Loss of asymmetry in D2 receptors of putamen in unaffected family members at increased genetic risk for schizophrenia

Objective: Dopamine dysregulation has been implicated in the pathophysiology of schizophrenia. The present study was performed to examine whether unaffected relatives at high genetic risk of schizophrenia have dopamine dysregulation in comparison with healthy controls. Method: Eleven unaffected relatives from families with two or more first‐ or second‐degree relatives with schizophrenia (n = 9) or with a monozygotic schizophrenic twin (n = 2) and 11 age‐ and sex‐matched controls were examined using positron emission tomography (PET) with [¹¹C] raclopride. Subjects also underwent extensive neuropsychological testing. Results: Subjects with high genetic risk showed a loss of asymmetry of D₂ receptors in the putamen in comparison with healthy controls. In addition, they showed significantly poorer performance on neuropsychological tests than controls. Conclusion: Our results suggest that dopamine dysregulation and neuropsychological dysfunction may be present in subjects at high genetic risk of schizophrenia. However, further studies are required to confirm these findings.     

Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia

BACKGROUND: The hypofunction of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors has been implicated in the pathophysiology of schizophrenia. Several lines of evidence suggest that D-serine may function as an endogenous agonist of the glycine site of the NMDA receptor. The aim of this study was to examine whether serum levels of D- and L-serine in patients with schizophrenia are different from those of healthy controls. METHODS: Forty-two patients with schizophrenia and 42 age- and sex-matched healthy controls were enrolled in this study. Symptoms were assessed using the Brief Psychiatric Rating Scale. Serum levels of total serine and D- and L-serine were measured by high-performance liquid chromatography. RESULTS: Serum levels of D-serine in the patients with schizophrenia were significantly (z = -3.30, P =.001) lower than those of healthy controls. In contrast, serum levels of total (D and L) serine (z = -2.40, P =.02) and L-serine (z = -2.49, P =.01) in the schizophrenic patients were significantly higher than those of controls. In addition, the percentage of D-serine in the total serine in the schizophrenic patients was significantly (z = -4.78, P<.001) lower than that of controls, suggesting that the activity of serine racemase, an enzyme catalyzing the formation of D-serine from L-serine, may have been reduced in the schizophrenic patients. CONCLUSIONS: Reduced levels of D-serine may play a role in the pathophysiology of schizophrenia, and serum D- and L-serine levels might provide a measurable biological marker for schizophrenia.     

Associations of serum brain-derived neurotrophic factor with cognitive impairments and negative symptoms in schizophrenia

Brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations of serum BDNF levels with the cognition and clinical characteristics in patients with schizophrenia. Sixty-three patients with schizophrenia and 52 age- and sex-matched healthy controls were examined with neuropsychological tests. Serum BDNF levels were determined by enzyme-linked immunosorbent assay (ELISA). There were no significant differences in serum BDNF levels between normal controls and patients with schizophrenia. Serum BDNF levels of normal controls showed negative correlations with verbal working memory, but this was not the case with schizophrenic patients. Meanwhile, serum BDNF levels of schizophrenic patients showed positive correlations with the scores of the Scale for the Assessment of Negative Symptoms (SANS) and the Information subtest scores of Wechsler Adult Intelligence Scale Revised (WAIS-R). Serum BDNF levels are related with the impairment of verbal working memory and negative symptoms in patients with schizophrenia.     

Movement disorder, memory, psychiatric symptoms and serum DHEA levels in schizophrenic and schizoaffective patients.

