16S rRNA gene sequencing reveals the effect of fluoxetine on gut microbiota in chronic unpredictable stress-induced depressive-like rats.

OBJECTIVES: Gut microbiota is relevant to the pathogenesis of mental disorders including depression. This study aimed to investigate the influence of fluoxetine (FLX) on the gut microbiota in rats with Chronic Unpredictable Mild Stresses (CUMS)-induced depression. RESULTS: We confirmed that the 28-day CUMS-induced depression rat model. Chronic FLX administration weakly improved depressive-like behaviors in rats. Illumina 16S rRNA gene sequencing on rat feces showed CUMS increased the relative abundance of Firmicutes (60.31% vs. 48.09% in Control, p < 0.05) and Lactobacillus genus (21.06% vs. 6.82% in control, p < 0.05); FLX and CUMS increased Bacilli class (20.00% ~ 24.08% vs. 10.31% in control, p < 0.05). CONCLUSION: Collectively, our study showed that both CUMS and FLX changed the compositions of gut microbiota in rats. FLX and CUMS distinctly regulated the gut microbiota in depressed rats.

Brain-derived neurotrophic factor, sex hormones and cognitive decline in male patients with schizophrenia receiving continuous antipsychotic therapy.

BACKGROUND: There are systematic differences in clinical features between women and men with schizophrenia (SCZ). The regulation of sex hormones may play a potential role in abnormal neurodevelopment in SCZ. Brain-derived neurotrophic factor (BDNF) and sex hormones have complex interacting actions that contribute to the etiology of SCZ. AIM: To investigate the influence of BDNF and sex hormones on cognition and clinical symptomatology in chronic antipsychotic-treated male SCZ patients. METHODS: The serum levels of follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E2), progesterone, testosterone (T), prolactin (PRL) and BDNF were compared between chronic antipsychotic-treated male (CATM) patients with SCZ (n = 120) and healthy controls (n = 120). The Positive and Negative Syndrome Scale was used to quantify SCZ symptoms, while neuropsychological tests were used to assess cognition. Neuropsychological tests, such as the Digit Cancellation Test (DCT), Semantic Verbal Fluency (SVF), Spatial Span Test (SS), Paced Auditory Serial Addition Test (PASAT), Trail Making Task (TMT-A), and Block Design Test (BDT), were used to assess executive functions (BDT), attention (DCT, TMT-A), memory (SS, PASAT), and verbal proficiency (SVF). RESULTS: Although E2 levels were significantly lower in the patient group compared to the healthy controls, T, PRL, and LH levels were all significantly higher. Additionally, the analysis revealed that across the entire sample, there were positive correlations between E2 Levels and BDNF levels as well as BDNF levels and the digital cancellation time. In CATM patients with SCZ, a significant correlation between the negative symptoms score and PRL levels was observed. CONCLUSION: Sex hormones and BDNF levels may also be linked to cognitive function in patients with chronic SCZ.

Antipsychotic drugs increase Neuregulin1ß1 serum levels in first-episode drug-naïve patients and chronic schizophrenia with suggestions for improving the treatment of psychotic symptoms.

BACKGROUND: Neuregulin1 (NRG1) plays a role in neuronal migration, regulation of synaptic plasticity, and neural survival, and has been considered to be among the candidate genes for schizophrenia. This study focused on the variations in serum NRG1ß1 levels following antipsychotic treatment and the relationship between NRG1ß1 levels and improvements in psychotic symptoms among first-episode drug-naïve (FEDN) patients and patients with chronic schizophrenia. METHODS: A total of 100 patients with schizophrenia were recruited and compared with 79 matched healthy controls. All patients had been drug-naïve for at least four weeks. Serum NRG1ß1 levels and positive and negative syndrome scale (PANSS) scores were measured at baseline and after four weeks. Serum NRG1ß1 levels were measured using sandwich enzyme-linked immunosorbent assays (ELISAs). RESULTS: Baseline NRG1ß1 levels were significantly lower in patients with schizophrenia than in healthy controls. NRG1ß1 levels increased significantly following antipsychotic treatment. NRG1ß1 levels gradually increased with declining PANSS scores and its three subscales during antipsychotic therapy. The levels of NRG1ß1 increased significantly in responders after four weeks of treatment, although nonresponders showed no such effect. Correlation analyses showed that the levels of NRG1ß1 were negatively correlated with the duration of illness and positively correlated with improvement in symptoms. CONCLUSION: The levels of serum NRG1ß1 and the therapeutic effects gradually increased following treatment, indicating that NRG1ß1 may be an indicator of therapy, and that it may also be associated with the pathophysiological mechanism causing schizophrenia, although this possible pathway requires further investigation.

