Non-psychiatric Control Group Research Articles

Obstructive Sleep Apnea Is Treatable With Continuous Positive Airway Pressure in People With Schizophrenia and Other Psychotic Disorders.

Obstructive sleep apnea (OSA) is a highly prevalent condition in people living with schizophrenia or other psychotic disorder. Its treatment with continuous positive airway pressure therapy (CPAP) can dramatically improve daytime and physical health function. People with a psychotic disorder, however, are rarely diagnosed and treated and there are no large-scale studies showing evidence of successful treatment with CPAP. Using a retrospective case-control study approach (N = 554), we examined adherence to and effectiveness of a CPAP trial in individuals with comorbid psychotic disorder and OSA (psychosis group, n = 165) referred for a CPAP trial at the West Australian Sleep Disorders Research Institute. Given that antipsychotic medication is an important confounder, we included a psychiatric (non-psychosis) comparison group taking antipsychotic medication (antipsychotic group, n = 82), as well as a nonpsychiatric control group (OSA control group, n = 307) also diagnosed with OSA and referred for CPAP. Variables included OSA symptom response, CPAP engagement, and usage at 3 months. The Psychosis group had the most severe OSA at baseline and they attended fewer clinic appointments overall. However, there were no other group differences either in CPAP adherence or treatment response. CPAP was equally effective in normalizing OSA symptoms and daytime sleepiness in all groups. CPAP usage was longer per night in the Psychosis and Antipsychotic groups, perhaps suggesting a role of sedation from antipsychotic medications. In conclusion, OSA is treatable and CPAP feasible in people with severe mental illness and antipsychotic medications are not a barrier to treatment response.

Spared performance but increased uncertainty in schizophrenia: Evidence from a probabilistic decision-making task

Aberrant attribution of salience to in fact little informative events might explain the emergence of positive symptoms in schizophrenia and has been linked to belief uncertainty. Uncertainty is thought to be encoded by neuromodulators, including norepinephrine. However, norepinephrinergic encoding of uncertainty, measured as task-related pupil dilation, has rarely been explored in schizophrenia. Here, we addressed this question by comparing individuals with a disorder from the schizophrenia spectrum to a non-psychiatric control group on behavioral and pupillometric measures in a probabilistic prediction task, where different levels of uncertainty were introduced. Behaviorally, patients performed similar to controls, but their belief uncertainty was higher, particularly when instability of the task environment was high, suggesting an increased sensitivity to this instability. Furthermore, while pupil dilation scaled positively with uncertainty, this was less the case for patients, suggesting aberrant neuromodulatory regulation of neural gain, which may hinder the reduction of uncertainty in the long run. Together, the findings point to abnormal uncertainty processing and norepinephrinergic signaling in schizophrenia, potentially informing future development of both psychopharmacological therapies and psychotherapeutic approaches that deal with the processing of uncertain information.

Dysregulation of circRNA expression in the peripheral blood of individuals with schizophrenia and bipolar disorder.

Circular RNAs (circRNAs) are head-to-tail back-spliced RNA transcripts that have been linked to several biological processes and their perturbation is evident in human disease, including neurological disorders. There is also emerging research suggesting circRNA expression may also be altered in psychiatric and behavioural syndromes. Here, we provide a comprehensive analysis of circRNA expression in peripheral blood mononuclear cells (PBMCs) from 39 patients with schizophrenia and bipolar disorder as well as 20 healthy individuals using deep RNA-seq. We observed systematic alternative splicing leading to a complex and diverse profile of RNA transcripts including 8762 high confidence circRNAs. More specific scrutiny of the circular transcriptome in schizophrenia and bipolar disorder, compared to a non-psychiatric control group, revealed significant dysregulation of 55 circRNAs with a bias towards downregulation. These molecules were predicted to interact with a large number of miRNAs that target genes enriched in psychiatric disorders. Further replication and cross-validation to determine the specificity of these circRNAs across broader diagnostic groups and subgroups in psychiatry will enable their potential utility as biomarkers to be established. KEY MESSAGES: • We identified 8762 high confidence circRNAs with systematic alternative splicing in human PBMCs. • CircRNAs were dysregulated in schizophrenia and bipolar disorder, compared to a non-psychiatric control group. • The DE circRNAs were predicted to interact with miRNAs with target genes enriched in psychiatric disorders. • Some circRNAs have the potential to serve as biomarkers in psychiatry.

