Elevated serum levels of C-reactive protein are associated with more severe psychopathology in a subgroup of patients with schizophrenia

The present study examined the hypothesis that elevated serum levels of C-reactive protein (CRP) would be associated with more severe clinical symptoms in patients with schizophrenia. Twenty-six inpatients with schizophrenia or schizoaffective disorder were enrolled. Serum levels of CRP were measured, and each patient was assessed with the Positive and Negative Syndrome Scale (PANSS). Subjects with CRP levels above the normal range (CRP>0.50 mg/dl, elevated CRP group, N=5) scored significantly higher than those with CRP levels in the normal range (CRP相似文献   

Higher estrogen levels are not associated with larger hippocampi and better memory performance

BACKGROUND: Estrogens may prevent cognitive decline and Alzheimer disease. Animal study findings have shown beneficial effects of estrogen on the brain, particularly on the hippocampus, a structure related to memory performance and early Alzheimer disease. OBJECTIVE: To investigate whether higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes on magnetic resonance imaging and better memory performance. DESIGN AND SETTING: Cross-sectional analysis within the Rotterdam Scan Study, a population-based study in the Netherlands of elderly subjects who do not have dementia. PARTICIPANTS: Two hundred ten women and 202 men, aged 60 to 90 years, with plasma levels of total estradiol and, in part, 162 women and 149 men also with levels of bioavailable and free estradiol. MAIN OUTCOME MEASURE: Hippocampal volumes on magnetic resonance imaging and memory performance (delayed recall). RESULTS: Women with higher total estradiol levels had smaller hippocampal volumes and poorer memory performance -0.29 mL (95% confidence interval, -0.57 to -0.00) and -0.4 (95% confidence interval, -1.3 to 0.5) fewer words in delayed recall testing for the highest tertile compared with the lowest tertile. Similar inverse associations were found among bioavailable and free estradiol levels, hippocampal volumes, and memory. In men, no association was observed between estradiol levels and hippocampal volume, but a trend was found for higher levels of total estradiol to be associated with poorer memory performance. CONCLUSION: Our data do not support the hypothesis that higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes and better memory performance.     

Elevated interleukin-18 serum levels in chronic schizophrenia: Association with psychopathology

BackgroundSchizophrenia is associated with various abnormalities in the immune system including elevated levels of Interleukin-18 (IL-18), a potent inflammatory cytokine in T-helper 1 (Th1) responses. The aim of this study was to assess the clinical significance of serum IL-18 levels in various stages of schizophrenia.MethodsWe measured serum IL-18 levels using a sandwich enzyme-linked immunosorbent assay (ELISA) from 78 never-medicated first-episode schizophrenia, 79 medicated chronic schizophrenia and 78 healthy control subjects. The symptoms of schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS).ResultsThe chronic patients had significantly greater serum IL-18 levels than both first-episode patients and controls. Serum IL-18 was also positively correlated with the PANSS general psychopathology subscore in chronic schizophrenic patients.ConclusionsOur results showed elevated IL-18 pathway activity may be involved in the psychopathology of schizophrenia.     

Increased S100B+ NK cell counts in acutely ill schizophrenia patients are correlated with the free cortisol index, but not with S100B serum levels

Several studies have provided evidence for increased S100B serum concentrations in schizophrenia. The pathophysiological significance of this finding is still uncertain because S100B is involved in many cellular mechanisms and is not astrocyte-specific as was previously assumed. S100B is also expressed by subsets of CD3+ CD8+ T cells and natural killer (NK) cells and may therefore be linked to the immune hypothesis of schizophrenia. We have quantified S100B+ CD3+ CD8+ T cells and NK cells by flow cytometry in the peripheral blood of 26 acutely ill schizophrenia cases and 32 matched controls. In parallel, S100B concentrations and the free cortisol index (FCI), a surrogate marker for stress axis activity, were determined in serum samples from the same blood draw. Psychopathology was monitored using the Positive and Negative Syndrome Scale (PANSS). The patient group had increased S100B+ NK cell counts (P=0.045), which correlated with the FCI (r=0.299, P=0.026) but not with the PANSS or the elevated (P=0.021) S100B serum concentrations. S100B+ CD3+ CD8+ T cell counts were not significantly changed in the patient group and did neither correlate with the FCI and PANSS, nor with S100B serum concentrations. In conclusion, despite the observation of an increase in S100B+ NK cells in schizophrenia patients, the lack of a correlation with serum S100B concentrations suggests that these cells are probably not a major source of S100B in the blood of schizophrenia patients. Notably, elevated S100B+ NK cell counts may be linked with stress axis activation.     

