Severity Of Psychosis Research Articles

Associations of substance use, psychosis, and mortality among people living in precarious housing or homelessness: A longitudinal, community-based study in Vancouver, Canada.

BackgroundThe “trimorbidity” of substance use disorder and mental and physical illness is associated with living in precarious housing or homelessness. The extent to which substance use increases risk of psychosis and both contribute to mortality needs investigation in longitudinal studies.Methods and findingsA community-based sample of 437 adults (330 men, mean [SD] age 40.6 [11.2] years) living in Vancouver, Canada, completed baseline assessments between November 2008 and October 2015. Follow-up was monthly for a median 6.3 years (interquartile range 3.1–8.6). Use of tobacco, alcohol, cannabis, cocaine, methamphetamine, and opioids was assessed by interview and urine drug screen; severity of psychosis was also assessed. Mortality (up to November 15, 2018) was assessed from coroner’s reports and hospital records. Using data from monthly visits (mean 9.8, SD 3.6) over the first year after study entry, mixed-effects logistic regression analysis examined relationships between risk factors and psychotic features. A past history of psychotic disorder was common (60.9%). Nonprescribed substance use included tobacco (89.0%), alcohol (77.5%), cocaine (73.2%), cannabis (72.8%), opioids (51.0%), and methamphetamine (46.5%). During the same year, 79.3% of participants reported psychotic features at least once. Greater risk was associated with number of days using methamphetamine (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.05–1.24, p = 0.001), alcohol (aOR 1.09, 95% CI 1.01–1.18, p = 0.04), and cannabis (aOR 1.08, 95% CI 1.02–1.14, p = 0.008), adjusted for demographic factors and history of past psychotic disorder. Greater exposure to concurrent month trauma was associated with increased odds of psychosis (adjusted model aOR 1.54, 95% CI 1.19–2.00, p = 0.001). There was no evidence for interactions or reverse associations between psychotic features and time-varying risk factors. During 2,481 total person years of observation, 79 participants died (18.1%). Causes of death were physical illness (40.5%), accidental overdose (35.4%), trauma (5.1%), suicide (1.3%), and unknown (17.7%). A multivariable Cox proportional hazard model indicated baseline alcohol dependence (adjusted hazard ratio [aHR] 1.83, 95% CI 1.09–3.07, p = 0.02), and evidence of hepatic fibrosis (aHR 1.81, 95% CI 1.08–3.03, p = 0.02) were risk factors for mortality. Among those under age 55 years, a history of a psychotic disorder was a risk factor for mortality (aHR 2.38, 95% CI 1.03–5.51, p = 0.04, adjusted for alcohol dependence at baseline, human immunodeficiency virus [HIV], and hepatic fibrosis). The primary study limitation concerns generalizability: conclusions from a community-based, diagnostically heterogeneous sample may not apply to specific diagnostic groups in a clinical setting. Because one-third of participants grew up in foster care or were adopted, useful family history information was not obtainable.ConclusionsIn this study, we found methamphetamine, alcohol, and cannabis use were associated with higher risk for psychotic features, as were a past history of psychotic disorder, and experiencing traumatic events. We found that alcohol dependence, hepatic fibrosis, and, only among participants <55 years of age, history of a psychotic disorder were associated with greater risk for mortality. Modifiable risk factors in people living in precarious housing or homelessness can be a focus for interventions.

