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Bipolar disorder (BD) and schizophrenia (SCZ) are debilitating disorders that are associated with significant burden and reduced quality of life. In this study, we leveraged microarray data derived from both the Illumina HumanMethylation450 platform to investigate the epigenetic age of individuals with SCZ (n = 40), BD (n = 40), and healthy controls (n = 38), across five epigenetic clocks. Various statistical metrics were used to identify discrepancies between epigenetic and chronological age across the three groups. We observed a significant increase in epigenetic age compared to chronological age in the BD group. Mean epigenetic age acceleration was also higher in individuals with bipolar disorder compared to healthy controls across four different epigenetic clocks (p0.05). Despite the study's relatively small sample size, these findings suggest that both individuals with bipolar disorder and schizophrenia may have epigenetic markers associated with a premature aging phenotype, which could be suggestive of negative outcomes associated with the disease. In our future studies, we hope to elucidate this finding further by elucidating the precise link between epigenetic age, symptomatology and disease progression.

While it is well established that individuals with schizophrenia exhibit a wide range of neurocognitive deficits, there is significant heterogeneity in this regard. Impairments in verbal fluency appear to present consistently across most individuals with the illness. The present study examined the stability of verbal fluency abilities in chronic schizophrenia longitudinally. It was hypothesized that semantic but not phonemic verbal fluency performance would be stable over one year. Data was extracted from a larger study that followed 53 outpatients (70% male; mean age = 39.2 years) diagnosed with schizophrenia or schizoaffective disorder. At each testing interval (baseline, 6, and 12 months), the Brief Assessment of Cognition in Schizophrenia was administered, which included phonemic (i.e., F, S) and semantic (i.e., animals) verbal fluency tasks. No significant differences were found across time points for semantic and phonemic verbal fluency with respect to mean number of words generated, clustering, and switching. The findings provide evidence of stability in semantic and phonemic verbal fluency abilities in chronic schizophrenia. Moving forward, it would be valuable to examine verbal fluency performance longitudinally across multiple stages of illness (i.e., clinically high-risk to chronic schizophrenia).

Cognitive biases may contribute to the formation and maintenance of positive symptoms in patients with schizophrenia. However, cognitive reflection (i.e., the ability to use analytical thinking to override intuitive responses) has not been explicitly examined in schizophrenia patients using the cognitive reflection test (CRT). Using the CRT, we examined the degree of analytical and intuitive reasoning employed during problem solving in patients with schizophrenia versus healthy controls. Fifty-eight outpatients with schizophrenia and fifty-eight age- and sex-matched healthy controls (18-35 years of age) participated in this study. In addition to CRT performance, neurocognition, apathy, impulsivity, depression, insight, and clinical symptoms were evaluated. Patients with schizophrenia produced significantly fewer analytical responses (U = 1167.00, p0.05) and more intuitive responses (U = 1273.50, p0.05) compared to healthy controls. Patients without significant cognitive impairment also produced fewer analytical responses compared to controls (U = 894.50, p0.05). Among patients, analytical thinking was positively correlated with working memory (r = 0.27, p0.05), and affective symptoms (r = 0.31, p0.05). Analytical reasoning was not significantly correlated with positive symptoms, avolition, or impulsivity. Patients with schizophrenia demonstrate less analytical and more intuitive reasoning while problem solving compared to healthy controls. This reduction in cognitive reflection is not significantly explained by global cognitive impairment or motivational deficits.