Decreased neuregulin1ß1 in first episode and drug-naïve patients with schizophrenia: Negative correlation with cognitive impairment.

BACKGROUND: Neuregulin1ß1 (NRG1ß1) is essential for neuronal migration during development and for the ongoing neural plasticity underlying cognitive function. This study investigated the relationship between cognitive impairment and serum NRG1ß1 concentration in first-episode drug-naïve (FEDN) patients with schizophrenia. METHOD: We measured serum NRG1ß1 from 65 FEDN schizophrenia patients and 67 healthy matched controls. Cognitive function was evaluated using the Hopkins Vocabulary Learning Test-Revised (HVLT-R), Verbal Fluency Test (VFT), Trail Making Test (TMT), Digit Span Test (DST), and Stroop Test. RESULTS: Serum NRG1ß1 concentration was significantly lower in the FEDN patient group than the control group (7.25±0.49 vs. 12.52±0.77 ng/mL; F=23.716, P<0.0001, Cohen's d=1.00). Further, serum NRG1ß1 concentration in FEDN schizophrenia patients was negatively correlated with TMT-part A score (r=-0.408, P=0.001) and positively correlated with Stroop color subtest score (r=0.246, P=0.048). Multiple regression analysis also revealed weak correlations among FEDN patients between TMT-part A score and both serum NRG1ß1 concentration (R2=0.116, F=8.235, P=0.011) and duration of untreated psychosis (R2=0.193, F=5.969, P=0.017). CONCLUSION: This preliminary study suggests that serum NRG1ß1 levels are reduced in FEDN patients with schizophrenia and that NRG1ß1 may be involved in the cognitive function.

Altered levels of BMD, PRL, BAP and TRACP-5b in male chronic patients with schizophrenia.

Bone mineral density (BMD) has been found to decrease in schizophrenia patients. We examined BMD and the levels of prolactin (PRL), bone alkaline phosphatase (BAP) and tartrate resistant acid phosphatase isoform 5b (TRACP-5b) in male chronic schizophrenia patients and compared them with healthy controls in a Chinese Han population, which has not been reported before. Male patients with chronic schizophrenia (SPs; n = 79) and healthy controls (HCs; n  = 56) were recruited. BMD and plasma PRL, BAP and TRACP-5b levels were measured and compared between the two groups. The SPs group was further divided into two subgroups: the elevated PRL group (PRL ≥ 25 ng/ml, EPRL; n  = 38) and the normal PRL group (PRL < 25 ng/ml, NPRL; n = 41) in accordance with PRL levels. The levels of BAP and TRACP-5b were measured using sandwich enzyme-linked immunosorbent assay (ELISA) while serum PRL was measured with an Access Immunoassay Analyzer. BMD was determined by quantitative computed tomography. BMD levels significantly decreased and serum PRL and TRACP-5b levels were significantly higher in male chronic schizophrenia patients. The EPRL group had remarkably lower BMD and BAP level and higher TRACP-5b levels compared with the NPRL group and HCs. Moreover, there was a negative correlation between BMD and TRACP-5b in the EPRL group. We found that BMD, BAP and TRACP-5b levels in the EPRL group were significantly different than HCs and the NPRL group. PRL levels in schizophrenia patients may be related to BMD and bone metabolism. Monitoring BMD and markers of bone metabolism in clinical practice may therefore be helpful to understand the bone health status of schizophrenia patients.

Decreased Serum EGF in First-episode and Chronic Schizophrenia Patients: Negative Correlation with Psychopathology.