T148. FIRST EPISODE PSYCHOSIS, TRAUMA AND SUBSTANCE USE IN A HIGH HIV PREVALENCE SETTING IN SUB-SAHARAN AFRICA

BackgroundHIV, substance use and trauma are associated with more severe symptoms and poorer outcomes in psychosis. We aim to describe the profile of adults with first episode psychosis (FEP) and associations with substance use and trauma in a cohort of patients in a low resource, high HIV prevalence setting in South Africa.MethodsWe recruited all adult patients (18–45 years) presenting with FEP to five psychiatric units in the eThekwini Municipality, KwaZulu-Natal Province. Psychiatric diagnosis was made using the MINI. We used the PANSS for psychotic symptoms, WHO ASSIST for substance use and CTQ for early childhood trauma. HIV status was confirmed by ELISA.ResultsSixty participants were recruited, mean age 26 years (SD 8, IQR 19–33), 68% (n=41) were male. Mean age at presentation was 24 and 31 years for males and females respectively, with males being significantly younger than females (p=0.0003). Duration of untreated psychosis (DUP) was 12.5 months (IQR 1–10.3 months). Lifetime tobacco, alcohol and cannabis use was reported at 57%, 55%, and 47% respectively. Substance use was more prevalent among males compared to females, p=0.10, 0.13 and 0.0001 for tobacco, alcohol and cannabis respectively. Lifetime cannabis use was associated with higher negative PANSS scores (mean score 32, SD 10) compared to non-users (mean score 17, SD 7), p=0.05. Sixty eight percent (n=41) reported any traumatic event. Sixty-two percent (n=37) experienced trauma before 18 years and 35% (n=21) reported traumatic experiences in adulthood. Individuals who reported trauma in adulthood had higher hostility scores in the PANSS compared to those who experienced no trauma in adulthood (p=0.05).Fifteen (25%) of the cohort was HIV infected. Females were more likely to be HIV infected (58% HIV infected females compared to 9.8% HIV infection in males, p=0.0001).Eleven of the 15 HIV infected patients had been on antiretroviral treatment prior to the psychosis onset and four were newly diagnosed at the time of psychosis presentation. Of the 11 individuals on antiretroviral treatment, 6 (45%) were virologically suppressed.There was no significant difference in PANSS scores by HIV status (p=0.5) and childhood trauma (p=0.5).DiscussionThe study found participants with FEP had a high prevalence of HIV, particularly in females, and high prevalence of tobacco, alcohol and cannabis use. This suggests that these individuals are particularly vulnerable to the triple burden of psychosis, substance use and HIV. In addition, they had long DUP suggesting delay in accessing treatment, which all serve as poorer prognostic indicators in an already overwhelmed health care setting.The high rates of trauma (more than half the sample reporting childhood trauma) is another major public health concern as trauma exposure has been associated with poorer physical and mental health outcomes. In this study the lack of association between childhood trauma and psychosis severity is inconsistent with literature and needs to be further explored. The association between adult exposure to trauma and increased hostility scores suggests the need to include psychological treatment strategies to address the trauma exposure to improve outcomes.

Are working memory and glutamate concentrations involved in early-life stress and severity of psychosis?

ObjectiveOccurrences of early‐life stress (ELS) are associated with the severity of psychotic symptoms and working memory (WM) deficits in patients with psychosis (PSY). This study investigated potential mediation roles of WM behavioral performance and glutamate concentrations in prefrontal brain regions on the association between ELS and psychotic symptom severity in PSY.MethodForty‐seven patients with PSY (established schizophrenia, n = 30; bipolar disorder, n = 17) completed measures of psychotic symptom severity. In addition, data on ELS and WM performance were collected in both patients with PSY and healthy controls (HC; n = 41). Resting‐state glutamate concentrations in the bilateral dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) were also assessed with proton magnetic resonance spectroscopy for both PSY and HC groups. t tests, analyses of variance, and regression analyses were utilized.ResultsParticipants with PSY reported significantly more ELS occurrences and showed poorer WM performance than HC. Furthermore, individuals with PSY displayed lower glutamate concentrations in the left DLPFC than HC. Neither ELS nor WM performance were predictive of severity of psychotic symptoms in participants with PSY. However, we found a significant negative correlation between glutamate concentrations in the left DLPFC and ELS occurrence in HC only.ConclusionIn individuals with PSY, the current study found no evidence that the association between ELS and psychotic symptoms is mediated by WM performance or prefrontal glutamate concentrations. In HC, the association between ELS experience and glutamate concentrations may indicate a neurometabolite effect of ELS that is independent of an illness effect in psychosis.

Suicidal ideation in an Egyptian sample of hospitalized patients with acute psychosis

ABSTRACT Background: Suicide mortality is 12 times higher in psychotic patients compared to the general population. Identifying the characteristics of suicidal patients among this group might help in preventing such behavior. Aims: To assess the predictors of suicidal risk in patients hospitalized due to acute psychosis. Methods: A total of 150 patients (age 18–60 years) admitted with acute psychotic features were recruited. Patients were evaluated clinically by the Arabic version of Mini International Neuropsychiatric Interview (MINI.) Suicidal ideation was assessed using the Scale for Suicide Ideation (SSI). Results: Forty-four out of 150 patients (29.33%) reported having current and/or previous history of suicidal ideation. Patients with major depression showed the highest suicidal tendencies followed by delusional disorder, bipolar disorder, psychosis related to substance abuse and schizophrenia. The more severe the psychotic symptoms, the more suicidal tendencies shown by patients. Predictors for suicidal ideation included diagnostic category, severity of psychotic features, unemployement and younger age. Conclusion: Patients with psychosis that require admission to hospital carry a high risk of suicidal ideation and behavior. Factors like unemployment, young age, psychiatric diagnosis and severity of psychosis could be predictors for suicidal ideation.

