Decreased serum VEGF and NRG1ß1 levels in male patients with chronic schizophrenia: VEGF correlation with clinical symptoms and cognitive deficits.

BACKGROUND: Vascular endothelial growth factor (VEGF) and neuregulin1 (NRG1) are multifunctional trophic factors reported to be dysregulated in schizophrenia. However, the relationships between serum concentrations and schizophrenia symptoms have differed markedly across studies, possibly because schizophrenia is a highly heterogenous disorder. The aim of this study was to investigate the associations of serum VEGF and NRG1 with clinical symptoms and cognitive deficits specifically in male patients with chronic schizophrenia. METHODS: The study included 79 male patients with chronic schizophrenia and 79 matched healthy individuals. Serum VEGF, NRG1ß1, S100B, S100A8, and neuropilin1 were measured using the Luminex liquid suspension chip detection method, psychopathological symptom severity using the Positive and Negative Symptom Scale (PANSS), and cognitive dysfunction using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: Serum VEGF and NRG1ß1 concentrations were significantly lower in male chronic schizophrenic patients than healthy controls (P < 0.05), while serum S100B, S100A8, and neuropilin1 concentrations did not differ between groups (P > 0.05). Serum VEGF concentration was negatively correlated with PANSS negative subscore (beta = -0.220, t = -2.07, P = 0.042), general psychopathology subscore (beta = -0.269, t = -2.55, P = 0.013), and total score (beta = -0.234, t = -2.12, P = 0.038), and positively correlated with RBANS language score (beta = 0.218, t = 2.03, P = 0.045). Alternatively, serum NRG1ß1 concentration was not correlated with clinical symptoms or cognitive deficits (all P > 0.05). CONCLUSION: Dysregulation of VEGF and NRG1ß1 signaling may contribute to the pathogenesis of chronic schizophrenia in males. Moreover, abnormal VEGF signaling may contribute directly or through intermediary processes to neuropsychiatric and cognitive symptom expression.

Association between elevated serum matrix metalloproteinase-2 and tumor necrosis factor-α, and clinical symptoms in male patients with treatment-resistant and chronic medicated schizophrenia.

BACKGROUND: Inflammation has an important role in the pathogenesis of schizophrenia. The aim of this study was to investigate the levels of tumor necrosis factor (TNF) and matrix metalloproteinase-2 (MMP-2) in male patients with treatment-resistant schizophrenia (TRS) and chronic medicated schizophrenia (CMS), and the relationship with psychopathology. METHODS: The study enrolled 31 TRS and 49 cm male patients, and 53 healthy controls. Serum MMP-2 and TNF-α levels were measured by the Luminex liquid suspension chip detection method. Positive and Negative Syndrome Scale (PANSS) scores were used to evaluate symptom severity and Repeatable Battery for the Assessment of Neuropsychological Status was used to assess cognitive function. RESULTS: Serum TNF-α and MMP-2 levels differed significantly between TRS, CMS and healthy control patients (F = 4.289, P = 0.016; F = 4.682, P = 0.011, respectively). Bonferroni correction demonstrated that serum TNF-α levels were significantly elevated in CMS patients (P = 0.022) and MMP-2 levels were significantly higher in TRS patients (P = 0.014) compared to healthy controls. In TRS patients, TNF-α was negatively correlated with age (r=-0.435, P = 0.015) and age of onset (r=-0.409, P = 0.022). In CMS patients, MMP-2 and TNF-α were negatively correlated with PANSS negative and total scores, and TNF-α was negatively correlated with PANSS general psychopathology scores (all P < 0.05). MMP-2 levels were positively correlated with TNF-α levels (P < 0.05), but not with cognitive function (P > 0.05). CONCLUSION: The results indicate the involvement of inflammation in the etiology of TRS and CMS. Further studies are warranted.

Abnormalities of electroencephalography microstates in patients with depression and their association with cognitive function.