The history of multiple adverse childhood experiences in patients with schizophrenia is associated with more severe symptomatology and suicidal behavior with gender-specific characteristics

The current study aims to compare the prevalence of adverse childhood experiences (ACEs) between patients with schizophrenia and non-psychiatric control group, and to analyze the association of having suffered multiple ACEs with clinical symptoms of schizophrenia and suicidal behavior. A multicenter, cross-sectional study was conducted across three facilities in Buenos Aires, Argentina. One-hundred patients with schizophrenia and 50 healthy subjects were assessed with the Adverse Childhood Experiences questionnaire (ACE-Q), the Positive and Negative Syndrome Scale (PANSS), and the Columbia-Suicide Severity Rating Scale (C-SSRS). We observed that the prevalence of at least one ACE in schizophrenic patients was almost double in comparison with the non-psychiatric control group. Multiple ACEs were associated with persistent auditory hallucinations and lower negative symptoms in both sexes. Higher frequency of death ideation and a higher number of suicide attempts were reported among women. The strength of this study is the possibility of comparing the presence of ACEs between schizophrenic patients and non-psychiatric control using the same questionnaire in an under-reported sample of low socio-economic patients assisted in public hospitals. A limitation is that the history of ACEs relied on the retrospective assessment of childhood experiences, and adults could over-report ACEs because of recall bias.

The French Version of the Revised Ritvo Autism and Asperger Diagnostic Scale: A Psychometric Validation and Diagnostic Accuracy Study.

The early recognition of ASD in adults is challenging, in particular due to the lack of appropriate and robust diagnostic tools. We performed a psychometric validation and diagnostic accuracy study of the French version of the RAADS-R on a sample of 305 adults: 105 with ASD without ID, 99 with psychiatric disorders, and 103 non-psychiatric control groups. The French version of the RAADS-R demonstrates good reliability and diagnostic validity, suggesting that it can help clinicians during the diagnostic process in adults with ASD without ID. However, the finding that a two-factor structure better fits the results requires further validation. This study point out the need of further study of RAADS in psychiatric disorders group due to the relatively high false positive rate (55.6%) of ASD.

Behavioral empathy failures and suicidal behavior

Impaired decision-making has recently gained recognition as a component of the suicidal diathesis. Yet, although precipitants and particularly deterrents to suicidal behavior are often interpersonal, little is known about social decision-making in suicidal individuals. This study employed a novel version of the Ultimatum Game to investigate how empathy moderates responses to social conflict in 149 older adults, comprising groups of suicide attempters (n = 49), suicide ideators (n = 32), non-suicidal depressed controls (n = 33), and a non-psychiatric control group (n = 35). Participants acted as responder to a series of single-shot financial offers that varied in fairness. Some offers were paired with social context information on the proposer, designed to evoke either empathy or punishment. Offer acceptance was sensitive to Fairness and Social Context, such that participants accepted more offers in the empathy condition and fewer offers in the punishment condition. A Group * Context interaction was observed, wherein the suicide attempters adjusted their acceptance rates less in the empathy condition than the non-psychiatric controls. Thus, older adults with a history of suicide attempt were less influenced by empathy scenarios, indicating that a failure to integrate others’ emotions into decisions may undermine social deterrents to suicide.