Randomized Controlled Trial of Paliperidone Extended Release Versus Risperidone for the Treatment of Methamphetamine-Associated Psychosis in Chinese Patients.

BackgroundThe efficacy or tolerability of paliperidone extended release (ER) in the treatment of methamphetamine (METH)-associated psychosis (MAP) is unknown. This study was designed to assess the tolerability and efficacy of paliperidone ER and risperidone for the treatment of MAP in China.MethodsThis 25-day randomized clinical trial involved 120 patients with acute MAP symptoms who were randomized to receive either paliperidone ER or risperidone from baseline to day 25 of an inpatient hospital stay. The primary outcome was changes in the severity of psychosis, which were assessed using the Positive and Negative Syndrome Scale (PANSS) total score changes from baseline to endpoint.ResultsOverall, 84% of the patients completed the entire study protocol. The PANSS total score, the Clinical Global Impressions-Severity of Illness scale (CGI-S) score, and a METH craving score assessed by a visual analog scale (VAS) showed statistically significant improvements from baseline for the patients in both groups (p < 0.01). The Simpson-Angus Scale (SAS) and the Barnes Akathisia Rating Scale (BARS) scores increased from baseline during treatment in both groups (p < 0.01); there were statistically significant differences between the treatment groups in the SAS scores (p < 0.01). Measures of hypermyotonia, salivation, and dizziness were significantly higher in the risperidone-treated patients than in the paliperidone ER-treated patients (all p < 0.05).ConclusionPaliperidone ER and risperidone had similar efficacy and were generally tolerable in the treatment of MAP; however, paliperidone ER had a more favorable adverse event profile than risperidone, particularly regarding extrapyramidal and prolactin-increasing effects.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01822730. Full date of first registration:03/28/2013.

Longitudinal effects of clozapine concentration and clozapine to N-desmethylclozapine ratio on cognition: A mediation model

Previous cross-sectional studies have found clozapine to N-desmethylclozapine (CLZ:NDMC) ratio to be negatively correlated with cognition in clozapine-treated patients with schizophrenia. However, no work has examined the association between CLZ:NDMC ratio and cognition using a within-subjects design. Here, we investigate the longitudinal effects of changes in the clozapine load and the CLZ:NDMC ratio on cognition whilst controlling for a range of independent factors. We analyzed data from a cohort of seventeen clozapine-treated patients who have been repeatedly assessed with the Brief Assessment of Cognition for Schizophrenia (BACS). The Positive symptoms sub-score of the Clinical Global Impression for Schizophrenia (CGI-P) was used to assess severity of psychosis. Blood samples were collected to measure the plasmatic levels of clozapine (CLZ) and of N-desmethylclozapine, allowing calculation of the CLZ:NDMC ratio. Our analyses included bivariate and partial correlations, along with a mediation model analysis. We found that both plasmatic levels of CLZ and the CLZ:NDMC ratio were negatively correlated with cognitive performance, and that these associations were independent of changes in both daily clozapine dose and severity of psychotic symptoms. Mediation analyses further revealed the association between CLZ concentration and cognition to be partially mediated by changes in the CLZ:NDMC ratio. This is the first longitudinal analysis of the influence of CLZ concentration and CLZ:NDMC ratio on cognition. Our findings suggest that reduction of CLZ concentration and the CLZ:NDMC ratio might favorably affect cognition. Thus, the CLZ:NDMC ratio may represent a promising target for novel therapeutic strategies aiming to ameliorate cognitive impairment in clozapine-treated patients.

Subjective cognitive complaints and its relation to objective cognitive performance, clinical profile, clinical insight, and social functioning in patients of schizophrenia: A cross-sectional study.

