Common Feature Of Schizophrenia Research Articles

The Effect of Cognitive Behavioral Therapy on Insomnia in Patients with Schizophrenia: A Randomized Controlled Trial

Abstract Background: Insomnia is a common feature of schizophrenia. Patients with schizophrenia also encounter the problem of insomnia, which impairs their cognitive functioning, quality of life, mental well-being, and functional recovery. Studies support pharmacological treatment of insomnia with certain drugs; however, these hypnotic medications also have adverse effects. There are no grounded recommendations about insomnia treatment in this clinical setting and research in nonpharmacological areas is sparse. To the best of our knowledge, this is the first study to see the effect of cognitive behavioural therapy for insomnia (CBT-I) in schizophrenia patients in an Indian population. Aims: To evaluate the effects of CBT-I in schizophrenia patients. Materials and Methods: It is a randomized controlled study. Forty schizophrenic patients were recruited and were randomly allocated into two groups. The CBT-I group (n = 20) received four sessions of CBT-I in addition to treatment as usual, whereas the control group (n = 20) received. no additional intervention. The Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) were administered at baseline, week 4, and week 8. Results: Both the groups showed significant time–group interactions on the ISI and PSQI. Post hoc testing showed that, compared to the control group, the CBT-I group showed significant reductions in ISI at both week 4 and week 8. Conclusion: CBT-I was effective for reducing insomnia symptoms in patients with schizophrenia and the effect lasted for 4 weeks after the intervention.

Societal Utilities for Cognitive Impairment in Schizophrenia: Developing a Preference-Based Scoring Algorithm Based on the Schizophrenia Cognition Rating Scale.

Loss of cognitive function is a common feature in schizophrenia. However, generic measures of health-related quality of life favored by decision-makers, such as the EQ-5D, are not designed to detect changes in cognitive function. We report the valuation of the Schizophrenia Cognition Rating Scale (SCoRS), a schizophrenia-specific measure of cognitive impairment. Expert opinion and psychometric analysis of the SCoRS from clinical trial data was undertaken to select 5 key items from the measure. These items were combined orthogonally to develop health-state vignettes. Vignettes were valued using composite time trade-off (cTTO) in one-on-one video calls. Several econometric models were fitted to the data to estimate disutilities. Performance of EQ-5D- and SCoRS-based utilities were compared in the trial data. The SCoRS items selected for the valuation study represented attention, learning, processing speed, social cognition and memory. Four hundred respondents participated in the valuation study. The best observed health state was valued at 0.855 [standard deviation (SD)=0.179] and the worst at 0.152 (SD=0.575). At the most severe levels, 'social cognition' received the largest disutility followed by 'learning' and 'memory'. The final model to estimate utilities had 15 parameters. SCoRS-based utilities were sensitive to change in cognition, but the EQ-5D was not. It is feasible to value different dimensions of cognition separately using a validated instrument for proxy assessment. The resulting utilities indicate loss of quality of life due to reduced cognitive functioning.

Core of sensory gating deficits in first-episode schizophrenia: attention dysfunction.

Sensory gating deficits are a common feature of schizophrenia and may be indicative of higher-order psychopathological impairments. It has been proposed that incorporating subjective attention components into prepulse inhibition (PPI) measures may improve the accuracy of assessing these deficits. This study aimed to investigate the relationship between modified PPI and cognitive function, with a specific focus on subjective attention, to gain a better understanding of the underlying mechanisms of sensory processing deficits in schizophrenia. Fifty-four unmedicated first-episode schizophrenia (UMFE) patients and 53 healthy controls participated in this study. The modified Prepulse Inhibition paradigm, including Perceived Spatial Separation PPI (PSSPPI) and Perceived Spatial Colocation PPI (PSCPPI), was used to evaluate sensorimotor gating deficits. Cognitive function was assessed in all participants using the Chinese version of the MATRICS Consensus Cognitive Suite Test (MCCB). UMFE patients had lower MCCB scores and deficient PSSPPI scores than healthy controls. PSSPPI was negatively correlated with total PANSS scores and positively correlated with the speed of processing, attention/ vigilance, and social cognition. Multiple linear regression analysis showed that the PSSPPI at 60 ms had a significant effect on attentional/ vigilance and social cognition, even after controlling for gender, age, years of education, and smoking. The study revealed notable impairments in sensory gating and cognitive function in UMFE patients, best reflected by the PSSPPI measure. Specifically, PSSPPI at 60 ms was significantly associated with both clinical symptoms and cognitive performance, suggesting that PSSPPI at 60 ms may capture psychopathological symptoms related to psychosis.