While moderate to vigorous physical activity may be one method of addressing common physical morbidities in schizophrenia, reducing sedentary time may be a low intensity adjunct. In order to determine whether sedentary behaviour is associated with health outcomes, valid and reliable tools for assessing sedentary time are necessary. In order to characterize the validity and reliability of the International Physical Activity Questionnaire (IPAQ) for assessing sitting (sedentary) time, participants completed the IPAQ at baseline and 4 weeks later and wore accelerometers for 7 days before the final assessment. Bland-Altman analyses and intraclass correlation coefficients (ICC) were used to compare agreement between measurements. One-hundred thirteen individuals completed the study. Mean difference between the IPAQ and accelerometer was 26.8 min (95% Limits of Agreement: −458.7–512.3) and ICCA,1 was 0.23 (95% CI: 0.06–0.39). Week 1 and Week 4 administrations of the IPAQ differed by an average of 26.6 min, (95% Limits of Agreement: −510.9–564.2) and ICCA,1 was 0.41 (95% CI: 0.21–0.59). The “minutes” of sitting reported by the IPAQ do not reflect objective sedentary behaviour measurements and this current measure may be unsuitable for the population level assessment of sitting time among individuals with schizophrenia.

Approximately one-third of patients with schizophrenia have treatment-resistant schizophrenia (TR-SCZ), which is a condition characterized by suboptimal response to antipsychotics other than clozapine. Importantly, treatment with clozapine-the only antipsychotic with an indication for TR-SCZ-is often delayed, which could contribute to negative outcomes. Given that the specific impact of delay in clozapine initiation is not well understood, we aimed to conduct a systematic search of the Ovid Medline® database to identify English language publications exploring the impact of delay in clozapine initiation on treatment outcomes in patients with TR-SCZ. Additionally, clinico-demographic factors associated with clozapine delay were examined. Our search identified four retrospective studies that showed an association between longer delay in clozapine initiation and poorer treatment outcomes, even after including covariates, such as age, sex, and duration of illness. In addition, we found six studies that showed an association between age and clozapine delay, but results with regard to other clinico-demographic variables were inconsistent. Overall, the available literature reveals a possible link between delay in clozapine use and poorer treatment outcomes in patients with TR-SCZ. However, given the relatively small number of studies on this clinically important topic, future research is warranted to draw more definitive conclusions.

The aim of this study was to develop self-report and clinician-rated versions of an insight scale that would be easy to administer, sensitive to small changes, and inclusive of the core dimensions of clinical insight into psychosis. Ten-item self-report (VAGUS-SR) and five-item clinician-rated (VAGUS-CR) scales were designed to measure the dimensions of insight into psychosis and evaluated in 215 and 140 participants, respectively (www.vagusonline.com). Tests of reliability and validity were performed. Both the VAGUS-SR and VAGUS-CR showed good internal consistency and reliability. They demonstrated good convergent and discriminant validity. Both versions were strongly correlated with one another and with the Schedule for the Assessment of Insight and Birchwood Insight Scale. Exploratory factor analyses identified three possible latent components of insight. The VAGUS-CR and VAGUS-SR are valid, reliable and easy to administer. They are build on previous insight scales with separate clinician-rated and self-report versions. The VAGUS-SR exhibited a multidimensional factor structure. Using a 10-point Likert scale for each item, the VAGUS has the capacity to detect small, temporally sensitive changes in insight, which is essential for intervention studies with neurostimulation or rapidly acting medications.

Amotivation and reduced goal-directed activity engagement are prominent features of schizophrenia. Previous investigations of patients' activities have relied on accounts of daily living activities, rather than objective measures. This study used wireless motion capture to objectively evaluate activity preference when individuals are provided an explicit choice between an active versus passive engagement option. Twenty outpatients with schizophrenia and twenty matched healthy controls completed the Activity Preference Task, in which participants play a motion-based game (active) or watch a film (passive), and were administered clinical and cognitive assessments. Schizophrenia participants' duration, intensity, and persistence of active engagement were associated with apathy and community functioning. No group differences emerged from comparisons of task measures; however, exploratory cluster analysis identified a distinct subgroup of schizophrenia patients with reduced engagement and increased apathy compared to other patients and controls. The Task provides a means of quantifying activity engagement, which may be particularly valuable given the lack of objective measures for intrinsically motivated behaviours. Our initial findings suggest that schizophrenia patients as a group are equally inclined as healthy individuals towards actively engaging activities when presented an explicit choice, but such provision may be insufficient for initiation and maintenance of functional behaviours among amotivated patients.

