Milton Depression Rating Scale, CDSS-G, Calgary Depression Rating Scale for Schizophrenia. *p,0.05. doi:10.1371/journal.pone.0068650.tMeasures CPZ PANSS positive PANSS negative PANSS composite score PANSS general SANS Affect SANS Alogia SANS Avolition SANS Anhedonia SANS Attention SANS composite score BRMS HAMD 17 CDSS GB 0.95 -CI 0.069; 0.20.014 20.154; 0.125 0.103 20.036; 0.20.086 20.241; 0.070 20.174 20.354; 0.006 0.207 0.094; 0.20.015 20.151; 0.121 20.101 20.228; 0.026 0.155 0.189 0.153 0.054 0.029; 0.282 0.036; 0.341 0.011; 0.296 20.129; 0.20.049 20.204; 0.106 20.055 20.184; 0.Abbreviations: CPZ, Chlorpromazine Dose Equivalence Ratios; PANSS, Positive and Negative Syndrome Scale; SANS, Scale for Assessment of Negative Symptoms; BRMS, Bech-Rafaelsen Melancholia Scale; HAMD, Hamilton Depression Rating Scale, CDSS-G, Calgary Depression Rating Scale for Schizophrenia. *p,0.05. doi:10.1371/journal.pone.0068650.tserotonergic neurotransmission. The results of this study provide new evidence in schizophrenia research. We would like to emphasize two remarkable findings. First, patients with schizophrenia showed a significantly stronger LDAEP than the control group. Based on the presumptions of the inverse relationship between LDAEP and 5-HT, this may indicate a difference in serotonergic neurotransmission. Moreover, the stronger LDAEP in patients with schizophrenia is highly associated with negative symptoms. Second, only the increased LDAEP in the right hemisphere 18204824 was associated with negative symptoms, underscoring the effects of laterality in brain functions and brain activity in 23148522 schizophrenia. The single electrode estimation at Cz did not show any significant differences between the groups, which may derive from additional frontal source activation involved in high intensities. This has also been reported by Hagenmuller et al. [58]. Our findings contrast with those of previous studies, which showed that patients with schizophrenia had a weaker LDAEP than healthy controls [37,38,39,40]. However, those studies were not designed to control for LDAEP differences between positive and negative symptoms. They focused on schizophrenic patients as a self-contained group. Nevertheless, Juckel et al. [39] reported a tendency toward a positive relationship between PANSS negative score and LDAEP whereas Gudlowski et al. [37] found a negative relationship between those scores. Our findings are contrary to the results of Gudlowski et al. [37]. One explanation for inconsistent findings could be due to a difference in methodology as sampling biases, gender effects, intensity of stimuli and methods of estimation (DSA vs. single-electrode) [32]. In particular, our data were analysed with DSA method, whereas Gudlowski et al. [37] used single-electrode estimation for LDAEP. According to Hagenmuller et al. [58], studies using different methods are difficult if not impossible to compare. Furthermore, the 125-65-5 sample in Gudlowski’s study included females and males. Even though some studies reported no gender effects [29,40,61], others 194423-15-9 web haveSerotonergic Dysfunction in Negative Symptomsdocumented some effects on the LDAEP [62,63,64]. The study by Juckel et al. (2008) [39] used comparable methodology to the present study and some results are in line with our findings, showing strong LDAEP in patients with negative symptoms among schizophrenic patients. Compared to healthy controls, they reported weaker LDAEP in the left hemisphere in patients, which states a contrary re.Milton Depression Rating Scale, CDSS-G, Calgary Depression Rating Scale for Schizophrenia. *p,0.05. doi:10.1371/journal.pone.0068650.tMeasures CPZ PANSS positive PANSS negative PANSS composite score PANSS general SANS Affect SANS Alogia SANS Avolition SANS Anhedonia SANS Attention SANS composite score BRMS HAMD 17 CDSS GB 0.95 -CI 0.069; 0.20.014 20.154; 0.125 0.103 20.036; 0.20.086 20.241; 0.070 20.174 20.354; 0.006 0.207 0.094; 0.20.015 20.151; 0.121 20.101 20.228; 0.026 0.155 0.189 0.153 0.054 0.029; 0.282 0.036; 0.341 0.011; 0.296 20.129; 0.20.049 20.204; 0.106 20.055 20.184; 0.Abbreviations: CPZ, Chlorpromazine Dose Equivalence Ratios; PANSS, Positive and Negative Syndrome Scale; SANS, Scale for Assessment of Negative Symptoms; BRMS, Bech-Rafaelsen Melancholia Scale; HAMD, Hamilton Depression Rating Scale, CDSS-G, Calgary Depression Rating Scale for Schizophrenia. *p,0.05. doi:10.1371/journal.pone.0068650.tserotonergic neurotransmission. The results of this study provide new evidence in schizophrenia research. We would like to emphasize two remarkable findings. First, patients with schizophrenia showed a significantly stronger LDAEP than the control group. Based on the presumptions of the inverse relationship between LDAEP and 5-HT, this may indicate a difference in serotonergic neurotransmission. Moreover, the stronger LDAEP in patients with schizophrenia is highly associated with negative symptoms. Second, only the increased LDAEP in the right hemisphere 18204824 was associated with negative symptoms, underscoring the effects of laterality in brain functions and brain activity in 23148522 schizophrenia. The single electrode estimation at Cz did not show any significant differences between the groups, which may derive from additional frontal source activation involved in high intensities. This has also been reported by Hagenmuller et al. [58]. Our findings contrast with those of previous studies, which showed that patients with schizophrenia had a weaker LDAEP than healthy controls [37,38,39,40]. However, those studies were not designed to control for LDAEP differences between positive and negative symptoms. They focused on schizophrenic patients as a self-contained group. Nevertheless, Juckel et al. [39] reported a tendency toward a positive relationship between PANSS negative score and LDAEP whereas Gudlowski et al. [37] found a negative relationship between those scores. Our findings are contrary to the results of Gudlowski et al. [37]. One explanation for inconsistent findings could be due to a difference in methodology as sampling biases, gender effects, intensity of stimuli and methods of estimation (DSA vs. single-electrode) [32]. In particular, our data were analysed with DSA method, whereas Gudlowski et al. [37] used single-electrode estimation for LDAEP. According to Hagenmuller et al. [58], studies using different methods are difficult if not impossible to compare. Furthermore, the sample in Gudlowski’s study included females and males. Even though some studies reported no gender effects [29,40,61], others haveSerotonergic Dysfunction in Negative Symptomsdocumented some effects on the LDAEP [62,63,64]. The study by Juckel et al. (2008) [39] used comparable methodology to the present study and some results are in line with our findings, showing strong LDAEP in patients with negative symptoms among schizophrenic patients. Compared to healthy controls, they reported weaker LDAEP in the left hemisphere in patients, which states a contrary re.