Cariprazine’s efficacy in treating depressive symptoms – pooled data from schizophrenia, bipolar depression and major depression trials

IntroductionDepressive symptoms are a common feature of schizophrenia (SCH) and define bipolar disorder and major depressive disorder (MDD). Their emergence is related to altered neurotransmission at the serotonin receptors and potentially at dopamine D3 receptors.ObjectivesThe aim of this analysis was to examine the efficacy of cariprazine (CAR) in treating depressive symptoms in SCH, bipolar depression (BD) and MDD.MethodsClinical trials with randomised, double-blind, placebo (PLB)-controlled designs were included in these analyses. Data from 3 SCH [NCT00694707, NCT01104766, NCT01104779; 1.5-9 mg/d] and 3 BD [NCT01396447, NCT02670538, NCT02670551; 1.5-3 mg/d] studies were pooled. In MDD, add-on CAR to antidepressant treatment was evaluated against PLB in two studies [NCT03738215: 1.5 and 3 mg/d; NCT01469377: 1-2 mg/d and 2-4.5 mg/d).Least square (LS) mean changes were analysed using Mixed Model Repeated Measures: from baseline (BL) to Week 6 in the Positive and Negative Syndrome Scale (PANSS)-derived Marder anxiety/depression factor items (schizophrenia); from BL to Week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total scores (bipolar depression); and from BL to Week 6 [NCT03738215] and Week 8 [NCT01469377] in MADRS total score (major depressive disorder).ResultsAltogether, 1466 SCH (PLB=442, CAR=1024) patients were included in the pooled analysis. In the BD analysis, data from 1383 (PLB=460, CAR=923) patients were pooled. In the MDD trials, there were 502 CAR (1.5mg/d=250, 3 mg/d=252) and 249 PLB-treated patients [NCT03738215], and 544 CAR (1-2 mg/d=273, 2-4.5 mg/d=271) and 264 PLB patients in the other study [NCT01469377]. In SCH, CAR achieved significantly greater reductions than PLB on the Marder anxiety/depression factor domain (LS mean change: PLB= -2.66, CAR= -3.26, p<0.01): the effect was driven by 3 out of 4 items. In BD, CAR yielded significantly greater improvement on the MADRS compared to PLB (LS mean change: PLB= -12.05, CAR= -14.69, p<0.001), which was driven by 9 out of 10 items. In MDD [NCT03738215], CAR 1.5 mg/d add-on significantly alleviated depressive symptoms compared to PLB (LS mean change: PLB= -11.5, CAR 1.5mg/d= -14.1, p<0.01), while in the other MDD trial [NCT01469377], CAR 2-4.5 mg/d add-on produced significantly greater reductions than PLB (LS mean change: PLB= -12.5, CAR 2-4.5 mg/d= -14.6, p<0.01).ConclusionsThese findings indicate that CAR is an effective treatment option for the treatment of depressive symptoms independent of disease (in SCH, BD and MDD), being a transdiagnostic broad-spectrum treatment option.Disclosure of InterestR. McIntyre Grant / Research support from: CIHR/GACD/National Natural Science Foundation of China (NSFC), the Milken Institute, Consultant of: Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Gedeon Richter, Recordati, Atai Life Sciences, Speakers bureau of: Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Gedeon Richter, Recordati, Atai Life Sciences, R. Csehi Employee of: Gedeon Richter Plc., G. Németh Employee of: Gedeon Richter Plc.

Impaired insight into illness is unrelated to subjective happiness, success, and life satisfaction in schizophrenia.

Impaired insight into illness is a common feature of schizophrenia. Improved insight is associated with better treatment adherence and clinical outcomes. At the same time, improving insight has been suggested to increase depressive symptoms and diminish quality of life. The aim of this study was to examine the associations between impaired insight and degree of subjective happiness, perceived level of success, and life satisfaction in patients with schizophrenia spectrum disorders. A total of 108 participants with schizophrenia or schizoaffective disorder were included. Data for this study were obtained from our group's previous investigation that examined the relationship between impaired insight and visuospatial attention. Insight into illness was measured by the VAGUS scale, which assesses general illness awareness, accurate symptom attribution, awareness of the need for treatment, and awareness of the negative consequences attributable to the illness. Our results revealed no association among the VAGUS average and subscale scores and degree of subjective happiness, perceived level of success, and life satisfaction. Our study suggests that insight into illness is not related to subjective happiness, life satisfaction, or perceived level of success in patients with schizophrenia, which is in contrast to previous reports that demonstrate an association between insight into illness and depression.