Previous studies have demonstrated that neurotrophic factors may play a critical role in the severity of clinical symptoms in schizophrenia. However, it remains unknown whether serum levels of epidermal growth factor (EGF) in schizophrenia are similar to those observed in the case of other neurotrophic factors. Therefore, we compared serum EGF concentrations in first-episode drug-naive (FEP) patients and medicated chronic schizophrenic patients with healthy controls in order to explore whether EGF levels are related to psychopathological symptoms. We measured the serum levels of EGF in 78 first-episode medication-naive schizophrenia patients, 76 medicated chronic schizophrenic patients, and 75 healthy controls using the sandwich ELISA method. Disease severity were measured using the positive and negative syndrome scale (PANSS). Serum EGF levels showed a significant decrease in schizophrenia patients in comparison to healthy subjects. Serum EGF levels in FEP patients are indistinguishable from chronic cases. EGF levels were related to PANSS general symptom subscales in both FEP never-medicated and medicated patients. It is interesting that serum EGF levels were negatively correlated with the PANSS cognitive subscales, with the exception of the patients with chronic schizophrenia. Our preliminary results indicated that EGF may play a role in this illness and that it could be used as a potential biomarker of disease severity. Moreover, EGF may be associated with cognitive subscales of PANSS in FEP patients. Future studies should investigate the relationship between EGF and cognitive function as measured using standardized neuropsychological assessments to identify potential biomarkers related with cognition.

Serum Epidermal Growth Factor is Low in Schizophrenia and Not Affected by Antipsychotics Alone or Combined With Electroconvulsive Therapy.

BACKGROUND: Epidermal growth factor (EGF) is implicated in the pathogenesis of schizophrenia, suggesting possible value as a biomarker for disease severity or treatment response. However, basal EGF levels and changes during treatment are inconsistent across studies. The goal of this study is to compare serum EGF in schizophrenia patients before and after treatment with antipsychotics alone or combined with electroconvulsive therapy (ECT). METHOD: Patients meeting DSM-IV diagnostic criteria for schizophrenia were recruited from June 2013 to December 2015 (n = 186) and followed up after 8 weeks of treatment with antipsychotics alone (n = 119, drug group) or combined with ECT (n = 67, ECT group). Serum EGF levels were measured by ELISA and compared among patients and 74 healthy control subjects. Psychopathology and clinical effects were assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Basal serum EGF was significantly lower in the entire patient cohort compared to healthy controls (P < 0.05). Repeated-measures ANOVA showed no main effect of time (F = 1.273; P = 0.261), time × group interaction (F = 1.228; P = 0.270), main effect of clinical response (F = 0.191; P = 0.663), or group × clinical interaction (F = 1.765; P = 0.186) on serum EGF. Serum EGF levels did not change significantly following antipsychotic drug or combined therapy (P > 0.05). Additionally, neither basal EGF nor EGF change was associated with the clinical response to drug or combined treatment (P > 0.05). However, baseline serum EGF was weakly associated with PANSS positive score (pretreatment: r = 0.206, posttreatment: r = 0.201) and general symptom score (pretreatment: r = -0.244). Serum EGF was also associated with duration of illness (pretreatment: r = 0.285, posttreatment: r = -0.231). CONCLUSIONS: Serum EGF concentration is low in schizophrenia but is unchanged following treatment with antipsychotics alone or combined with ECT, regardless of clinical response. Thus, serum EGF is not a surrogate biomarker for treatment response and is unlikely to be involved in the therapeutic mechanisms of antipsychotics or ECT.

Neurotrophic factor changes are essential for predict electroconvulsive therapy outcome in schizophrenia.

Brain-derived neurotrophic factor (BDNF) plays an important role in the treatment of schizophrenia with electroconvulsive therapy (ECT) or antipsychotic (AP) drugs. However, it is unclear whether BDNF is a mediator; we therefore assumed that baseline BDNF level can mediate the efficacy of ECT-AP treatment. A total of 160 patients with schizophrenia were examined; 80 received AP monotherapy and the other 80 were treated with a combination of ECT and AP. BDNF concentration was measured by enzyme-linked immunosorbent assay using the Emax Immunoassay System kit (Promega, Madison, WI, USA) according to the manufacturer's instructions.Log-linear analyses were used to examine the relationship between demographic characteristics, BDNF level, and clinical features and response status. The baseline BDNF levels and BDNF level increment were the best predictors of clinical outcome (OR1 = 3.358, P = 0.000; OR2 = 3.243, P = 0.000).The higher baseline BDNF levels and greater BDNF level increment were found to be associated with good outcome.

Neurocognition and social cognition in remitted first-episode schizophrenia: correlation with VEGF serum levels.