Aggression and psychopathology in treatment-resistant inpatients with schizophrenia and schizoaffective disorder

Positive psychotic symptoms, such as threat/"control-override" delusions or command hallucinations, have been related to aggression in patients with schizophrenia. However, retrospective data collection has hampered evaluation of the direct influence of psychopathology on aggressive behavior. In this study, we monitored aggressive behavior and psychopathology prospectively and in close temporal proximity in 157 treatment-resistant inpatients diagnosed with chronic schizophrenia or schizoaffective disorder participating in a 14-week double-blind clinical trial. Aggressive behavior was rated with the overt aggression scale (OAS). Psychopathology was assessed using the positive and negative syndrome scale (PANSS). At baseline, subjects who would be aggressive during the study had higher scores on only two PANSS items: hostility and poor impulse control. During the study PANSS positive subscale scores were significantly higher in aggressive subjects. Total PANSS scores were higher within 3 days of an aggressive incident, as were positive and general psychopathology subscale scores. However, in a smaller subsample for whom PANSS ratings were available within 3 days before aggressive incidents, only scores on the PANSS positive subscale were significantly higher. These findings in chronic, treatment resistant inpatients support the view that positive symptoms may lead to aggression.     

Haloperidol and reduced haloperidol serum levels: correlation with psychopathology in acute schizophrenia.

Serum levels of haloperidol (HPL) and reduced haloperidol (RHPL) as well as the RHPL/HPL ratio were determined in 55 acute schizophrenics on oral haloperidol medication and correlated over 28 days with psychopathology and extrapyramidal symptom scores. Linear and nonlinear models of serum concentration and psychopathology were tested at several time points. No single consistent model could be established for either HPL or RPHL. However, when non-parametrical methods are used HPL levels between 10 and 25 ng/ml can be shown to be significantly associated with better outcome during the first three weeks of treatment. RHPL is unsuitable for therapy monitoring, since equilibrium is not reached in the first four weeks of treatment. The RHPL/HPL ratio was found to rise continuously during the study, and it neither separated responders from nonresponders nor did it correlate with clinical outcome.     

Attachment patterns are associated with symptomatology and course of schizophrenia in male inpatients

The authors tested the hypotheses that the insecure attachment styles of adult patients with schizophrenia are associated with (a) diagnosis, (b) psychopathological syndromes, and (c) course of the disorder. Thirty schizophrenic and 30 age-matching control males answered a self-report questionnaire tapping secure, avoidant, and anxious/ambivalent attachment styles. The patients were diagnosed using the Structured Clinical Interview for DSM-IV (M. B. First, R. L. Spitzer, M. Gibbon, & J. B. W. Williams, 1995), and their symptoms were quantified using the Positive and Negative Syndrome Scale (PANSS; S. R. Kay, A. Fizhbein, & L. A. Opler, 1987). Patients with schizophrenia did not significantly differ from nonpatient controls in secure style mean scores, but they exceeded the latter in both avoidant and anxious/ambivalent style scores. There were no significant correlations between secure attachment style and any PANSS symptom dimensions, whereas avoidant style correlated positively with both positive and negative syndromes, and anxious/ambivalent style correlated only with positive syndrome. Compared with patients with secure style, those with insecure attachment styles were younger at onset of the illness and had longer psychiatric hospitalizations. The preliminary results suggest that the insecure types of attachment, in particular the avoidant style, are associated with schizophrenic symptomatology and course of the illness in male inpatients. Further studies using a longitudinal design on extended samples are needed to determine the direction of causality in the composite relationships among the distinct attachment styles, psychopathology, and course of schizophrenia.     

