Prebiotic Treatment in People With Schizophrenia.

BACKGROUND: Preliminary evidence suggests that people with schizophrenia have decreased relative abundance of butyrate-producing bacteria in the gut microbiota. Butyrate plays a critical role in maintaining the integrity of the gut-blood barrier and has a number of anti-inflammatory effects. This proof-of-concept study was designed to assess whether the addition of the oligofructose-enriched inulin (OEI) prebiotic: Prebiotin could increase the production of butyrate. METHODS: Twenty-seven people who met the criteria for either Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, schizophrenia or schizoaffective disorder were entered into a 10-day, double-blind, placebo-controlled, randomized clinical trial. The study was conducted on an inpatient unit to standardize the participant diet and environment. Participants were randomized to either OEI (4 g, 3 times a day) or a placebo (4 g of maltodextrin, 3 times a day). In order to assess the effect of OEI treatment on butyrate levels, participants underwent pretreatment and posttreatment OEI challenges. The primary outcome measure was relative change in postchallenge plasma butyrate levels after 10 days of OEI treatment. RESULTS: In both the intent-to-treat and completer analyses, OEI treatment was associated with a greater number of participants who met the OEI challenge responder criteria than those treated with placebo. OEI treatment was also associated with an increase in baseline butyrate levels (effect size for the group difference in the change of baseline butyrate levels was 0.58). CONCLUSIONS: We were able to demonstrate that treatment with the prebiotic OEI selectively increased the level of plasma butyrate in people with schizophrenia.Trial registration:ClinicalTrials.gov identifier NCT03617783.

Evaluating the Use of Online Self-Report Questionnaires as Clinically Valid Mental Health Monitoring Tools in the Clinical Whitespace.

Although digital health solutions are increasingly popular in clinical psychiatry, one application that has not been fully explored is the utilization of survey technology to monitor patients outside of the clinic. Supplementing routine care with digital information collected in the "clinical whitespace" between visits could improve care for patients with severe mental illness. This study evaluated the feasibility and validity of using online self-report questionnaires to supplement in-person clinical evaluations in persons with and without psychiatric diagnoses. We performed a rigorous in-person clinical diagnostic and assessment battery in 54 participants with schizophrenia (N = 23), depressive disorder (N = 14), and healthy controls (N = 17) using standard assessments for depressive and psychotic symptomatology. Participants were then asked to complete brief online assessments of depressive (Quick Inventory of Depressive Symptomatology) and psychotic (Community Assessment of Psychic Experiences) symptoms outside of the clinic for comparison with the ground-truth in-person assessments. We found that online self-report ratings of severity were significantly correlated with the clinical assessments for depression (two assessments used: R = 0.63, p < 0.001; R = 0.73, p < 0.001) and psychosis (R = 0.62, p < 0.001). Our results demonstrate the feasibility and validity of collecting psychiatric symptom ratings through online surveys. Surveillance of this kind may be especially useful in detecting acute mental health crises between patient visits and can generally contribute to more comprehensive psychiatric treatment.

Combined Oxytocin and Cognitive Behavioral Social Skills Training for Social Function in People With Schizophrenia.

BACKGROUND: A significant proportion of people with schizophrenia are characterized by impaired ability to socially engage with others. The development of effective interventions for social functioning remains a central therapeutic challenge. Cognitive-behavioral social skills training (CBSST) has been found to improve social functioning in schizophrenia, but with only medium effect sizes. Intranasal oxytocin also has prosocial effects, but also only with modest effect sizes. This study assessed whether the addition of intranasal oxytocin to CBSST can strengthen their impact on social function. METHODS: Participants (N = 62) with schizophrenia or schizoaffective disorder entered a 24-week, double-blind, placebo-controlled, randomized clinical trial with a 3-month follow-up evaluation at 2 sites: Maryland and San Diego. Participants were randomized to either intranasal oxytocin 36 IU (3 sprays) twice a day (n = 31) or intranasal placebo-oxytocin (3 sprays) twice a day (n = 31). All participants received CBSST plus a social cognition skills training module (48 total sessions). RESULTS: There were no significant treatment group differences in social functioning, positive symptoms, negative symptoms, defeatist beliefs, or asocial beliefs. The interpretation of treatment effects was complicated by site effects, whereby participants in San Diego began the trial with greater severity of impairments and subsequently showed greater improvements compared with participants in Maryland. CONCLUSIONS: The results did not support the utility of add-on intranasal oxytocin to psychosocial rehabilitation interventions like CBSST for improvement in social function (ClinicalTrials.gov trial number: NCT01752712).