Identifying common and distinct subcortical volumetric abnormalities in 3 major psychiatric disorders: a single-site analysis of 640 participants.

BackgroundSubcortical volumetric abnormalities in schizophrenia, bipolar disorder and major depressive disorder (MDD) have been consistently found on a single-diagnosis basis in previous studies. However, whether such volumetric abnormalities are specific to a particular disorder or shared by other disorders remains unclear.MethodsWe analyzed the structural MRIs of 160 patients with schizophrenia, 160 patients with bipolar disorder, 160 patients with MDD and 160 healthy controls. We calculated the volumes of the thalamus, hippocampus, amygdala, accumbens, putamen, caudate, pallidum and lateral ventricles using FreeSurfer 7.0 and compared them among the groups using general linear models.ResultsWe found a significant group effect on the volumes of the thalamus, hippocampus, accumbens and pallidum. Further post hoc analysis revealed that thalamic volumes in patients with schizophrenia, bipolar disorder and MDD were significantly reduced compared to those in healthy controls, but did not differ from one another. Patients with schizophrenia and bipolar disorder also shared a significant reduction in hippocampal volumes. Among the 3 clinical groups, patients with schizophrenia showed significantly lower hippocampal volumes and higher pallidal volumes than patients with bipolar disorder and MDD.LimitationsDifferences in psychotropic use and duration of illness among the patient groups may limit the interpretation of our findings.ConclusionOur findings indicate that decreased thalamic volume is a common feature of schizophrenia, bipolar disorder and MDD. Smaller hippocampal and larger pallidal volumes differentiate schizophrenia from bipolar disorder and MDD and may provide clues to the biological basis for the Kraepelinian distinction between these illnesses.

Association of polygenic risk for schizophrenia with fast sleep spindle density depends on pro-cognitive variants

Cognitive impairment is a common feature in schizophrenia and the strongest prognostic factor for long-term outcome. Identifying a trait associated with the genetic background for cognitive outcome in schizophrenia may aid in a deeper understanding of clinical disease subtypes. Fast sleep spindles may represent such a biomarker as they are strongly genetically determined, associated with cognitive functioning and impaired in schizophrenia and unaffected relatives. We measured fast sleep spindle density in 150 healthy adults and investigated its association with a genome-wide polygenic score for schizophrenia (SCZ-PGS). The association between SCZ-PGS and fast spindle density was further characterized by stratifying it to the genetic background of intelligence. SCZ-PGS was positively associated with fast spindle density. This association mainly depended on pro-cognitive genetic variants. Our results strengthen the evidence for a genetic background of spindle abnormalities in schizophrenia. Spindle density might represent an easily accessible marker for a favourable cognitive outcome which should be further investigated in clinical samples.

Cariprazine’s efficacy in treating affective symptoms – pooled data from schizophrenia and bipolar depression trials

IntroductionAffective symptoms are a common feature of schizophrenia and define bipolar disorder. Alterations in dopamine neurotransmission and activity at D3-D2 receptors is associated with depressive symptoms providing the rationale for targeting D3-D2 receptors with partial agonists.ObjectivesThe aim of the analysis herein is to examine and compare the efficacy of cariprazine in treating affective symptoms in both schizophrenia and bipolar depression.MethodsData from 3 schizophrenia [NCT00694707, NCT01104766, NCT01104779] and 3 bipolar I depression studies [NCT013896447, NCT02670538, NCT0267055] were pooled for the analyses. To investigate efficacy across individual affective symptoms, the Marder anxiety/depression and negative symptom items of the Positive and Negative Syndrome Scale (PANSS) and single items of the Montgomery-Asberg Depression Rating Scale (MADRS) were analysed. Improvement across affective symptoms was examined primarily evaluating least square mean differences (LSMDs) in comparison to placebo in mean change from baseline.ResultsThe pooled ITT population was comprised of persons with schizophrenia (placebo=442, cariprazine=1024) and bipolar disorder (placebo=460, cariprazine=923). Cariprazine resulted in a significantly greater reduction when compared to placebo in three out of the four Marder anxiety/depression items; anxiety (p<0.01), tension (p<0.001) and depression (p<0.05). Similarly, cariprazine was significantly better than placebo in 9 out of the 10 MADRS individual items; apparent sadness (p<0.001), reported sadness (p<0.001), reduced sleep (p<0.05), reduced appetite (p<0.001), concentration difficulties (p<0.001), lassitude (p<0.001), inability to feel (p<0.001), pessimistic thoughts (p<0.01) and suicidal thoughts (p<0.05).ConclusionsThe results herein indicate that cariprazine treatment is significantly effective at treating affective symptoms in persons with both schizophrenia and bipolar I depression.DisclosureI am an employee of Gedeon Richter Plc.