Obsessive compulsive symptoms are associated with better functioning independently of cognition in schizophrenia

ObjectivesAlthough the relationship of obsessive–compulsive symptoms (OCSs) with both cognition and social functioning (SF) has already been the focus of research in schizophrenia, the moderation of the relationship of OCSs with SF by cognition has not been explored to date. We investigated the association of OCSs with SF and its interaction with cognition in schizophrenia.MethodsWe recruited 110 schizophrenia patients and assessed OCSs (Yale-Brown Scale), schizophrenia symptoms (Positive and Negative Syndrome Scale), SF (Strauss-Carpenter Scale) and cognition. 51 patients had one obsessive–compulsive symptom or more, whereas 59 patients had no obsessive compulsive-symptom, according to the Yale-Brown Scale. We mainly investigated: a) the predictive effect of OCSs on SF, controlling for cognition, illness duration and symptoms' severity and b) the moderating effect of cognition on the OCSs-SF relationship.ResultsThe mean score of OCSs for patients having at least one symptom was 13.43 (SD = 8.32). Higher OCSs predicted increased SF (B = 0.98, t = 2.41, df = 88, p = 0.018). This relationship was driven by the association of compulsions with job functioning (B = 0.074, t = 2.029, df = 88, p = 0.046). Patients without OCSs demonstrated worse functioning compared with those having at least one obsessive–compulsive symptom (mean difference = 2.496, t = 3.732, df = 88, p < 0.001). We failed to find evidence that cognition moderates the effect of OCSs on SF.ConclusionThere may be a beneficial effect of OCSs on SF in patients with schizophrenia which is independent of their cognitive performance.     

Low insulin-like growth factor-1 levels are associated with anaemia in adult non-diabetic subjects

Anaemia is a risk factor for cardiovascular morbidity and mortality. Among factors responsible for anaemia, insulin-like growth factor-1 (IGF-1) is a plausible candidate. We evaluated the association of IGF-1 with haemoglobin (Hb) concentration and anaemia in a cohort of 1,039 Caucasians subjects. Subjects with anaemia exhibited lower IGF-1 (p=0.006), and higher hsCRP levels (p=0.003). To estimate the independent contribution of variables to Hb concentration, a multivariable regression analysis was modeled including age, gender, body mass index (BMI), waist circumference, blood pressure, fasting glucose, fasting insulin, IGF-1, fibrinogen, hsCRP, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), serum iron, estimated glomerular filtration rate (eGFR), and treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). The variables significantly associated with Hb concentration were gender (p<0.0001), IGF-1 (p<0.0001), waist circumference (p=0.02), hsCRP (p<0.04), MCH (p<0.0001), MCV (p<0.0001), serum iron (p=0.001), IGF-1 (p=0.003), hsCRP (p=0.008), and waist circumference (p=0.01), accounting for 54.0% of its variation. Hb concentration was significant lower in subjects in the lowest IGF-1 quartile as compared with those in the third (p=0.02) and fourth (p=0.001). In a logistic regression model adjusted for age, gender, BMI, waist circumference, blood pressure, fasting glucose, fasting insulin, fibrinogen, hsCRP, MCH, MCV, serum iron, eGFR, and treatment with ACE inhibitors or ARBs, subjects in the first quartile of IGF-1 had a 2.49-fold higher risk of having anaemia as compared with those in the fourth (odds ratio 2.70, 95% confidence interval 1.02-7.16). Our data suggest that low IGF-1 may be an important contributor to mild anaemia.     

Brain structure,cognition and negative symptoms in schizophrenia are associated with serum levels of polysialic acid-modified NCAM

The neural cell adhesion molecule (NCAM) is a glycoprotein implicated in cell–cell adhesion, neurite outgrowth and synaptic plasticity. Polysialic acid (polySia) is mainly attached to NCAM (polySia-NCAM) and has an essential role in regulating NCAM-dependent developmental processes that require plasticity, that is, cell migration, axon guidance and synapse formation. Post-mortem and genetic evidence suggests that dysregulation of polySia-NCAM is involved in schizophrenia (SZ). We enrolled 45 patients diagnosed with SZ and 45 healthy individuals who were submitted to polySia-NCAM peripheral quantification, cognitive and psychopathological assessment and structural neuroimaging (brain volumes and diffusion tensor imaging). PolySia-NCAM serum levels were increased in SZ patients, independently of antipsychotic treatment, and were associated with negative symptoms, blunted affect and declarative memory impairment. The increased polySia-NCAM levels were associated with decreased volume in the left prefrontal cortex, namely Brodmann area 46, in patients and increased volume in the same brain area of healthy individuals. As this brain region is involved in the pathophysiology of SZ and its associated phenomenology, the data indicate that polySia-NCAM deserves further scrutiny because of its possible role in early neurodevelopmental mechanisms of the disorder.     