Feasibility and patient-reported satisfaction using a novel point-of-care fingerstick method for monitoring absolute neutrophil count for clozapine.

BACKGROUND: Clozapine is an effective antipsychotic for treatment-resistant schizophrenia. One limitation of clozapine use is required monitoring of absolute neutrophil count (ANC) because of the risk of clozapine-induced neutropenia. Standard monitoring requires venous blood draws, which is a significant barrier to clozapine use. METHODS: This study assesses the feasibility of use and physician and patient satisfaction of a novel point-of-care (POC) measure of ANC using Athelas One, a device that calculates white blood cell count and ANC using a fingerstick blood sample. This is a subanalysis of a prospective, open-label clinical trial of clozapine treatment, during which patients received a venous blood draw and a capillary fingerstick at baseline and Week 2 of the study, and completed a 5-point Likert scale, comparing the 2 methods. RESULTS: Patients reported benefits from the fingerstick technology, including POC testing being important for their doctors and their health, improved treatment, avoiding sending blood away, and convenience. There was a trend for less concern about the effects of blood draws on health with a fingerstick, and greater physician satisfaction with POC sampling. CONCLUSIONS: This study suggests the feasibility, satisfaction, and ease by both clinicians and patients of using POC testing for ANC monitoring during clozapine treatment.

Anti-inflammatory Combination Therapy for the Treatment of Schizophrenia.

BACKGROUND: Despite adequate antipsychotic treatment, most people with schizophrenia continue to exhibit persistent positive and negative symptoms and cognitive impairments. The current study was designed to examine the efficacy and safety of adjunctive anti-inflammatory combination therapy for these illness manifestations. METHODS: Thirty-nine people with either Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, schizophrenia or schizoaffective disorder were entered into a 12-week double-blind, 2-arm, triple-dummy, placebo-controlled, randomized clinical trial: 19 were randomized to anti-inflammatory combination therapy and 20 were randomized to placebo. The Brief Psychiatric Rating Scale positive symptom item total score was used to assess positive symptom change, the Scale for the Assessment of Negative Symptoms total score was used to assess negative symptom change, the Calgary Depression Scale total score was used to assess depressive symptom change, and the MATRICS Consensus Cognitive Battery was used to assess neuropsychological test performance. RESULTS: There was a significant time effect for Brief Psychiatric Rating Scale positive symptom item score (t226 = -2.66, P = 0.008), but the treatment (t54=1.52, P = 0.13) and treatment × time (t223 = 0.47, P = 0.64) effects were not significant. There were no significant time (t144 = 0.53, P = 0.72), treatment (t58=0.48, P = 0.63), or treatment × time (t143 = -0.20, P = 0.84) effects for the Scale for the Assessment of Negative Symptoms total score; or for any of the other symptom measures. There were no significant group differences in the change in the MATRICS Consensus Cognitive Battery composite score over the course of the study (F1,26=2.20, P = 0.15). CONCLUSIONS: The study results suggest that there is no significant benefit of combined anti-inflammatory treatment for persistent positive symptoms or negative symptoms or cognitive impairments (clinicaltrials.gov trial number: NCT01514682).

Comparison of Novel Immunoassay With Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) for Therapeutic Drug Monitoring of Clozapine.

BACKGROUND: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia. Although serum clozapine levels can help guide treatment, they are underutilized owing to requirements for frequent venous blood draws and lack of immediate results. METHODS: Clozapine levels measured with a novel immunoassay technology (which enables point-of-care development) were compared with those measured by standard liquid chromatography/tandem mass spectrometry (LC-MS/MS). Frozen serum aliquots of 117 samples (N = 48 patients with schizophrenia on clozapine; N = 24 patients with schizophrenia not on clozapine; N = 45 healthy controls) were sent to a national reference laboratory (NRL) for clozapine level determination by LC-MS/MS, and matching samples were subjected to novel immunoassay (3 runs). At a later date, another frozen aliquot from the same date was sent to the NRL for repeat testing. RESULTS: The NRL obtained 18 false-positive clozapine results (mean 42.39 ± 32.06, range 21-159 ng/mL) in participants not on clozapine (N = 3) and healthy controls (N = 15). The immunoassay showed no false-positive clozapine results. The clozapine levels were correlated between both assays (r = 0.84, P < 0.0001), despite 16% higher clozapine levels with immunoassay (482.08 ± 270.88 ng/mL immunoassay, 414.98 ± 186.29 ng/mL LC-MS/MS [P = 0.03]). Agreement analysis using concordance correlation coefficient (CCC) for LC-MS/MS of the 2 aliquots yielded CCC = 0.869; 95% confidence interval = 0.690-0.970, whereas higher agreement results were observed for the 3 runs of immunoassay (CCC = 0.99; 95% confidence interval = 0.979-0.997). CONCLUSIONS: The lack of false positives observed with immunoassay, higher repeat performance agreement, and good correlation with LC-MS/MS may indicate the more robust performance of immunoassay than that of LC-MS/MS clozapine-level determination.

