Cognition in schizophrenia is a topic of major importance and steadily increasing interest. As evidence of this fact, the Mount Sinai School of Medicine Conference on cognition in schizophrenia has had increased attendance at each of its six meetings over the last 10 years. These meetings are official satellites of the International Congress on Schizophrenia Research, a meeting that has had skyrocketing attendance figures over the last decade. The articles in this issue of CNS Spectrum are among those presented at the latest Mount Sinai meeting, in April of 2003 in Colorado Springs, Colorado.

One of the factors that has lead to the increased interest in cognition is a clearer appreciation of the functional relevance of cognitive impairments. Since functional deficits are a major source of the indirect cost of schizophrenia and a major source of the reductions in quality of life seen in schizophrenia, which are substantial, cognition has the potential to be a major point of intervention. In addition to “purely cognitive” impairments, patients with schizophrenia have deficits in what is typically referred to as “social cognition” as well. This ability area is defined as the ability to understand social cues and affective displays. It may serve as a critical intermediate function that mediates the performance of socially skilled acts.

The study of social cognition in psychiatric disorders has become increasingly popular in recent years. This is due to the its proposed link to social functioning and the inability of general neurocognitive skills to explain the spectrum of impairments observed in patients. This article reviews research into two of the processes thought to underlie social cognition (emotion perception and theory of mind) in schizophrenia and autism. This is followed by a look at neuroimaging studies and their efforts to localize the neural correlates of emotion perception and theory of mind in the two disorders. We concluded that while a specific impairment in emotion perception and theory of mind skills cannot be generalized to all individuals with autism and schizophrenia, there are subpopulations that have lingering deficits of social cognition tasks. Neuroimaging work consistently points to the involvement of the fusiform gyrus and amygdala in emotion processing, while the medial prefrontal and frontal cortex are implicated in tasks invoking theory of mind. We propose that deficits of social cognition may benefit from cognitive remediation therapy and pharmacological cognitive enhancers.

Substantial evidence suggests that alterations in noradrenergic function contribute to the cognitive impairments of schizophrenia. Activation of post-junctional α2a-adrenergic receptors in the prefrontal cortex by the α2a-selective agonist guanfacine has demonstrated some preliminary benefit in subjects with schizophrenia treated with atypical antipsychotics.α1-drenergic receptor activity may be less important in mediating the cognitive impairments of schizophrenia, β-adrenergic receptors may serve as another potential target for cognitive remediation in schizophrenia. However, the potential increase in memory consolidation in schizophrenia patients produced by β-adrenergic agonists may be outweighed by the impairment in cognitive flexibility and executive functioning produced by α-adrenergic agonists. Finally, norepinephrine reuptake inhibitors, such as atomoxetine, hold promise as potential cognitive enhancers in schizophrenia because of their ability to indirectly but selectively increase extracellular dopamine concentrations in the prefrontal cortex.

Background: Cognitive, social, and affective impairments are major features of schizophrenia, despite not being represented in the formal diagnostic criteria. These impairments are associated with major reductions in quality of life for patients with schizophrenia. Treatment with newer antipsychotic medications has been reported to improve all of these areas of functioning, but most studies have not examined the direct association between changes in cognitive functioning and other aspects of the illness.

Objectives: The goal of this analysis was to examine relationships between cognitive and affective symptoms and their impact on social impairments in patients switched to ziprasidone treatment.

Methods: In this study, which is a re-analysis of previously published data, 270 patients were switched from previous treatment with conventional antipsychotics, risperidone, or olanzapine to treatment with ziprasidone. Patients were tested with a cognitive assessment battery, rated with the Positive and Negative Syndrome Scale (PANSS), and received other assessments of safety and tolerability. PANSS scores were divided into factors based on previously published factor analyses, with a focus on the cognitive, prosocial, and anxiety-depression factors.

Results: Statistically significant improvements for global cognitive functioning and the three PANSS subscales were found across the studies. When the data were pooled for a path analysis, changes in cognitive functioning indexed by the PANSS cognitive subscales was the primary predictor of improvements in PANSS prosocial functions, with changes in anxiety-depression accounting for much less variance.

Conclusion: These results suggest a direct relationship between improvements in cognitive and prosocial functioning in patients with schizophrenia and indicate that treatments that enhance cognitive functioning, such novel antipsychotics, have the potential to improve aspects of outcome in schizophrenia even in short-term treatment studies. This issue should be addressed in future double-blind studies of the effects of atypical medications in schizophrenia.

Background: Studies on the effects of antipsychotics on cognitive deficits in schizophrenia mostly suggest a superior effect of atypical over typical compounds, although findings are inconsistent and effect sizes small. Several methodological issues, such as heterogenous patient samples, incomparable drug doses, effects of prior medication, construct validity, and retest effects on neuropsychological tasks, confound most results and the comparability between studies. Consequently, the conclusion concerning effects of antipsychotics on cognition is still equivocal.

Objective: The present randomized clinical trial examined the effects on cognition of comparatively low doses of a typical antipsychotic (zuclopenthixol) and an atypical antipsychotic (risperidone) in a homogenous group of drug-naïve first-episode schizophrenic patients in a longitudinal setting.

Methods: First-episode schizophrenic patients who had never previously been exposed to antipsychotic treatment (N-25) were randomly allocated to treatment with flexible doses of zuclopenthixol or risperidone in an open-label design. Cognitive functions were examined both when patients were drug-naïve, and after 13 weeks of treatment. A comprehensive neuropsychological battery was used in order to optimize construct validity, and principal components of cognitive functions were extrapolated in order to reduce type I errors. A healthy control group was tested at baseline and after 13 weeks, in order to examine retest effects. The cognitive domains studied were executive functions, selective attention, and reaction time.

Results: The patients showed considerable cognitive deficits when drug-naïve. There were few differential effects of risperidone and zuclopenthixol on cognitive deficits, except for a differential significance, respectively, tendency towards improved reaction and movement times in the risperidone group, and a lack of such in the zuclopenthixol group. These differences were no longer significant after covarying for extrapyramidal side effects and anticholinergic medication that were more prevalent in the zuclopenthixol group and the increases after medication were comparable with retest effects in controls.

Conclusion: The study underscores the importance of examining impact of factors, such as clinical improvement, extrapyramidal side effects, anticholinergic medication and retest effects in longitudinal efficacy studies. This study does not support efficacy of either risperidone or zuclopenthixol on cognitive functions in drug-naïve schizophrenia patients after 3 months of medication, because neither could be distinguished from retest effects of the healthy control group.

Depersonalization disorder is a poorly understood and treatment-resistant condition. This report describes a patient with depersonalization disorder who underwent six sessions of repetitive transcranial magnetic stimulation on the left dorsolateral prefrontal cortex. Repetitive transcranial magnetic stimulation produced a 28% reduction on depersonalization scores.

Alzheimer's disease is a progressive, neurodegenerative condition characterized by deficits in cognition, inability to perform activities of daily living, and alterations in behavior. Galantamine hydrobromide is the newest acetylcholin esterase inhibitor (AChEI) approved in the United State for the treatment of mild-to-moderate AD. The safety and efficacy of galantamine has been demonstrated in multiple randomized, Phase III trials of > 2,600 patients with mild-to-moderate AD. Studies have found that galantamine improved or maintained performance in all domains of AD (cognition, function, behavior, and caregiver burden in the short term and slowed the decline in performance or maintained baseline performance through 12 months. The dual mechanism of action may make galantamine a reasonable treatment option for both newly diagnosed patients and patients who have not benefitted from or have poorly tolerated current therapy.