Severity Of Positive Psychotic Symptoms Research Articles

Influence of perceived harm due to substance use on the relationships between positive psychotic experiences and suicidal experiences in people with non-affective psychosis.

The ways in which perceived harm due to substance use affects relationships between psychotic and suicidal experiences are poorly understood. The goal of the current study was to redress this gap by investigating the moderating effects of harm due to substance use on pathways involving positive psychotic symptoms, the perceived cognitive-emotional sequelae of those symptoms, and suicidal ideation. The design was cross-sectional. Mediation and moderated mediation pathways were tested. The predictor was severity of positive psychotic symptoms. Cognitive interpretative and emotional characteristics of both auditory hallucinations and delusions were mediators. Suicidal ideation was the outcome variable. General symptoms associated with severe mental health problems were statistically controlled for. There was evidence of an indirect pathway between positive psychotic symptom severity and suicidal ideation via cognitive interpretation and emotional characteristics of both auditory hallucinations and delusions. Harm due to drug use, but not alcohol use, moderated the indirect pathway involving delusions such that it was most prominent when harm due to drug use was at medium-to-high levels. The components of suicidal ideation that were most strongly affected by this moderated indirect pathway were active intent, passive desire, and lack of deterrents. From both scientific and therapy development perspectives, it is important to understand the complex interplay between, not only the presence of auditory hallucinations and delusions, but the ensuing cognitive and emotional consequences of those experiences which, when combined with harm associated with substance use, in particular drug use, can escalate suicidal thoughts and acts.

Impulsivity as a predictor of clinical and psychological outcomes in a naturalistic prospective cohort of subjects at ultra-high risk (UHR) for psychosis from Tunisia

BackgroundImpulsivity is associated with serious detrimental consequences on physical, mental, behavioral and social aspects of health among patients with psychosis. The present prospective 12-month follow-up study aimed to determine the prevalence of highly impulsive individuals among Ultra High Risk (UHR) patients, how impulsivity evolves over the follow-up period, and whether impulsivity impacts clinical, psychological and functional outcomes in this population. MethodUHR patients were invited to complete a battery of measurements at three-time points: at baseline, and at 6 and 12 months of follow-up. Impulsivity was assessed using both behavioral (the Wisconsin Card Sorting Test, WCST) and self-report (the Barratt Impulsiveness Scale, BIS-11) measures. ResultsFindings showed that at 6 months of follow-up, higher 6-month BIS-11 attentional and motor impulsivity were significantly associated with lower quality of life and greater general psychological distress. In addition, higher baseline BIS-11 motor impulsivity significantly predicted more severe positive psychotic symptoms at 12 months of follow-up. However, WCST scores did not show any significant associations with study variables at the different times of follow-up. ConclusionInterventions targeting impulsivity in UHR individuals could help decrease psychological distress and positive psychotic symptoms’ severity, as well as improve quality of life in UHR individuals.

Thalamic contributions to psychosis susceptibility: Evidence from co-activation patterns accounting for intra-seed spatial variability (μCAPs).

The temporal variability of the thalamus in functional networks may provide valuable insights into the pathophysiology of schizophrenia. To address the complexity of the role of the thalamic nuclei in psychosis, we introduced micro-co-activation patterns (μCAPs) and employed this method on the human genetic model of schizophrenia 22q11.2 deletion syndrome (22q11.2DS). Participants underwent resting-state functional MRI and a data-driven iterative process resulting in the identification of six whole-brain μCAPs with specific activity patterns within the thalamus. Unlike conventional methods, μCAPs extract dynamic spatial patterns that reveal partially overlapping and non-mutually exclusive functional subparts. Thus, the μCAPs method detects finer foci of activity within the initial seed region, retaining valuable and clinically relevant temporal and spatial information. We found that a μCAP showing co-activation of the mediodorsal thalamus with brain-wide cortical regions was expressed significantly less frequently in patients with 22q11.2DS, and its occurrence negatively correlated with the severity of positive psychotic symptoms. Additionally, activity within the auditory-visual cortex and their respective geniculate nuclei was expressed in two different μCAPs. One of these auditory-visual μCAPs co-activated with salience areas, while the other co-activated with the default mode network (DMN). A significant shift of occurrence from the salience+visuo-auditory-thalamus to the DMN + visuo-auditory-thalamus μCAP was observed in patients with 22q11.2DS. Thus, our findings support existing research on the gatekeeping role of the thalamus for sensory information in the pathophysiology of psychosis and revisit the evidence of geniculate nuclei hyperconnectivity with the audio-visual cortex in 22q11.2DS in the context of dynamic functional connectivity, seen here as the specific hyper-occurrence of these circuits with the task-negative brain networks.