Low serum VEGF levels are associated with Alzheimer's disease

OBJECTIVE: As vascular endothelial growth factor (VEGF) determines important neurotrophic and neuroprotective actions, we postulated serum VEGF levels could be abnormally low in patients with Alzheimer's disease (AD). METHODS: We measured serum VEGF levels (VEGF(165) isoform by ELISA) in 51 patients with AD by National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorder Association criteria and compared with 66 age- and gender-matched non-demented controls. Patients with AD were stratified into levels of dementia severity by the Clinical Dementia Rating scale. Serum VEGF levels were stratified into upper (>309 pg/ml), middle (207-309 pg/ml), and lower (<207 pg/ml) tertiles. VEGF (-2,578) (rs 699,947) and VEGF (-634) (rs 2,010,963) polymorphisms were genotyped in patients with AD and controls. RESULTS: The mean concentration of VEGF in the serum of patients with AD (215.9 pg/ml, SD 101.5) was significantly lower than that of the controls (308.6 pg/ml, SD 223.9, P = 0.004), and decreased serum VEGF levels were associated with AD in a dose-dependent manner, the lower tertile of serum VEGF levels being associated with a fivefold increased risk for AD when compared with the upper tertile. There was no significant correlation between serum VEGF levels and age, sex, APOE alleles, AD dementia severity nor VEGF gene polymorphisms. CONCLUSION: Decrease in serum VEGF levels could contribute to the neurodegenerative process in AD.     

Altered interleukin-18 levels are associated with cognitive impairment in chronic schizophrenia

The pathophysiology of cognitive deficits in schizophrenia may involve the neuroinflammation mediated by cytokines. This study examined the IL-18 levels, the cognitive function, and their association in schizophrenia. We recruited 70 chronic patients and 75 normal controls and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and IL-18 levels. Positive and Negative Syndrome Scale (PANSS) was assessed in chronic patients. IL-18 levels were increased in chronic patients as compared to normal controls (p < 0.01). RBANS total score and the subscales of immediate memory and delayed memory were lower in patients than controls (all p < 0.001). In patients, IL-18 levels were positively associated with RBANS total score and the subscales of immediate and delayed memory (all p < 0.05). Multiple regression analysis further confirmed that IL-18 was an independent contributor to RBANS total score and the aforementioned two indexes (all p < 0.05). Our data demonstrate that immune responses may play an important role in cognitive deficits in schizophrenia and the abnormal levels of IL-18 reflecting the disturbed balance of proinflammatory and anti-inflammatory mechanisms may be relevant to cognitive deficits of this disorder.     

Higher serum clozapine level is associated with increased antiphospholipid antibodies in schizophrenia patients

Objectives

This study was to evaluate the relationship between clozapine and aPL in schizophrenia patients.

Methods

163 Participants were evaluated: 37 unmedicated schizophrenia patients, 50 clozapine-treated schizophrenia patients and 76 age- and sex-matched healthy controls. A fasting blood sample was taken for serum aPL and serum clozapine level. Serum aPL were measured by ELISA technique and HPLC method was used for the determination of serum clozapine level.

Results

The unmedicated schizophrenia patients showed higher IgG aCL level [mean ± SD: 1.51 ± 0.81 and 1.25 ± 0.13 U, respectively (t = 2.77, df=111, p<0.01)] and IgM aCL level [mean±SD: 1.53 ± 0.54. and 1.33 ± 0.15 U, respectively (t = −2.98, df = 111, p < 0.01)] compared with the healthy controls. The comparison of the clozapine-treated schizophrenia patients and the healthy controls showed significant difference in IgG aCL level [mean ± SD: 1.74 ± 0.90 and 1.25 ± 0.13 U, respectively (t = −4.77, df = 124, p < 0.01)] and IgM aCL level [mean ± SD: 1.62 ± 0.83 and1.33 ± 0.15 U, respectively (t = −4.35, df = 124, p < 0.01)]. In clozapine-treated schizophrenia patients, the results of Pearson correlation coefficients showed that there was a significant positive relationship between serum IgM aCL and serum clozapine level (r = 0.461, p < 0.01), and serum IgG aCL were significantly correlated with serum IgM aCL (r = 0.279, p < 0.05). Stepwise multiple regression analysis was performed with various characteristics, such as duration of medication, daily dose and serum clozapine level as candidate factors for serum aCL (IgG and IgM isotypes) in clozapine-treated schizophrenia patients. Only serum clozapine level was able to enter into the regression model of IgM aCL (Model R² = 0.212, p < 0.05).