Shorter telomere length in schizophrenia: Evidence from a real-world population and meta-analysis of most recent literature

Schizophrenia is a severe, chronic mental disorder. Schizophrenia is visualized as an accelerated cellular aging syndrome characterized by early onset of cardiovascular disease causing premature mortality. In human aging involves alterations in telomere length (TL). To investigate the presence of TL shortening in schizophrenia and psychiatric syndromes associated, this condition was studied in leukocytes (LTL) of a sample of patients suffering from schizophrenia and other psychotic disorders, and compared with a group of non-psychiatric controls. We explored the relationship between LTL and age, gender, and smoking habit with the aim to control whether these potential confounding factors may influence the rate of telomeres shortening. We also performed a new comprehensive meta-analysis including studies on LTL in schizophrenia patients compared to healthy subjects published in the last two years and the results of the present study. Our results suggest that a diagnosis of schizophrenia, more than gender, age, cigarette smoking or alcohol drinking, is the most important condition responsible of the LTL shortening. A strong LTL shortening was observed in patients affected by schizophrenia, Schizoaffective disorder, and Psychosis not otherwise specified when they were younger than 50 years, while in the group of older subjects no major differences were observed. Additional evidence supporting the causal link of schizophrenia with accelerated telomeres shortening came from the analysis of the updated meta-analysis. The availability of a personalized profile of mechanistic pathways, risk factors, and clinical features may pose the basis for a rehabilitative treatment addressing individual needs of the psychiatric patients.

Early maladaptive schemas in depression and somatization disorder

Cognitive theories of depression posit that early maladaptive schemas (EMSs) are key vulnerability factors for psychological disorders. In this study, we investigated specific EMSs as shared or distinct cognitive vulnerability factors for depression and somatization disorder. The sample consisted of patients with Major depressive disorder (N = 30) and Somatization disorder (N = 30) from a community hospital or a psychiatric clinic. Participants completed the Structured Clinical Interview for DSM-IV (SCID), the Beck Depression Inventory-II (BDI-II), and the short form of the Young Schema Questionnaire (YSQ-SF). Depressed patients exhibited significantly higher levels of all five schema domains and specific maladaptive schemas, including emotional deprivation, mistrust and abuse, social isolation and alienation, defectiveness and shame, failure, subjugation, emotional inhibition, and insufficient self-control or self-discipline. Moreover, depressed patients exhibited significantly higher levels of social isolation, emotional inhibition, as well as the overvigilance and inhibition domain when depressive symptom severity was controlled. Our results provide preliminary evidence that specific EMSs distinguish patients with depression and somatization. Suggestions for future research include the need to have a non-psychiatric control group, to evaluate the absolute role of EMSs in Somatization Disorder.

DNA redox modulations and global DNA methylation in bipolar disorder: Effects of sex, smoking and illness state

DNA redox modulations and methylation have been associated with bipolar disorder (BD) pathophysiology. We aimed to investigate DNA redox modulation and global DNA methylation and demethylation levels in patients with BD during euthymia, mania or depression in comparison to non-psychiatric controls. The roles of sex and smoking as susceptibility factors for DNA redox modulations and global DNA methylation and demethylation were also explored. Levels of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were assessed in DNA samples of 75 patients with DSM-IV BD type I (37 euthymic, 18 manic, 20 depressive) in comparison to 60 non-psychiatric controls. Levels of 5-mC and 5-hmC were assessed using Dot Blot as a screening process, and verified using ELISA. Levels of 8-OHdG were assessed using ELISA. The levels of 8-OHdG significantly differed among non-psychiatric control, euthymia, mania and depression groups [F (3,110) = 2.771, p = 0.046], whereas there were no alterations in the levels of 5-hmC and 5-mC. Linear regression analyses revealed the significant effects of smoking (p = 0.031) and sex (p = 0.012) as well as state of illness on the levels of 8-OHdG (p = 0.025) in patients with BD. Our results suggest that levels of 8-OHdG may be affected by sex, illness states and smoking in BD.

Disrupted cortico-limbic connectivity during reward processing in remitted bipolar I disorder.

