Search

Background Mismatch negativity (MMN) amplitude is reduced in psychotic disorders and associated with symptoms and functioning. Due to these robust associations, it is often considered a biomarker for psychotic illness. The relationship between MMN and clinical outcomes has been examined well in early onset psychotic illness; however, its stability and predictive utility in chronic samples are not clear. Method We examined the five-year stability of MMN amplitude over two timepoints in individuals with established psychotic disorders (cases; N = 132) and never-psychotic participants (NP; N = 170), as well as longitudinal associations with clinical symptoms and functioning. Results MMN amplitude exhibited good temporal stability (cases, r = 0.53; never-psychotic, r = 0.52). In cases, structural equation models revealed MMN amplitude to be a significant predictor of worsening auditory hallucinations (β = 0.19), everyday functioning (β = −0.13), and illness severity (β = −0.12) at follow-up. Meanwhile, initial IQ (β = −0.24), negative symptoms (β = 0.23), and illness severity (β = −0.16) were significant predictors of worsening MMN amplitude five years later. Conclusions These results imply that MMN measures a neural deficit that is reasonably stable up to five years. Results support disordered cognition and negative symptoms as preceding reduced MMN, which then may operate as a mechanism driving reductions in everyday functioning and the worsening of auditory hallucinations in chronic psychotic disorders. This pattern may inform models of illness course, clarifying the relationships amongst biological mechanisms of predictive processing and clinical deficits in chronic psychosis and allowing us to better understand the mechanisms driving such impairments over time.

Delusions are aberrant beliefs that are maintained in the face of conflicting evidence. Promising mechanistic frameworks are suggested by cognitive control theory which delineates detection and resolution stages of conflict processing and an augmented dual-process framework which proposes acquiescence to intuitive beliefs despite awareness that they conflict with rationality. We measured intuitive processes using one-shot decision-making and analytic processes using cognitive reflection (CRT) and Stroop tasks. Higher intuitive strength and lower CRT/Stroop conflict resolution was associated with increased acquiescence. Importantly, those less prone to delusions were more likely to override a strong irrational intuition as their analytic strength (on CRT and Stroop) increased; however, in those high on delusion-proneness, analytic strength predicted an increased likelihood of acquiescing to intuition. These findings highlight an interactive role of intuitive and analytic processes such that those prone to delusions may tend to rally cognitive resources to rationalize their intuitions.

Recent work has shown that emotional arousal influences decision-making in sacrificial moral dilemmas, with heightened levels of arousal associated with increased aversion to committing moral transgressions to maximize utilitarian outcomes. Patients with anxiety disorders experience pathologically heightened states of arousal and thus may be expected to exhibit reduced utilitarian responding on such dilemmas. Extant evidence has been mixed, however, regarding whether anxious patients differ in their moral decisions from controls, and no study has conducted a careful examination of emotions experienced during decision-making. We administered sacrificial moral dilemmas to a cohort of 95 patients from across the spectrum of anxiety disorders to test whether they differed from matched controls on a) utilitarian decision-making, and b) ratings of experienced emotion during the moral deliberative process. Results showed no group differences between patients and controls on endorsement of utilitarian sacrificial action or on reported experience of emotionality during the experiment. Additionally, exploratory analysis revealed that specific emotions were correlated with utilitarian judgments. These results are in line with the Dual Process Theory model’s prediction that decreased utilitarian responding will be concomitant with an increased emotional arousal. Our findings support past work indicating that moral cognition is intact in anxiety disorders despite the emotional dysregulation characteristic of anxious psychopathology. Future work would benefit from the use of process-dissociation techniques to further clarify whether emotional or cognitive processes may differ in anxiety disorders during moral cognition.

