Rational downstream development for adeno-associated virus full/empty capsid separation - A streamlined methodology based on high-throughput screening and mechanistic modeling.

Recombinant adeno-associated virus (AAV) has emerged as one of the most promising systems for therapeutic gene delivery and has demonstrated clinical success in a wide range of genetic disorders. However, manufacturing of high-quality AAV in large amounts still remains a challenge. A significant difficulty for downstream processing is the need to remove empty capsids that are generated in all currently utilized expression systems and that represent product-related impurities that adversely affect safety and efficacy of AAV vectors. Empty and full capsids exhibit only subtle differences in surface charge and size, making chromatography-based separations highly challenging. Here, we present a rapid methodology for the systematic process development of the crucial AAV full/empty capsid separation on ion-exchange media based on high-throughput screening and mechanistic modeling. Two of the most commonly employed serotypes, AAV8 and AAV9, are used as case studies. First, high-throughput studies in filter-plate format are performed that allow the rapid and comprehensive study of binding and elution behavior of AAV on different resins, using different buffer systems, pH, salt conditions, and solution additives. Small amounts of separated empty and full AAV capsids are generated by iodixanol gradient centrifugation that allow studying the binding and elution behavior of the two vector species separately in miniaturized format. Process conditions that result in maximum differences in elution behavior between empty and full capsids are then transferred to benchtop chromatography systems that are used to generate calibration data for the estimation of steric mass-action isotherm and mass transport parameters for process simulation. The resulting column models are employed for in-silico process development that serves to enhance understanding of separation constraints and to identify optimized conditions for the removal of empty particles. Finally, optimized separation conditions are verified experimentally. The methodology presented in this work provides a systematic framework that affords mechanistic understanding of the crucial empty/full capsid separation and accelerates the development of a scalable AAV downstream process.

International comparisons of intraocular pressures, as measured by Tono-Pen and Goldmann applanation tonometry, in healthy adults: A meta-analysis.

BACKGROUND: Investigate intraocular pressure (IOP), as measured by Tono-Pen (TP) and Goldmann applanation tonometry (GAT), in healthy adults. Provide an updated synthesis of multinational, primary studies, reported during the 10-year period 2011 to 2021 and offer an evidence-based benchmark, against which IOP can be evaluated across subject variables and pathologies. Three primary research questions are investigated: Is there a statistically significant difference between IOP measured by TP and GAT? If yes, is the difference clinically significant? Is measurement of IOP affected by the country or setting location, in which the measurements are made? METHODS: An aggregate meta-analysis was conducted on 22 primary studies, from 15 different countries. IOP measurements were made from each healthy adult subject, with both the TP and GAT. Primary studies were identified and data extracted according to recommended preferred reporting items for systematic reviews and meta-analysis protocol guidelines. Meta-analysis summary results are reported as the point estimate of the raw mean difference of IOP. RESULTS: Meta-analysis reveals a statistically significant difference in raw mean differences in IOP, when measured by TP and GAT, in the healthy adult population. Tono-Pen IOP measurements are higher than GAT IOP measurements. The point estimate for the summary effect size = -0.73 mm Hg, P = .03. The prediction interval for the true effect size, in 95% of all comparable populations, is -4.03 to 2.58 mm Hg. There is no clinically significance difference in IOP when measured by TP and GAT. Meta-regression analysis reveals statistically significant differences in measurement of IOP by countries, R2 analog = 0.75, P = .001. There is no statistically significant difference in measurement of IOP as a function of measurement location setting, R2 analog = -0.17, P = .65. CONCLUSIONS: IOP measured by TP are marginally higher compared to GAT, in the healthy adult population. However, from a clinical practice perspective, TP and GAT produce similar IOP measurements. There is evidence of significant variabilities in IOP measurements as a function of country. IOP measurements collected in a research laboratory setting are similar to IOP collected in a clinical setting. Results have implications for the primary care physician requiring a portable, inexpensive, reliable, and easily administered instrument to assess IOP.

Demonstration of continuous gradient elution functionality with automated liquid handling systems for high-throughput purification process development.