Cognitive Endophenotypes: Powerful Tools for Modern Neuropsychiatric Genomics Research

Profound cognitive deficits are a common feature of schizophrenia, and substantial impairments are also seen in bipolar disorder (BD) and major depressive disorder, albeit less frequently recognized. These impairments span the range of fluid intelligence functions, with the most severe tending to be in processing speed, working and episodic memory, and executive functioning, and can affect crystallized intelligence by reducing educational attainment. Cognitive deficits are highly correlated with impairments in the ability to perform everyday tasks, called functional capacity, affecting independence in residence, social capability, and employment, and thus directly contribute to the disability associated with these disorders.

Cortical Thickness in Patients With Schizophrenia With Impaired Insight Into Illness

Impaired insight into illness is a common feature of schizophrenia that is associated with poor clinical and functional outcomes. Prior neuroimaging studies that examined the structural correlates of impaired insight have reported mixed results. This study aimed to examine the relationship of impaired insight with (i) cortical thickness and (ii) subcortical volumes in a large sample of patients with schizophrenia.

Increased Regional Cerebral Blood Flow in the Parietal Regions in Patients With Schizophrenia With Impaired Insight

Impaired insight into illness is a common feature of schizophrenia that negatively contributes to clinical outcomes. Previous functional MRI studies suggest that impaired insight may be related to posterior parietal area (PPA) function. Arterial spin labeling (ASL) is a non-invasive brain imaging technique that provides an absolute measure of regional cerebral blood flow(rCBF). Little research has explored the relationship between rCBF and insight into illness in schizophrenia. We aimed to use pseudo-continuous ASL (pCASL) to examine the association between rCBF and impaired insight in patients with schizophrenia.

Exploring the relationship between impaired illness awareness and visuospatial inattention in patients with schizophrenia

Anosognosia, described as impairment in an individual's ability to perceive and understand their illness, and visuospatial inattention commonly co-occur as a result of structural brain lesions in the right posterior parietal area. Anosognosia or impaired illness awareness is a common feature of schizophrenia that contributes to medication nonadherence and poor clinical outcomes. A recent pilot study suggests patients with impaired illness awareness have a rightward visuospatial bias. We aimed to examine this relationship in a large sample of patients. This study consisted of 106 patients with schizophrenia spectrum disorder (henceforth, schizophrenia) and 20 healthy controls. Visuospatial attention was assessed using the line bisection test (LBT). Illness awareness was assessed using the VAGUS self-report version. A Welch's t-test was used to examine differences in LBT scores between patients with schizophrenia and healthy controls. Correlation analyses between LBT and VAGUS scores were performed in patients with schizophrenia. For exploratory purposes, intra-subject reliability of the LBT was also examined using a two-way mixed intra-class correlation coefficient (ICC). There were no differences in LBT scores between patients with schizophrenia and healthy controls. In patients, there were no associations between LBT and VAGUS scores. ICCs between two consecutively acquired LBTs were 0.92 (95% CI: 0.81–0.96) in patients with schizophrenia and 0.93 (95% CI: 0.81–0.97) in healthy controls. Our results, using a reliable measure, did not support our previous preliminary finding that suggested a relationship between impaired illness awareness and visuospatial bias in patients with schizophrenia. Future studies should consider more sensitive visuospatial attention tasks when testing this hypothesis.

Disrupted Sleep and Circadian Rhythms in Schizophrenia and Their Interaction With Dopamine Signaling.