Functionality appreciation is inversely associated with positive psychotic symptoms in overweight/obese patients with schizophrenia

BackgroundWhile the relationship between negative aspects of body image and positive schizophrenia symptoms was extensively investigated and is relatively well-established, there is a dearth of literature on the relationship between positive symptoms and positive aspects of body image, such as body appreciation and functionality appreciation, in patients with schizophrenia. This study aimed to (1) compare weight stigma, body and functionality appreciation between obese/overweight and normal-weight patients with schizophrenia, and (2) explore the associations between these variables and positive psychotic symptoms in the obese/overweight group.MethodA cross-sectional study was conducted in the Psychiatric Hospital of the Cross, Lebanon during September 2022 recruiting selected in-patients diagnosed with schizophrenia. Patients were classified as overweight/obese if they had a BMI > 25 (N = 76 (37.25%), aged 55.57 ± 11.30 years, 42.6% females). The Weight self‑stigma questionnaire, the Functionality Appreciation Scale, and the Body Appreciation Scale, and the Positive and Negative Syndrome Scale (PANSS) were used.ResultsNo significant difference was found between overweight/obese and normal-weight patients for all variables, except for weight stigma; a significantly higher weight stigma score was significantly found in overweight/obese compared to normal-weight patient. In the bivariate analysis, higher functionality appreciation was significantly associated with higher positive PANSS scores. The results of the linear regression, taking the positive PANSS score as the dependent variable, showed that higher functionality appreciation (Beta = − 0.52) and higher social support (Beta = − 0.16) were significantly associated with lower positive PANSS scores, whereas having a secondary education level compared to illiteracy (Beta = 7.00) was significantly associated with higher positive PANSS scores.ConclusionAlthough based on cross-sectional data, these findings preliminarily suggest that higher functionality appreciation can help reduce the severity of positive psychotic symptoms in overweight/obese schizophrenia patients, and that interventions aimed at improving functionality appreciation could be regarded beneficial therapeutic targets in the treatment of psychosis.

Increased affective reactivity to daily social stressors is associated with more severe psychotic symptoms in youths with 22q11.2 deletion syndrome.

Increased reactivity to minor stressors is considered a risk factor for psychosis, especially in vulnerable individuals. In the present study, we investigated affective and psychotic stress reactivity as well as its link with psychotic symptoms and psychopathology in youths with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition associated with a high risk for psychosis. A 6-day ecological momentary assessment protocol was used to assess perceived daily-life stress as well as affective and psychotic reactivity to stress in participants with 22q11DS (n = 38, age = 18.4) and healthy controls (HC; n = 53, age = 19.1). Psychotic symptoms, general psychopathology, and coping strategies were also assessed through clinical interviews and questionnaires. Participants with 22q11DS reported higher levels of perceived social stress (b = 0.21, p = 0.036) but lower levels of activity-related stress (b = -0.31, p = 0.003) in their daily lives compared to HC. The groups did not differ in affective or psychotic reactivity to stress, but individuals with 22q11DS who reported increased affective reactivity to social stressors showed more severe positive psychotic symptoms (rs = 0.505, p = 0.008). Finally, avoidance coping strategies moderated the association between stress and negative affects. Our results suggest an increased vulnerability for daily social stress in youths with 22q11DS, and link elevated social stress reactivity to heightened psychotic symptom severity. Given the high risk for psychosis in 22q11DS, interventions should focus on reducing social stress and developing adaptive coping strategies.