Context:Neurocognitive deficits are well documented in schizophrenia. Neurocognitive insight (NI), described as awareness of neurocognitive deficits, has not been evaluated in the Indian context. Its relation to clinical profile and social functioning also remains unexplored.Aims:The aim of this study was to evaluate the subjective cognitive complaints (SCCs) and their relation to objective cognitive performance, clinical profile, clinical insight, and social functioning in patients of schizophrenia.Settings and Design:This was a cross-sectional study at the outpatient department of a tertiary care teaching hospital.Materials and Methods:One hundred individuals with schizophrenia were evaluated using Positive and Negative Syndrome Scale, Subjective Scale To Investigate Cognition in Schizophrenia, abbreviated version of Scale to Assess Unawareness in Mental Disorders, and Schizophrenia Research Foundation–Social Functioning Index. Cognitive performance was assessed using (1) Digit Span Test (attention) from Wechsler Adult Intelligence Scale, 3rd edition and (2) Passages Test (explicit memory), (3) Verbal n-back Test (working memory), and (4) Stroop Test (executive functioning) from the National Institute of Mental Health and Neuro Sciences Battery.Statistical Analysis:Statistical analysis was done using descriptive statistics, nonparametric tests, and Pearson's coefficient of correlation.Results:Participants showed impairment in all cognitive domains. Except for working memory, there was no correlation between SCC and objective performance for other cognitive domains correspondingly, implying poor NI. Severity of psychosis and clinical insight did not have any correlation with SCC. Higher SCC correlated with poorer social functioning, especially in “occupational” and “other social roles” domains.Conclusions:Individuals with schizophrenia have poor NI. This is independent of severity of psychosis or clinical insight into illness. Socio-occupational functioning and depression should be actively enquired into when patients present with SCC.

Personality Traits as Markers of Psychosis Risk in Kenya: Assessment of Temperament and Character.

Specific personality traits have been proposed as a schizophrenia-related endophenotype and confirmed in siblings at risk for psychosis. The relationship of temperament and character with psychosis has not been previously investigated in Africa. The study was conducted in Kenya, and involved participants at clinical high-risk (CHR) for psychosis (n = 268) and controls (n = 251), aged 15–25 years. CHR status was estimated using the Structured Interview of Psychosis-Risk Syndromes (SIPS) and the Washington Early Psychosis Center Affectivity and Psychosis (WERCAP) Screen. Student’s t-tests were used to assess group differences on the Temperament and Character Inventory (TCI). Neurocognitive functioning, stress severity, and substance use were correlated with the TCI, correcting for psychosis severity. CHR participants were more impulsive (ie, higher novelty seeking [NS]) and asocial (ie, lower reward dependence) than controls. They were also more schizotypal (ie, high self-transcendence [ST] and lower self-directedness [SD] and cooperativeness [CO] than controls). CO was related to logical reasoning, abstraction, and verbal memory. Stress severity correlated with high HA and schizotypal character traits. Lifetime tobacco use was related to NS, and lifetime marijuana use to high NS, low SD and high ST. Temperament and character of Kenyan CHR youth is similar to that observed in schizophrenia. Psychosis risk in Kenya is associated with impulsive, asocial, and schizotypal traits. CHR adolescents and young adults with schizophrenia-specific personality traits may be most at risk for developing a psychotic disorder and to require early intervention to improve outcomes.

Methamphetamine-associated psychosis: links to drug use characteristics and similarity to primary psychosis

Objectives: Despite the prevalence of methamphetamine-associated psychosis, how characteristics of drug use affect the severity and clinical course, and its optimal treatments have not been established. We addressed these questions, assessing clinical features of methamphetamine-associated psychosis, and compared it with primary psychosis.Methods: Hospitalised patients with methamphetamine-associated (n = 70) or primary schizophrenic psychosis (n = 70) were matched on sex, age and duration of psychosis. Association of drug use variables (age at initiation, duration of methamphetamine use) with the Brief Psychiatric Rating Scale (BPRS) scores and psychosis duration were examined for patients with methamphetamine-associated psychosis, and the groups were compared on the BPRS scores.Results: Methamphetamine use initiation age correlated negatively with the BPRS total score and the Activation subscale score; methamphetamine use duration correlated positively with psychosis duration. Methamphetamine-associated psychosis group scored lower on the Hostility-Suspiciousness and Anergia subscales of the BPRS (adjusted p values < .05).Conclusions: Association of early initiation of methamphetamine with psychosis severity may suggest a lasting effect on brain development. Correlation of drug use and psychosis durations may suggest a cumulative effect of methamphetamine exposure. Less severe paranoia and negative symptoms in the methamphetamine-using group could implicate better social functioning of these patients. Further mechanistic studies are warranted.Key pointsEarly initiation of methamphetamine use is associated with psychosis severity.Methamphetamine use duration associates with psychosis duration.Methamphetamine-associated and primary schizophrenic psychoses were similar in symptoms.Methamphetamine psychosis patients were less severe in paranoia and negative symptoms.

