Schizophrenia patients using atypical medication perform better in visual tasks than patients using typical medication
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.
Section snippets
Participants
Fifty healthy controls (HCs; mean age = 35.4 years, SD = 8.05 years), 25 patients who were diagnosed with SCZ and using typical antipsychotics (mean age = 35.1 years, SD = 8.14 years), and 25 patients who were diagnosed with SCZ and using atypical antipsychotics (mean age = 38.4 years, SD = 7.46 years) were recruited from the Psychosocial Care Center. Psychiatrists at the same institution diagnosed SCZ according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5;
Participants
Hundred and fifty-eight HCs (mean age = 34.7 years, SD = 8.8 years), 49 SCZ patients taking typical antipsychotics (mean age = 38.2 years, SD = 7.9 years) and 48 SCZ patients taking atypical antipsychotics (mean age = 35.4 years, SD = 8.8 years) were recruited from the Asiatani psychiatric hospital or the rehabilitation center or outpatients of the Gotsiridze psychoneurological dispensary. Patients were diagnosed according to DSM-4 by means of an interview based on the SCID, information of the
Discussion
We investigated how typical and atypical antipsychotics influence vision and, to a secondary extent, cognition. For contrast detection, patients with atypical antipsychotics had superior performance than patients treated with typical medication for all spatial frequencies. Similarly, we found that patients with atypical medication performed better in vernier duration and visual backward masking than patients with typical medication. We did not observe any influence of symptom severity (using
Acknowledgments
The present study followed the ethical principles of the Declaration of Helsinki and was approved by the Committee of Ethics in Research of the Health Sciences Center of Federal University da Paraiba, Brazil, and from the Georgian National Council on Bioethics, Georgia. Written informed consent was obtained from all of the participants. We would like to thank the Coordination for the Improvement of Higher Education Personnel (CAPES).
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