Anhedonia has traditionally been considered a characteristic feature of schizophrenia, but the true nature of this deficit remains elusive. This study sought to investigate consummatory and anticipatory pleasure as it relates to motivation deficits. Eighty-four outpatients with schizophrenia and 81 healthy controls were administered the Temporal Experience of Pleasure Scale (TEPS), as well as a battery of clinical and cognitive assessments. Multivariate analyses of variance were used to examine the experience of pleasure as a function of diagnosis, and across levels of motivation deficits (i.e. low vs. moderate. vs. high) in schizophrenia. Hierarchical regression analyses were also conducted to evaluate the predictive value of amotivation in relation to the TEPS. There were no significant differences between schizophrenia and healthy control groups for either consummatory or anticipatory pleasure. Within the schizophrenia patients, only those with high levels of amotivation were significantly impaired in consummatory and anticipatory pleasure compared to low and moderate groups, and compared to healthy controls. Further, our results revealed that amotivation significantly predicts both consummatory and anticipatory pleasure, with no independent contribution of group. Utilizing study samples with a wide range of motivation deficits and incorporating objective paradigms may provide a more comprehensive understanding of hedonic deficits.

Cognitive impairment represents a significant source of disability among individuals with schizophrenia. Therefore, the aim of this study was to investigate, at a proof-of-concept level, whether one single bout of exercise can improve executive function among these individuals. In this within-participant, counterbalanced experiment, participants with schizophrenia ( n =36) completed two sessions (cycling at moderate-intensity and passively sitting) for 20 min, with a one-week washout period between the two sessions. Participants completed the Wisconsin Card Sorting Test (WCST) before and after each session to measure changes in executive function. The inclusion of both sessions completed by each participant in the analyses revealed a significant carryover effect. Consequently, only the WCST scores from the first session completed by each participant was analyzed. There was a significant time by session interaction effect for non-perseverative errors. Post-hoc Tukey's HSD contrasts revealed a significant reduction in non-perseverative errors in the exercise group that was of moderate-to-large effect. Furthermore, there was also a moderate between-group difference at post-testing. Therefore, an acute bout of exercise can improve performance on an executive function task in individuals with schizophrenia. Specifically, the reduction in non-perseverative errors on the WCST may reflect improved attention, inhibition and overall working memory.

This study aimed to assess patient's capacity to perform a patient-reported outcome (PRO) measure (i.e., a self-rating scale) and examine its relationship with clinical characteristics including cognition. Fifty patients with schizophrenia were asked to rate the Subjective Well-being under Neuroleptics scale – Short form (SWNS) twice; the second rating was started immediately after they completed the first to minimize the gap between ratings. At the same time, the Positive and Negative Symptoms Scale (PANSS) and Brief Neurocognitive Assessment (BNA) were administered. The correlations between the two ratings for the SWNS total and each item scores were high ( r s =0.94 and r s =0.60–0.84, respectively); however, for 16 (80%) of 20 items, 5 or more patients (i.e., ≥10%) demonstrated a>1 point score difference. There was no significant correlation between the SWNS total score difference and any clinical characteristics including age, education duration, illness duration, antipsychotic dose, psychopathology, and cognition. In contrast, the number of items with a>1 point score difference was significantly correlated with disorganized symptoms and overall severity ( r s =0.29 for both), as well as working memory and global cognition ( r s =−0.41 and r s =−0.40, respectively). These findings suggest that PROs should be interpreted with caution in patients with schizophrenia with prominent disorganization and cognitive impairment.

Sixty-one patients with schizophrenia stably treated with risperidone or olanzapine were randomly assigned to dose-reduction-by-half group or dose maintenance group. Subjective experiences were assessed at baseline and 28 weeks using three different self-rating scales. No significant differences in changes of subjective experiences were observed between the two groups.