Racial Differences in S100b Levels in Persons with Schizophrenia.

The calcium-binding protein S100b is secreted by glial cells in the brain and is also expressed by melanocytes. In nanomolar concentrations, S100b is considered to be a neurotrophic factor, but in micromolar concentrations, it is thought to reflect CNS injury and inflammation. Seen as a potential biomarker in traumatic brain injury, meta-analytic data from several studies report that S100b levels are significantly higher in persons with long standing schizophrenia, but also among first-episode patients compared to healthy control subjects. However, ethnic or racial differences are typically not mentioned when reporting levels of S100b. We assessed serum S100b levels in persons with schizophrenia (n = 136) who were participants in two independent research studies using the same enzyme-linked immunoassay (ELISA). African-American subjects had significantly higher levels of S100b (41.9 pg/ml ± 62.2) than Caucasian subjects (24.9 pg/ml ± 45.4) in the combined dataset (Mann-Whitney U = 1307, p < 0.001), as well as in each independent study. There were no significant differences in S100b levels between men and women. No significant correlations were observed between S100b levels and demographic or clinical variables. These data suggest that ethnicity or race should be given serious consideration when studying and interpreting S100b levels in persons with schizophrenia.

The effects of combined oxytocin and cognitive behavioral social skills training on social cognition in schizophrenia.

BACKGROUND: Individuals with schizophrenia have deficits in social cognition that are associated with poor functional outcome. Unfortunately, current treatments result in only modest improvement in social cognition. Oxytocin, a neuropeptide with pro-social effects, has significant benefits for social cognition in the general population. However, studies examining the efficacy of oxytocin in schizophrenia have yielded inconsistent results. One reason for inconsistency may be that oxytocin has typically not been combined with psychosocial interventions. It may be necessary for individuals with schizophrenia to receive concurrent psychosocial treatment while taking oxytocin to have the context needed to make gains in social cognitive skills. METHODS: The current study tested this hypothesis in a 24-week (48 session) double-blind, placebo-controlled trial that combined oxytocin and Cognitive-Behavioral Social Skills Training (CBSST), which included elements from Social Cognition and Interaction Training (SCIT). Participants included 62 outpatients diagnosed with schizophrenia (placebo n = 31; oxytocin n = 31) who received 36 IU BID, with supervised administration 45 min prior to sessions on CBSST group therapy days. Participants completed a battery of measures administered at 0, 12, and 24 weeks that assessed social cognition. RESULTS: CBSST generally failed to enhance social cognition from baseline to end of study, and there was no additive benefit of oxytocin beyond the effects of CBSST alone. CONCLUSIONS: Findings suggest that combined CBSST and oxytocin had minimal benefit for social cognition, adding to the growing literature indicating null effects of oxytocin in multi-dose trials. Methodological and biological factors may contribute to inconsistent results across studies.

Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study

Background: Approximately one-third of people with schizophrenia have elevated levels of anti-gliadin antibodies of the immunoglobulin G type (AGA IgG) ­ a higher rate than seen in healthy controls. We performed the first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were positive for AGA IgG. Methods: In this pilot feasibility study, 16 participants with schizophrenia or schizoaffective disorder who had elevated AGA IgG (≥ 20 U) but were negative for celiac disease were admitted to an inpatient unit for a 5-week trial. All participants received standardized gluten-free meals and were randomized in a double-blind fashion to receive a shake containing 10 g of gluten flour or 10 g of rice flour each day. Participants were rated for psychiatric, cognitive and gastrointestinal symptoms at baseline and endpoint. Results: Of the 16 participants, 14 completed the 5-week trial (2 discontinued early for administrative reasons). Compared with participants on the gluten-containing diet, participants on the gluten-free diet showed improvement on the Clinical Global Impressions scale (Cohen d = ­0.75) and in negative symptoms (Cohen d = ­0.53). We noted no improvement in positive or global cognitive symptoms, but did observe an improvement in attention favouring the gluten-free diet (Cohen d = 0.60). Robust improvements in gastrointestinal adverse effects occurred in the gluten-free group relative to the glutencontaining group. Adverse effects were similar between groups. Limitations: This study was limited by its small sample size; larger studies are needed. Conclusion: This feasibility study suggests that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with schizophrenia or schizoaffective disorder.