BACKGROUND: Accumulating evidence suggests that serum vascular endothelial growth factor (VEGF) in many neurobiological processes potentially contributes to the pathophysiology of psychiatric disorders, particularly cognitive decline. The purpose of this study was to explore the differences in neurocognition, social cognition and VEGF among remitted first-episode schizophrenic patients, non-remitters and normal control subjects. Moreover, we investigated the association between serum VEGF levels and cognitive functions. METHOD: 65 remission (RS) and 45 nonremission patients (NRS) after first-episode schizophrenia, as well as 58 healthy controls (HC) were enrolled in this study. Social cognition was assessed using the Chinese Facial Emotion Test (CFET); neurocognition was measured with a test battery consisting of Hopkins Verbal Learning Test-Revised, Verbal Fluency Test, Trail Making Tests, Digit Span Tests (DST) and Stroop Tests. Blood samples were collected for VEGF measurements. Data was analyzed with SPSS 22.0 (Chicago, IL, USA). RESULTS: On nearly all neurocognitive tests (except for DST), RS performed significantly worse than HC but better than NRS (P < 0.05). NRS, but not RS, exhibited markedly poorer social cognition than HC (except for Happiness and Surprise subscales of the CFET) (P < 0.05). VEGF levels showed a gradient change among three groups (HC > RS > NRS). CONCLUSION: Compared to HC, RS demonstrated poorer neurocognitive but intact social cognition functioning. These results indicate that VEGF levels decreased gradually with the severity of cognitive impairment in schizophrenia. VEGF may be involved in the pathological mechanism of cognitive performance in RS.

Serum BDNF and GDNF in Chinese male patients with deficit schizophrenia and their relationships with neurocognitive dysfunction.

BACKGROUND: To measure the serum levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in deficit schizophrenia (DS), in order to examine the association between these two neurotrophic factors (NFs) and cognitive performance. METHODS: A total of 109 male patients [51 DS and 58 non-deficit schizophrenia (NDS)] with schizophrenia and 40 sex and age matched healthy controls (HC) participated in this study. Processing speed, attention, executive function, and working memory of all subjects were assessed by means of a battery of classical neuropsychological tests. Serum BDNF and GDNF levels were measured simultaneously using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: There were significant differences in the overall cognitive test scores between three groups (all p < 0.001). Serum BDNF levels were significantly lower in patients (DS and NDS) than in HC (p < 0.001). Furthermore, BDNF levels were lower in the DS compared to the NDS group, although not significantly. However, there was no difference in the GDNF levels between patients (DS and NDS) and HC. GDNF levels were positively correlated with scores of Stroop words only (r = 0.311, p = 0.033), Stroop colors only (r = 0.356, p = 0.014) and Stroop interference (r = 0.348, p = 0.016) in DS group. CONCLUSION: Serum BDNF may be an unsuitable biomarker for DS, despite a significant decrease in schizophrenia patients. The different neurocognitive performance between the DS and NDS patients indicates that DS may be a separate clinical entity of schizophrenia. Finally, higher serum GDNF levels are associated with better cognitive performance in DS patients, indicating a possible neuroprotective function in DS.

Elevated serum vascular endothelial growth factor in treatment-resistant schizophrenia treated with electroconvulsive therapy: Positive association with therapeutic effects.

OBJECTIVES: As the name implies, vascular endothelial growth factor (VEGF) enhances angiogenesis, promotes vascular permeability, and stimulates neurogenesis in the adult brain. Furthermore, animal model studies have shown that electroconvulsive therapy (ECT), which is primarily utilised in cases of treatment-resistant schizophrenia (TRS), regulates the expression of VEGF. The current study focuses largely on the effect of ECT on VEGF serum concentration, and the relationship between VEGF and therapeutic effects in patients diagnosed with TRS. METHODS: Participants comprised 40 TRS patients and 43 healthy controls. Clinical severity was assessed (i.e. 1 day before commencement of ECT and 1 day following ECT) using the positive and negative syndrome scale (PANSS). Blood samples were also collected for VEGF measurements at corresponding time points. RESULTS: Pre-treatment serum VEGF levels were significantly lower in TRS patients compared to healthy controls. VEGF concentrations increased significantly following ECT, whereas no difference was found in controls. Moreover, there was a positive correlation between the change in VEGF and therapeutic effects. CONCLUSIONS: Elevated serum VEGF in TRS treated with ECT is positively associated with therapeutic effects, suggesting that alterations in VEGF levels may constitute an index by which to evaluate the improvement in clinical condition.

