between-group (asymptomatic, symptomatic, AIDS) differences in each neuropsychological domain. Relatively small effect sizes were obtained for the asymptomatic (0.05–0.21) patients, and generally small to moderate effect sizes were obtained for symptomatic (0.18–0.65) HIV+ patients, with motor functioning exhibiting the greatest effects in this later disease stage. The most notable deficits in cognitive functioning were found in the AIDS group with moderate (attention and concentration) to large (motor functioning) effect sizes with values ranging from 0.42–0.82. Comparison of cognitive functioning as a function of disease progression revealed that motor functioning, executive skills, and information processing speed were among the cognitive domains showing the greatest decline from early to later stages of HIV. These findings indicate that cognitive deficits in the early stages of HIV are small and increase in the later phases of the illness, and that specific patterns of cognitive deficits can be detected with disease progression. These results and their clinical utility are further discussed. (JINS, 2002, 8, 410–424.)