Clozapine-treated Schizophrenia Patients Research Articles

Early versus late risk factors for deficit and nondeficit schizophrenia

AimWe examined whether timing of known risk factors for schizophrenia may influence the development of schizophrenia with primary negative symptoms. MethodThis cross-sectional single-centre study in England used a clinical cohort of 167 clozapine-treated schizophrenia patients. Deficit and nondeficit schizophrenia models were used as clinical proxies of patients with and without primary negative symptoms respectively. Patients were assessed using the Schedule for the Deficit Syndrome. We examined previously replicated risk factors (family history of psychosis, advanced paternal age, male gender, birth weight <3000g, summer birth, cannabis use, exposure to physical or sexual abuse and/or bullying) as well as other traumatic events for deficit and nondeficit schizophrenia. ResultsWe found a distinct risk factor pattern for the two groups. Compared to the nondeficit group, patients with deficit schizophrenia reported a significantly lower prevalence of cannabis use (p=0.005) at the time of first-episode psychosis (FEP), physical or sexual abuse (p=0.033) prior to FEP, less exposure to crime-related traumatic events (p=0.012) and significantly associated with summer birth (p=0.017). The groups did not differ in terms of family history of psychosis, advanced paternal age, male gender, or low birth weight. To account for multiple comparisons, a confirmatory analysis was performed using logistic regression which yielded similar results except that summer birth no longer reached statistical significance. ConclusionOur results suggest the timing of the insult may influence the symptom presentation, with insults later in life (cannabis or traumatic events) being associated with psychotic presentation and less with primary negative symptoms.

Characteristics of the corpus callosum in chronic schizophrenia treated with clozapine or risperidone and those never-treated

BackgroundThe corpus callosum (CC) deficits have been well documented in chronic schizophrenia. However, the long-term impacts of antipsychotic monotherapies on callosal anatomy remain unclear. This cross-sectional study sought to explore micro- and macro-structural characteristics of the CC in never-treated patients and those with long-term mono-antipsychotic treatment.MethodsThe study included 23 clozapine-treated schizophrenia patients (CT-SCZ), 19 risperidone-treated schizophrenia patients (RT-SCZ), 23 never-treated schizophrenia patients (NT-SCZ), and 35 healthy controls (HCs). High resolution structural images and diffusion tensor imaging (DTI) data for each participant were obtained via a 3.0 T MR scanner. FreeSurfer was used to examine the volumes and fractional anisotropy (FA) values of the CC for each participant.ResultsThere were significant deficits in the total and sub-regional CC volume and white matter integrity in NT-SCZ in comparison with healthy subjects. Compared with NT-SCZ, both CT-SCZ and RT-SCZ showed significantly increased FA values in the anterior CC region, while only RT-SCZ showed significantly increased volume in the mid-anterior CC region. Moreover, the volume of the mid-anterior CC region was significantly smaller in CT-SCZ compared to HCs. No correlations of clinical symptoms with callosal metrics were observed in schizophrenia patients.ConclusionsOur findings provide insight into micro- and macro-structural characteristics of the CC in chronic schizophrenia patients with or without antipsychotics. These results suggest that the pathology itself is responsible for cerebral abnormalities in schizophrenia and that chronic exposure to antipsychotics may have an impact on white matter structure of schizophrenia patients, especially in those with risperidone treatment.

Early versus late risk factors for deficit and nondeficit schizophrenia.

We examined whether timing of known risk factors for schizophrenia may influence the development of schizophrenia with primary negative symptoms. This cross-sectional single-centre study in England used a clinical cohort of 167 clozapine-treated schizophrenia patients. Deficit and nondeficit schizophrenia models were used as clinical proxies of patients with and without primary negative symptoms respectively. Patients were assessed using the Schedule for the Deficit Syndrome. We examined previously replicated risk factors (family history of psychosis, advanced paternal age, male gender, birth weight <3000g, summer birth, cannabis use, exposure to physical or sexual abuse and/or bullying) as well as other traumatic events for deficit and nondeficit schizophrenia. We found a distinct risk factor pattern for the two groups. Compared to the nondeficit group, patients with deficit schizophrenia reported a significantly lower prevalence of cannabis use (p=0.005) at the time of first-episode psychosis (FEP), physical or sexual abuse (p=0.033) prior to FEP, less exposure to crime-related traumatic events (p=0.012) and significantly associated with summer birth (p=0.017). The groups did not differ in terms of family history of psychosis, advanced paternal age, male gender, or low birth weight. To account for multiple comparisons, a confirmatory analysis was performed using logistic regression which yielded similar results except that summer birth no longer reached statistical significance. Our results suggest the timing of the insult may influence the symptom presentation, with insults later in life (cannabis or traumatic events) being associated with psychotic presentation and less with primary negative symptoms.

Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?

Rationale and objectiveClozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders.MethodsWe measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue.ResultsFollowing clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-β levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients’ BMI, blood glucose, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1β and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α.ConclusionFindings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.

P.580 Metabolic predictors for mortality among clozapine–treated schizophrenia patients. An Israeli nationwide longitudinal study

P.580 Metabolic predictors for mortality among clozapine–treated schizophrenia patients. An Israeli nationwide longitudinal study

Effects of Smoking Status on Remission and Metabolic and Cognitive Outcomes in Schizophrenia Patients Treated with Clozapine.

Even though clozapine is the recommended last-resort antipsychotic, many patients fail to respond and show treatment-refractory psychotic symptoms. Smoking has been suggested as a possible risk factor for poor clozapine response, hampering remission and negatively impacting somatic outcomes. Our aim was to test whether smoking status is associated with remission rates and other symptomatic and somatic outcomes. We therefore assessed remission rates according to The Remission in Schizophrenia Working Group (RSWG) criteria, and metabolic and cognitive outcomes among patients with schizophrenia-spectrum disorders treated with clozapine for at least 6 months. For analyses, we grouped our cohort into 3 groups according to clozapine treatment duration (6 months, 2 years, 5 years). One hundred five patients were included in our analyses and grouped according to their clozapine treatment duration. In the 6-months analyses, patients who smoked were significantly more likely to be younger of age (p=0.002) despite on average shorter duration of clozapine treatment (p=0.041) and significantly more likely to be treated with mood-stabilizing co-medication (p=0.030) compared to nonsmokers. Remission rates (p=0.490), as well as a set of metabolic and cognitive variables did not differ between the 2 groups. A related pattern could be observed for the 2- and 5-years analyses. Smoking behavior among clozapine-treated schizophrenia patients might delineate a cohort with an earlier onset of the disease. Nevertheless, most findings comparing disease-specific and clinical outcomes among smokers and nonsmokers were negative. Further research is needed to identify strategies to overcome insufficient remission rates in this patient group.

Low levels of serum vitamin D in clozapine-treated schizophrenia patients are associated with high levels of the proinflammatory cytokine IL-6.

Low levels of vitamin D are prevalent among patients with schizophrenia and have been linked to the risk and outcome of the disorder. Vitamin D has a regulatory effect on the inflammatory system, which is dysfunctional in schizophrenia. We investigated the association between serum vitamin D levels, inflammatory status, and severity of schizophrenia symptoms. A total of 39 clozapine-treated schizophrenia patients were recruited to the study. Blood samples for biochemical analysis were collected from all participants. Serum levels of vitamin D and cytokines (IL-4, IL-6, IL-10, and TNF-α) were analyzed and the association between biochemical and clinical measures was assessed. Most of the sample (82%) had insufficient levels of vitamin D. There was a significant inverse correlation between serum vitamin D and IL-6 levels (Pearson's r = -0.38, P < 0.05). Vitamin D levels correlated with the severity of positive symptoms (r = 0.39, P < 0.05). These results suggest that within clozapine-treated schizophrenia patients, high levels of vitamin D are associated with lower serum levels of the proinflammatory cytokine IL-6. This relationship may indicate an immunomodulatory effect of vitamin D in treatment-resistant patients with schizophrenia maintained on clozapine.

Can e-cigarettes improve the well-being of people with mental health disorders?