Neural substrates of psychosis revealed by altered dependencies between brain activity and white-matter architecture in individuals with 22q11 deletion syndrome

BackgroundDysconnectivity has been consistently proposed as a major key mechanism in psychosis. Indeed, disruptions in large-scale structural and functional brain networks have been associated with psychotic symptoms. However, brain activity is largely constrained by underlying white matter pathways and the study of function-structure dependency, compared to conventional unimodal analysis, allows a biologically relevant assessment of neural mechanisms. The 22q11.2 deletion syndrome (22q11DS) constitutes a remarkable opportunity to study the pathophysiological processes of psychosis. Methods58 healthy controls and 57 deletion carriers, aged from 16 to 32 years old,underwent resting-state functional and diffusion-weighted magnetic resonance imaging. Deletion carriers were additionally fully assessed for psychotic symptoms. Firstly, we used a graph signal processing method to combine brain activity and structural connectivity measures to obtain regional structural decoupling indexes (SDIs). We use SDI to assess the differences of functional structural dependency (FSD) across the groups. Subsequently we investigated how alterations in FSDs are associated with the severity of positive psychotic symptoms in participants with 22q11DS. ResultsIn line with previous findings, participants in both groups showed a spatial gradient of FSD ranging from sensory-motor regions (stronger FSD) to regions involved in higher-order function (weaker FSD). Compared to controls, in participants with 22q11DS, and further in deletion carriers with more severe positive psychotic symptoms, the functional activity was more strongly dependent on the structure in parahippocampal gyrus and subcortical dopaminergic regions, while it was less dependent within the cingulate cortex. This analysis revealed group differences not otherwise detected when assessing the structural and functional nodal measures separately. ConclusionsOur findings point toward a disrupted modulation of functional activity on the underlying structure, which was further associated to psychopathology for candidate critical regions in 22q11DS. This study provides the first evidence for the clinical relevance of function-structure dependency and its contribution to the emergence of psychosis.

CLINICAL AND SOCIAL FACTORS ASSOCIATED WITH VIOLENT BEHAVIOR IN PERSONS WITH SCHIZOPHRENIA SPECTRUM DISORDERS

Study of the relationship between mental disorder and violent behavior is critical both from a public health perspective and for the proper planning and development of mental health services.However, the complex contribution of clinical, historical and environmental risk factors for violence in persons with schizophrenia remains unclear. The aim of the study was to identify clinical and social risk factors for violence in patients with schizophrenia and schizophrenia spectrum disorders (SSD) using a case-control design. Cases were defined as patients with SSD who had committed at least one act of offence in the past (94 patients wereenrolled from forensic psychiatricward). Controls were genderand age matched patients with SSD who had never committed violent acts (106 patients from general psychiatric services).A standard set of instruments was used to assess patients exposure to a variety of risk factors. Data were collected through patient interviews and medical records.Study results showed, that increased risk of violence was associated with severity of positive psychotic symptoms, diagnosis of delusional disorder, irregular or no contacts with mental health services. Significant risk factors for serious violent acts were associated with comorbid alcohol misuse, impulsivity,persecutory delusions,decreased emotional responseand unsatisfactory living environment. Study confirmed that the interaction of social andclinicalfactorswith treatment related factors played an important role as determinants of violence. These factors should be the focus of treatment and management of patients with SSD to prevent violent behavior.

Cannabidiol for at risk for psychosis youth: A randomized controlled trial.

No biological treatment has been firmly established for the at-risk stage of psychotic disorder. In this study we aim to test if subthreshold psychotic symptoms can be effectively treated with cannabidiol (CBD), a non-psychoactive compound of the plant Cannabis sativa. The question has taken on increased importance in the wake of evidence questioning both the need and efficacy of specific pharmacological interventions in the ultra-high risk (UHR) for psychosis group. Three-arm randomized controlled trial of 405 patients (135 per arm) aged 12-25 years who meet UHR for psychosis criteria. The study includes a 6-week lead-in phase during which 10% of UHR individuals are expected to experience symptom remission. Participants will receive CBD (per oral) at doses 600 or 1000 mg per day (fixed schedule) for 12 weeks. Participants in the third arm of the trial will receive matching placebo capsules. Primary outcome is severity of positive psychotic symptoms as measured by the Comprehensive Assessment of At-Risk Mental States at 12 weeks. We hypothesize that CBD will be significantly more effective than placebo in improving positive psychotic symptoms in UHR patients. All participants will also be followed up 6months post baseline to evaluate if treatment effects are sustained. This paper reports on the rationale and protocol of the Cannabidiol for At Risk for psychosis Youth (CanARY) study. This study will test CBD for the first time in the UHR phase of psychotic disorder.