OBJECTIVE: Reports of low levels of dehydroepiandrosterone (DHEA) or its sulphate (DHEA-S) in some schizophrenic patients and in some persons with poorer motoric and cognitive functioning led us to examine clinical correlates of serum DHEA and DHEA-S levels in schizophrenic patients. METHOD: Ratings of abnormal movements, memory and psychiatric symptoms in 17 medicated chronic schizophrenic or schizoaffective inpatients at a state hospital were correlated with serum DHEA and DHEA-S levels, and their ratios with serum cortisol. RESULTS: Controlling for age, higher DHEA levels and/or higher DHEA/cortisol ratios were significantly correlated with lower symptom ratings on the Brief Psychiatric Rating Scale, better performance on some measures of memory, and lower ratings of parkinsonian symptoms. CONCLUSION: Relatively low DHEA levels or DHEA/cortisol ratios may identify a particularly impaired subgroup of medicated patients with chronic schizophrenia. Potential implications are discussed.     

Movement Disorder,Memory, Psychiatric Symptoms and Serum DHEA Levels in Schizophrenic and Schizoaffective Patients

Objective: Reports of low levels of dehydroepiandrosterone (DHEA) or its sulphate (DHEA-S) in some schizophrenic patients and in some persons with poorer motoric and cognitive functioning led us to examine clinical correlates of serum DHEA and DHEA-S levels in schizophrenic patients.

Method: Ratings of abnormal movements, memory and psychiatric symptoms in 17 medicated chronic schizophrenic or schizoaffective inpatients at a state hospital were correlated with serum DHEA and DHEA-S levels, and their ratios with serum cortisol.

Results: Controlling for age, higher DHEA levels and/or higher DHEA/cortisol ratios were significantly correlated with lower symptom ratings on the Brief Psychiatric Rating Scale, better performance on some measures of memory, and lower ratings of parkin-sonian symptoms.

Conclusion: Relatively low DHEA levels or DHEA/cortisol ratios may identify a particularly impaired subgroup of medicated patients with chronic schizophrenia. Potential implications are discussed.     

Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in schizophrenia: a study of patients treated with haloperidol or clozapine

There is strong evidence that oxygen free radicals may play an important role in the pathophysiology of schizophrenia. Impaired antioxidant defense and increased lipid peroxidation have been previously reported in drug-na?ve, first episode and chronically medicated schizophrenic patients using typical neuroleptics. We measured serum SOD and TBARS in two groups of chronic medicated DSM-IV schizophrenic patients, under haloperidol (n = 10) or clozapine (n = 7) and a group of healthy controls (n = 15). Serum SOD and TBARS were significantly higher (p = 0.001) in schizophrenic patients (7.1 +/- 3.0 and 3.8 +/- 0.8) than in controls (4.0 +/- 1.6 and 2.5 +/- 0.7). Among patients, serum TBARS was significantly higher (p = 0.008) in those under clozapine (4.4 +/- 0.7) than in those under haloperidol treatment (3.4 +/- 0.7). For SOD levels the difference between groups was not found. It is reasonable to argue that the difference found in TBARS levels might be due to the course of the disease, instead of medication. Further investigation on the role of oxidative tonus and lipid peroxidation in different schizophrenia subtypes and different outcome patterns in this disorder is warranted. Additionally it could also address questions concerning a possible oxidant/antioxidant imbalance in schizophrenia.     

Cortisol, the cortisol-dehydroepiandrosterone ratio, and pro-inflammatory cytokines in patients with current major depressive disorder comorbid with borderline personality disorder.

BACKGROUND: Major depression in young women is often comorbid with borderline personality disorder (BPD); however, adrenal steroids and pro-inflammatory cytokines in patients with comorbid current major depressive disorder and BPD (MDD/BPD) have not been systematically examined. Therefore, our study aimed at examining serum profiles of cortisol, cytokines, and the cortisol/dehydroepiandrosterone (cortisol/DHEA) ratio in MDD/BPD patients and a healthy comparison group. METHODS: Twelve medication-free female patients with MDD/BPD and 12 healthy women were included. Serum profiles of cortisol, DHEA, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1beta were sampled, and the molar cortisol/DHEA ratio was determined. RESULTS: Concentrations of serum cortisol, TNF-alpha, and IL-6, as well as the cortisol/DHEA ratios were significantly increased in MDD/BPD patients as compared with the healthy comparison group. CONCLUSIONS: Depressed patients with comorbid BPD display endocrine and immune alterations similar to those observed in cases of melancholic MDD without BPD. Elevated concentrations of serum cortisol, cortisol/DHEA ratios, and pro-inflammatory cytokines might indicate a state marker in these patients and might contribute to long-term metabolic alterations that have also been associated with MDD.     