Sleep and circadian rhythm disruption (SCRD) is a common feature of schizophrenia, and is associated with symptom severity and patient quality of life. It is commonly manifested as disturbances to the sleep/wake cycle, with sleep abnormalities occurring in up to 80% of patients, making it one of the most common symptoms of this disorder. Severe circadian misalignment has also been reported, including non-24 h periods and phase advances and delays. In parallel, there are alterations to physiological circadian parameters such as body temperature and rhythmic hormone production. At the molecular level, alterations in the rhythmic expression of core clock genes indicate a dysfunctional circadian clock. Furthermore, genetic association studies have demonstrated that mutations in several clock genes are associated with a higher risk of schizophrenia. Collectively, the evidence strongly suggests that sleep and circadian disruption is not only a symptom of schizophrenia but also plays an important causal role in this disorder. The alterations in dopamine signaling that occur in schizophrenia are likely to be central to this role. Dopamine is well-documented to be involved in the regulation of the sleep/wake cycle, in which it acts to promote wakefulness, such that elevated dopamine levels can disturb sleep. There is also evidence for the influence of dopamine on the circadian clock, such as through entrainment of the master clock in the suprachiasmatic nuclei (SCN), and dopamine signaling itself is under circadian control. Therefore dopamine is closely linked with sleep and the circadian system; it appears that they have a complex, bidirectional relationship in the pathogenesis of schizophrenia, such that disturbances to one exacerbate abnormalities in the other. This review will provide an overview of the evidence for a role of SCRD in schizophrenia, and examine the interplay of this with altered dopamine signaling. We will assess the evidence to suggest common underlying mechanisms in the regulation of sleep/circadian rhythms and the pathophysiology of schizophrenia. Improvements in sleep are associated with improvements in symptoms, along with quality of life measures such as cognitive ability and employability. Therefore the circadian system holds valuable potential as a new therapeutic target for this disorder.

S55. PRAGMATIC INFERENCES IN SCHIZOPHRENIA: RELATIONSHIP WITH SYMPTOM DOMAINS, THEORY OF MIND AND NEUROCOGNITIVE FUNCTIONS

BackgroundSevere impairment in interpersonal functioning is a common feature of schizophrenia. Deficits in communicative abilities are likely to be among the important factors contributing to social dysfunction in schizophrenia. Difficulties in pragmatic language abilities including understanding intended meaning, beyond explicit and literal content of conversational statements can significantly hamper interpersonal and occupational functioning.An important aspect of pragmatic inference is the ability to derive scalar implicatures (SIs), which are based on linguistic expressions like some, or, often etc. For deriving SIs, one need to go beyond simple semantic and logical level. To date, only a single study has investigated SIs in schizophrenia (Wampers et al 2018). In this study, people with psychosis were less likely to derive SIs than controls. A preliminary analysis of 17 patients with schizophrenia in the same study also showed that better ToM was associated with a higher ability to derive SIsImportantly, the association with schizophrenia and abnormalities in pragmatic infererence might be mediated by clinical features of this illness including formal thought disorder and negative symptoms. Also, difficulties in pragmatic inferences might potentially be secondary to neurocognitive dysfunction rather than being primary deficits. No previous study has investigated clinical and neurocognitive correlates of impairment in ability to derive SIs in schizophrenia.MethodsThe study included 79 patients with schizophrenia-spectrum disorders (66 schizophrenia and 13 schizoaffective disorder) and 49 healthy controls who completed a SI task. SAPS, SANS were also administered. Comprehension of irony, metaphor and faux pas were assessed using verbal story tasks. A subgroup of patients were also administered a comprehensive neuropsychological battery and two ToM tasks (Hinting task and RMET (Reading the Mind from the Eyes).ResultsThere were no significant group difference between schizophrenia and healthy controls for age (F=0.69, p=0.41) and gender (Chi square=2.2, p=0.13). The schizophrenia sample had a shorter duration of education compared to the healthy controls (F=27.2, p<0.001). The patients with schizophrenia had significant impairment in understanding the SIs (F=8.2, p=0.005). Comprension impairment of SIs were significantly associated with SANS negative symptoms (r=-0.29, p= 0.009) but not with SAPS positive formal thought disorder (r=-0.09, p=0.44) and symptoms ratings for hallucinations and delusions. Understanding SIs in schizophrenia was significantly related to better performance in RMET (r=0.34, p=0.036) and irony comprehension (r=-0.38, p=0.001).DiscussionSchizophrenia is associated with significant deficits in understanding pragmatic utterances. These deficits were significantly related to some aspects of social cognition but not neurocognition. Current findings do not support the proposed relationship between formal thought disorder and pragmatic abnormalities in schizophrenia. These findings might have implications in management of social functioning deficits in schizophrenia.