Redox Is a Global Biodevice Information Processing Modality.

Biology is well-known for its ability to communicate through (i) molecularly-specific signaling modalities and (ii) a globally-acting electrical modality associated with ion flow across biological membranes. Emerging research suggests that biology uses a third type of communication modality associated with a flow of electrons through reduction/oxidation (redox) reactions. This redox signaling modality appears to act globally and has features of both molecular and electrical modalities: since free electrons do not exist in aqueous solution, the electrons must flow through molecular intermediates that can be switched between two states - with electrons (reduced) or without electrons (oxidized). Importantly, this global redox modality is easily accessible through its electrical features using convenient electrochemical instrumentation. In this review, we explain this redox modality, describe our electrochemical measurements, and provide four examples demonstrating that redox enables communication between biology and electronics. The first two examples illustrate how redox probing can acquire biologically relevant information. The last two examples illustrate how redox inputs can transduce biologically-relevant transitions for patterning and the induction of a synbio transceiver for two-hop molecular communication. In summary, we believe redox provides a unique ability to bridge bio-device communication because simple electrochemical methods enable global access to biologically meaningful information. Further, we envision that redox may facilitate the application of information theory to the biological sciences.

Effects of Cigarette Smoking and Clozapine Treatment on 20-Year All-Cause & Cardiovascular Mortality in Schizophrenia.

To estimate 20-year mortality risk in people with schizophrenia treated with second-generation antipsychotics (SGA) and examine the effects of cigarette smoking on mortality. Of the 1199 individuals with schizophrenia in the study, estimated 20-year all-cause mortality risk by Kaplan Meier Curve was 30% and leading causes of death included 27% cardiovascular disease, 13% cancer, 12% non-HIV infection, 5% respiratory causes, 20% other causes and 18% had unknown cause of death. For all-cause mortality, we found that white race and male sex were significant risk factors (HR = 1.5, p = 0.002 and HR = 1.33, p = 0.033, respectively). For cardiovascular mortality risk, we showed that cigarette smokers and white race were at higher risk (HR = 1.86, p = 0.017 and HR = 1.71, p = 0.045, respectively). Cardiovascular mortality risk at 20-years is 11%. Kaplan-Meier Survival Curve showed a statistical difference for smokers and non-smokers in cardiovascular mortality over the 20-year follow-up (Log rank chi-square = 5.35, df = 1, p = 0.02). 20-year all-cause mortality risk for individuals with schizophrenia was found to be 30% with cardiovascular disease as a leading cause. Cigarette smokers and white race were associated with an increased risk of death. Regarding cardiovascular mortality specifically, cigarette smoking increased risk by 86% over a 20-year period. Clozapine was neither a risk factor for all-neither cause nor cardiovascular mortality. This data suggests that long-term cardiovascular mortality continues to be increased in schizophrenia for those who are or have been cigarette smokers.

Anti gliadin antibodies (AGA IgG) related to peripheral inflammation in schizophrenia.

Altered immune function and inflammation are seen in schizophrenia, however, peripheral inflammatory markers are not consistently elevated in all people, suggesting inflammation may be present only in a subgroup. We measured TNF-α and IL-Iß in 100 people with schizophrenia or schizoaffective disorder and correlated these with antibodies to gliadin, a protein found in wheat, barley and rye that has been found to be elevated in some people with schizophrenia. We hypothesized that higher peripheral antigliadin antibodies (AGA IgG) would be associated with higher peripheral inflammation as measured by TNF-α and IL-1ß. Mean log transformed values of TNF-α, (p=.029) and IL-1ß (p=.016) were over twofold higher in people with schizophrenia who had high levels of AGA IgG (≥7 U) compared to those who did not have positivity to AGA IgG. We found a significant positive correlation between AGA IgG and the log transformed TNF-α (r=0.42, p<.0001) as well as IL-Iß (r=0.51, p<.0001). The relationship was independent of cigarette smoking, body mass index and antipsychotic medications. People with schizophrenia having higher levels of AGA IgG show higher levels of peripheral inflammation and may define a subgroup with distinct pathophysiology and potentially novel treatment targets.