Bipolar disorder (BD) is associated with elevated reward sensitivity and persistent positive affect, yet the neural mechanisms underlying these patterns are not well understood. In the present study, we examined putative disruptions in communication within a well-known cortico-limbic reward circuit during reward processing as a potential contributing mechanism to these symptoms. The present investigation employed a within- and between-subjects design utilizing a monetary and social incentive delay task among adults with bipolar disorder type I (BD; N=24) and a healthy non-psychiatric control group (HC; N=25) during functional magnetic resonance imaging (fMRI). Participants in the BD group were remitted at the time of testing. Functional connectivity analyses revealed increased connectivity between the ventral striatum (VS) seed region and orbitofrontal cortex (OFC) as well as the amygdala during processing of reward receipt in the BD group. After omission of expected rewards, the BD group showed decreased functional connectivity between the VS and a medial frontopolar cortex (mFPC) region associated with consideration of behavioral alternatives. Follow-up analyses within the BD group showed that increased VS-OFC connectivity after reward receipt, and decreased VS-mFPC connected after reward omission, were associated with higher levels of subthreshold mania symptoms. Results point toward potential mechanisms implicated in elevated reward sensitivity in BD. Enhanced VS-OFC connectivity after reward receipt may be involved in elevated valuation of rewards whereas blunted VS-mFPC connectivity after reward omission may reflect a failure to consider behavioral alternatives to reward pursuit.

The association among smoking, HSV-1 exposure, and cognitive functioning in schizophrenia, bipolar disorder, and non-psychiatric controls

Previous investigations have found that smokers with schizophrenia demonstrate reduced performance on cognitive tasks compared to non-smokers. However previous studies have not taken into account other environmental factors associated with cognitive functioning such as exposure to Herpes Simplex Virus type 1 (HSV-1). We examined these factors in a sample consisting of individuals with schizophrenia (n=773), bipolar disorder (n=493), or controls without a psychiatric disorders (n=548). Participants were assessed on a cognitive battery, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and had a blood sample drawn to measure seropositivity to HSV-1. Within each group linear regression models were constructed to determine whether cigarette smoking and HSV-1 seropositivity were jointly associated with cognitive functioning after adjusting for relevant covariates. Within the schizophrenia group, the effect size of lower total cognitive score was −0.279 (p<0.0001) for individuals who were both smokers and HSV-1 seropositive and a significant effect was found in all cognitive domains. The odds of being in the highest quartile of RBANS Total score were significantly lower for smokers (OR=0.58, 95% CI 0.41, 0.82, p=0.002). Smoking was not as consistently associated with levels of cognitive functioning in the bipolar disorder or the non-psychiatric control group. While experimental studies show that nicotine transiently improves functioning on sensory gating and attention tasks known to be deficient in schizophrenia, long-term nicotine exposure via smoking appears to have an adverse effect on cognitive functioning.

Elevated striatal reactivity across monetary and social rewards in bipolar I disorder.

Bipolar disorder (BD) is associated with increased reactivity to rewards and heightened positive affectivity. It is less clear to what extent this heightened reward sensitivity is evident across contexts and what the associated neural mechanisms might be. The present investigation used both a monetary and social incentive delay task among adults with remitted BD Type I (n = 24) and a healthy nonpsychiatric control group (HC; n = 25) using fMRI. Both whole-brain and region-of-interest analyses revealed elevated reactivity to reward receipt in the striatum, a region implicated in incentive sensitivity, in the BD group. Post hoc analyses revealed that greater striatal reactivity to reward receipt, across monetary and social reward tasks, predicted decreased self-reported positive affect when anticipating subsequent rewards in the HC but not in the BD group. Results point toward elevated striatal reactivity to reward receipt as a potential neural mechanism of persistent reward pursuit in BD.

Late-life Depression, Suicidal Ideation, and Attempted Suicide: The Role of Individual Differences in Maximizing, Regret, and Negative Decision Outcomes.

Suicide rates are highest in adults of middle and older age. Research with psychiatric patients has shown that proneness to feel regret about past decisions can grow so intense that suicide becomes a tempting escape. Here, we examine the additional role of individual differences in maximizing, or the tendency to strive for the best decision, rather than one that is good enough. We provided individual-differences measures of maximizing, regret proneness, and negative life decision outcomes (as reported on the Decision Outcome Inventory or DOI) to a non-psychiatric control group, as well as three groups of psychiatric patients in treatment for suicide attempts, suicidal ideation, or non-suicidal depression. We found that scores on the three individual-differences measures were worse for psychiatric patients than for non-psychiatric controls, and were correlated to clinical assessments of depression, hopelessness, and suicidal ideation. More importantly, maximizing was associated with these clinical assessments, even after taking into account maximizers' worse life decision outcomes. Regret proneness significantly mediated those relationships, suggesting that maximizers could be at risk for clinical depression because of their proneness to regret. We discuss the theoretical relevance of our findings and their promise for clinical practice. Ultimately, late-life depression and suicidal ideation may be treated with interventions that promote better decision making and regret regulation.