Abstract This Viewpoint considers the merits of e-cigarettes as a harm-minimisation tool for clozapine-treated schizophrenia patients. It argues that e-cigarettes may be a gateway not to smoking tobacco, but rather to engagement in more desirable health attitudes amongst this particularly marginalised population group. In our opinion, this presents clinicians with valuable opportunities to engage their patients more effectively in healthcare strategies, beginning with but not limited to tobacco-free e-cigarettes.

SA107 - ELEVATED PERIPHERAL EXPRESSION OF NEUREGULIN-1 (NRG1) MRNA ISOFORMS IN PATIENTS WITH TREATMENT-RESISTANT SCHIZOPHRENIA

Background Differential expression of Neuregulin-1 (NRG1) mRNA isoforms and proteins has been reported in schizophrenia, primarily in post-mortem brain tissue. In this study, we examined 12 NRG1 SNPs, eight NRG1 mRNA isoforms (type I, type I(Ig2), type II, type III, type IV, EGFα, EGFβ, pan-NRG1) in whole blood, and NRG1-β1 protein in serum of clozapine-treated schizophrenia patients (N=71) and healthy controls (N=57). In addition, using cultured Peripheral Blood Mononuclear Cells (PBMC) from 15 healthy individuals, we examined the effect of clozapine on NRG1 mRNA isoform and protein expression. Methods RT-PCR was used to measure gene expression level of different NRG1 isoforms in the whole blood of the schizophrenia patients and healthy controls in the clinical cohort as well as from the total RNA extracted from the In-Vitro clozapine exposure study. ELISA was used to measure NRG1-β1 protein level in serum in the clinical cohort and also in the total protein extracted from the in vitro clozapine exposure study. Results We found elevated levels of NRG1 mRNA, specifically the EGFα (P=0.0175), EGFβ (P=0.002) and typeI(Ig2) (P=0.023) containing transcripts, but lower NRG1-β1 serum protein levels (p=0.019) in schizophrenia patients compared to healthy controls. However, adjusting for smoking status attenuated the difference in NRG1-β1 serum levels (p=0.050). Examination of clinical factors showed NRG1 EGFα (p=0.02) and EGFβ (p=0.02) isoform expression was negatively correlated with age of onset. However, we found limited evidence that NRG1 mRNA isoform or protein expression was associated with current chlorpromazine equivalent dose or clozapine plasma levels, the latter corroborated by our PBMC clozapine exposure experiment. Our SNP analysis found no robust expression quantitative trait loci. Discussion Our results represent the first comprehensive investigation of NRG1 isoforms and protein expression in the blood of clozapine-treated schizophrenia patients and suggest NRG1 transcription is up-regulated in those with schizophrenia and perhaps more specifically in treatment-resistant schizophrenia.

S41. SHORT- AND LONG-TERM OUTCOMES OF VITAMIN D SUPPLEMENTATION IN CLOZAPINE TREATED CHRONIC SCHIZOPHRENIA PATIENTS

BackgroundVitamin D deficiency is highly prevalent in patients with psychosis. While accumulating data suggests that vitamin D deficiency may be involved in the clinical and metabolic outcomes of schizophrenia, there are no vitamin D supplementation studies in this context. Objective: To assess the short- and long-term impact of vitamin D supplementation on psychiatric and metabolic status in chronic clozapine-treated schizophrenia patients.MethodsFollowing a first phase of eight-week, randomized, double blind, placebo-controlled clinical trial, in which schizophrenia patients who had been maintained on clozapine treatment for at least 18 weeks with total PANSS scores >70 and with low levels of vitamin D (<75 nmol/L) were recruited, a second phase, post-RCT, was performed. In the RCT patients were randomly allocated to either weekly oral drops of vitamin D (14,000 IU) or placebo and subsequently assessed at two-week intervals regarding psychosis severity, mood, cognition and metabolic status. In the post-RCt phase, all participants were assessed at 24 weeks’ time point, while being prescribed 800 IU vitamin D daily supplementation in an open-label design.ResultsTwenty-four patients were randomly assigned to vitamin D and the other 23 patients to the placebo arm. No between-group differences were found in baseline measures. After eight weeks, the vitamin D group had higher increase in vitamin D levels (31.4 vs -0.4 nM, p<0.0001). There was no significant effect of vitamin D on PANSS score, depression or metabolic parameters. The vitamin D group, however, showed a positive small effect on cognitive function (effect size=0.17). On the long-term follow up, 37 patients completed the 24-week assessment. Mean vitamin D levels did not change from baseline (57.56 nM to 57.28 nM) and no association was found between this change and the changes in psychiatric, metabolic and cognitive measures. The only significant inverse association was found between vitamin D levels and HDL (p=0.007).DiscussionThis is the first study to assess the outcomes of vitamin D as an adjunct to clozapine in chronic schizophrenia patients, in the short and long term. The increase in vitamin D levels on the short-term was associated with a small positive effect on cognition, without any effect on psychosis, mood or metabolic status. There were no significant effects of vitamin D supplementation on the assessed measures in the long-term either.