BACKGROUND: A growing number of recent studies have explored underlying activity in the brain by measuring electroencephalography (EEG) in people with depression. However, the consistency of findings on EEG microstates in patients with depression is poor, and few studies have reported the relationship between EEG microstates, cognitive scales, and depression severity scales. AIM: To investigate the EEG microstate characteristics of patients with depression and their association with cognitive functions. METHODS: A total of 24 patients diagnosed with depression and 32 healthy controls were included in this study using the Structured Clinical Interview for Disease for The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. We collected information relating to demographic and clinical characteristics, as well as data from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS; Chinese version) and EEG. RESULTS: Compared with the controls, the duration, occurrence, and contribution of microstate C were significantly higher [depression (DEP): Duration 84.58 ± 24.35, occurrence 3.72 ± 0.56, contribution 30.39 ± 8.59; CON: Duration 72.77 ± 10.23, occurrence 3.41 ± 0.36, contribution 24.46 ± 4.66; Duration F = 6.02, P = 0.049; Occurrence F = 6.19, P = 0.049; Contribution F = 10.82, P = 0.011] while the duration, occurrence, and contribution of microstate D were significantly lower (DEP: Duration 70.00 ± 15.92, occurrence 3.18 ± 0.71, contribution 22.48 ± 8.12; CON: Duration 85.46 ± 10.23, occurrence 3.54 ± 0.41, contribution 28.25 ± 5.85; Duration F = 19.18, P < 0.001; Occurrence F = 5.79, P = 0.050; Contribution F = 9.41, P = 0.013) in patients with depression. A positive correlation was observed between the visuospatial/constructional scores of the RBANS scale and the transition probability of microstate class C to B (r = 0.405, P = 0.049). CONCLUSION: EEG microstate, especially C and D, is a possible biomarker in depression. Patients with depression had a more frequent transition from microstate C to B, which may relate to more negative rumination and visual processing.

Prevalence and risk factors for psychotic symptoms in young, first-episode and drug-naïve patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a common psychiatric disorder worldwide. Psychotic depression has been reported to be frequently under-diagnosed due to poor recognition of psychotic features. Therefore, the purpose of this study was to reveal the rate and risk factors of psychotic symptoms in young, drug-naïve patients with major depressive disorder at the time of their first episode. METHODS: A total of 917 patients were recruited and divided into psychotic and non-psychotic subgroups based on the Positive and Negative Syndrome Scale (PANSS) positive subscale score. Anxiety symptoms and depressive symptoms were measured by the Hamilton Anxiety Rating Scale (HAMA) and the 17-item Hamilton Depression Rating Scale (HAMD-17), respectively. Several biochemical indicators such as total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were also measured. RESULTS: The rate of psychotic symptoms among young adult MDD patients was 9.1%. There were significant differences in TSH (p<0.001), FBG (p<0.001), TC (p<0.0001), TG (p = 0.001), HDL-C (p = 0.049), LDL-C (p = 0.010), diastolic blood pressure (DP) (p<0.001), systolic blood pressure (SP) (p<0.001), and HAMD total score (p<0.001) between young MDD patients with and without psychotic depression. HAMD, TSH, TC, and severe anxiety were independently associated with psychotic symptoms in young adult MDD patients. In addition, among young MDD patients, the rate of suicide attempts in the psychotic subgroup was much higher than in the non-psychotic subgroup (45.8% vs. 16.9%). CONCLUSIONS: Our findings suggest that psychotic symptoms are common in young MDD patients. Several clinical variables and biochemical indicators are associated with the occurrence of psychotic symptoms in young MDD patients.

Alterations of serum neuropeptide levels and their relationship to cognitive impairment and psychopathology in male patients with chronic schizophrenia.