Interactions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to adverse outcomes

Preclinical models propose that increased hippocampal activity drives subcortical dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. Here, we used multimodal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis and investigated its association with subsequent clinical and functional outcomes. Ninety-five participants (67 CHR and 28 healthy controls) underwent arterial spin labeling MRI and 18F-DOPA PET imaging at baseline. CHR participants were followed up for a median of 15 months to determine functional outcomes with the global assessment of function (GAF) scale and clinical outcomes using the comprehensive assessment of at-risk mental states (CAARMS). CHR participants with poor functional outcomes (follow-up GAF < 65, n = 25) showed higher rCBF in the right hippocampus compared to CHRs with good functional outcomes (GAF ≥ 65, n = 25) (pfwe = 0.026). The relationship between rCBF in this right hippocampal region and striatal dopamine synthesis capacity was also significantly different between groups (pfwe = 0.035); the association was negative in CHR with poor outcomes (pfwe = 0.012), but non-significant in CHR with good outcomes. Furthermore, the correlation between right hippocampal rCBF and striatal dopamine function predicted a longitudinal increase in the severity of positive psychotic symptoms within the total CHR group (p = 0.041). There were no differences in rCBF, dopamine, or their associations in the total CHR group relative to controls. These findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of adverse outcomes in the CHR state.

Dysmaturation Observed as Altered Hippocampal Functional Connectivity at Rest Is Associated With the Emergence of Positive Psychotic Symptoms in Patients With 22q11 Deletion Syndrome

BackgroundHippocampal alterations are among the most replicated neuroimaging findings across the psychosis spectrum. Moreover, there is strong translational evidence that preserving the maturation of hippocampal networks in mice models prevents the progression of cognitive deficits. However, the developmental trajectory of hippocampal functional connectivity (HFC) and its contribution to psychosis is not well characterized in the human population. 22q11 deletion syndrome (22q11DS) offers a unique model for characterizing early neural correlates of schizophrenia. MethodsWe acquired resting-state functional magnetic resonance imaging in 242 longitudinally repeated scans from 84 patients with 22q11DS (30 with moderate to severe positive psychotic symptoms) and 94 healthy control subjects in the age span of 6 to 32 years. We obtained bilateral hippocampus to whole-brain functional connectivity and employed a novel longitudinal multivariate approach by means of partial least squares correlation to evaluate the developmental trajectory of HFC across groups. ResultsRelative to control subjects, patients with 22q11DS failed to increase HFC with frontal regions such as the dorsal part of the anterior cingulate cortex, prefrontal cortex, and supplementary motor area. Concurrently, carriers of the deletion had abnormally higher HFC with subcortical dopaminergic areas. Remarkably, this aberrant maturation of HFC was more prominent during midadolescence and was mainly driven by patients exhibiting subthreshold positive psychotic symptoms. ConclusionsOur findings suggest a critical period of prefrontal cortex–hippocampal–striatal circuit dysmaturation, particularly during late adolescence, which in light of current translation evidence could be a target for short-term interventions to potentially achieve long-lasting rescue of circuit dysfunctions associated with psychosis.

Potential contribution of pineal atrophy and pineal cysts toward vulnerability and clinical characteristics of psychosis