Paliperidone Extended-Release Tablets for the Treatment of Methamphetamine Use Disorder in Chinese Patients After Acute Treatment: A Randomized, Double-Blind, Placebo-Controlled Exploratory Study.

Background: To test paliperidone extended-release (ER) for efficacy in decreasing methamphetamine (METH) use and reducing psychotic symptoms in METH-dependent patients after detoxification. Rates of adverse events with paliperidone ER versus placebo were also compared. Methods: After discharge and 7 days without medication, 80 treatment-seeking METH-dependent participants were randomly assigned to paliperidone ER (3 mg once daily; n = 40) or placebo (once daily; n = 40) for 84 days under double-blind conditions. The participants attended clinics weekly to provide urine samples that were analyzed for METH metabolites, to complete research assessments, and to receive substance use and medication counseling. Results: Fifty-six percent of follow-up visits and final visits were completed. The placebo group had a significantly lower retention [51.5 days; 95% confidence interval (CI), 41.6–61.4] than the paliperidone ER group (69.4 days,; 95% CI, 61.9–76.9; p = 0.016). Paliperidone ER was a protective factor against psychotic symptom relapse [hazard ratio (HR) = 0.15, p = 0.003]. Moreover, there were statistically significant effects of paliperidone ER on psychosis severity and METH craving, assessed by mean changes in Positive and Negative Syndrome Scale (PANSS) total scores, Clinical Global Impression—Severity (CGI-S) scores, and METH craving scores over time (p = 0.006, p = 0.002, and p = 0.03 for the medication-by-time interaction effect, respectively). There were no statistically significant differences between the two groups in METH use. There were no serious adverse events related to the study drug. Conclusion: Compared with placebo, paliperidone ER administration resulted in a better retention rate and lower psychotic symptom relapse, but we did not find significantly reduced METH use among adults after acute METH detoxification treatment.

Personality and the Expression of Symptomatology in Schizophrenia and Bipolar Disorder.

Researchers and clinicians have begun using dimensions rather than categories to classify psychopathology with a reliance on personality questionnaires to tap traits that can inform dimensional characterizations. A neglected concern is whether in severe psychopathology questionnaire-based assessments of personality reflect a lifetime propensity toward a diagnosis, as some personality-psychopathology models posit, or reflect the transient effects of current symptoms, as a complication model of personality-psychopathology would suggest. Accurate characterization of psychopathology is necessary to understand etiology and prescribe clinical care. We studied 127 adults with schizophrenia, schizoaffective, or bipolar disorder who completed well-validated measures of personality, current symptomatology, and lifetime psychopathology. We found that normative personality traits were related to current symptoms but unrelated to lifetime symptomatology, whereas the schizotypal trait of cognitive-perceptual distortions predicted lifetime psychosis severity. Questionnaire-based assessments of normative personality are likely affected by current symptom states and may fail to yield a stable characterization of psychopathology.

Distinct Differences in Emotional Recognition According to Severity of Psychotic Symptoms in Early-Stage Schizophrenia.