Adjunct Aripiprazole Reduces Prolactin and Prolactin-Related Adverse Effects in Premenopausal Women With Psychosis: Results From the DAAMSEL Clinical Trial.

PURPOSE/BACKGROUND: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes. METHODS/PROCEDURES: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (>24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored. FINDINGS/RESULTS: Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (<24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (<16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain. IMPLICATIONS/CONCLUSIONS: Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.

Relationship of Interferon-γ to Cognitive Function in Midlife Women with Schizophrenia.

Recent literature suggests that schizophrenia is linked to an abnormal response of the immune system. Interferon-γ is a cytokine that acts as a mediator between immune stimulation and the kynurenine pathway and may be related to cognitive abilities. The objectives of the present study are to determine if serum cytokines are correlated with cognitive function differently in patients with schizophrenia compared to controls. Fourteen midlife (30-70 year-old) females with DSM-IV diagnosis of schizophrenia or schizoaffective disorder and 13 midlife control females were analyzed. Cytokines were collected from serum blood draws and analyzed at the Cytokine Core Lab at the University of Maryland, Baltimore. The RBANS, HVLT-R, and UPSA were performed to measure cognition and social performance. The results demonstrate a non-significant difference between interferon-γ levels in women with schizophrenia compared to controls, but this cytokine appears to correlate to cognitive abilities differently in these groups. There were several significant negative correlations between interferon-γ and cognition in midlife patients with schizophrenia, but only one in the midlife control group. The negative correlations between interferon-γ and cognition in patients with schizophrenia suggest the hypothesis that inflammation and the kynurenine pathway have important roles in this disorder.

Clozapine in Reducing Aggression and Violence in Forensic Populations.

Popular media often portray people with a mental illness as being aggressive, violent, and incarcerated as a result of their behavior. Despite exaggeration in the media, risks for some aggressive behaviors are in fact higher in individuals with schizophrenia. This is often the case with influence of comorbid substance use disorders. It is essential that mental health professionals are aware of treatments that may help with attenuating and treating behaviors that contribute to violence, aggression and incarceration. This paper reviews violence and incarceration in individuals with schizophrenia as well as recommendations, guidelines and benefits for the use of clozapine in this population. Clozapine remains one of the most underutilized evidence-based medications available in the psychiatric arena in the United States. It is a viable and recommended option in the forensic population and it may be helpful on the path to recovery as well as bring substantial savings to the criminal justice system.

Adjunctive Minocycline in Clozapine-Treated Patients with Schizophrenia: Analyzing the Effects of Minocycline on Clozapine Plasma Levels.

Clozapine is the sole antipsychotic agent effective for the treatment of refractory schizophrenia. Sixty percent of clozapine-treated patients, however, fail to adequately respond. Minocycline, a tetracycline antibiotic, possesses antiinflammatory and neuroprotective properties that may play a role in schizophrenia. Clozapine is mainly metabolized by CYP1A2 enzymes, and minocycline may potentially inhibit CYP1A2 as hypothesized by case report data. To date, no pharmacokinetic interaction has been reported between minocycline and clozapine. This is a secondary analysis of a 10-week controlled study of adjunctive minocycline to clozapine in treatment refractory schizophrenia. Clozapine plasma levels were collected every two weeks during the study. 28 participants assigned to receive minocycline and 22 assigned to placebo were included. No differences existed in baseline demographics, clozapine dose or plasma levels. Average changes from baseline in clozapine plasma level (p = 0.033) were significantly higher in the minocycline group despite maintenance of stable doses. No statistically significant treatment differences were found in the norclozapine (p = 0.754) or total clozapine (p = 0.053) changes in plasma levels, although possible changes in total clozapine levels require further investigation. This analysis suggests that minocycline administration may lead to increased clozapine plasma levels. Further study is needed to examine possible explanations.

Redox Probing for Chemical Information of Oxidative Stress.

Oxidative stress is implicated in many diseases yet no simple, rapid, and robust measurement is available at the point-of-care to assist clinicians in detecting oxidative stress. Here, we report results from a discovery-based research approach in which a redox mediator is used to probe serum samples for chemical information relevant to oxidative stress. Specifically, we use an iridium salt (K2IrCl6) to probe serum for reducing activities that can transfer electrons to iridium and thus generate detectable optical and electrochemical signals. We show that this Ir-reducing assay can detect various biological reductants and is especially sensitive to glutathione (GSH) compared to alternative assays. We performed an initial clinical evaluation using serum from 10 people diagnosed with schizophrenia, a mental health disorder that is increasingly linked to oxidative stress. The measured Ir-reducing capacity was able to discriminate people with schizophrenia from healthy controls (p < 0.005), and correlations were observed between Ir-reducing capacity and independent measures of symptom severity.