Altered serum levels of glial cell line-derived neurotrophic factor in male chronic schizophrenia patients with tardive dyskinesia.

OBJECTIVES: Many research indicate that the tardive dyskinesia (TD) is generally linked with long-term antipsychotic therapy for schizophrenia. Glial cell line-derived neurotrophic factor (GDNF) is a critical role in the protection of catecholaminergic, dopaminergic, and cholinergic neurons. Thus, we examined the serum GDNF levels in schizophrenia patients with TD (WTD) and without TD (NTD) and compared with healthy controls (HC), respectively. METHODS: Totally 75 males with schizophrenia were recruited into this study. All were measured by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, the Positive and Negative Syndrome Scale, and the Abnormal Involuntary Movement Scale (AIMS). The patient group was divided into two subgroups: WTD (n = 32) and NTD (n = 43) according to the AIMS score. Fifty-three healthy controls matching in age and gender were also enlisted from the region. GDNF levels were examined with sandwich enzyme-linked immunosorbent assay. RESULTS: Analysis of variance indicated significant differences between the three groups (P = 0.012); GDNF levels in the WTD group were significantly different from those in the NTD (P = 0.030) and HC (P = 0.003) groups. CONCLUSION: Decreased GDNF levels in TD patients indicated that alterations in neurotrophic factors may be involved in the pathophysiology of TD, but the exact mechanisms need further investigation.

Baseline serum vascular endothelial growth factor levels predict treatment response to antipsychotic medication in patients with schizophrenia.

Vascular endothelial growth factor (VEGF) is implicated in angiogenesis, blood flow, and neuroplasticity, which have previously been shown to contribute to schizophrenia and the mechanisms of action of antipsychotic medication. The aim of the present study was to investigate whether baseline serum VEGF levels predict treatment responses to antipsychotic medication. Drug-free adults with schizophrenia were administered monotherapy with atypical antipsychotic drugs for 6 weeks. Participants' psychiatric symptoms were assessed using the positive and negative symptom scale (PANSS) before and after treatment. Blood samples for VEGF measurements were collected from 201 participants comprising 83 healthy controls and 118 patients (i.e. only on admission). Baseline VEGF levels in adults with schizophrenia were significantly lower than those in the control group (t = 3.656, df = 199, P < 0.001). In particular, pretreatment VEGF levels were significantly higher in patients responding to drug treatment at follow-up (≥ 50% reduction in initial PANSS total) (t = 4.743, df = 116, P < 0.001). The predictive power of serum VEGF levels was investigated using receiver operating characteristic curves. The area under the curve was 0.774 (95% confidence interval 0.688-0.846); for fixed specificity of 78.8%, the corresponding sensitivity was 63.5%. Results from this preliminary experiment suggest high baseline serum concentrations of VEGF may predict a better response to antipsychotic medications in adults with schizophrenia. Further studies using larger sample sizes are needed to verify the findings.

Altered serum levels of vascular endothelial growth factor in first-episode drug-naïve and chronic medicated schizophrenia.

There is much evidence of a relationship between alterations in the brain's regional cellular energy metabolism and blood flow in schizophrenic. Vascular endothelial growth factor (VEGF) plays a role in the pathogenesis of neuropsychiatric illnesses. So, we compared serum VEGF levels in drug-naïve first-episode psychotic (FEP) and chronically medicated schizophrenic to examine if a correlation existed between VEGF and psychopathological symptoms. The serum VEGF levels were assessed in 46 FEP patients, 47 chronic medicated patients and 50 healthy controls. Symptoms of schizophrenia were evaluated with the Positive and Negative Syndrome Scale (PANSS) and sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure serum VEGF levels. VEGF levels were significantly lower in FEP patients compared to both chronically medicated schizophrenic patients and healthy controls, while VEGF levels in chronically medicated patients were markedly higher than in healthy controls. Furthermore, a significant correlation was detected between the levels and the PANSS negative subscale among patient groups. However, no significant correlation was observed between VEGF and clinical variables in patients. This study suggested that imbalanced neurotrophic factors may be associated with the onset of schizophrenia, but subsequent increased VEGF may be related to medication or other factors in disease progression.