Serum neuropeptide levels may be linked to schizophrenia (SCZ) pathogenesis. This study aims to examine the relation between five serum neuropeptide levels and the cognition of patients with treatment-resistant schizophrenia (TRS), chronic stable schizophrenia (CSS), and in healthy controls (HC). Three groups were assessed: 29 TRS and 48 CSS patients who were hospitalized in regional psychiatric hospitals, and 53 HC. After the above participants were enrolled, we examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the blood serum levels of α-melanocyte stimulating hormone (α-MSH), ß-endorphin (BE), neurotensin (NT), oxytocin (OT) and substance.P (S.P). Psychiatric symptoms in patients with SCZ were assessed with the Positive and Negative Syndrome Scale. SCZ patients performed worse than HC in total score and all subscales of the RBANS. The levels of the above five serum neuropeptides were significantly higher in SCZ than in HC. The levels of OT and S.P were significantly higher in CSS than in TRS patients. The α-MSH levels in TRS patients were significantly and negatively correlated with the language scores of RBANS. However, the BE and NT levels in CSS patients were significantly and positively correlated with the visuospatial/constructional scores of RBANS. Moreover, the interaction effect of NT and BE levels was positively associated with the visuospatial/constructional scores of RBANS. Therefore, abnormally increased serum neuropeptide levels may be associated with the physiology of SCZ, and may cause cognitive impairment and psychiatric symptoms, especially in patients with TRS.

Prevalence and clinical correlates of psychotic symptoms in first-episode untreated female chinese patients with major depressive disorder.

BACKGROUND: Recent studies have reported that psychotic symptoms are common in patients with major depressive disorder (MDD). However, few studies have reported the relationship between thyroid function, lipid metabolism and clinical profiles in female MDD patients. Thus, this study aimed to investigate the prevalence of psychotic depression (PD) and its risk factors in first-episode and drug naive (FEDN) depression among the female population in China. METHODS: This was a cross-sectional study involving a representative probability sample of 1,130 FEDN female outpatients with MDD (aged 18 years or older) in China. We collected information relating to socio-demographic characteristics, clinical data and blood samples. The Hamilton Depression Rating Scale 17-item version (HAMD-17), Hamilton Anxiety Rating Scale 14-item version (HAMA-14), and Positive and Negative Syndrome Scale (PANSS) were used to evaluate depressive, anxiety, and psychotic symptoms. RESULTS: The prevalence of psychotic symptoms in female MDD patients was 10.97%. The findings revealed significant differences between MDD female patients with psychotic symptoms and non-PD female patients in the following areas: higher HAMD scores, higher HAMA scores, more severe anxiety and an increased risk of suicide attempts. Further logistic regression analysis showed that psychotic symptoms were associated with higher thyroid-stimulating hormone (TSH) levels and an odds ratio of 1.168. CONCLUSIONS: Our findings supported the hypothesis that higher TSH levels were correlated with psychotic symptoms in female MDD patients. Therefore, serum TSH levels may be a potential biomarker of PD in female MDD patients. In addition, we found that PD was closely associated with suicide attempts and lipid levels, but did not reach statistical significance.

Clinical correlates of autoimmune thyroiditis and non-autoimmune hypothyroidism in treatment-naïve patients with major depressive disorders.

BACKGROUND: Thyroid autoimmunity is a potentially critical factor that is often neglected in the association between subclinical hypothyroidism (SCH) and depressive disorders. This study aimed to investigate the clinical correlates of autoimmune thyroiditis (AIT) and non-autoimmune hypothyroidism (NAIH) in treatment-naïve patients with major depressive disorder (MDD). METHOD: Using a cross-sectional design, we recruited a total of 1718 outpatients with treatment-naïve MDD. Demographic and relevant clinical information including duration of MDD, severity of depression and anxiety, psychotic symptoms, suicide attempts, thyroid function parameters, etc. were collected. According to thyroid function parameters, patients were classified as AIT, NAIH, latent Hashimoto's thyroiditis (LH) and euthyroidism (ET). RESULTS: Patients with SCH (including AIT and NAIH) had older age at onset, and were more likely to have psychotic symptoms compared to those with ET. Multiple linear regression analysis showed that SCH was associated with duration of MDD and HAMD scores. Logistic regression analysis showed that the odds of having more severe anxiety and metabolic syndrome were greater among patients with SCH compared to those with ET. The odds of having suicide attempts were greater among patients with AIT than among those with ET. LIMITATION: Because of the cross-sectional design of this study, we were unable to sort out causality between MDD and SCH. CONCLUSION: Our findings suggested that AIT and NAIH were associated with duration of MDD, HAMD scores, severity of anxiety, and metabolic syndrome. However, only AIT in SCH was associated with suicide attempts.