Thalamocortical abnormalities in auditory brainstem response patterns distinguish DSM-IV bipolar disorder type I from schizophrenia

BackgroundBipolar disorder type I (BP-I) belongs to a spectrum of affective disorders that are expressed in many different ways and therefore can be difficult to distinguish from other conditions, especially unipolar depression, schizoaffective disorder, schizophrenia (SZ), but also anxiety and personality disorders. Since early diagnosis and treatment have shown to improve the long-term prognosis, complementary specific biomarkers are of great value. The auditory brainstem response (ABR) has previously been applied successfully to identify specific abnormal ABR patterns in SZ and Asperger syndrome. MethodsThe current study investigated the early auditory processing of complex sound stimuli e.g. forward masking, in BP-I compared to SZ patients. The ABR curves of BP-I patients (n=23) and SZ patients (n=20) were analyzed in terms of peak amplitudes and correlation with an ABR norm curve based on a non-psychiatric control group (n=20). ResultsBP-I patients had significantly higher wave III (p=0.0062) and wave VII (p=0.0472) amplitudes compared with SZ patients. Furthermore, BP-I patients, and to a lesser extent SZ patients, showed low correlation with the norm ABR curve in the part of the curve comprising waves VI–VII. LimitationsSample size was relatively small and study groups were not matched for age and gender. ConclusionsBP-I patients showed specific aberrances, specifically in the latter part of the ABR curve, implicating abnormalities in thalamocortical circuitry. The abnormal ABR wave patterns significantly separated BP-I patients from SZ patients suggesting that ABR might serve as a biomarker for BP-I.

Selective Attention to Threat is Specific to Delusions in First-Episode Psychosis

People diagnosed with a psychotic disorder show a selective attention to threat bias. However, it is unknown whether this attentional bias is specifically related to delusions or more generally to psychosis since the absence of the bias has not been established in people with psychosis (without delusions). It is also unknown when this bias develops in the course of psychotic disorder. These issues are investigated in people with first episode psychosis (FEP). The Stroop task was administered to three participant groups: a FEP group with current delusions (n = 31), a FEP group without current delusions (n = 11), and a non-psychiatric control group (n = 25). The FEP with delusions group showed a selective attention to threat words compared to the other groups (p = .02). Selective attention to threat is specifically related to delusions, is present early in the course of psychosis and may be candidate for new cognitive-behavioural therapies to treat medication-resistant delusions.

Sound improves diminished visual temporal sensitivity in schizophrenia

Visual temporal processing and multisensory integration (MSI) of sound and vision were examined in individuals with schizophrenia using a visual temporal order judgment (TOJ) task. Compared to a non-psychiatric control group, persons with schizophrenia were less sensitive judging the temporal order of two successively presented visual stimuli. However, their sensitivity to visual temporal order improved as in the control group when two accessory sounds were added (temporal ventriloquism). These findings indicate that individuals with schizophrenia have diminished sensitivity to visual temporal order, but no deficits in the integration of low-level auditory and visual information.

Are children with obsessive–compulsive disorder at risk for problematic peer relationships?