Conclusions

A higher serum clozapine level is associated with an increased aPL in schizophrenia patients.     

High insulin levels are positively associated with peripheral nervous system function

Objective – The aim of this study was to analyze peripheral nervous system (PNS) function in overweight and obese individuals. Materials and Methods – Forty‐four adult non‐diabetic overweight individuals were recruited. Peroneal motor nerve conduction and radial, sural, and medial plantar sensory nerve conduction were studied. Insulin and glucose levels were determined twice (over a 2‐ to 3‐year period) with an oral glucose tolerance test (OGTT). Multiple stepwise linear regression models adjusted for age, height, weight, and skin temperature were used to analyze the data. Results – Analysis revealed that baseline insulin levels measured 120 min after an OGTT explained 18% of the variation in peroneal F‐wave minimum latency, 8% of peroneal F‐wave maximum latency variation, 15% of sural sensory latency variation, 13% of sural sensory nerve conduction velocity (NCV) variation, and 10% of the variation in medial plantar sensory NCV. Discussion and Conclusion – Our study shows that serum insulin levels measured 120 min after an OGGT are positively associated with PNS function. High insulin levels without notably high glucose levels appear to be beneficial for the function of the PNS.     

High glycine levels are associated with prepulse inhibition deficits in chronic schizophrenia patients

Prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating, is decreased in schizophrenia. The validity of a glutamatergic, N-methyl-d-aspartate receptor (NMDAR)-mediated model of PPI disruption is presently equivocal. The NMDAR antagonist ketamine disrupts PPI in rodents, but may increase PPI in healthy volunteers. Glycine (GLY), which acts as an obligatory co-agonist at the NMDAR-GLY site, induces PPI deficits in rats although, consistent with the hypo-NMDAR hypothesis, improves negative and cognitive symptoms in schizophrenia patients. We assessed the hypothesis that GLY serum levels may affect PPI parameters in schizophrenia. Forty-five chronically ill medicated schizophrenia patients and 37 matched healthy comparison subjects were tested for PPI of the eyeblink component of the startle reflex measured by electromyogram recording. Patients' demographic variables, symptom severity scores and GLY, serine and glutamate serum levels were obtained. Patients showed deficient PPI in blocks two and three of the PPI session and differed from controls in terms of change of degree of PPI as a function of the prepulse to eliciting stimulus interval. GLY levels correlated negatively with PPI parameters, such that patients with the highest GLY levels showed decreased PPI (rs=-0.4, p=0.03). These preliminary findings indirectly support previous observations on ketamine effects upon PPI in humans and suggest a dissociation of symptomatology and PPI changes as function of NMDAR modulation in schizophrenia.     

Decreased galanin serum levels are associated with alcohol-craving during withdrawal

Background

The hypothalamic galanin expression has been associated with increased intake of carbohydrates and fats in preclinical studies. The appetite stimulating effect of galanin is thought to underlie the positive association between alcohol consumption and hypothalamic galanin expression observed in preclinical studies.

Methods

In this pilot study we investigated alterations in galanin serum levels (33 male patients) in alcohol-dependent patients during alcohol withdrawal (days 1, 7 and 14) in comparison to healthy controls (19 male controls). In order to assess the putative association between appetite regulation, galanin serum levels and alcohol consumption we additionally investigated the serum levels of insulin, glucose and triglycerides.

Results

The galanin serum levels on day 1 of alcohol withdrawal were significantly reduced in the alcohol-dependent patients (T = − 3.302, p = 0.002) and increased significantly from day 1 to day 14 of alcohol withdrawal (F = 6.437, p = 0.002). We found a significant negative association between the galanin serum levels and alcohol craving measured by the Obsessive Compulsive Drinking Scale (OCDS) (r=−0.449, p=0.009) and the obsessive subscale of the OCDS (r = − 0.521, p = 0.002) on day 1 of alcohol withdrawal. There was no association between the galanin serum levels and the parameters of energy homeostasis (triglycerides, cholesterol, insulin, and glucose) investigated.

Conclusions

Acute alcohol withdrawal was associated with decreased galanin serum levels in this pilot study. There was no association between the galanin serum levels and the parameters of energy homeostasis. Further research of galanin serum levels in active drinkers will be necessary to clarify the putative association between galanin serum levels, appetite regulation and alcohol consumption.