Various high-throughput systems and strategies are employed by the biopharmaceutical industry for early to late-stage process development for biologics manufacturing. The associated increases to experiment productivity and reduction in material consumption makes high throughput tools integral for bioprocess development. While these high-throughput systems have been successfully leveraged to generate high quality data representative of manufacturing scale processes, their data interpretation often requires complex data transformation and time-intensive system characterization. With respect to high throughput purification development, RoboColumns by Repligen operated on Tecan automated liquid handling systems offer superior performance scalability, but lack an optimized liquid delivery system that is representative of preparative chromatography. Particularly, stock Tecan liquid handling systems lack the capability to provide high-capacity continuous liquid flow and ideal linear gradient chromatography conditions. These limitations impact protein chromatography performance and hinder the application of high-throughput gradient elution experiments. In this work, we describe a Tecan Freedom EVO high-throughput purification tool that provides more continuous liquid delivery enabling continuous gradient elution capability for RoboColumn experiments as demonstrated by generation of highly linear conductivity gradients. Results demonstrate that the tool can provide RoboColumn performance and product quality data that is in agreement with larger, bench scale chromatography formats for two model purification methods. The described gradient purification method also provides more consistent performance between RoboColumns and larger column formats compared to step elution methods using the same optimized Tecan system. Lastly, new insights into the impact of discontinuous flow on RoboColumn elution performance are introduced, which may help further improve application of these data towards bioprocess development.

Endogenous oxytocin levels are associated with facial emotion recognition accuracy but not gaze behavior in individuals with schizophrenia.

OBJECTIVE: Difficulties in social cognition are common in individuals with schizophrenia (SZ) and are not ameliorated by antipsychotic treatment. Intranasal oxytocin (OT) administration has been explored as a potential intervention to improve social cognition; however, results are inconsistent, suggesting potential individual difference variables that may influence treatment response. Less is known about the relationship between endogenous OT and social cognition in SZ, knowledge of which may improve the development of OT-focused therapies. We examined plasma OT in relationship to facial emotion recognition and visual attention to salient facial features in SZ and controls. METHODS: Forty-two individuals with SZ and 23 healthy controls viewed photographs of facial expressions of varying emotional intensity and identified the emotional expression displayed. Participants' gaze behavior during the task was recorded via eye tracking. Plasma oxytocin concentrations were determined by radioimmunoassay. RESULTS: SZ were less accurate than controls at identifying high-intensity fearful facial expressions and low-intensity sad expressions. Lower overall and high-intensity facial emotion recognition accuracy was associated with lower plasma OT levels in SZ but not controls. OT was not associated with visual attention to salient facial features; however, SZ had reduced visual attention to the nose region compared to controls. CONCLUSION: Individual differences in endogenous OT predict facial emotion recognition ability in SZ but are not associated with visual attention to salient facial features. Increased understanding of the association between endogenous OT and social cognitive abilities in SZ may help improve the design and interpretation of OT-focused clinical trials in SZ.

Understanding the effects of system differences for parameter estimation and scale-up of high throughput chromatographic data.

In this paper, we evaluate how employing fraction collection and multistep gradients with RoboColumns® (Repligen, formally Atoll) affects both comparison to benchtop experimental data and column simulation parameter estimation. These operational differences arise from the RoboColumn® system (operated on an automated liquid handling device) requiring offline analysis for determination of elution profiles rather than the continuous in-line UV curves obtained with larger scale systems. In addition, multistep gradients are used to model the smooth linear gradients of larger scale systems because sequential injections are used to provide liquid flow. Comparisons of two sets of column simulations was first carried out to demonstrate that fraction collection reduced the first moments of the elution peaks by 1/2 of the fraction volumes. Additional column simulations determined that the effect of a multistep gradient approximation on retention volume was dependent upon the gradient step length. An empirical transformation was then developed to correct the first moments obtained from gradient experimental data using the RoboColumn® system. These corrected values provided a more direct comparison of the experimental data at different scales and resulted in a significant improvement in agreement with results obtained using a 20 mL benchtop column. Linear steric mass-action (SMA) parameters were then estimated using the corrected values and employed to successfully predict the performance of the benchtop system data. Finally, these parameters were demonstrated to be well suited for modeling the RoboColumn® gradient data when properly accounting for multistep gradients and fraction collection. This work continues previous investigations into understanding system differences associated with robotic liquid handling devices and proposes a methodology for properly accounting for operational differences to predict operation at larger scales using conventional chromatography systems.

Using multimodal chromatography for post-conjugation antibody-drug conjugate purification: A methodology from high throughput screening to in-silico process development.