The current study examined social functioning and peer relationships among pre-adolescent children with obsessive–compulsive disorder (OCD) and a non-psychiatric control group. The sample included 23 children with a primary diagnosis of OCD and 30 children with no psychiatric disorders. All children were diagnosed using the Anxiety Disorders Interview Schedule-Child Version (ADIS-CV) and assessed on social functioning (Pediatric Quality of Life Inventory – Child Report), fear of negative evaluation (Brief Fear of Negative Evaluation Scale), peer victimization, bullying behavior, and pro-social behavior (Peer Relations Questionnaire), and several aspects of their friendships (ADIS-CV Interpersonal Relationships). Children with OCD were also assessed on symptom severity (Children's Yale–Brown Obsessive–Compulsive Scale Severity Ratings). Children with OCD reported significantly worse social functioning, more fear of negative evaluation, more peer victimization, less bullying behavior, and less pro-social behavior compared to controls. Additionally, children with OCD were significantly more likely than controls to endorse difficulties in peer relationships, including having fewer friends than most kids, wanting more friends, and having trouble making friends. Findings suggest that OCD interferes with social functioning among pre-adolescent children. Parents and teachers are encouraged to facilitate social interactions for children with OCD, and treatment providers are encouraged to attend to peer difficulties.

Pathological Gamblers and a Non-Psychiatric Control Group Taking Gender Differences into Account

The current study aimed to identify personality traits, emotional states and adjustment variables in a sample of pathological gamblers as compared to a non-gambling control group taking gender differences into account. The sample for this study consisted of 206 subjects (103 pathological gamblers and 103 non-psychiatric subjects from the general population matched for age and gender). Pathological gamblers had a lower educational level and a family history of alcohol abuse higher than non-gamblers. In turn, female gamblers were affected by unemployment and a lower socioeconomic status more often than female non-gamblers. Pathological gamblers were more anxious and impulsive and suffered from a poorer self-esteem than non-gamblers. Likewise, pathological gamblers had a greater history of other Axis I psychiatric disorders and were more often affected by anxiety and depression symptoms and showed a more problematic adjustment to everyday life than non-gamblers. Alcohol abuse was not higher in pathological gamblers than in non-gamblers, but, when gender was taken into account, male gamblers were more affected by alcohol abuse than male non-gamblers. Importantly 68.6% of female gamblers versus 9.8% of control group women reported being victims of intimate partner violence. These findings can be used to specifically inform prevention and intervention efforts.

Social impairment in children with obsessive compulsive disorder: Do comorbid problems of inattention and hyperactivity matter?

Available studies examining the social relationships of children with obsessive compulsive disorder (OCD) suggest the presence of significant social difficulties. A notable limitation of these studies, however, is a lack of consideration for the potential impact of comorbidity on social variables. Given the high rate of attention-deficit/hyperactivity disorder (ADHD) in youth with OCD, and extensive evidence for ADHD-specific social impairments, the current study examined the interpersonal functioning and peer relationships of youth, ages 6–15 years, with primary OCD (n=24) and a non-psychiatric control group (n=18) while accounting for comorbid problems of inattention/hyperactivity. Overall results based on parent and child reports revealed that children with OCD, regardless of ADHD symptomology, were less socially-competent, had fewer dyadic friendships, and greater difficulty making new friends compared to controls. Children with OCD were just as likely, however, to have a best friend. Findings are considered in terms of their potential implications for intervention.

The relationship between reward-based learning and nicotine dependence in smokers with schizophrenia

Cigarette smoking rates remain remarkably high in schizophrenia relative to smoking in other psychiatric groups. Impairments in the reward system may be related to elevated rates of nicotine dependence and lower cessation rates in this psychiatric group. Smokers with schizophrenia and schizoaffective disorder (SWS; n=15; Mage=54.87, S.D.=6.51, 100% male) and a non-psychiatric control group of smokers (NCL; n=16; Mage=50.38, S.D.=11.52; 93.8% male) were administered a computerized signal detection task to measure reward-based learning. Performance on the signal detection task was assessed by response bias, discriminability, reaction time, and hit rate. Clinician-assessed and self-reported measures of smoking and psychiatric symptoms were completed. SWS exhibited similar patterns of reward-based learning compared to control smokers. However, decreased reward-based learning was associated with increased levels of nicotine dependence in SWS, but not among control smokers. Nicotine withdrawal and urge to smoke were correlated with anhedonia within the SWS group. Among SWS, reduced reward responsiveness and increased anhedonia were associated with and may contribute to greater co-occurring nicotine dependence. These findings emphasize the importance of targeting reward system functioning in smoking cessation treatment for individuals with schizophrenia.