Patients with schizophrenia are characterized by deficits in their ability to identify facial expressions of emotion, which are associated with impaired social and occupational function. An understanding of the deficits of facial affect recognition (FAR) early in the course of the illness can improve early intervention efforts to ameliorate potential functional deterioration. This study aimed to investigate the characteristics and correlations between psychotic symptoms and FAR deficits in patients with early-stage schizophrenia using data from the Korean Early Psychosis Cohort Study. Patients with schizophrenia were divided into three groups: 1) severely and markedly ill (n = 112), 2) moderately ill (n = 96), and 3) mildly ill (n = 115). These groups were compared with age- and sex-matched healthy controls. The FAR test was developed using Korean emotional faces from the Korean Facial Expressions of Emotion database. Error rates, correct response times, and nonresponse rates of each subset were calculated. Several psychopathology assessments were also performed. There were significantly more deficits associated with the recognition of anger (p < 0.01), fear (p < 0.01), and contempt (p < 0.01) in the three patient groups than in the healthy control group. In the severely and markedly ill states, all emotions apart from surprise had impaired error rates (p < 0.01 for all analyses). The error rates for happiness, sadness, disgust, surprise, and neutral faces were not significantly different between mildly ill patients and healthy controls. All emotions, except for sadness, had significantly more delayed correct response times in all patient groups than in the healthy controls (p < 0.01 for all analyses). The severity of psychotic symptoms was positively correlated with the happiness and neutral error rates, and depression was positively correlated with the happiness error rates. General social function was negatively correlated with the error rates for happiness, sadness, fear, disgust, and surprise. Overall, our results show that the severity of psychosis and clinical symptoms leads to distinct differences in certain emotions of patients with early-stage schizophrenia. It is considered that these specific emotional characteristics will help deepen our understanding of schizophrenia and contribute to early intervention and recovery of social function in patients with schizophrenia.

Reduced integrity of superior longitudinal fasciculus and arcuate fasciculus as a marker for auditory hallucinations in schizophrenia: A DTI tractography study.

The study aimed to assess and compare fractional anisotropy (FA) in bilateral superior longitudinal fasciculi (SLF) and arcuate fasciculi (AF) across schizophrenia with auditory hallucinations(AH), without AH, and healthy controls using diffusion tensor imaging (DTI) tractography. Right-handed adult (18-50 years) individuals with DSM-5 diagnosis of schizophrenia with AH (group-I; n=30) were compared to those without lifetime AH (group-II; n=32) and healthy controls (group-III; n=30). Severity of psychosis in groups-I and II was assessed using SAPS, SANS, and CGI-SCH, and psychopathology was assessed using PSYRATS. The FA was calculated for all images on DTI studio-version 3.0 using tractography technique. All three groups were comparable for age, gender, education and illness-severity. Schizophrenia subjects with AH had significantly lower FA values in bilateral SLF and AF compared to those without AH and healthy controls. No difference was observed in corresponding FA values between schizophrenia without AH and healthy controls. White matter disruptions in bilateral SLF and AF appear to be specific to schizophrenia with AH and must be explored further as potential marker of AH, pending replication in other studies.

White matter microstructure and network-connectivity in emerging adults with subclinical psychotic experiences

Group comparisons of individuals with psychotic disorder and controls have shown alterations in white matter microstructure. Whether white matter microstructure and network connectivity is altered in adolescents with subclinical psychotic experiences (PE) at the lowest end of the psychosis severity spectrum is less clear. DWI scan were acquired in 48 individuals with PE and 43 healthy controls (HC). Traditional tensor-derived indices: Fractional Anisotropy, Axial Diffusivity, Mean Diffusivity and Radial Diffusivity, as well as network connectivity measures (global/local efficiency and clustering coefficient) were compared between the groups. Subclinical psychopathology was assessed with the Community Assessment of Psychic Experiences (CAPE) and Montgomery–Åsberg Depression Rating Scale (MADRS) questionnaires and, in order to capture momentary subclinical expression of psychosis, the Experience Sampling Method (ESM) questionnaires. Within the PE-group, interactions between subclinical (momentary) symptoms and brain regions in the model of tensor-derived indices and network connectivity measures were investigated in a hypothesis-generating fashion. Whole brain analyses showed no group differences in tensor-derived indices and network connectivity measures. In the PE-group, a higher positive symptom distress score was associated with both higher local efficiency and clustering coefficient in the right middle temporal pole. The findings indicate absence of microstructural white matter differences between emerging adults with subclinical PE and controls. In the PE-group, attenuated symptoms were positively associated with network efficiency/cohesion, which requires replication and may indicate network alterations in emerging mild psychopathology.