Association among serum cortisol,dehydroepiandrosterone-sulfate levels and psychiatric symptoms in men with chronic schizophrenia

PurposeThe purpose of this study was to examine possible associations of serum levels of cortisol and dehydroepiandrosterone-sulfate (DHEA-S) with psychiatric symptoms in men with chronic schizophrenia.MethodsThis retrospective study involved 162 men with schizophrenia and 138 age-matched healthy controls, for whom data were collected on demographic characteristics, age at disease onset, disease duration, positive and negative syndrome scale (PANSS) scores, and history of atypical antipsychotic treatment. Serum levels of cortisol and DHEA-S were calculated, as well as the ratios of the two levels. Possible correlations were explored between these levels and psychiatric symptoms before and after antipsychotic treatment.ResultsSerum levels of cortisol and DHEA-S levels as well as the ratios of cortisol to DHEA-S levels were higher in patients than in controls (p < 0.01). Among patients, serum levels of cortisol and DHEA-S were significantly lower after treatment than before (p < 0.01), although the ratios of cortisol to DHEA-S levels remained similar. Serum levels of cortisol, DHEA-S and the ratios of the two levels were positively correlated with the negative symptoms score on the PANSS.ConclusionsThe pathophysiology of schizophrenia may involve in the spread levels of cortisol and DHEA-S. These levels may serve as biomarkers for diagnosing schizophrenia and monitoring treatment efficacy.     

精神分裂症患者及其亲属免疫学研究

目的 :了解散发性首发精神分裂症患者及其一级亲属免疫球蛋白及补体成份与正常人是否存在差异。　方法 :用免疫透射比浊法测精神分裂症患者及其一级亲属及健康者血清中免疫球蛋白及补体成份的含量 ,并相互比较。　结果 :精神分裂症患者及其一级亲属IgA、IgG及C4显著高于正常人(P <0 .0 5～ 0 0 1)。　结论 :精神分裂症患者及其一级亲属存在同样免疫学异常 ,遗传因素可能是构成精神分裂症免疫学异常的基础     

The role of NGF and IL-2 serum level in assisting the diagnosis in first episode schizophrenia

Development of reliable diagnostic bio-markers for schizophrenia remains a diagnostic challenge. Serum NGF and IL-2 were analyzed to examine the diagnostic efficiency and predictive capability of these two biomarkers in relation to schizophrenia diagnosis. Thirty neuroleptic naïve subjects with first-episode schizophrenia, thirty patients with major depressive disorder (MDD) and twenty-eight healthy control subjects participated in the study. One-way ANOVA demonstrated significantly lower serum IL-2 and NGF among schizophrenic patients and patients with MDD compared with healthy controls. Receiver operating characteristic (ROC) curve analysis was used to ascertain diagnostic efficiency of serum IL-2 and NGF levels. Area under the ROC curve (AUC) revealed a high level of differentiation between schizophrenic patients and healthy controls for both IL-2 and NGF serum concentrations. Diagnostic efficiency of combined NGF and IL-2 serum levels was also high in schizophrenic patients compared with healthy controls. Serum NGF and IL-2 are promising as potential screening or diagnostic biomarkers for schizophrenia and may be a useful adjunct for clinical assessment.     