‘Doing Things Little by Little’: Smoking and Vaping While Being Pharmaceutically Treated for Schizophrenia

ABSTRACTThis paper explores the experiences of smoking and ‘vaping’ while being pharmaceutically treated for schizophrenia, as well as what the experiences of breathing smoke and vapour in and out can reveal about health ‘care’, toward the self and others. Drawing on ethnographic data collected over 2015–2016 in Australia and the UK, and particularly on patient experiences in the UK where electronic cigarettes had become an endorsed Nicotine Replacement Therapy, I argue that inhaling nicotine via e-cigarettes can, like tobacco cigarettes, be experienced in terms of temporal opportunities for self-reclamation and experiences of health. When patients opted to vape instead of smoke, their sense of self-reclamation allowed for shifted attention toward the movement and materiality of exhalations, and toward how second-hand vapour (compared to smoke) is socially received. Experiences of vaping were, however, contingent on the clinical endorsement of e-cigarettes and were inconsistent inside and outside of clinical spaces. Further consideration should be given to vaping as a harm minimisation tool in Western societies dealing with widening disparities in health. Ultimately, clozapine-treated schizophrenia patients continue to smoke or vape for reasons that speak to the desire to make ‘time’; to find connections to life rather than focusing on death.

Elevated peripheral expression of neuregulin-1 (NRG1) mRNA isoforms in clozapine-treated schizophrenia patients

Differential expression of neuregulin-1 (NRG1) mRNA isoforms and proteins has been reported in schizophrenia, primarily in post-mortem brain tissue. In this study, we examined 12 NRG1 SNPs, eight NRG1 mRNA isoforms (type I, type I(Ig2), type II, type III, type IV, EGFα, EGFβ, pan-NRG1) in whole blood, and NRG1-β1 protein in serum of clozapine-treated schizophrenia patients (N = 71) and healthy controls (N = 57). In addition, using cultured peripheral blood mononuclear cells (PBMC) from 15 healthy individuals, we examined the effect of clozapine on NRG1 mRNA isoform and protein expression. We found elevated levels of NRG1 mRNA, specifically the EGFα (P = 0.0175), EGFβ (P = 0.002) and type I(Ig2) (P = 0.023) containing transcripts, but lower NRG1-β1 serum protein levels (P = 0.019) in schizophrenia patients compared to healthy controls. However, adjusting for smoking status attenuated the difference in NRG1-β1 serum levels (P = 0.050). Examination of clinical factors showed NRG1 EGFα (P = 0.02) and EGFβ (P = 0.02) isoform expression was negatively correlated with age of onset. However, we found limited evidence that NRG1 mRNA isoform or protein expression was associated with current chlorpromazine equivalent dose or clozapine plasma levels, the latter corroborated by our PBMC clozapine exposure experiment. Our SNP analysis found no robust expression quantitative trait loci. Our results represent the first comprehensive investigation of NRG1 isoforms and protein expression in the blood of clozapine-treated schizophrenia patients and suggest levels of some NRG1 transcripts are upregulated in those with schizophrenia.

Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial

BackgroundWhile accumulating evidence suggests that vitamin D deficiency may be involved in the risk to develop schizophrenia and its outcome, there are no studies on vitamin D supplementation in this context. We sought to assess the effect of vitamin D supplementation on psychiatric, cognitive and metabolic parameters in chronic clozapine-treated schizophrenia patients. MethodsThis eight-week, randomized, double-blind, placebo-controlled clinical trial, recruited schizophrenia patients who had been maintained on clozapine treatment for at least 18weeks and had low levels of vitamin D (<75nmol/l) and total PANSS scores >70 (to ascertain the presence of residual symptoms). Patients were randomly allocated to either weekly oral drops of vitamin D (14,000IU) or placebo and subsequently assessed at two-week intervals for psychosis severity, mood, cognition and metabolic profile. ResultsTwenty four patients were randomly assigned to vitamin D (aged 39.4±9.6years, 75% males) and the other 23 patients to the placebo arm (aged 42.5±11.2years, 60.9% males). After eight weeks, the vitamin D group exhibited a significant increase in vitamin D levels (31.4 vs −0.4nmol/l, p<0.0001). There was no significant effect of vitamin D on psychotic, depressive or metabolic parameters. However, in the vitamin D group, there was a trend towards improved cognition (effect size=0.17, significance lost following Bonferroni correction). ConclusionsVitamin D supplementation was associated with a trend towards improved cognition, but did not affect psychosis, mood or metabolic status. It is possible that the robust decrease in the PANSS scores in both groups may have obscured an effect of vitamin D supplementation.

120. Benign Ethnic Neutropenia in a Sample of Nigerian Healthy Controls and Clozapine-Treated Schizophrenia Patients With DARC Null Variant

120. Benign Ethnic Neutropenia in a Sample of Nigerian Healthy Controls and Clozapine-Treated Schizophrenia Patients With DARC Null Variant

Actively Negotiating the Mind-Body Divide: How Clozapine-Treated Schizophrenia Patients Make Health for Themselves.

It is well recognised that antipsychotic treatments impact the whole body, not just the target area of the brain. For people with refractory schizophrenia on clozapine, the gold standard antipsychotic treatment in England and Australia, the separation of mental and physical regimes of health is particularly pronounced, resulting in multiple, compartmentalised treatment registers. Clinicians often focus on the mental health aspects of clozapine use, using physical indicators to determine whether treatment can continue. Our observations of 59 participants in England and Australia over 18months revealed that patients did not observe this hierarchisation of mental treatments and physical outcomes. Patients often actively engaged in the management of their bodily symptoms, leading us to advance the figure of the active, rather than passive, patient. In our paper, we do not take the position that the facility for active management is a special one utilised only by these patients. We seek instead to draw attention to what is currently overlooked as an ordinary capacity to enact some sort of control over life, even under ostensibly confined and confining circumstances. We argue that clozapine-treated schizophrenia patients utilise the clinical dichotomy between mental and physical domains of health to rework what health means to them. This permits patients to actively manage their own phenomenological 'life projects' (Rapport, I am Dynamite: an Alternative Anthropology of Power, Routledge, London 2003), and forces us to reconsider the notion of clinical giveness of what health means. This making of one's own meanings of health may be critical to the maintenance of a sense of self.

Effectiveness of the repeated administration of scopolamine ointment on clozapine-induced hypersalivation in patients with treatment-resistant schizophrenia: A preliminary study.

This study investigated the efficacy of scopolamine (an anticholinergic agent) ointment against clozapine-induced hypersalivation. The patients enrolled in this study consisted of 10 clozapine-treated schizophrenia patients and 10 healthy adult men. A prospective, randomized, double-blind, crossover, placebo-controlled clinical trial was designed. A total of 10 patients and 10 healthy adult men completed the study. No significant reduction in the saliva production of the clozapine-treated patients was observed; however, that of the healthy adult men decreased significantly. Scopolamine ointment was not effective against clozapine-induced hypersalivation. A further study is necessary for confirming its effect.