Hallucinations are characterized by disturbances of perceptual processes involved in decision-making about environmental stimuli. Here, we examine whether cognitive and computational processes by which sensory information is integrated may offer insight into the perceptual mechanisms of hallucinatory symptoms. We used a multi-element perceptual averaging task in which observers made dichotomous judgments about the “average color” (red or blue) of an array of stimuli in trials that varied in the strength (mean) and reliability (variance) of the decision-relevant perceptual evidence. Generally, observers excluded or down-weighted extreme (outlying) perceptual evidence akin to a statistician excluding outlying data points; however, individuals prone to hallucinations afforded more weight to more extreme or untrustworthy evidence. Computational modeling showed that individuals prone to hallucinations tended not to use the optimal model in which evidence is integrated as a function of the log odds of each perceptual option leading to “robust averaging”. Finally, observers generally adapted to trials with unreliable evidence by increasingly downweighting extreme evidence, but the weighting strategy in hallucination prone individuals remained insensitive to the reliability of evidence. By showing that hallucination proneness is associated with reduced attenuation of untrustworthy evidence in perceptual decision-making, our findings suggest a novel perceptual mechanism underlying hallucinations. Our findings also provide support for the view that hallucination-proneness relates to alterations in the perceptual systems that track statistical regularities in environmental stimuli.

Data support the notion that 40–60% of patients with bipolar disorder (BD) have neurocognitive deficits. It is increasingly accepted that functioning in BD is negatively impacted by these deficits, yet they have not been a successful target for treatment. The biomarkers that predict cognitive deficits in BD are largely unknown, however recent evidence suggests that inflammation may be associated with poorer cognitive outcomes in BD. We measured C-reactive protein (CRP), a marker of systemic inflammation and risk of inflammatory disease, in 222 euthymic BD patients and 52 healthy controls. Within the patient sample, using multivariate analyses of covariance (MANCOVA) we compared cognitive performance of those with high CRP (≥5 mg/L) versus the remaining subjects (

Background Childhood adversity has been shown to exert profound effects on basic psychological processes well into adulthood. Some of these processes, such as those related to reward and emotion, play critical roles in moral decision-making. As a population with high rates of childhood trauma as well as heterogenous clinical presentation, individuals with bipolar disorder (BD) constitute an enriched group in which to examine the correlates of trauma and other clinical variables with moral cognition. Methods 62 euthymic BD patients and 27 controls responded to moral dilemma scenarios and completed the Childhood Trauma Questionnaire. Results Results revealed a main effect of diagnosis on moral decision-making only when both personal force and an intention were required, indicating a more utilitarian style in BD patients relative to controls. Several interesting patterns also emerged regardless of diagnostic status. Higher ratings of physical neglect were significantly associated with higher ratings of acceptability (a utilitarian tendency) across dilemma types, and a similar pattern was observed at the trend level for experiences of emotional neglect. Significant main effects on moral decision-making were also observed for sex, illness duration, and history of psychotic features in the BD sample. Limitations The present study is limited by the self-reported nature of the CTQ and by the small number of trials of moral dilemmas. In addition, practical and clinical implications of the moral dilemmas paradigm are limited due to its abstract nature. Conclusions Our results indicate that certain clinical features as well as childhood maltreatment (in particular neglect) may significantly impact moral decision making in adult life. Surprisingly, childhood trauma was associated with a more utilitarian style, which is in the opposite direction from previous effects shown in PTSD. Although speculative, our results suggest that there may be a protective quality associated with utilitarian moral decision-making tendencies.

Negative symptoms are among the greatest sources of functional impairment for individuals with schizophrenia, yet their mechanisms remain poorly understood. Olfactory impairment is associated with negative symptoms. The processing of pleasant olfactory stimuli is subserved by reward-related neural circuitry while unpleasant olfactory processing is subserved by emotion-related neural circuitry, suggesting that these two odor dimensions may offer a window into differential mechanisms of negative symptoms. We examined whether pleasant and unpleasant odor identification bears differential relationships with avolition and inexpressivity dimensions of negative symptoms, whether these relationships are transdiagnostic, and whether pleasant and unpleasant odor processing also relate differently to other domains of functioning in a sample of individuals diagnosed with schizophrenia (N = 54), other psychotic disorders (N = 65), and never-psychotic adults (N = 160). Hierarchical regressions showed that pleasant odor identification was uniquely associated with avolition, while unpleasant odor identification was uniquely associated with inexpressivity. These relationships were largely transdiagnostic across groups. Additionally, pleasant and unpleasant odor identification displayed signs of specificity with other functional and cognitive measures. These results align with past work suggesting dissociable pathomechanisms of negative symptoms and provide a potential avenue for future work using valence-specific olfactory dysfunction as a semi-objective and low-cost marker for understanding and predicting the severity of specific negative symptom profiles.