Association of Subclinical Hypothyroidism With Anxiety Symptom in Young First-Episode and Drug-Naïve Patients With Major Depressive Disorder.

Backgrounds: Subclinical hypothyroidism (SCH) was reported to be associated with depression; however, its role in coexisting anxiety symptom in young patients with major depressive disorder (MDD) remains unclear. The objective of this study was to explore the relationship between SCH and anxiety symptom in young first-episode and drug-naïve (FEDN) MDD patients. Methods: A total of 520 outpatients diagnosed as FEDN MDD with SCH were recruited in this study. Their socio-demographic, clinical data and thyroid function parameters were collected. The Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD) were employed to measure the severity of anxiety symptom and depressive symptom, respectively. Based on the HAMA scores, patients who scored ≥ 25 were defined as anxious major depressive disorder (A-MDD) while others as non-anxious major depressive disorder (NA-MDD). Results: The prevalence rate of A-MDD was 15.8% in young FEDN MDD patients with comorbid SCH. Moreover, serum thyroid stimulating hormone (TSH) levels were significantly higher in patients with A-MDD compared with those with NA-MDD (p < 0.001). Multivariate binary logistic regression analysis indicated that A-MDD was associated with serum TSH levels with an odds ratio (OR) of 1.602. Serum TSH level of 6.17 mIU/L was the critical value to distinguish A-MDD and NA-MDD, with sensitivity of 0.805 and specificity of 0.539. There were no statistically significant differences between NA-MDD and A-MDD patients in terms of socio-demographic variables, serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidases antibody (TPOAb) and anti-thyroglobulin (TgAb) levels. Conclusions: A-MDD patients presented higher serum TSH level. It is suggested that serum TSH level may be a potential biomarker for predicting moderate and severe anxiety symptoms in young FEDN MDD patients with SCH.

Association Between Depressive Symptoms and Serum Brain-Derived Neurotrophic Factor Levels in Patients With First-Episode and Drug-Naïve Schizophrenia.

Previous studies have revealed that brain-derived neurotrophic factor (BDNF) levels are inversely associated with the severity of depressive symptoms. In addition, serum BDNF levels tend to increase with improvement in depressive symptoms. There is also evidence that BDNF has a possible role in the pathophysiology of schizophrenia. Therefore, the purpose of this study was to determine whether BDNF levels correlated with depressive symptoms in patients with first-episode and drug-naïve (FEDN) schizophrenia. In this study, 90 patients with FEDN schizophrenia and 60 healthy controls were recruited. The Positive and Negative Syndrome Scale (PANSS) and the 17-item Hamilton Depression Scale (HAMD-17) were used to gage psychopathological and depressive symptoms, respectively. All participants had their BDNF levels measured using a sandwich enzyme-linked immunosorbent test. Serum BDNF levels were lower in patients with FEDN schizophrenia compared with healthy controls. Moreover, patients with depressive symptoms exhibited a higher PANSS total score and a higher general psychopathology score than those without depressive symptoms (p < 0.05). For patients with depressive symptoms, serum BDNF levels were higher than in those without depressive symptoms (p < 0.05). An association between BDNF levels and the positive subscore was also observed (p < 0.01). However, there was no significant association between BDNF levels and HAMD scores (p > 0.05). In conclusion, BDNF levels were shown to be higher in the serum of patients with FEDN schizophrenia with depressive symptoms than in those without. Additionally, low levels of serum BDNF may contribute to the positive symptoms of FEDN schizophrenia but not to depressive symptoms.