Cognitive impairment in first-episode drug-naïve patients with schizophrenia: Relationships with serum concentrations of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor.

OBJECTIVES: Evidence suggests that brain-derived neurotrophic factor (BDNF) and glial cell line -derived neurotrophic factor (GDNF) are important in the regulation of synaptic plasticity, which plays a key role in the cognitive processes in psychiatric disorders. Our work aimed at exploring the associations between serum BDNF and GDNF levels and cognitive functions in first-episode drug-naïve (FEDN) patients with schizophrenia. METHODS: The BDNF and GDNF levels of 58 FEDN patients and 55 age- and sex-matched healthy controls were measured and test subjects were examined using several neurocognitive tests including the verbal fluency test (VFT), the trail making test (TMT), the digit span test (DST), and the Stroop test. RESULTS: Patients performed significantly worse than controls in nearly all neurocognitive performances except the forward subscale part of the DST. BDNF levels were inversely correlated to TMT-part B scores and positively correlated to VFT-action in the FEDN group. GDNF levels showed a positive correlation with VFT-action scores and a negative correlation with TMT-part B scores of these patients. CONCLUSION: Current data suggests that cognitive dysfunction widely exists in the early stages of schizophrenia. BDNF and GDNF may be jointly contributed to the pathological mechanisms involved in cognitive impairment in FEDN patients with schizophrenia.

Atypical antipsychotic treatment increases glial cell line-derived neurotrophic factor serum levels in drug-free schizophrenic patients along with improvement of psychotic symptoms and therapeutic effects.

Glial cell line-derived neurotrophic factor (GDNF) plays an increasingly vital role in the pathogenesis of neuropsychiatric illnesses. Antipsychotic medications were shown to stimulate GDNF secretion from C6 glioma cells. The aims of this study were to investigate the serum concentration of GDNF, to monitor the therapeutic effect of atypical antipsychotics related to GDNF levels in drug-free schizophrenia patients, and to examine these levels in relation to psychotic symptoms. We recruited 138 drug-free schizophrenic patients and compared them with 77 matched healthy subjects. All patients were treated with atypical antipsychotic monotherapy. GDNF serum levels and psychiatric symptoms were assessed at baseline and after 2, 4, 6 and 8 weeks. GDNF levels gradually increased accompanied by a reduction in psychiatric symptoms during antipsychotic therapy. The levels of GDNF in responders were significantly increased after 8 weeks of treatment, however, no significant change was found in non-responders. Furthermore, a negative association between GDNF levels following pharmacotherapy and disease duration in schizophrenic subjects could be observed. The present study suggests that GDNF may be involved in the etiology of schizophrenia and pharmacological treatment.

Relationship of serum testosterone levels with cognitive function in chronic antipsychotic-treated male patients with schizophrenia.

INTRODUCTION: Some evidence suggests that testosterone might be involved in the cognitive impairments of schizophrenia. We assessed major cognitive domains and serum testosterone levels in male long-term inpatients with schizophrenia. This study aimed to test whether testosterone in serum was abnormal in patients, and whether it was related to the cognitive impairment of schizophrenia. METHODS: Serum testosterone levels in male schizophrenics (n = 80) and normal controls (n = 40) were measured by immunoassay. All patients were assessed for performance on executive functions, sustaining and focusing of attention, memory functions, and verbal fluency using the Digit Cancellation Test (DCT), Semantic Fluency Test, Spatial Span (SS), Trail Making Test, part A (TMT-A), Block Design, and Paced Auditory Serial Addition Test. RESULTS: Serum testosterone levels in schizophrenic patients were similar to control subjects (P > 0.05). We found that serum testosterone levels were significantly correlated with total time taken (in seconds) in the DCT (r = 0.261, P < 0.05) and SS score (r = -0.240, P < 0.05) in schizophrenic patients. Moreover, backward linear regression revealed that testosterone levels significantly predicted performance in DCT (ß = 0.240, P = 0.028) and SS score (ß = -0.207, P = 0.047) in patients. DISCUSSION: Our findings suggest that there is no significant difference in serum testosterone levels between groups, and that serum testosterone levels are associated with the spatial memory and attention deficits in chronic antipsychotic-treated male patients with schizophrenia.