Mismatch negativity (MMN) amplitude is reliably reduced in psychotic disorders. While several studies have examined this effect in first-degree relatives of individuals with schizophrenia, few have sought to quantify deficits in relatives of individuals with other psychotic disorders. While some conclude that, compared to healthy subjects, first-degree relatives of schizophrenia show reduced MMN, others contradict this finding. Furthermore, though MMN is often shown to be associated with cognitive impairments and clinical symptoms in psychotic disorders, to our knowledge no studies have sought to fully examine these relationships in studies of first-degree relatives. The present study sought to clarify the extent of MMN amplitude reductions in a large sample of siblings of individuals with diverse psychotic disorders (n = 67), compared to probands with psychosis (n = 221) and never psychotic comparison subjects (n = 251). We further examined associations of MMN amplitude with cognition and schizotypal symptoms across these groups. We found that MMN amplitude was intact in siblings compared to probands. MMN amplitude was associated with cognition and schizotypal symptoms dimensionally across levels of familial risk. The present results imply that MMN reductions do not reflect genetic risk for psychotic disorders per se, and instead emerge as a result of, or in conjunction with, clinical features associated with psychosis. Such findings carry important implications for the utility of MMN amplitude as an indicator of inherited risk, and suggest that this component may be best conceptualized as an endophenotype for clinical symptoms and cognitive impairments, rather than risk for psychosis per se.

The novel coronavirus COVID-19 pandemic is associated with elevated rates of anxiety and relatively lower compliance with public health guidelines in younger adults. To develop strategies for reducing anxiety and increasing adherence with health guidelines, it is important to understand the factors that contribute to anxiety and health compliance in the context of COVID-19. Earlier research has shown that greater perceived risk of negative events and their costs are associated with increased anxiety and compliance with health behaviors, but it is unclear what role they play in a novel pandemic surrounded by uncertainty. In the present study we measured (1) perceived risk as the self-reported probability of being infected and experiencing serious symptoms due to COVID-19 and (2) perceived cost as financial, real-world, physical, social, and emotional consequences of being infected with COVID-19. Worry was assessed using the Penn State Worry Questionnaire (PWSQ) and health compliance was measured as endorsement of the World Health Organization (WHO) health directives for COVID-19. Our results showed that greater perceived risk and costs of contracting the COVID-19 virus were associated with greater worry and while only costs were associated with greater compliance with health behaviors. Neither self-reported worry nor its interaction with cost estimates was associated with increased engagement in health behaviors. Our results provide important insight into decision making mechanisms involved in both increased anxiety and health compliance in COVID-19 and have implications for developing psychoeducational and psychotherapeutic strategies to target both domains.

Background: Mismatch negativity (MMN) amplitude is reliably reduced in psychotic disorders. While several studies have examined this effect in first-degree relatives of individuals with schizophrenia, few have sought to quantify deficits in relatives of individuals with other psychotic disorders. While some studies conclude that, compared to healthy subjects, first-degree relatives of schizophrenia show reduced MMN, others contradict this finding, a discrepancy which extends to two recent meta-analyses. Furthermore, though MMN is often shown to be associated with cognitive impairments and clinical symptoms in psychotic disorders, to our knowledge no studies have sought to examine these relationships in studies of first-degree relatives. Method: The present study sought to clarify the extent of MMN amplitude reductions in a large sample of siblings of individuals with diverse psychotic disorders (n=65), compared to cases with psychosis (n=220) and never psychotic comparison subjects (n=252). We further examined associations of MMN amplitude with cognition and schizotypal symptoms across these groups. Results: We found that MMN amplitude was intact in siblings compared to cases with psychosis. MMN amplitude was associated with cognition and schizotypal symptoms dimensionally across levels of familial risk. Conclusions: The present results imply that MMN amplitude reductions emerge as a result of, or in conjunction with, clinical features associated with psychosis. Such findings carry important implications for the utility of MMN amplitude as an indicator of inherited risk, and suggest that this component may be best conceptualized as a marker for clinical symptoms and cognitive impairments, rather than risk for psychosis per se.