Improving Insight in Non-Treatment-Resistant Patients With Schizophrenia With Transcranial Direct Current Stimulation

Impaired insight into illness is a common feature of schizophrenia that is frequently associated with worse clinical and functional outcomes. Transcranial direct current stimulation (tDCS) is a method of brain stimulation that delivers a weak electric current to targeted brain regions. In this pilot randomized-sham controlled study, we aimed to examine the efficacy of adjunctive tDCS on insight in patients with schizophrenia.

Colour discrimination among patients with schizophrenia in Lebanon

Background: Abnormalities and contrast sensitivity have already been studied in schizophrenia. However, the relationship between symptom severity in schizophrenia and colour vision sensitivity has not been studied systematically.Aim: Our objective was to evaluate colour discrimination in patients with schizophrenia compared to controls and examine if this colour discrimination is correlated with schizophrenia symptoms’ severity.Methods: This case–control study, performed between January and April 2017, included 50 schizophrenic patients and 50 healthy controls matched for age and sex. The Positive and Negative Symptoms Scale (PANSS) was used to determine the schizophrenia symptoms’ severity. Colour discrimination was evaluated using the total error score (TES) generated using the Farnsworth D-15 test. The higher the TES, the more severe colourblindness.Results: A significantly higher mean TES was found in schizophrenics (30.32) compared to healthy patients (13.07) (p < 0.001). Colour blindness was correlated to the severity of schizophrenic symptoms only in the subgroup of patients with severe schizophrenia.Conclusion: Colour vision defect is a common feature in schizophrenia, and may be more significant when related to psychotic symptoms.KEY POINTSA significantly higher mean TES was found in schizophrenics compared to healthy patients.Colour blindness was correlated to the severity of schizophrenic symptoms only in the subgroup of patients with severe schizophrenia.Colour vision defect is a common feature in schizophrenia, and may be more significant when related to psychotic symptoms.

Abnormal Space Experiences in Persons With Schizophrenia: An Empirical Qualitative Study.

Abnormal space experience (ASE) is a common feature of schizophrenia, despite its absence from current diagnostic manuals. Phenomenological psychopathologists have investigated this experiential disturbance, but these studies were typically based on anecdotal evidence from limited clinical interactions. To better understand the nature of ASE in schizophrenia and attempt to validate previous phenomenological accounts, we conducted a qualitative study of 301 people with schizophrenia. Clinical files were analyzed by means of Consensual Qualitative Research, an inductive method for analyzing descriptions of lived experience. Our main findings can be summed up as follows: (1) ASEs are a relevant feature in schizophrenia (70.1% of patients reported at least 1 ASE). (2) ASE in schizophrenia are characterized by 5 main categories of phenomena (listed from more represented to less represented): (a) experiences of strangeness and unfamiliarity (eg "Everything appeared weird. Face distorted, world looks terrible, nasty"); (b) experiences of centrality/invasion of peripersonal space (eg "Handkerchief on scaffolding: message telling him something"); (c) alteration of the quality of things (eg "Buildings leaning down"); (d) alteration of the quality of the environment (eg "Person sitting six feet away seemed to be at an infinite distance"); and (e) itemization and perceptive salience (eg "All patients [in ward] have bright eyes"). (3) ASEs are much more frequent in acute (91.9%) than in chronic (28.15%) schizophrenia patients. Moreover, our findings further empirical support for phenomenological accounts of schizophrenia, including those developed by Jaspers, Binswanger, Minkowski, and Conrad, among others and provide the background for translational research.