In this paper, a methodology for the development of a multimodal chromatography process is presented that is aimed at removal of under-conjugated antibody-drug conjugate (ADC) species. Two ADCs are used as case studies: One ADC results from site-directed conjugation to inserted cysteine residues and has a drug-to-antibody ratio (DAR) of two, the other is the product of conjugation to interchain disulfide bonds with a DAR of eight. First, filter plate screening studies are designed for the unconjugated antibody and the ADCs. Different metrics for the analysis of these data sets are presented and discussed. From this analysis, the selected process conditions are then carried out using a benchtop chromatography system to confirm the separations observed in the filter plate studies while simultaneously generating data to estimate steric mass-action isotherm and mass transport parameters for process simulation. This column model is then employed to develop separation processes in-silico for the removal of the unconjugated parent antibody and under-conjugated product variants. The optimized process conditions identified using the model are then verified experimentally. The methodology presented in this work utilizes multimodal chromatography for ADC purification and provides the framework for a streamlined systematic approach to process development.

Endogenous oxytocin levels are associated with impaired social cognition and neurocognition in schizophrenia.

Intranasal administration of the neuropeptide oxytocin (OT) has yielded inconsistent effects on social cognition and general cognition in individuals with schizophrenia (SZ). Few studies have examined whether endogenous peripheral OT levels are also associated with social and general cognition in SZ. The current study examined whether plasma OT levels are associated with performance on a higher-order social cognition measure (i.e., a task that requires inferential processes and knowledge not directly presented in social stimuli), as well as domains of general cognition. Participants included 30 individuals with SZ and 21 demographically matched healthy controls (CN). The MATRICS Consensus Cognitive Battery was administered to assess neuropsychological impairment in relation to 7 domains (processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving, and social cognition). Plasma OT levels were measured via radioimmunoassay. SZ had significantly lower endogenous OT levels and poorer MCCB performance on all 7 domains than CN. In CN and SZ, lower endogenous OT was associated with poorer social cognition. In SZ, lower endogenous OT was also associated with poorer processing speed and working memory. The significant association between OT and social cognition in both CN and SZ highlights the importance of endogenous OT levels as a biological predictor of social cognition, irrespective of clinical status. Significant associations between plasma OT and general neurocognition may reflect either an anxiolytic effect of plasma OT that results in better neurocognitive performance, or OT's action on dopamine and enhancement of dopamine tone that results in improved cognition.

Antidiuretic hormone release associated with increased intracranial pressure independent of plasma osmolality.

OBJECTIVE: Introduce and evaluate a new model which explains the release of brain antidiuretic hormone (ADH) independent of plasma osmolality. METHODS: Systematic review and critical analysis of the professional literature. RESULTS: Primary electronic database searches using key terms revealed 57,432 hits. Secondary searches with application of specific inclusion and exclusion criteria and manual inspection for completeness reduced the total number of studies to fourteen (N = 14). Twelve (N = 12) studies investigated human subjects in the hospital settings, and two (N = 2) studies investigated animals (rhesus monkeys and dog) under invasive experimental conditions. All fourteen studies included direct or indirect indicators of intracranial pressure (ICP), measurements of plasma ADH, and plasma osmolality or urine osmolality. Findings, in brief, reveal a stable and positive association between increased intracranial pressure (ICP) and increased ADH release, in patients with low or normal blood osmolality. Findings are reliable and reproducible across human and animal populations. CONCLUSIONS: Findings support the proposed model, which explains increase secretion of brain ADH when plasma osmolality is low or within normal limits. Mechanical pressures exerted on hypothalamic nuclei, especially paraventricular and supra-optic nuclei, as a consequence of increased intracranial pressure, produce release of ADH, independent of plasma osmolality. The mechanical pressure model explains release of ADH previously unexplained by traditional plasma osmolality models. Findings have important clinical implications for the medical and surgical management of patients.

Anhedonia reflects impairment in making relative value judgments between positive and neutral stimuli in schizophrenia.