BackgroundMagnetic resonance imaging (MRI) studies reported pineal gland atrophy in schizophrenia patients and individuals at a clinical high risk of developing psychosis, implicating abnormalities in melatonin secretion in the pathophysiology of psychosis. However, it currently remains unclear whether the morphology of the pineal gland contributes to symptomatology and sociocognitive functions. MethodsThis MRI study examined pineal gland volumes and the prevalence of pineal cysts as well as their relationship with clinical characteristics in 57 at risk mental state (ARMS) subjects, 63 patients with schizophrenia, and 61 healthy controls. The Social and Occupational Functioning Assessment Scale (SOFAS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Brief Assessment of Cognition in Schizophrenia (BACS) were used to assess sociocognitive functions, while the Positive and Negative Syndrome Scale was employed to evaluate clinical symptoms in ARMS subjects and schizophrenia patients. ResultsPineal gland volumes were significantly smaller in the ARMS and schizophrenia groups than in the controls, while no significant differences were observed in the prevalence of pineal cysts. Although BACS, SCoRS, and SOFAS scores were not associated with pineal morphology, patients with pineal cysts in the schizophrenia group exhibited severe positive psychotic symptoms with rather mild negative symptoms. ConclusionThe present results indicate the potential of pineal atrophy as a vulnerability marker in various stages of psychosis and suggest that pineal cysts influence the clinical subtype of schizophrenia.

Cerebellar Activation Deficits in Schizophrenia During an Eyeblink Conditioning Task.

The cognitive dysmetria theory of psychotic disorders posits that cerebellar circuit abnormalities give rise to difficulties coordinating motor and cognitive functions. However, brain activation during cerebellar-mediated tasks is understudied in schizophrenia. Accordingly, this study examined whether individuals with schizophrenia have diminished neural activation compared to controls in key regions of the delay eyeblink conditioning (dEBC) cerebellar circuit (eg, lobule VI) and cerebellar regions associated with cognition (eg, Crus I). Participants with schizophrenia-spectrum disorders (n = 31) and healthy controls (n = 43) underwent dEBC during functional magnetic resonance imaging (fMRI). Images were normalized using the Spatially Unbiased Infratentorial Template (SUIT) of the cerebellum and brainstem. Activation contrasts of interest were “early” and “late” stages of paired tone and air puff trials minus unpaired trials. Preliminary whole brain analyses were conducted, followed by cerebellar-specific SUIT and region of interest (ROI) analyses of lobule VI and Crus I. Correlation analyses were conducted between cerebellar activation, neuropsychological test scores, and psychotic symptom scores. In controls, the largest clusters of cerebellar activation peaked in lobule VI during early dEBC and Crus I during late dEBC. The schizophrenia group showed robust cortical activation to unpaired trials but no significant conditioning-related cerebellar activation. Crus I ROI activation during late dEBC was greater in the control than schizophrenia group. Greater Crus I activation correlated with higher working memory scores in the full sample and lower positive psychotic symptom severity in schizophrenia. Findings indicate functional cerebellar abnormalities in schizophrenia which relate to psychotic symptoms, lending direct support to the cognitive dysmetria framework.

Elucidating the Impact of Childhood, Adulthood, and Cumulative Lifetime Trauma Exposure on Psychiatric Symptoms in Early Schizophrenia Spectrum Disorders.

Cumulative lifetime trauma has a profound impact on the development of schizophrenia spectrum disorders. However, few studies have determined participants' most distressing (i.e., "worst") life event in childhood or adulthood or examined whether this event contributes to poorer clinical outcomes. The present study aimed to (a) determine the associations between the worst life event and demographic/clinical variables and (b) examine the associations between the worst life event and psychiatric symptoms (i.e., positive, negative, depressive, and anxiety symptoms). Participants (N = 150) were outpatients newly diagnosed with schizophrenia spectrum disorders who were assessed for lifetime trauma exposure, positive and negative symptoms of schizophrenia, and symptoms of depression and anxiety. Multinomial logistic regression analysis was conducted to examine the associations between demographic and clinical variables and worst life events (none, childhood, or adulthood). Multiple linear regression analyses were performed to examine the associations between worst life events and psychiatric symptoms. More participants reported that their worst life event occurred during adulthood (31.1%) than childhood (21.3%). Adulthood trauma was associated with male gender, older age, non-Chinese ethnicity, and psychiatric comorbidities; childhood trauma was associated with a family history of depression/anxiety. Adulthood trauma was significantly associated with more severe positive psychotic symptoms, f2 = 0.19, whereas childhood and adulthood trauma exposure were both significantly associated with more severe depressive and anxiety symptoms, f2 s = 0.19 and 0.25, respectively. Our findings underscore the importance of conducting assessments for worst life events and the associated risk factors to develop meaningful formulations and appropriate trauma-focused treatment plans.