Plasma cortisol-dehydroepiandrosterone (DHEA) ratios in schizophrenia and bipolar disorder

Hypercortisolaemia is a feature of many severe psychiatric illnesses and has been suggested to be both a causal and exacerbating factor of clinical symptoms and neurocognitive impairment. The adrenal steroid dehydroepiandrosterone (DHEA) has antiglucocorticoid properties that may have regulatory effects on glucocorticoid action in the brain. However, there is a paucity of data on these steroids and their ratio in schizophrenia and bipolar disorder. We therefore sought to assess cortisol and DHEA levels and the cortisol-DHEA ratio in patients with schizophrenia (n = 20) and bipolar disorder (n = 20), on stable medication for a minimum of 6 weeks, and healthy age- and sex-matched control subjects (n = 20). Steroid levels were measured from plasma samples collected at 30 min intervals from 1:00 p.m. to 4:00 p.m. Cortisol levels were found to be significantly elevated in both patient groups compared with controls. DHEA levels were elevated in schizophrenic patients compared with bipolar patients and controls, but there was no evidence of a difference in the cortisol-DHEA ratio of the groups. These data suggest that afternoon hypercortisolaemia is evident in symptomatic bipolar and schizophrenic patients compared to controls. However, an elevation in DHEA levels may represent a specific endocrine marker in schizophrenia.     

Reduced anticardiolipin antibodies in first episode and chronic schizophrenia

The objective of this study was to measure anticardiolipin antibodies (aCL) in major psychiatric diseases. In Experiment 1, 96 subjects were evaluated: 20 first episode schizophrenia patients, [SCZ1] 20 chronic schizophrenia patients in acute exacerbation [SCZ2], l9 bipolar patients, 20 schizoeffective patients and 17 healthy age matched controls. In Experiment 2, 97 subjects were studied: 20 first episode schizophrenia patients [SCZ1], 60 chronic schizophrenia patients in acute exacerbation [SCZ2] and 17 healthy matched controls. Diagnosis was performed according to DSM-IV. Serum samples were tested for aCL in parallel by enzyme-linked immunosorbent assay in the presence of bovine serum. Five positive control samples with high levels of aCL were run in parallel. Background binding to wells uncoated with cardiolipin (CL) was also measured. In Experiment 1, aCL levels were similar in the control, bipolar and schizoeffective groups. In contrast, aCL levels in the SCZ1 and SCZ2 groups were significantly lower than in controls. In Experiment 2, Significantly lower levels of aCL antibodies were found in all schizophrenic patients versus controls. Interestingly, background levels in both experiments were higher in the schizophrenic groups than in controls. Serum aCL levels are lower in schizophrenic patients, and especially in first episode cases, than in controls. One possible explanation for the lower levels of aCL in schizophrenic patients is the consumption of these antibodies in the acute phase and exacerbation of the disease. The higher background levels in schizophrenic patients may indicate a high level of antibodies to some serum component in schizophrenic patients that is still unclear and needs further elucidation.     

Increased serum S100B in never-medicated and medicated schizophrenic patients

S100B is a calcium-binding protein, which is produced primarily by glial cells. It modulates the proliferation and differentiation of neurons and glia by affecting protective and apoptotic mechanisms. Recently, several studies have shown increased serum S100B levels in patients with schizophrenia, suggesting that S100B might be relevant to the pathophysiology of schizophrenia. S100B levels were assessed using ELISA in the serum of 80 never-medicated early-stage and 82 medicated chronic schizophrenia patients and 97 healthy controls subjects. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Our results showed significantly increased serum S100B levels in both never-medicated and medicated patients compared to normal controls (both p < 0.0001). S100B in never-medicated patients was also markedly increased, compared with medicated patients (p < 0.0001). S100B changes observed were irrespective of neuroleptic medication, gender, age, and smoking. Increased S100B levels in the early stage of schizophrenia suggest that glial cell activation or structural damage may be part of a neurodegenerative process in schizophrenia. The lower S100B levels in chronic than early-stage patients further suggest that antipsychotic treatment may reduce this neurodegeneration.     