Anhedonia (i.e., diminished capacity to experience pleasure) has traditionally been viewed as a core symptom of schizophrenia (SZ). However, modern laboratory-based studies suggest that this definition may be incorrect, as hedonic capacity may be intact. Alternative conceptualizations have proposed that anhedonia may reflect an impairment in generating mental representations of affective value that are needed to guide decision-making and initiate motivated behavior. The current study evaluated this hypothesis in 42 outpatients with SZ and 19 healthy controls (CN) who completed two tasks: (a) an emotional experience task that required them to indicate how positive, negative, and calm/excited they felt in response to a single emotional or neutral photograph; (b) a relative value judgment task where they selected which of 2 photographs they preferred. Results indicated that SZ and CN reported similar levels of positive emotion and arousal in response to emotional and neutral stimuli; however, SZ reported higher negative affect for neutral and pleasant stimuli than CN. In the relative value judgment task, CN displayed clear preference for stimuli differing in valence; however, SZ showed less distinct preferences for positive over neutral stimuli. Findings suggest that although in-the-moment experiences of positive emotion to singular stimuli may be intact in SZ, the ability to make relative value judgments that are needed to guide decision-making is impaired. Original conceptualizations of anhedonia as a diminished capacity for pleasure in SZ may be inaccurate; anhedonia may more accurately reflect a deficit in relative value judgment that results from impaired value representation.

Bioassay-Guided Isolation of Antioxidant and Cytoprotective Constituents from a Maqui Berry (Aristotelia chilensis) Dietary Supplement Ingredient As Markers for Qualitative and Quantitative Analysis.

Bioassay-guided phytochemical investigation of a commercially available maqui berry (Aristotelia chilensis) extract used in botanical dietary supplement products led to the isolation of 16 compounds, including one phenolic molecule, 1, discovered for the first time from a natural source, along with several known compounds, 2-16, including three substances not reported previously in A. chilensis, 2, 14, and 15. Each isolate was characterized by detailed analysis of NMR spectroscopic and HRESIMS data and tested for their in vitro hydroxyl radical scavenging and quinone-reductase inducing biological activities. A sensitive and accurate LC-DAD-MS method for the quantitative determination of the occurrence of six bioactive compounds, 6, 7, 10-12, and 14, was developed and validated using maqui berry isolates purified in the course of this study as authentic standards. The method presented can be utilized for dereplication efforts in future natural product research projects or to evaluate chemical markers for quality assurance and batch-to-batch standardization of this botanical dietary supplement component.

Understanding operational system differences for transfer of miniaturized chromatography column data using simulations.

In this paper, a simulation tool was employed to identify and appropriately incorporate differences between MiniColumns and benchtop column systems. It was first demonstrated that including multi-step gradients and fraction collection into the simulations resulted in improved agreement between simulated and experimental linear gradient profiles as well as calculated first moments in the MiniColumn experiments. Step elution experiments of binary mixtures (a monoclonal antibody and one of three model proteins) were then carried out to examine comparability of the MiniColumns to the benchtop system. Although the peak shapes were qualitatively similar, peak elution began earlier in the MiniColumn system while improved separation was observed between overlapping peaks using the benchtop format. Simulations were then carried out to demonstrate that increased dispersion of the eluent breakthrough in the benchtop system could readily explain these observed differences. Importantly, by incorporating these system differences into the simulations, we were able to predict benchtop step elution performance using the parameters solely obtained from the MiniColumns. The findings presented in this paper illustrate that the appropriate consideration of system differences can facilitate the implementation of miniature chromatography columns as scale-down models for bioprocess development.

Synergistic in vitro antioxidant activity and observational clinical trial of F105, a phytochemical formulation including Citrus bergamia, in subjects with moderate cardiometabolic risk factors.

We examined the clinical safety and efficacy of F105 in 11 subjects with moderate dyslipidemia. F105 is a combination of bergamot fruit extract (Citrus bergamia, BFE) and 9 phytoextracts selected for their ability to improve the antioxidant and anti-inflammatory activity of BFE. In vitro F105 exhibited a synergistic inhibition of oxygen radical absorbing capacity, peroxynitrite formation, and myeloperoxidase activity. Following 12 weeks of F105 daily, no treatment-related adverse events or changes in body mass were seen. Statistically significant changes were noted in total cholesterol (-7.3%), LDL-cholesterol (-10%), non-HDL cholesterol (-7.1%), cholesterol/HDL (-26%), and apolipoprotein B (-2.8%). A post hoc analysis of 8 subjects with HbA1c > 5.4 and HOMA-IR score > 2 or elevated triglycerides revealed additional statistically significant changes in addition to those previously observed in all subjects including triglycerides (-27%), oxLDL (-19%), LDL/HDL (-25%), triglycerides/HDL (-27%), oxLDL/HDL (-25%), and PAI-1 (-37%). A follow-up case report of a 70-year-old female patient, nonresponsive to statin therapy and placed on F105 daily, demonstrated improved cardiometabolic variables over 12 weeks similar to the subgroup. In summary, F105 was clinically well-tolerated and effective for ameliorating dyslipidemia in subjects with moderate cardiometabolic risk factors, particularly in the individuals with HbA1c > 5.4%.