The relationship between childhood abuse and severity of psychosis is mediated by loneliness: an experience sampling study

BackgroundThis study tested the hypotheses that (i) the relationship between a history of childhood abuse and severity of psychosis is mediated by loneliness; (ii) the relationship between loneliness and psychosis is mediated by within-person fluctuations in depressive and anxious feelings. MethodsFifty-nine individuals with non-affective psychotic disorder rated the intensity of loneliness, positive symptoms, and depressive and anxious feelings during repeated moments in daily life (Experience Sampling Method). Childhood abuse was assessed retrospectively using the ‘Childhood Experience of Care and Abuse’ interview. To test the mediation hypotheses, a multilevel structural equation modeling paradigm was used. ResultsAs predicted, the relationship between severity of childhood abuse and positive symptoms was mediated by loneliness (b=0.08, 95% CI [0.02, 0.13], p=0.005). In turn, the relationship between loneliness and positive symptoms was mediated by within-person fluctuations in both depressive (b=0.04, 95% CI [0.02, 0.06], p<0.001) and anxious (b=0.02, 95% CI [0.01, 0.03], p=0.002) symptomatology. Depression was a stronger mediator than anxiety (b=0.02, 95% CI [0.00, 0.04], p=0.027). ConclusionsOur findings highlight the role of childhood abuse and loneliness in the severity of psychosis in daily life.

Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain

Neuromelanin-sensitive MRI (NM-MRI) purports to detect the content of neuromelanin (NM), a product of dopamine metabolism that accumulates with age in dopamine neurons of the substantia nigra (SN). Interindividual variability in dopamine function may result in varying levels of NM accumulation in the SN; however, the ability of NM-MRI to measure dopamine function in nonneurodegenerative conditions has not been established. Here, we validated that NM-MRI signal intensity in postmortem midbrain specimens correlated with regional NM concentration even in the absence of neurodegeneration, a prerequisite for its use as a proxy for dopamine function. We then validated a voxelwise NM-MRI approach with sufficient anatomical sensitivity to resolve SN subregions. Using this approach and a multimodal dataset of molecular PET and fMRI data, we further showed the NM-MRI signal was related to both dopamine release in the dorsal striatum and resting blood flow within the SN. These results suggest that NM-MRI signal in the SN is a proxy for function of dopamine neurons in the nigrostriatal pathway. As a proof of concept for its clinical utility, we show that the NM-MRI signal correlated to severity of psychosis in schizophrenia and individuals at risk for schizophrenia, consistent with the well-established dysfunction of the nigrostriatal pathway in psychosis. Our results indicate that noninvasive NM-MRI is a promising tool that could have diverse research and clinical applications to investigate in vivo the role of dopamine in neuropsychiatric illness.

Increased amygdala-visual cortex connectivity in youth with persecutory ideation.

Subclinical delusional ideas, including persecutory beliefs, in otherwise healthy individuals are heritable symptoms associated with increased risk for psychotic illness, possibly representing an expression of one end of a continuum of psychosis severity. The identification of variation in brain function associated with these symptoms may provide insights about the neurobiology of delusions in clinical psychosis. A resting-state functional magnetic resonance imaging scan was collected from 131 young adults with a wide range of severity of subclinical delusional beliefs, including persecutory ideas. Because of evidence for a key role of the amygdala in fear and paranoia, resting-state functional connectivity of the amygdala was measured. Connectivity between the amygdala and early visual cortical areas, including striate cortex (V1), was found to be significantly greater in participants with high (n = 43) v. low (n = 44) numbers of delusional beliefs, particularly in those who showed persistence of those beliefs. Similarly, across the full sample, the number of and distress associated with delusional beliefs were positively correlated with the strength of amygdala-visual cortex connectivity. Moreover, further analyses revealed that these effects were driven by those who endorsed persecutory beliefs. These findings are consistent with the hypothesis that aberrant assignments of threat to sensory stimuli may lead to the downstream development of delusional ideas. Taken together with prior findings of disrupted sensory-limbic coupling in psychosis, these results suggest that altered amygdala-visual cortex connectivity could represent a marker of psychosis-related pathophysiology across a continuum of symptom severity.

The interactive effect of autism and psychosis severity on theory of mind and functioning in schizophrenia.