A Randomized Clinical Trial of Oxytocin or Galantamine for the Treatment of Negative Symptoms and Cognitive Impairments in People With Schizophrenia.

PURPOSE/BACKGROUND: Negative symptoms and cognitive impairments tend to co-occur in people with schizophrenia. If their association with each other is due, in part, to shared pathophysiology, then this suggests that a single drug could potentially be effective for both domains. The current study was designed to examine this hypothesis. METHODS/PROCEDURES: Fifty-eight participants with either Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision schizophrenia or schizoaffective disorder entered into a 6-week double-blind, placebo-controlled, double-dummy, randomized clinical trial of intranasal oxytocin and galantamine. Seventeen participants were randomized to intranasal oxytocin, 20 were randomized to galantamine, and 21 were randomized to placebo. The Scale for the Assessment of Negative Symptoms total score was used to assess change in negative symptoms (the primary outcome measure for oxytocin). The MATRICS Consensus Cognitive Battery composite score was used to assess cognition (the primary outcome measure for galantamine). FINDINGS/RESULTS: There were no significant group differences for negative symptoms (oxytocin vs placebo: F2,47.4 = 0.19, P = 0.83; galantamine vs placebo: F2,52.5 = 0.41, P = 0.67). There were no significant group differences for cognitive impairments (galantamine vs placebo: t40 = 0.71, P = 0.48; oxytocin vs placebo: t40 = 0.50, P = 0.62). There were also no significant group differences for the functional capacity or ancillary symptom measures. IMPLICATIONS/CONCLUSIONS: The lack of an efficacy signal for either compound precluded our ability to test whether pharmacological treatment pathways for negative symptoms and cognitive impairments overlap or are independent.

The interplay of electrode- and bio-materials in a redox-cycling-based clozapine sensor.

We investigate gold, TiN, and platinum in combination with a chitosan-catechol-based redox-cycling system (RCS) for electrochemical detection of the antipsychotic clozapine. We have previously demonstrated the RCS for detection of clozapine in serum, but challenges remain regarding low signal-to-noise ratios. This can be mitigated by selection of electrode materials with beneficial surface morphologies and/or compositions. We employ cyclic voltammetry to assess the redox current generated by clozapine, and differentiate solely surface-area-based effects from clozapine-specific ones using a standard redox couple. We find that nano- and microstructured platinum greatly amplifies the clozapine signal compared to gold (up to 1490-fold for platinum black). However, the material performs poorly in the presence of chloride ions, and RCS modification provides no further amplification. The RCS combined with atomic-layer-deposited (ALD) TiN, on the other hand, increases the signal by 7.54 times, versus 2.86 times for RCS on gold, with a 9.2-fold lower variability, indicating that the homogenous and chemically inert properties of ALD-TiN may make it an ideal electrode material.

Predictors of the Perception of Smoking Health Risks in Smokers With or Without Schizophrenia.

OBJECTIVE: This study sought to examine the predictors of health risk perception in smokers with or without schizophrenia. METHODS: The health risk subscale from the Smoking Consequences Questionnaire was dichotomized and used to measure health risk perception in smokers with (n = 67) and without schizophrenia (n = 100). A backward stepwise logistic regression was conducted using variables associated at the bivariate level to determine multivariate predictors. RESULTS: Overall, 62.5% of smokers without schizophrenia and 40.3% of smokers with schizophrenia completely recognize the health risks of smoking (p ≤ .01). Multivariate predictors for smokers without schizophrenia included: sex (Exp (B) = .3; p < .05), Smoking Consequences Questionnaire state enhancement (Exp (B) = .69; p < .01), and craving relief (Exp (B) = 1.8; p < .01). Among smokers with schizophrenia, predictors were education (Exp (B) = .7; p < .05), nicotine dependence (Exp (B) = .5; p < .01), motivation to quit (Exp (B) = 1.8; p < .01), and Smoking Consequences Questionnaire craving relief (Exp (B) = 1.8; p < .01). CONCLUSIONS: There was overlap and differences between predictors in smokers with and without schizophrenia. Commonly used techniques for education on the health consequences of cigarettes may work in smokers with schizophrenia, but intervention efforts specifically tailored to smokers with schizophrenia might be more efficacious.