BackgroundLife events (LEs) are a risk factor for first onset and relapse of psychotic disorders. However, the impact of LEs on specific symptoms – namely reality distortion, disorganization, negative symptoms, depression, and mania – remains unclear. Moreover, the differential effects of negativev.positive LEs are poorly understood.MethodsThe present study utilizes an epidemiologic cohort of patients (N= 428) ascertained at first-admission for psychosis and followed for a decade thereafter. Symptoms were assessed at 6-, 24-, 48-, and 120-month follow-ups.ResultsWe examined symptom change within-person and found that negative events in the previous 6 months predicted an increase in reality distortion (β= 0.07), disorganized (β= 0.07), manic (β= 0.08), and depressive symptoms (β= 0.06), and a decrease in negative symptoms (β= −0.08). Conversely, positive LEs predicted fewer reality distortion (β= −0.04), disorganized (β= −0.04), and negative (β= −0.13) symptoms, and were unrelated to mood symptoms. A between-person approach to the same hypotheses confirmed that negative LEs predicted change in all symptoms, while positive LEs predicted change only in negative symptoms. In contrast, symptoms rarely predicted future LEs.ConclusionsThese findings confirm that LEs have an effect on symptoms, and thus contribute to the burden of psychotic disorders. That LEs increase positive symptoms and decrease negative symptoms suggest at least two different mechanisms underlying the relationship between LEs and symptoms. Our findings underscore the need for increased symptom monitoring following negative LEs, as symptoms may worsen during that time.

Cognitive impairment is a prominent and difficult to treat symptom in schizophrenia (SZ), which is directly related to functional disability. A variant in the gene coding for the alpha 1C subunit of L-type voltage gated calcium channel (CACNA1C) has been shown to negatively affect several neurocognitive domains. We conducted a 4-week, open label, pilot study of isradipine, a calcium channel blocker, to determine its feasibility, safety, and efficacy in improving cognition in SZ patients. Ten adults with stable SZ were started on a flexible dose of isradipine 5 mg/day (up to 10 mg/day) for 4 weeks. Weekly in-person visits tracked side effects and symptoms while neurocognition and functional capacity were assessed at baseline and week 4. There were no serious adverse events reported. Newly emergent side effects were dizziness (1 new incidence at week 4); difficulty sleeping (2 new incidences at week 4); and decreased energy (3 new incidences at week 4). 1 patient discontinued medication and was withdrawn. Treatment did not exacerbate clinical symptoms. Although power is limited, results indicate no clear benefit on neurocognition but a positive effect (baseline mean = 6.8 ± 1.3 to week 4 mean = 7.9 ± 1.1; t = 2.91, p = 0.017) on functional capacity was noted. This open label, pilot study provides preliminary evidence that isradipine is a relatively safe medication when used adjunctively in SZ patients. This study suggests that isradipine offers no clear cognitive and only minimal functional benefit; however, additional studies may be warranted in symptomatic patients, or those with specific CACNA1C genotypes.

Life events (LEs) are a risk factor for first onset and relapse of psychotic disorders. However, the impact of LEs on specific symptoms—namely psychosis, disorganization, negative symptoms, depression, and mania—remains unclear. Moreover, the differential effects of negative versus positive LEs is poorly understood. The present study utilizes an epidemiologic cohort of patients (N=428) ascertained at first-admission for psychosis and followed for a decade thereafter. Symptoms were assessed at 6-, 24-, 48- and 120-month follow-ups. We examined symptom change within-person and found that negative events in the previous 6 months predicted an increase in psychotic (β= .07), disorganized (β= .07), manic (β= .08), and depressive symptoms (β= .06), and a decrease in negative symptoms (β= -.08). Conversely, positive LEs predicted fewer psychotic (β= -.04), disorganized (β= -.04), and negative (β= -.13) symptoms, and were unrelated to mood symptoms. Structural equation modeling confirmed that negative LEs predicted change in all symptoms, while positive LEs predicted change only in negative symptoms. In contrast, symptoms rarely predicted future LEs. These findings confirm that LEs have an effect on symptoms, and thus contribute to the burden of psychotic disorders. That LEs increase positive symptoms and decrease negative symptoms suggests at least two different mechanisms underlying the relationship between LEs and symptoms. Our findings underscore the need for close symptom monitoring in months following negative LEs, as symptoms may worsen during that time.

