Schizophrenia patients using atypical medication perform better in visual tasks than patients using typical medication

Highlights

• Atypical medication leads to superior performance in visual tasks than typical medication.

• In line with previous studies, similar results were found for cognition but to a weaker extent.

• One needs to be careful comparing studies when medication is not comparable.

Abstract

Schizophrenia (SCZ) patients show deficits in many domains, including cognition and perception. However, results are often mixed. One reason for mixed results may be differences in medication. Very little is known about the role of medication in visual processing. Here, we investigated the effects of typical vs. atypical medication on contrast sensitivity (spatial frequencies ranging from 0.2 to 20 cycles per degree), vernier acuity, and visual backward masking. From a large pool of patients, we selected 50 patients (Study 1, conducted in Brazil) and 97 patients (Study 2, conducted in Georgia) taking either only typical or atypical medication. Patients with atypical medication performed significantly better than patients with typical medication for contrast sensitivity, vernier duration, and backward masking. As a secondary result, we found similar, but not significant, trends for the cognitive tasks (Stroop, Flanker, Trail-Making Test-B, Wisconsin Card Sorting Test and Continuous Performance Test) in the same patients. No correlations were found between demographics, psychopathology, chlorpromazine equivalents and visual processing. A conclusion of our study is that one needs to be careful comparing studies when medication is not comparable.

Introduction

Schizophrenia (SCZ) is a debilitating disorder affecting about 1.0% of the population worldwide (Jablensky, 2010, Mathers and Loncar, 2006). Deficits of SCZ patients are ample, including many cognitive and perceptual functions. One of the most important questions is to what extent medication influences or even causes these deficits. This question is not only important for SCZ research but also for neuroscience in general because it addresses the question how drugs modify brain processing. Here, we investigated how medication influences performance in visual and, to a secondary extent, in cognitive tasks.

A major challenge of antipsychotic medication is to reduce positive symptoms, caused by dopaminergic hyperfunction in mesolimbic pathways, and negative symptoms, caused by dopaminergic hypofunction in mesocortical pathways, without drastically reducing neurotransmission (Brisch et al., 2014). Antipsychotic drugs are usually subdivided into typical (or first-generation) and atypical (or second-generation) drugs. Typical medication causes extrapyramidal side effects and tardive dyskinesia, which is not the case for atypical drugs. Each antipsychotic drug has its own receptor specificity. Characteristic for typical antipsychotics is their strong affinity to dopaminergic D₂ receptors, whereas atypical antipsychotics have a lower affinity to D₂ receptors acting on a spectrum of other receptors, such as e.g. 5-HT (Meltzer, 2017, Li et al., 2016).

In general, SCZ patients perform worse than healthy controls in most visual tests, including contrast detection (Cadenhead et al., 2013, Fernandes et al., 2018d, Kiss et al., 2010, Shoshina and Shelepin, 2015; Slaghuis, 1998;) and visual backward masking (Braff and Saccuzzo, 1981, Chkonia et al., 2010, Green et al., 1994; review: Herzog and Brand, 2015). Very little is known to what extent the visual deficits depend on medication. In particular, there are only a few studies that investigated the effects of typical vs. atypical medication on contrast detection (for a review, see Silverstein, 2016). Kéri et al. (2002) found that the higher the dosage of typical antipsychotic medication, the more impaired was contrast detection (n = 20). Chen et al. (2003) found that contrast detection was worse in typical (n = 8) than atypical (n = 25) medicated patients with the latter performing at about the same level as healthy controls (n = 39). Unmedicated patients (n = 6) performed even better than healthy controls. Cadenhead et al. (2013) also found that unmedicated patients (n = 5) performed better than controls (n = 53). Shoshina et al. (2014) found that contrast detection was worse in typical medicated patients (n = 20) for low spatial frequencies, but not for medium spatial frequencies, for which atypically medicated patients (n = 25) performed worse. It needs to be noted that the sample sizes were very small in these studies.

In visual backward masking, SCZ patients perform in general worse than healthy controls (Braff and Saccuzzo, 1981, Green et al., 1994, Chkonia et al., 2010). Comparing unmedicated and medicated SCZ patients, Brody et al. (1980; n = 6 unmedicated, n = 6 medicated patients, respectively), Braff et al. (1982; n = 16; n = 20), Butler et al. (1996; n = 7; n = 7), and Cadenhead et al. (1997; n = 14; n = 76) did not find any significant differences of medication on backward masking. Again, sample sizes are small.

Here, we investigated whether typical medication has different effects than atypical medication on contrast detection, vernier duration and backward masking. Patients were very carefully selected. In Study 1, conducted in Brazil, we assessed contrast sensitivity and three cognitive measures (Stroop Test, Trail Making Test B and Flanker Test). Out of a large pool of 158 patients, we selected 50 patients, who had clear-cut either typical or atypical single drug medication (patients were using the same class of antipsychotics for at least five years). In Study 2, conducted in Georgia, we assessed vernier duration, backward masking and two cognitive measures (Wisconsin Card Sorting Test and Continuous Performance Test). From a pool of 276 SCZ patients, we included 97 patients, who took either typical or atypical medication. Some patients, however, took more than one antipsychotic drug.

In both studies, patients also performed cognitive tests. SCZ patients usually suffer from a broad range of cognitive deficits (meta-analysis: Fioravanti et al., 2012; but see Buchsbaum et al., 1990, for the Continuous Performance Test (CPT). Some studies explored the effects of antipsychotic medication on cognition in schizophrenia. Results are mixed ranging from no effect (see Harvey et al., 1990, Liu, 2000 for CPT) to improvements for medicated patients (Nestor et al., 1991, Orzack et al., 1967). Several studies compared the medication effects of typical and atypical drugs with mixed results again. Some studies reported that atypical medication resulted in better neurocognitive performance than typical medication (Désaméricq et al., 2014, Hagger et al., 1993, Harvey and Keefe, 2001, Keefe et al., 2007a, Lee et al., 1997, Woodward et al., 2005). In contrast, Keefe et al. (2007b) showed in the CATIE study that atypical medication had no superior effects to perphenzine. Since data of patients treated with one drug is scarce, we report performance in the cognitive tests here as secondary results because the data may be of interest, for example, for meta-analysis. We do not propose that there is a direct link between perception and cognition.

To preface our results, we found a reduction in visual performance for all SCZ patients compared to controls in line with almost all studies. Patients taking atypical antipsychotics performed better in all three visual tasks than patients with typical antipsychotics. We found similar trends for the cognitive tasks, where patients taking atypical performed slightly (but not significantly) better than patients taking typical antipsychotics.