LC-MS-Based Quality Assessment of a Traditional Chinese Medicine YANG XIN Formulation.

YANG XIN is a traditional Chinese medicine formulation used for nervous fatigue and consists of a proprietary blend of concentrated extracts from 18 plant ingredients. The 18 constituent plant ingredients, YANG XIN capsules, and formulations 2014-005_1 A and 1B were extracted by consecutive 24-hour macerations with dichloromethane followed by methanol. Metabolite separation was carried out through LC-MS in 40 minutes. Data acquisitions for qualitative and quantitative analyses of the samples were collected under (±) ESI modes and (+) APCI mode using full spectrum scan analysis.A total of 18 analytical markers were identified by LC-MS for YANG XIN formulations based on accurate mass measurements, molecular formula, double bond equivalent, MFG score, and error (ppm) of the measurement. Aditionally, a comparison of the data with previously reported results for the compounds, followed by identity confirmation with standard compounds, was performed. Seventeen analytical markers representing 17 plant ingredients in the different YANG XIN formulations were quantified for the first time. The YANG XIN capsules and the 2014-005_1B formulation were similar to each other and different from the 2014-005_1 A formulation based on the fact that both YANG XIN capsules and the 2014-005_1B formulation contain the same analytical markers. This method provides good linearity (r(2) > 0.9945), intraday precision (R. S. D. < 3.9 %), interday precision (R. S. D. < 5.6 %), accuracy (99.2-101 %), recovery (145.7 %), limit of detection (0.0011-0.0732 µg/mL), and limit of quantitation (0.0038-0.2441 µg/mL).

Hyperdeactivation of the Default Mode Network in People With Schizophrenia When Focusing Attention in Space.

When studying selective attention in people with schizophrenia (PSZ), a counterintuitive but replicated finding has been that PSZ display larger performance benefits than healthy control subjects (HCS) by cues that predicts the location of a target stimulus relative to non-predictive cues. Possible explanations are that PSZ hyperfocus attention in response to predictive cues, or that an inability to maintain a broad attentional window impairs performance when the cue is non-predictive. Over-recruitment of regions involved in top-down focusing of spatial attention in response to predictive cues would support the former possibility, and an inappropriate recruitment of these regions in response to non-predictive cues the latter. We probed regions of the dorsal attention network while PSZ (N = 20) and HCS (N = 20) performed a visuospatial attention task. A central cue either predicted at which of 4 peripheral locations a target signal would appear, or it gave no information about the target location. As observed previously, PSZ displayed a larger reaction time difference between predictive and non-predictive cue trials than HCS. Activity in frontoparietal and occipital regions was greater for predictive than non-predictive cues. This effect was almost identical between PSZ and HCS. There was no sign of over-recruitment when the cue was predictive, or of inappropriate recruitment when the cue was non-predictive. However, PSZ differed from HCS in their cue-dependent deactivation of the default mode network. Unexpectedly, PSZ displayed significantly greater deactivation than HCS in predictive cue trials, which may reflect a tendency to expend more processing resources when focusing attention in space.

Use of MiniColumns for linear isotherm parameter estimation and prediction of benchtop column performance.

In this paper, a comparison between experimental chromatography data and column simulations is carried out to determine the efficacy of using miniaturized chromatography columns (MiniColumns) for both column modeling parameter estimation and process development. Normalization of the data with respect to column volumes along with appropriate translations to account for system differences is shown to result in comparability of the experimental data for the MiniColumn and benchtop systems. A parameter estimation protocol is then employed to determine the linear steric mass-action (SMA) isotherm and lumped mass transport parameters for two cation exchange resins. The models are then validated and simulations using different parameter sets from the MiniColumn and benchtop systems are shown to result in similar predicted chromatography profiles and calculated retention volumes. The parameters generated from the MiniColumn system are demonstrated to be well suited for predicting experimental data from the benchtop system. These simulation results, the ability to operate MiniColumns in parallel, and the significantly lower material requirements per experiment support an industry trend toward increased usage of miniaturized chromatography columns as a scale-down model for process development.