Background Schizophrenia (SZ) studies suggest that neurocognition predicts functional outcome and that social cognition mediates this relationship. Bipolar disorder (BD) patients also have cognitive, social, and functional impairments but the relationship among these factors in BD is not well established. We assessed whether social cognition modulates the influence of neurocognition on community functioning in BD, as found in SZ. Methods 200 BD patients and 49 healthy controls (HC) were administered and compared on a battery of tests assessing neurocognition, social cognition, and community functioning. We conducted a series of regression analyses to investigate potential mediation or moderation of social cognition on the relationship between neurocognition and community functioning. Results BD patients performed worse on neurocognitive domains of processing speed, attention, verbal learning, and global neurocognition. Also, BD patients performed worse on theory of mind, the social cognition composite score, and community functioning. Neurocognition did not significantly predict functional outcome in our BD sample. However, we found a moderating effect of social cognition: among patients with poor social cognition, better neurocognition was associated with better community functioning, a relationship not seen in BD patients with good social cognition. Limitations The study was limited by a relatively small HC group and assessing one subtype of functioning status. Conclusions The relationship between neurocognition and community functioning in BD may be dependent on social cognition status, implying the presence of social cognitive heterogeneity. Results may be relevant to choosing proper treatment interventions depending on the patient's social cognitive level.

BackgroundOur previous work revealed substantial heterogeneity in the cognitive profile of bipolar disorder (BD) due to the presence of three underlying cognitive subgroups characterized as: globally impaired, selectively impaired, or cognitively intact. In an effort to determine whether these subgroups are differentially related to genetic risk for the illness, we investigated whether cognitive deficits were more pronounced in unaffected siblings (UAS) of BD probands within identified clusters.MethodsCluster analysis was used to identify cognitive clusters in BD (N = 60). UAS (N = 49) were classified into groups according to their proband sibling's cluster assignment; comparisons were made across all clusters and healthy controls (HCs; N = 71).ResultsThree cognitive clusters in BD emerged: a globally impaired (36.7%), a selectively impaired (30%), and a cognitively intact cluster (33.3%). UAS showed a qualitatively similar pattern to their BD siblings; UAS of the globally impaired BD cluster showed verbal memory and general cognitive impairments relative to HCs. In contrast, UAS of the other two clusters did not differ from HCs.ConclusionsThis study corroborates findings from prior work regarding the presence of cognitive heterogeneity in BD. UAS of subjects in the globally impaired BD cluster presented with a qualitatively similar cognitive profile to their siblings and performed worse than all other BD clusters and UAS groups. This suggests that inherited risk factors may be contributing to cognitive deficits more notably in one subgroup of patients with BD, pointing toward differential causes of cognitive deficits in discrete subgroups of patients with the disorder.

Background: Verbal memory (VM) impairment is prominent in bipolar disorder (BD) and is linked to functional outcomes. However, the intricacies of VM impairment have not yet been studied in a large sample of BD patients. Moreover, some have proposed VM deficits that may be mediated by organizational strategies, such as semantic or serial clustering. Thus, the exact nature of VM break-down in BD patients is not well understood, limiting remediation efforts. We investigated the intricacies of VM deficits in BD patients versus healthy controls (HCs) and examined whether verbal learning differences were mediated by use of clustering strategies. Methods: The California Verbal Learning Test (CVLT) was administered to 113 affectively stable BD patients and 106 HCs. We compared diagnostic groups on all CVLT indices and investigated whether group differences in verbal learning were mediated by clustering strategies. Results: Although BD patients showed significantly poorer attention, learning, and memory, these indices were only mildly impaired. However, BD patients evidenced poorer use of effective learning strategies and lower recall consistency, with these indices falling in the moderately impaired range. Moreover, relative reliance on semantic clustering fully mediated the relationship between diagnostic category and verbal learning, while reliance on serial clustering partially mediated this relationship. Conclusions: VM deficits in affectively stable bipolar patients were widespread but were generally mildly impaired. However, patients displayed inadequate use of organizational strategies with clear separation from HCs on semantic and serial clustering. Remediation efforts may benefit from education about mnemonic devices or “chunking” techniques to attenuate VM deficits in BD. (JINS, 2017, 23, 358–366)