Imaging Brain Fatty Acid Amide Hydrolase in Untreated Patients With Psychosis

BackgroundThe brain’s endocannabinoid system, the primary target of cannabis, has been implicated in psychosis. The endocannabinoid anandamide is elevated in cerebrospinal fluid of patients with schizophrenia. Fatty acid amide hydrolase (FAAH) controls brain anandamide levels; however, it is unknown if FAAH is altered in vivo in psychosis or related to positive psychotic symptoms. MethodsTwenty-seven patients with schizophrenia spectrum disorders and 36 healthy control subjects completed high-resolution positron emission tomography scans with the novel FAAH radioligand [11C]CURB and structural magnetic resonance imaging. Data were analyzed using the validated irreversible 2-tissue compartment model with a metabolite-corrected arterial input function. ResultsFAAH did not differ significantly between patients with psychotic disorders and healthy control subjects (F1,62.85 = 0.48, p = .49). In contrast, lower FAAH predicted greater positive psychotic symptom severity, with the strongest effect observed for the positive symptom dimension, which includes suspiciousness, delusions, unusual thought content, and hallucinations (F1,26.69 = 12.42, p = .002; Cohen’s f = 0.42, large effect). Shorter duration of illness (F1,26.95 = 13.78, p = .001; Cohen’s f = 0.39, medium to large effect) and duration of untreated psychosis predicted lower FAAH (F1,26.95 = 6.03, p = .021, Cohen’s f = 0.27, medium effect). These results were not explained by past cannabis exposure or current intake of antipsychotic medications. FAAH exhibited marked differences across brain regions (F7,112.62 = 175.85, p < 1 × 10−56; Cohen’s f > 1). Overall, FAAH was higher in female subjects than in male subjects (F1,62.84 = 10.05, p = .002; Cohen’s f = 0.37). ConclusionsThis first study of brain FAAH in psychosis indicates that FAAH may represent a biomarker of disease state of potential utility for clinical studies targeting psychotic symptoms or as a novel target for interventions to treat psychotic symptoms.

Direction of the relationship between methamphetamine use and positive psychotic symptoms in regular methamphetamine users: evidence from a prospective cohort study.

Methamphetamine has been consistently associated with positive psychotic symptoms, but little is known about whether the reverse also occurs. This study determined whether the relationship between methamphetamine use and positive psychotic symptoms is bidirectional over 12 months. The impact of lifetime psychotic disorders and methamphetamine dependence on these relationships was also examined. A total of 201 regular (at least monthly) primary methamphetamine users were recruited from free needle and syringe programmes in three Australian cities. Data on the frequency of methamphetamine and other drug use (from Timeline Followback inteviews) and the severity of positive psychotic symptoms (using the Brief Psychiatric Rating Scale) in the past 2 weeks were collected in 12 contiguous monthly face-to-face interviews (mean of 9.14/11 (s.d. = 3.16) follow-ups completed). Diagnoses were derived using the Psychiatric Research Interview for DSM-IV Substance and Mental Disorders. The mean age of participants was 31.71 years (s.d. = 8.19) and 39% (n = 77) were women. At baseline 55% (n = 110) were dependent on methamphetamine and 51% (n = 102) had a lifetime psychotic disorder. Cross-lagged dynamic panel models found a significant bidirectional relationship between psychotic symptoms and methamphetamine use (Comparative Fit Index (CFI) = 0.94, standardised root mean square residual (SRMR) = 0.05, root mean square error of approximation (RMSEA) = 0.05, 95% CI 0.04-0.06). The magnitude of the relationship in each direction was similar, and the presence of methamphetamine dependence or a lifetime psychotic disorder did not have an impact on results. A dynamic, bidirectional relationship between methamphetamine and psychotic symptoms of similar magnitude in each direction was found over 1 year. This suggests integrated treatments that target methamphetamine, psychotic symptoms and their interrelationship may be of most benefit.

