Sult to our findings. Nonetheless, our results are consistent with those

Sult to our findings. Nonetheless, our results are consistent with those of previous research on neurotransmitter alterations in negative symptoms and suggest the role of an impaired serotonergic system [12]. Although many studies on the direct involvement of the serotonin system in schizophrenia exist, here we focus on results concerning negative symptoms. Direct evidence is provided from a post-mortem study, which reported a decreased 5-HT2 receptor density in frontal cortex in patients with chronic schizophrenia [65]. Furthermore, a PET study Epigenetics showed lower availability of 5-HT1A receptors in patients with schizophrenia compared to healthy controls and receptor binding was negatively associated with negative symptoms, estimated by the PANSS scale [66]. Moreover, a genetic study by Reynolds [67] gives support to an involvement of the serotonergic system in the pathogenesis of negative symptoms, since the 5-HT2C receptor promoter polymorphism is associated with negative symptoms. From studies on the mechanism of action of atypical neuroleptics in negative symptoms an indirect evidence for serotonergic involvement is provided. In this context, it remains unclear why serotonin antagonists as well as agonists have an impact on the serotonergic system and improve the outcome of negative symptoms. Silver [20] suggests that these pharmacologically distinct treatments may share common final mechanism. This paradoxical finding needs further investigation. Moreover, one has to consider that different 5-HT receptors have opposite effects on the function of neurons by means of inhibition and 23148522 excitation [15]. Further research is needed to clarify, if negative symptoms are caused directly by a primary abnormality in serotonergic transmission or in a secondary way via modulation of dopamine release [11,68,69]. With regard to the laterality effect, the present results showed a positive association between LDAEP and negative symptoms (SANS subscale affective flattening, anhedonia and attentional impairment, SANS composite score) in the right hemisphere, and a negative association between LDAEP and depressive symptoms (BRMS and CDSS G scale) in the left hemisphere in schizophrenic patients. A possible explanation could be that the LDAEPs in patients with high scores on depressive scales converge towards the LDAEP values of healthy controls (weaker LDAEP). This conclusion is in line with the inhibitor literature about LDAEP in depressive patients, where no significant effect on the LDAEP has been shown [40,63,70]. Our results could also be due to serotonergic interhemispheric asymmetry, respectively to a reduced leftward asymmetry of brain structures of the auditory cortex in schizophrenia as observed by Salisbury et al. [71] and Shenton et al. [72]. At that juncture, that the role of the laterality effect in schizophrenia and in particular in negative symptoms is not known, interpretation is limited. Nevertheless, our study is not without limitations: The sample size was relatively small, which had an effect on the statistical power. Furthermore, the effects of education were not considered. With regard to the influence of attention to the LDAEP [48] and given that patients with negative symptoms often show an attention deficit during auditory performances [73], an objective procedure controlling attention would have been necessary to add further consistency to our findings. A biased effect of medication isplausible since all patients were treated with atypical ne.Sult to our findings. Nonetheless, our results are consistent with those of previous research on neurotransmitter alterations in negative symptoms and suggest the role of an impaired serotonergic system [12]. Although many studies on the direct involvement of the serotonin system in schizophrenia exist, here we focus on results concerning negative symptoms. Direct evidence is provided from a post-mortem study, which reported a decreased 5-HT2 receptor density in frontal cortex in patients with chronic schizophrenia [65]. Furthermore, a PET study showed lower availability of 5-HT1A receptors in patients with schizophrenia compared to healthy controls and receptor binding was negatively associated with negative symptoms, estimated by the PANSS scale [66]. Moreover, a genetic study by Reynolds [67] gives support to an involvement of the serotonergic system in the pathogenesis of negative symptoms, since the 5-HT2C receptor promoter polymorphism is associated with negative symptoms. From studies on the mechanism of action of atypical neuroleptics in negative symptoms an indirect evidence for serotonergic involvement is provided. In this context, it remains unclear why serotonin antagonists as well as agonists have an impact on the serotonergic system and improve the outcome of negative symptoms. Silver [20] suggests that these pharmacologically distinct treatments may share common final mechanism. This paradoxical finding needs further investigation. Moreover, one has to consider that different 5-HT receptors have opposite effects on the function of neurons by means of inhibition and 23148522 excitation [15]. Further research is needed to clarify, if negative symptoms are caused directly by a primary abnormality in serotonergic transmission or in a secondary way via modulation of dopamine release [11,68,69]. With regard to the laterality effect, the present results showed a positive association between LDAEP and negative symptoms (SANS subscale affective flattening, anhedonia and attentional impairment, SANS composite score) in the right hemisphere, and a negative association between LDAEP and depressive symptoms (BRMS and CDSS G scale) in the left hemisphere in schizophrenic patients. A possible explanation could be that the LDAEPs in patients with high scores on depressive scales converge towards the LDAEP values of healthy controls (weaker LDAEP). This conclusion is in line with the literature about LDAEP in depressive patients, where no significant effect on the LDAEP has been shown [40,63,70]. Our results could also be due to serotonergic interhemispheric asymmetry, respectively to a reduced leftward asymmetry of brain structures of the auditory cortex in schizophrenia as observed by Salisbury et al. [71] and Shenton et al. [72]. At that juncture, that the role of the laterality effect in schizophrenia and in particular in negative symptoms is not known, interpretation is limited. Nevertheless, our study is not without limitations: The sample size was relatively small, which had an effect on the statistical power. Furthermore, the effects of education were not considered. With regard to the influence of attention to the LDAEP [48] and given that patients with negative symptoms often show an attention deficit during auditory performances [73], an objective procedure controlling attention would have been necessary to add further consistency to our findings. A biased effect of medication isplausible since all patients were treated with atypical ne.