Well-being in clozapine-treated schizophrenia patients: The significance of positive symptoms

ObjectivesWell-being perception is seldom explored in schizophrenia patients. Recurrent limitations, such as the questionable applicability of gold standard definitions of health and well-being, and fewer tools available to assess well-being, are pronounced in this subpopulation. This cross-sectional study sought to explore potential clinical factors that may predict subjective well-being scores in chronic schizophrenia patients (N=142) receiving clozapine treatment. MethodsThe Short Warwick–Edinburgh Mental Well-being Scale (SWEMWBS) was used to measure well-being. We correlated SWEMWBS scores and 27 clinically recognized factors, spanning socio-demographics, symptom severity scores, physical health diagnosis, clozapine side effects, habits and prescribed medication. Factors with a p<0.2 correlation were included as a predictors in a linear regression model. ResultsTen factors were included in the linear regression model, however only positive symptom severity was a significant predictor of SWEMWBS score (p<0.0001). ConclusionsWe suggest that greater levels of clinical attention given to positive symptoms compared with other symptoms and aspects of well-being, during biomedical treatment for chronic schizophrenia, may partially explain the finding that only positive symptoms significantly predicted patient perceptions of low well-being.

Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients With Persistent Symptoms.

Clozapine is the most effective antipsychotic for treatment refractory people with schizophrenia, yet many patients only partially respond. Accumulating preclinical and clinical data suggest benefits with minocycline. We tested adjunct minocycline to clozapine in a 10-week, double-blind, placebo-controlled trial. Primary outcomes tested were positive, and cognitive symptoms, while avolition, anxiety/depression, and negative symptoms were secondary outcomes. Schizophrenia and schizoaffective participants (n = 52) with persistent positive symptoms were randomized to receive adjunct minocycline (100 mg oral capsule twice daily; n = 29) or placebo (n = 23). Brief Psychiatric Rating Scale (BPRS) psychosis factor (P = 0.098; effect size [ES], 0.39) and BPRS total score (P = 0.075; ES, 0.55) were not significant. A change in total BPRS symptoms of more than or equal to 30% was observed in 7 (25%) of 28 among minocycline and 1 (4%) of 23 among placebo participants, respectively (P = 0.044). Global cognitive function (MATRICS Consensus Cognitive Battery) did not differ, although there was a significant variation in size of treatment effects among cognitive domains (P = 0.03), with significant improvement in working memory favoring minocycline (P = 0.023; ES, 0.41). The Scale for the Assessment of Negative Symptoms total score did not differ, but significant improvement in avolition with minocycline was noted (P = 0.012; ES, 0.34). Significant improvement in the BPRS anxiety/depression factor was observed with minocycline (P = 0.028; ES, 0.49). Minocycline was well tolerated with significantly fewer headaches and constipation compared with placebo. Minocycline's effect on the MATRICS Consensus Cognitive Battery composite score and positive symptoms were not statistically significant. Significant improvements with minocycline were seen in working memory, avolition, and anxiety/depressive symptoms in a chronic population with persistent symptoms. Larger studies are needed to validate these findings.

MMN responsivity to manipulations of frequency and duration deviants in chronic, clozapine-treated schizophrenia patients

Event-related potential (ERP) probing of abnormal sensory processes in schizophrenia with the mismatch negativity (MMN) has shown impairments in auditory change detection, but knowledge of the acoustic features leading to this deficit is incomplete. Changes in the duration and frequency properties of sound stimuli result in diminished MMNs in schizophrenia but it is unclear as to whether this reduced responsiveness is seen with more subtle changes in sound frequency. In a sample of 19 healthy controls and 21 patients with chronic schizophrenia treated with clozapine, MMN was assessed in response to tone frequency changes of 5%, 10% and 20%, and to tone duration changes. Patients exhibited reduced amplitudes and shorter latencies than controls to all frequency changes, and attenuated amplitudes to tone duration increments and decrements. Clozapine dose was related to MMN, with increasing dose being positively associated with frequency-MMN amplitudes (10% ∆f , 20% ∆f) and negatively associated with the amplitude and latency of duration-MMNs. These data support the well-established findings of auditory sensory abnormality in schizophrenia and underscore the sensitivity of MMN to relatively small auditory change detection deficits that may appear to characterize chronic schizophrenia.

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 R 2 = 0.212, p < 0.05). Conclusions A higher serum clozapine level is associated with an increased aPL in schizophrenia patients.