Higher levels of serum copper in schizophrenic patients treated with depot neuroleptics

The findings of previous research on the status of trace elements in patients with schizophrenia have been controversial. We studied 62 outpatients with a DSM-IV diagnosis of schizophrenia, and compared them with sex- and age-matched healthy controls. Serum copper levels were significantly higher in schizophrenic patients (mean 117.4 microg/dl; S.D. 23.4) than in healthy controls (105.6+/-27.9). Those patients on treatment with depot neuroleptics had higher copper levels. Zinc levels did not differ between patients and healthy controls. Altered levels of trace elements in schizophrenic patients may be a consequence of antipsychotic treatment.     

P300 in first degree relatives of schizophrenics.

It has been reported that the amplitude of P300 is low in schizophrenic patients and high risk children. We recorded P300 components of the event-related potentials in first degree relatives of schizophrenic propositi who were considered to be over the age limit of the risk period for manifestation of schizophrenia and compared them with those of schizophrenic patients and controls. Both the first degree relatives and the schizophrenic patients showed lower P300 amplitude than the controls. There was no significant difference between the first degree relatives and schizophrenic patients in the P300 amplitude. These results would indicate that a low P300 amplitude is a trait marker for schizophrenia.     

Prolactin levels in drug-naïve patients with schizophrenia and other psychotic disorders

Objective: Hyperprolactinaemia as a side effect of dopamine receptor blockers is common in patients with schizophrenia and other psychotic disorders and may lead to amenorrhoea, galactorrhoea, hypogonadism, subfertility and osteoporosis. The aim of our study was to determine whether hyperprolactinaemia occurs also in patients with schizophrenia and other psychotic disorders prior to any antipsychotic treatment.

Methods: Serum prolactin, thyroid-stimulating hormone (TSH), triiodothyronine (T3), free tetraiodothyronine (FT4) and cortisol levels were measured in 40 newly diagnosed, drug naïve, patients with schizophrenia and other psychotic disorders and in 40 age and gender matched healthy subjects.

Results: The median prolactin value was 12.5?ng/ml (range: 2–38?ng/ml) for patients and 8.6?ng/ml (range: 4–17.6?ng/ml) for healthy subjects (p?=?0.011). Patients had lower levels of T3 compared to healthy controls (mean: 1.08?ng/ml, SD: 0.16 vs. 1.18?ng/ml, 0.18, respectively; p?=?0.008). Serum TSH, FT4 and cortisol levels were similar between the two groups. Multiple regression analysis revealed that the difference in serum prolactin values was independent of thyroid function (TSH, FT4, T3) and serum cortisol levels.

Conclusions: A higher serum prolactin level was found in drug naïve, newly diagnosed patients with schizophrenia and other psychotic disorders compared to healthy controls, prior to starting any antipsychotic treatment.     

Reduced serum BDNF levels in schizophrenic patients on clozapine or typical antipsychotics

Neurotrophic factors regulate neuronal development and synaptic plasticity, possibly playing a role in the pathophysiology of schizophrenia and other psychiatric disorders. Decreased brain-derived neurotrophic factor (BDNF) levels have been found in brains and in the serum of schizophrenic patients, but results are inconsistent. Also, clozapine may upregulate brain BDNF expression. In the present study, we assessed serum BDNF immunoreactivity in 44 schizophrenic patients (20 on clozapine and 24 on typical antipsychotics) and in 25 healthy volunteers. Serum BDNF levels were measured using an enzyme immunoassay. Healthy controls showed significantly higher levels of BDNF compared to the whole group of schizophrenic patients (p<0.001) as well as to the subgroups on typical antipsychotics and clozapine (p<0.001). Serum BDNF values for controls were 168.8+/-26.3pg/ml, for the clozapine group were 125.4+/-44.5pg/ml and for the group on typicals were 101.3+/-51.6pg/ml. BDNF values from patients on clozapine were non-significantly higher than values from patients on typical antipsychotics (p=0.09). Serum BDNF was strongly and positively correlated with clozapine dose (r=0.643; p=0.002) but not with other demographic characteristics. These results reinforce previous findings of reduced serum BDNF levels in schizophrenic patients and suggest a differential effect of clozapine compared to typical antipsychotics on such levels.     