Autism and schizophrenia are characterized by impairments in social cognition and functioning. They can co-occur at both the trait/symptom and diagnostic levels. We investigated the concurrent effect of autism and psychotic symptom severity on social cognition and functioning in schizophrenia. Individuals with schizophrenia or schizoaffective disorder were included (N = 81; 32 women). Symptoms were measured with the Positive and Negative Syndrome Scale using the Positive subscale (PANSSpos; Kay, Fiszbein, & Opler, 1987) and the PANSS Autism Severity Score (PAUSS; Kästner et al., 2015). Theory of mind (ToM) was assessed with the Movie for the Assessment of Social Cognition (MASC; Dziobek et al., 2006), which yields scores for three error types: overmentalizing, undermentalizing, and no mentalizing. Functioning was assessed with the Global Assessment of Functioning (GAF-f; Pedersen, Hagtvet, & Karterud, 2007) and the Social Functioning Scale (SFS; Birchwood, Smith, Cochrane, Wetton, & Copestake, 1990). The sample was bimodally distributed and therefore divided into low and high PAUSS groups. We used generalized linear models to examine the effect of PANSSpos, PAUSS, and their interaction on GAF-f, SFS, and MASC scores. For the entire cohort, the PANSSpos × PAUSS interaction was significantly associated with better GAF-f (p = .005), SFS (p = .029), and overall ToM (p = .035), and for the high-PAUSS group, with reduced overmentalizing errors (p = .002), resulting in better overall ToM. Concurrent elevated levels of autism and positive psychotic symptoms seem to benefit functioning and social cognition in schizophrenia. The results are consistent with the diametric model, which posits that autism and schizophrenia are characterized by opposing patterns in mentalizing, and promote the radical idea that the presence of both disorders may be associated with attenuated impairments. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The nature of bradykinesia in schizophrenia treated with antipsychotics

Recognizing drug-induced parkinsonian bradykinesia in psychosis patients can be challenging due to overlapping presentation with psychomotor slowing associated with depression, negative symptoms, or cognitive disturbances. In this study, we apply prior findings on the pathophysiology of bradykinesia in Parkinson's disease to gain an understanding of motor slowing in psychosis patients. Handwriting movements from 57 healthy participants and 70 psychosis patients were recorded on a digitizing tablet. Temporal and kinematic features were extracted from handwritten loops and circles. An independent objective measure based on peak velocity for circles written at maximum speed was used to classify patients as bradykinetic. Using a statistical cut-point derived from normative data, 64% of the patients met criterion for bradykinesia compared with 46% using a conventional observer-based severity rating scale. Bradykinetic patients produced handwriting movements with longer stroke durations, smaller amplitudes and lower peak velocities compared with non-bradykinetic patients. Thirty-six percent of the pen strokes produced by the bradykinetic patients were non-ballistic compare with 20% for the non-bradykinetic patients. The proportion of nonballistic movements observed in handwriting was unrelated to current antipsychotic dose, severity of negative psychosis or depression. The ease-of-use and standardization of a tablet-based approach to quantifying parkinsonian bradykinesia can aid in diagnosing parkinsonian bradykinesia in patients treated with antipsychotics.

Beliefs about voices and their relation to severity of psychosis in chronic schizophrenia patients.

Background:Auditory hallucinations may persist in a subset of chronic psychotic patients in spite of treatment. It is important to understand the personal meaning and significance of voices in these patients. In spite of its relevance, only a limited literature is available.Aim:This exploratory study aimed to assess the beliefs regarding voices in treatment-seeking patients with chronic schizophrenia having persistent auditory verbal hallucinations (AVHs) and assess their relation to the severity of psychosis.Materials and Methods:We recruited thirty adult patients with chronic schizophrenia as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition with both lifetime and current significant AVHs (≥50% days/month). Co-occurring psychiatric disorders were ruled out using the Mini International Neuropsychiatric Interview-7.0.0. Patients were assessed using a semi-structured proforma, Beliefs about Voices Questionnaire-Revised (BAVQ-R), Psychotic Symptom Rating Scale (PSYRATS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), and Clinical Global Impression-Schizophrenia (CGI-SCH)-severity.Results:The median age of the patients was 32 years (interquartile range [IQR]: 23.8–40.5). The median duration of illness and treatment was 7 years (IQR: 3.4–15.0) and 3 years (IQR: 1.9–10.5), respectively. Higher BAVQ-R scores were found on “malevolence,” “omnipotence,” and “emotional and behavioral resistance.” These beliefs had a significant positive correlation with PSYRATS hallucination subscale, but not with the severity of psychosis (SAPS, SANS, and CGI-SCH). The sample had lower scores for “benevolence” and “engagement” subscales of BAV-Q.Conclusion:Overall, the study sample believed AVH to be more malicious and omnipotent rather than benevolent, and resisted the voices, engaging only minimally with them. These beliefs were not related to the severity of psychosis, but were related to the severity of hallucinations. Assessing the beliefs regarding AVH in larger, diverse samples may help to plan behavioral interventions.