Social cognition deficits are recognized as key features of psychotic disorders, causing significant disability. Recent evidence supports that oxytocin may be a promising treatment to enhance social cognition. In this chapter, we review the biology of endogenous oxytocin, the mechanisms of action of exogenous oxytocin, and the role of oxytocin in social cognition. We present an overview of the current evidence by summarizing clinical trials of oxytocin across the spectrum of psychotic disorders. We also describe the results of clinical trials combining oxytocin with either psychotherapy or cognitive behavioral interventions. The latest literature has demonstrated that oxytocin may improve social cognition in severe mental disorders. Further studies are needed to clarify the therapeutic potential of oxytocin as a treatment for social cognitive deficits in psychotic disorders, and to develop specific evidence-based clinical guidelines.

According to the Justified True Belief account of knowledge (JTB), a person can only truly know something if they have a belief that is both justified and true (i.e., knowledge is justified true belief). This account was challenged by Gettier (1963), who argued that JTB does not explain knowledge attributions in certain situations, later called Gettier-type cases, wherein a protagonist is justified in believing something to be true but their belief was only correct due to luck. Lay people may not attribute knowledge to protagonists with justified but only luckily true beliefs. While some research has found evidence for these so-called Gettier intuitions (e.g., Machery et al., 2017a), Turri et al. (2015) found that participants attributed knowledge in Gettier-type cases at rates similar to cases of justified true belief. In a large-scale, cross-cultural conceptual replication of Turri and colleagues’ (2015) Experiment 1 (N = 4724), we failed to replicate this null result using a within-subjects design and three vignettes across 19 geopolitical regions. Instead, participants demonstrated Gettier intuitions; they were 1.86 times more likely to attribute knowledge to protagonists in standard cases of justified true belief than to protagonists in Gettier-type cases. These results suggest that Gettier intuitions may be common across different scenarios and cultural contexts. When assessing the knowledge of others, lay people may rely on a shared set of epistemic intuitions (i.e., a core folk epistemology) that requires more than simply justification, belief, and truth. However, the size of the Gettier intuition effect did vary by vignette, and the Turri et al. (2015) vignette produced the smallest effect. Thus, epistemic intuitions may also depend on contextual factors unrelated to the criteria of knowledge, such as the characteristics of the protagonist being evaluated.

Despite the overlap between schizophrenia and bipolar disorder, neurodevelopmental abnormalities are thought to be associated primarily with schizophrenia. Transdiagnostic and empirical identification of subgroups based on premorbid adjustment (PMA) may enhance understanding of illness trajectories. 160 patients with bipolar I or II disorder (BD; n = 104) or schizophrenia or schizoaffective disorder (SZ; n = 56) were assessed on PMA course from childhood to late adolescence and current symptoms and functioning. A hierarchical cluster analysis was performed using social and academic PMA scores, resulting in three optimal clusters. Cluster 1 (n = 28 SZ, 65 BD) had normal social and academic PMA, the most education, and mildest current symptoms. Cluster 2 (n = 15 SZ, 24 BD) had normal social PMA but an impaired-declining academic course and had a greater proportion of males than Cluster 1. Cluster 3 (n = 13 SZ, 15 BD) had an impaired-stable social PMA and an impaired-declining academic course and the most severe current negative symptoms and childhood trauma. The proportions of SZ and BD diagnoses, current neurocognition, and functioning did not differ between clusters. These findings suggest shared neurodevelopmental abnormalities between SZ and BD, with subgroups exhibiting distinct PMA trajectories that cut across disorders.