Disentangling compliance with command hallucinations: Heterogeneity of voice intents and their clinical correlates

BackgroundEarlier studies suggested that perceptions of voice intents (benevolence, malevolence) are associated with different psychological and behavioral responses including compliance with command hallucinations (CH). However, to our knowledge, no studies have examined the clinical differences between subgroups of clients with different perceptions of the intents of their CH. In order to better understand the risk for compliance with CH, our objectives were 1) to compare sociodemographic and clinical profiles of subgroups of clients (based on perceptions of CH intents); and 2) to investigate their specific associated risk factors for compliance with CH. MethodWe analyzed the MacArthur Violence Risk Assessment Study, focusing on 181 participants with psychosis reporting CH. Group comparisons and within-group ordinal logistic regression analyses were performed using sociodemographic and clinical measures such as the BPRS, BIS-11 and NAS-PI. ResultsOf the 181 participants, 102 (56.4%) reported having only malevolent voices, 14 (7.7%) rated them as benevolent only, 58 (32.03%) as benevolent and malevolent, and only 7 (3.86%) as neutral only. Results showed that individuals with malevolent voices had more emotional disturbance while those with benevolent CH had more severe positive psychotic symptoms and were more certain that they would comply in the future. Moreover, childhood physical abuse, belief about having to obey as well as psychotic symptoms significantly predict compliance with malevolent CH in a multivariate model. ConclusionsOur results suggest that researchers and clinicians should consider perceptions of voice intents when both assessing risk of compliance with CH and developing relevant intervention targets.

The development of Kraepelin's mature diagnostic concept of hebephrenia: a close reading of relevant texts of Hecker, Daraszkiewicz, and Kraepelin.

In developing his mature concept of hebephrenic dementia praecox (DP) in his 4th (1893) through 6th textbook editions (1899), Kraepelin worked from the hebephrenic syndrome first described by Hecker (1871) and then carefully studied by his student Daraszkiewicz (1892). Working under Kraepelin's supervision, Daraszkiewicz followed Hecker in emphasizing several key features of hebephrenia (distinctive deteriorative course, importance of silliness and minimal positive psychotic symptoms) but expanded the syndrome to include cases developing severe dementia, rejected the link to prodromal depressive and manic phases, and reduced the emphasis on thought disorder. Daraszkiewicz proposed a soft subtyping of hebephrenia based on level of deterioration, which Kraepelin adopted in his 4th edition with an additional emphasis on severe positive psychotic symptoms. In his 5th edition, Kraepelin created a third subform with even more pronounced and bizarre delusions and hallucinations. In his 6th edition, which contained his first articulation of DP, Kraepelin eliminated his hebephrenia subforms presenting a single syndrome, which, compared to Hecker, included more emphasis on positive psychotic and catatonic symptoms and severe dementia. Kraepelin's paths to hebephrenic and paranoid DP differed in important ways. Paranoid DP was a de novo syndrome created by differentiation from paranoia. Hebephrenia, by contrast, evolved from a disorder created in the Kahlbaum/Hecker paradigm of the iterative study of clinical features, course and outcome. Kraepelin further implemented this approach in substantially reworking, over several drafts, the hebephrenic syndrome to fit into his emerging construct of dementia praecox.

Rates, determinants and outcomes associated with the use of community treatment orders in young people experiencing first episode psychosis

BackgroundCommunity treatment orders (CTOs) are a controversial form of involuntary treatment for individuals affected by mental health disorders and yet little is known about the use of CTOs in first presentations. Therefore, this study aimed to determine the rates, determinants and outcomes associated with the use of CTOs in young people with a first episode of psychosis (FEP). MethodsThis epidemiological cohort study included all individuals aged 15–24 who presented with a FEP to the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne between 01.01.2011 and 31.12.13. ResultsA total of 544 young people presented with a FEP during the study period and of these, 93 (17.3%) were subject to a CTO during their episode of care. A total of 69.7% of CTOs were commenced after the first three months of treatment and the median duration of CTOs was 168.5 days. Males, a diagnosis of a schizophrenia spectrum disorder and a concurrent substance abuse disorder were associated with the use of CTOs. Additionally, young people with more severe positive psychotic symptoms were more likely to be subject to a CTO. At the time of discharge, only 38.7% of those subject to a CTO were in education or employment compared to 65.4% of those who had not been subject to a CTO. ConclusionsThe majority of CTOs are commenced after at least three months of treatment, however the optimal timing of CTO implementation needs to be determined. The poor functioning of young people on a CTO should be the focus of future interventional studies.