Modulation of brain activity with transcranial direct current stimulation: Targeting regions implicated in impaired illness awareness in schizophrenia

BackgroundImpaired illness awareness or insight into illness (IIA) is a common feature of schizophrenia that contributes to medication nonadherence and poor clinical outcomes. Neuroimaging studies suggest IIA may arise from interhemispheric imbalance in frontoparietal regions, particularly in the posterior parietal area (PPA) and the dorsolateral prefrontal cortex (dlPFC). In this pilot study, we examined the effects of transcranial direct current stimulation (tDCS) on brain regions implicated in IIA. MethodsEleven patients with schizophrenia with IIA (≥3 PANSS G12) and 10 healthy controls were included. A crossover design was employed where all participants received single-session bi-frontal, bi-parietal, and sham stimulation in random order. For each condition, we measured (i) blood oxygen level-dependent (BOLD) response to an illness awareness task pre- and post-stimulation, (ii) regional cerebral blood-flow (rCBF) prior to and during stimulation, and (iii) changes in illness awareness. ResultsAt baseline, patients with schizophrenia showed higher BOLD-response to an illness awareness task in the left-PPA compared to healthy controls. Bi-parietal stimulation reduced the interhemispheric imbalance in the PPA compared to sham stimulation. Relatedly, bi-parietal stimulation increased rCBF beneath the anode (21% increase in the right-PPA), but not beneath the cathode (5.6% increase in the left-PPA). Bi-frontal stimulation did not induce changes in rCBF. We found no changes in illness awareness. ConclusionAlthough single-session tDCS did not improve illness awareness, this pilot study provides mechanistic justification for future investigations to determine if multi-session bi-parietal tDCS can induce sustained changes in brain activity in the PPA in association with improved illness awareness.

Treatment Options for Insomnia in Schizophrenia: A Systematic Review.

Insomnia is a common feature of schizophrenia. Although several studies have been published about the influence of certain drugs on schizophrenia patients' sleep, there are no well-grounded recommendations about insomnia treatment in this clinical setting. The present review aimed to identify relevant empirical evidence on available treatments of insomnia in patients with schizophrenia, assessing their safety and efficacy. This is a systematic review of clinical trials investigating the effect of treatments for insomnia in patients with a diagnosis of schizophrenia. Data were obtained from Medline/PubMed, Embase, PsycInfo, and the Cochrane Library. Risk of bias was assessed in individual studies for selection, performance, detection, attrition, and reporting bias. Four studies met inclusion criteria; 2 using melatonin, 1 using paliperidone, and 1 with eszopiclone. All reported positive results: melatonin increased sleep efficiency and total duration of sleep; paliperidone decreased sleep latency onset and increased total sleep time and sleep efficiency; eszopiclone decreased insomnia severity index. Despite a very limited number of specific studies on this matter, all 4 studies have shown good benefit/risk ratios and reviewed options-melatonin, paliperidone, and eszopiclone-might represent valid options for residual insomnia in schizophrenia.

Impact on the Onset of Psychosis of a Polygenic Schizophrenia-Related Risk Score and Changes in White Matter Volume

Background: Reductions in the volume of brain white matter are a common feature in schizophrenia and bipolar disorder while the association between white matter and polygenic schizophrenia-related risk is unclear. To look at the intermediate state between health and the full-blown disorder, we investigated this aspect in groups of patients before and after the onset of psychosis. Methods: On a 3 Tesla scanner, total and regional white matter volumes were investigated by structural magnetic resonance imaging (MRI) in the following groups: 37 at-risk mental state patients (ARMS), including 30 with no transition to psychosis (ARMS-NT) and 7 with a transition to psychosis (ARMS-T) pooled with 25 first episode psychosis (FEP) patients. These T₁-weighted images were automatically processed with the FreeSurfer software and compared with an odds-ratio-weighted polygenic schizophrenia-related risk score (PSRS) based on the publicly available top white matter single-nucleotide polymorphisms. Results: We found no association, only a trend, between PSRS and white matter volume over all groups (β = 0.24, p = 0.07, 95% confidence interval = [-0.02 – 0.49]). However, a higher PSRS was significantly associated with a higher probability of being assigned to the ARMS-T + FEP group rather than to the ARMS-NT group (β = 0.70, p = 0.02, 95% confidence interval = [0.14 – 1.33]); there was no such association with white matter volume. Additionally, a positive association was found between PSRS and the Brief Psychiatric Rating Scale (BPRS) total score for the pooled ARMS-NT/ARMS-T+FEP sample and for the ARMS-T + FEP group also, but none for the ARMS-NT group only. Conclusion: These findings suggest that at-risk mental state patients with a transition and first-episode psychosis patients have a higher genetic risk for schizophrenia than at-risk mental state patients with no transition to psychosis; this risk was associated with psychopathological symptoms. Further analyses may allow polygenic schizophrenia-related risk scores to be used as biomarkers to predict psychosis.