In addition to offering many physical health benefits, exercise may help improve mental health among individuals with schizophrenia through regulating affect. Therefore, the purpose of this study is to characterize affective responses experienced before, during and after a 10-min bout of exercise versus passive sitting among individuals with schizophrenia. A randomized crossover design compared affect related to feelings of pleasure and arousal at baseline, 6-min into the task, immediately post-task, and 10min post-task to sitting. Thirty participants enroled in the study; 28 participants completed the study. Separate mixed model analyses of variance were conducted for pleasure and arousal, with test order as the between-subject factor, and time and task as within-subject factors. For pleasure, a significant main effect for time and a time x task interaction effect emerged. Post-hoc Bonferroni corrected t-tests (α=.0125) revealed significant differences between pleasure at baseline and both immediately post-task and 10min post-task. No other main effects or interactions emerged. Individuals with schizophrenia derive acute feelings of pleasure from exercise. Thus, exercise may provide a method of regulating affect to improve mental health. Future studies should examine the links between affective responses to health behaviours such as long-term adherence to exercise within this population.

Negative symptoms are a prominent feature of schizophrenia that are intimately linked to poor outcomes characterizing the illness. One mechanistic model suggests that these symptoms are produced and maintained, at least in part, through maladaptive attitudes. Beyond mechanisms, it remains phenomenologically unclear if these symptoms are particularly distressing. In the present study we examined whether subclinical negative symptoms evaluated in a non-clinical sample of young adults (N=370) were distressful or bothersome to participants and, further, whether these symptoms were associated with dysfunctional attitudes. We found that greater severity of subclinical negative symptoms such as amotivation and anhedonia were associated with higher ratings of distress specifically attributable to these symptoms. This relationship held even after controlling for severity of depressive symptoms. Moreover, greater negative symptom burden was associated with greater endorsement of defeatist performance beliefs. Negative symptoms expressed in the general population were found to be particularly distressing. Maladaptive cognitive schemas are implicated in the expression of these symptoms, as well as the amount of distress these symptoms instil. A greater understanding of the mechanisms underlying negative symptoms, including both neurobiological and cognitive, is needed in order to effectively develop treatment strategies for these disabling symptoms.

NALCN (sodium leak channel, non-selective) is located on chromosome 13q (suggested linkage region for schizophrenia). We analyzed 21 polymorphisms in 464 schizophrenia subjects, 220 controls subjects and 119 small nuclear families. We observed nominal association with rs9518320 and rs9518331, suggesting that NALCN is not related to schizophrenia risk.

Treatment-resistant schizophrenia (TRS) has been defined mainly by severity of (positive) symptoms and response to antipsychotics derived from a relative change in the representative scales (most frequently ≥ 20% decrease in the Positive and Negative Syndrome Scale: PANSS), but these definitions have not necessarily been consistent. Integrating past evidence and real-world practicability, we propose that TRS be defined by at least two failed adequate trials with different antipsychotics (at chlorpromazine-equivalent doses of ≥ 600mg/day for ≥ 6 consecutive weeks) that could be retrospective or preferably include prospective failure to respond to one or more antipsychotic trials. In addition, our proposed criteria require both a score of ≥ 4 on the Clinical Global Impression (CGI)-Severity and a score of ≤ 49 on the Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz) or ≤ 50 on the Global Assessment of Functioning (GAF) scales to define TRS. Once TRS is established, we propose that subsequent treatment response be defined based on a CGI-Change score of ≤ 2, a ≥ 20% decrease on the total PANSS or Brief Psychiatric Rating Scale (BPRS) scores, and an increase of ≥ 20 points on the FACT-Sz or GAF. While these suggestions provide a pragmatic framework for TRS classification, they need to be tested in future trials.

After a 7-day washout period, 16 subjects suffering from unipolar depression were randomly assigned to either desipramine (DMI) or DMI plus propranolol treatment for 21 days. Both groups showed a significant improvement in their scores on the Hamilton Rating Scale for Depression (HRSD) after 21 days of drug treatment. However, there was no significant difference in the improvement in HRSD scores between the two groups. The results of this pilot study support the need to reevaluate the popular belief that propranolol induces or worsens depression.