The novel oxidative stress marker thioredoxin is increased in first-episode schizophrenic patients

Excessive free radical production leading to oxidative stress may be involved in the pathophysiology of schizophrenia. Oxidative stress increases serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative-stress marker. The aim of this study was to assess the clinical significance of serum TRX levels in various stages of schizophrenia. Serum TRX levels were determined using ELISA from 60 never-medicated first-episode and 66 medicated chronic schizophrenia patients and 66 healthy control subjects matched for age and gender. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Our results showed that group comparison between first-episode and chronic patients and control groups revealed significantly increased serum TRX only in first-episode patients. Increased levels of TRX in patients experiencing an acute stage schizophrenic episode was also significantly higher compared to chronic schizophrenic patients on antipsychotic medication. Serum TRX was also positively correlated with positive symptoms of schizophrenia. Our results suggest oxidative stress occurs in an acute stage of schizophrenic episode and may have an important role in pathogenesis and symptomology of schizophrenia. Lower TRX levels in chronic patients treated with antipsychotics may have implications for treatment outcome.     

Increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and those with major depressive disorder

Elevated peripheral levels of interleukin-6 (IL-6) are common findings in schizophrenia and depression. However, previous studies that measured cerebrospinal fluid (CSF) IL-6 levels in these disorders reported controversial results. The present study examined whether CSF IL-6 levels are altered in patients with schizophrenia and those with depression. Lumbar punctures were performed in 32 patients with schizophrenia, 30 with major depressive disorder (MDD), and 35 healthy controls. Serum samples were simultaneously collected from all subjects in the patient groups and from 32 of the control group. CSF and serum IL-6 levels were determined by enzyme-linked immunosorbent assay. Both the patients with schizophrenia and MDD had significantly higher CSF IL-6 levels compared to the controls (schizophrenia: P = 0.0027; MDD: P = 0.012). IL-6 levels were significantly higher in the CSF than in the serum. No significant correlation was observed between CSF and serum IL-6 levels. The present findings suggest that IL-6 of central origin is associated with the pathophysiology of schizophrenia and MDD, although confounding effect of smoking status can not be entirely excluded.     

首发未服药精神分裂症患者血清S100B蛋白浓度变化

目的 探讨血清S100B蛋白浓度与首发未服用抗精神病药的精神分裂症患者精神病理症状间的关系.方法 采用酶联免疫(ELISA)方法 检测64例首发未服用抗精神病药精神分裂症患者和66名正常对照的血清S100B蛋白浓度,比较2组间的差异;采用阳性和阴性症状量表(PANSS)评定精神病理症状,分析血清S100B蛋白浓度与PANSS评分、患者年龄、发病年龄、病程间的关系.结果 ①患者组血清S100B浓度明显高于对照组,筹异有统计学意义[(0.27±0.13)μg/L vs(0.11±0.04)μg/L,t=10.89,P＜0.001];②患者组中偏执型、瓦解型、未分化型、残留型4个亚组间血清S100B浓度的差异有统计学意义(F=4.63,P=0.006),残留型组明显高于偏执型组(P=0.001)、瓦解型组(P=0.012);且各亚型组均明显高于对照组(P＜0.001).③患者组血清S100B浓度与年龄、总病程、PANSS总分及其阴性症状因子分相关(r为0.36、0.46、0.42、-0.38,P均小于0.005).结论 首发未服药的精神分裂症患者血清S100B浓度升高,并与某些病理症状尤其是阴性症状关联,在一定程度上可反映疾病严重程度.