Computer-Assisted Structure Elucidation of Black Chokeberry (Aronia melanocarpa) Fruit Juice Isolates with a New Fused Pentacyclic Flavonoid Skeleton.

Melanodiol 4″-O-protocatechuate (1) and melanodiol (2) represent novel flavonoid derivatives isolated from a botanical dietary supplement ingredient, dried black chokeberry (Aronia melanocarpa) fruit juice. These noncrystalline compounds possess an unprecedented fused pentacyclic core with two contiguous hemiketals. Due to having significant hydrogen deficiency indices, their structures were determined using computer-assisted structure elucidation software. The in vitro hydroxyl radical-scavenging and quinone reductase-inducing activity of each compound are reported, and a plausible biogenetic scheme is proposed.

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

OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Plasma oxytocin levels predict social cue recognition in individuals with schizophrenia.

Lower endogenous levels of the neuropeptide oxytocin may be an important biological predictor of social cognition impairments in schizophrenia (SZ). Prior studies have demonstrated that lower-level social cognitive processes (e.g., facial affect perception) are significantly associated with reduced plasma oxytocin levels in SZ; however, it is unclear whether higher-level social cognition, which requires inferential processes and knowledge not directly presented in the stimulus, is associated with endogenous oxytocin. The current study explored the association between endogenous oxytocin levels and lower- and higher-level social cognition in 40 individuals diagnosed with SZ and 22 demographically matched healthy controls (CN). All participants received the Social Cue Recognition Test (SCRT), which presents participants with videotaped interpersonal vignettes and subsequent true/false questions related to concrete or abstract aspects of social interactions in the vignettes. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ and CN did not differ on SCRT hits, but SZ had more false positives and lower sensitivity scores than CN. Higher plasma oxytocin levels were associated with better sensitivity scores for abstract items in CN and fewer false positives for concrete items in individuals with SZ. Findings indicate that endogenous oxytocin levels predict accurate encoding of lower-level socially relevant information in SZ.

Endogenous oxytocin levels are associated with the perception of emotion in dynamic body expressions in schizophrenia.

Lower endogenous oxytocin levels have been associated with impaired social cognition in schizophrenia, particularly facial affect identification. Little is known about the relationship between oxytocin and other forms of emotion perception. In the current study, 41 individuals with schizophrenia (SZ) and 22 demographically matched healthy controls (CN) completed a forced-choice affective body expression classification task. Stimuli included dynamic videos of male and female actors portraying 4 discrete emotions: happiness, sadness, anger, and neutral. Plasma oxytocin levels were determined via radioimmunoassay. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ were also less accurate at identifying expressions of happiness and sadness; however, there were no group differences for anger or neutral stimuli. A group×sex interaction was also present, such that female CN were more accurate than male CN, whereas male SZ were more accurate than female SZ. Higher endogenous oxytocin levels were associated with better total recognition in both SZ and CN; this association was specific to females in SZ. Findings indicate that sex plays an important role in identifying emotional expressions in body gestures in SZ, and that individual differences in endogenous oxytocin predict emotion perception accuracy.

Plasma oxytocin levels predict olfactory identification and negative symptoms in individuals with schizophrenia.

Basic neuroscience research provides strong evidence for the role of oxytocin in olfactory processes and social affiliation in rodents. Given prior indication of olfactory impairments that are linked to greater severity of asociality in schizophrenia, we examined the association between plasma oxytocin levels and measures of olfaction and social outcome in a sample of outpatients with schizophrenia (n=39) and demographically matched healthy controls (n=21). Participants completed the 40-item University of Pennsylvania Smell Identification Test (UPSIT), and rated each odor for how positive and how negative it made them feel. Results indicated that individuals with schizophrenia had higher plasma oxytocin levels and lower overall accuracy for UPSIT items than controls. Individuals with schizophrenia also reported experiencing more negative emotionality than controls in response to the olfactory stimuli. Lower plasma oxytocin levels were associated with poorer accuracy for pleasant and unpleasant odors and greater severity of asociality in individuals with schizophrenia. These findings suggest that endogenous oxytocin levels may be an important predictor of olfactory identification deficits and negative symptoms in schizophrenia.