Elevated allostatic load early in the course of schizophrenia

Stress plays a significant role in schizophrenia from disease onset to exacerbation of psychotic symptoms. Allostatic load (AL) is a measure of cumulative stress to the organism. This study is an extension of our previous work on AL and its relationship to brain structures. Here, we further determined whether elevated AL is a function of illness chronicity, or if it is already present early in the course of schizophrenia. AL was compared in schizophrenia patients early in the illness (within 5 years of disease onset), patients with chronic schizophrenia (more than 5 years of illness), and two groups of healthy controls that were age-and sex-matched to the two patient groups. This work is presented with an expanded sample and includes about two-thirds of the participants who were previously reported. We found that patients with early psychosis had significantly elevated AL score compared with their age-matched controls (p = 0.005). Chronic course patients also had elevated AL compared with age-matched controls (p = 0.003). Immune and stress hormone AL subcomponents were nominally higher in early-stage patients compared with controls (p = 0.005 and 0.04, respectively). Greater AL was also associated with more severe positive psychotic symptoms in early-stage patients (r = 0.54, p = 0.01). Elevated levels of allostatic load are already present in the early years of the schizophrenia illness, particularly in patients with more severe psychotic symptoms. AL may be a useful evaluation for the need of early intervention on psychosomatic comorbidity.

Bidirectional Relationship Between Methamphetamine Use and Positive Psychotic Symptoms in Regular Methamphetamine Users: Evidence From a Prospective Cohort Study

Background: Methamphetamine (MA) use is a major public health concern worldwide. MA has been causally associated with positive psychotic symptoms, but research is yet to determine if the reverse also occurs. This study prospectively determined whether the relationship between MA use and positive psychotic symptoms is bidirectional. impact of lifetime psychotic disorders and MA dependence on these relationships was also examined. Methods: This 12-month prospective study recruited a cohort of 201 regular (at least monthly use) primary MA users from free needle syringe programs in three Australian cities. Data on the frequency of MA use (Timeline Followback) and the severity of positive psychotic symptoms (Brief Psychiatric Rating Scale subscale) in the past 2 weeks were collected in 12 contiguous monthly face-to-face interviews. Diagnoses were derived using the Psychiatric Research Interview for DSM-IV Substance and Mental Disorders. Outcomes: Participants had a mean age of 31.71 years (SD=8.10) and 38% (n=77) were female. At baseline 55% (n=110) were dependent on MA and 51% (n=101) had a lifetime psychotic disorder, comprised of 23% (n=23) primary and 77% (n=79) substance-induced psychotic disorders. Participants completed a mean of 9.14 (SD=3.16) out of the 11 follow up interviews were completed, 52% (n=104) completed all 11 interviews. Cross-lagged dynamic panel models were used to simultaneously test whether psychotic symptoms predicted higher levels of MA use in the next wave; and higher MA use predicted psychotic symptoms in the same next wave. This indicated there was a significant bidirectional relationship between psychotic symptoms and MA use (CFI = 0.94, RMSEA = 0.05 (95% CI = 0.04, 0.06). magnitude of the relationship in each direction was similar, indicating neither direction predominated. This bidirectional relationship was found, regardless of whether participants had MA dependence or a lifetime psychotic disorder. Interpretation: A bidirectional relationship between MA use and psychotic symptoms, of similar magnitude in each direction was found over one year. This highlights the dynamic and reciprocal nature of the relationship between MA and psychotic symptoms among MA users, and suggests integrated treatments that simultaneously target both of these variables may be of most benefit. Funding Statement: This project was funded by an Australian National Health and Medical Research Council (NHMRC) Project Grant (APP326220). Leanne Hides and Maree Teesson are supported by NHMRC Senior Research and Principal Research Fellowships. Gary Chan and Rebecca McKetin are supported by University of Queensland and Curtin University Research Fellowships. Declaration of Interests: authors state: The authors have no conflicts of interest. Ethics Approval Statement: This project was approved by the relevant ethics review board and all participant provided written informed consent after receiving a description of the study.