Organic psychosis: The pathobiology and treatment of delusions

Organic or secondary psychosis can be seen in diverse conditions such as toxic/metabolic disorders, neurodegenerative disease, and stroke. Poststroke psychosis is a rare phenomenon, but its study has significantly contributed to the understanding of delusion formation. The evidence from case studies of patients with focal strokes shows that delusions develop following unilateral damage of the right hemisphere. The majority of patients with right hemisphere stroke do not develop delusions however, and advanced neuroimaging analysis has elucidated why this symptom develops in only a small proportion. Lesions of the right lateral prefrontal cortex or lesions with connectivity to this area correlate with delusional beliefs in this subgroup. Studies of patients with primary psychosis, for example schizophrenia, or under the influence of the psychotogenic drug ketamine, also show abnormal function of this area in relation to the severity of their abnormal beliefs. The conclusion of these studies is that the right lateral prefrontal cortex is 1 hub in a neural network which includes the basal ganglia and limbic system and receives inputs from midbrain dopamine neurones. In patients with schizophrenia, or at risk of psychosis, dopamine is dysregulated and evidence suggests that faulty dopamine signaling is the precursor of delusion formation. It is therefore likely that the mechanism of delusion formation is the same in both primary and secondary psychosis. This is consistent with the mainstay of treatment of both conditions being antipsychotic medication. However, antipsychotic medication in people with cerebrovascular disease should be avoided if at all possible. This is because epidemiological studies have found that antipsychotic use is associated with an increased risk of stroke and will thus compound the possibility of a further cerebrovascula

Neural and behavioral correlates of aberrant salience in individuals at risk for psychosis

Correction to the original article published in Schizophrenia Bulletin, Volume 39, Issue 6, 1 November 2013, Pages 1328–1336; https://doi.org/10.1093/schbul/sbs147

The effect of cannabis use and cognitive reserve on age at onset and psychosis outcomes in first-episode schizophrenia

Cannabis use is associated with a younger age at onset of psychosis, an indicator of poor prognosis, but better cognitive function, a positive prognostic indicator. We aimed to clarify the role of age at onset and cognition on outcomes in cannabis users with first-episode schizophrenia as well as the effect of cannabis dose and cessation of use

A window into the brain: an in vivo study of the retina in schizophrenia using optical coherence tomography.

Retinal nerve fibre layer (RNFL) thickness and macular volume (MV) can be measured in vivo using optical coherence tomography (OCT) providing a "window into the brain". RNFL and MV are promising biomarkers in neurological diseases. This study explores the potential of RNFL and MV to detect axonal abnormalities in vivo in schizophrenia and their correlations with clinical features. OCT was performed in 49 patients (38 schizophrenia, 11 schizoaffective disorder) and 40 healthy controls matched for age and gender. Group comparisons were made between whole retina and quadrant RNFL thickness and MV using multi-level analyses. In patients, associations were sought between RNFL and MV with symptom severity (positive/negative). Patients and controls had similar whole retina RNFL thickness (p=0.86) and MV (p=0.64), but RNFL in the right nasal quadrant of the schizoaffective group was thinner than in the schizophrenia group (p=0.02). In patients, positive symptom severity was associated with smaller MV (right β=-0.54, p=0.02; left β=-0.49, p=0.04). Normal MV and RNFL thickness suggests unmyelinated axons in patients with schizophrenia/schizoaffective disorder remain unaffected. Longitudinal studies using higher resolution OCT will clarify whether progressive RNFL and MV changes occur and whether they can be used as state or trait markers in schizophrenia

Are socioenvironmental factors associated with psychotic symptoms in people with first-episode psychosis? A cross-sectional study of a West London clinical sample.

OBJECTIVES: To determine whether neighbourhood-level socioenvironmental factors including deprivation and inequality predict variance in psychotic symptoms after controlling for individual-level demographics. DESIGN: A cross-sectional design was employed. SETTING: Data were originally collected from secondary care services within the UK boroughs of Ealing, Hammersmith and Fulham, Wandsworth, Kingston, Richmond, Merton, Sutton and Hounslow as part of the West London First-Episode Psychosis study. PARTICIPANTS: Complete case analyses were undertaken on 319 participants who met the following inclusion criteria: aged 16 years or over, resident in the study's catchment area, experiencing a first psychotic episode, with fewer than 12 weeks' exposure to antipsychotic medication and sufficient command of English to facilitate assessment. OUTCOME MEASURES: Symptom dimension scores, derived from principal component analyses of the Scale for the Assessment of Positive Symptoms and Scale for the Assessment of Negative Symptoms, were regressed on neighbourhood-level predictors, including population density, income deprivation, income inequality, social fragmentation, social cohesion, ethnic density and ethnic fragmentation, using multilevel regression. While age, gender and socioeconomic status were included as individual-level covariates, data on participant ethnicity were not available. RESULTS: Higher income inequality was associated with lower negative symptom scores (coefficient=-1.66, 95% CI -2.86 to -0.46, p<0.01) and higher levels of ethnic segregation were associated with lower positive symptom scores (coefficient=-2.32, 95% CI -4.17 to -0.48, p=0.01) after adjustment for covariates. CONCLUSIONS: These findings provide further evidence that particular characteristics of the environment may be linked to specific symptom clusters in psychosis. Longitudinal studies are required to begin to tease apart the underlying mechanisms involved as well as the causal direction of such associations

The component structure of the scales for the assessment of positive and negative symptoms in first-episode psychosis and its dependence on variations in analytic methods.

A secondary analysis was undertaken on Scales for the Assessment of Positive and Negative Symptoms (SAPS/SANS) data from 345 first-episode psychosis (FEP) patients gathered in the West London FEP study. The purpose of this study was to determine: (i) the component structure of these measures in FEP (primary analyses), and (ii) the dependence of any findings in these primary analyses on variations in analytic methods. Symptom ratings were exposed to data reduction methods and the effects of the following manipulations ascertained: (i) level of analysis (individual symptom vs. global symptom severity ratings), (ii) extraction method (principal component vs. exploratory factor analysis) and (iii) retention method (scree test vs. Kaiser criterion). Whilst global ratings level analysis rendered the classic triad of psychotic syndromes (positive, negative and disorganisation), symptom level analyses revealed a hierarchical structure, with 11 first-order components subsumed by three second-order components, which also mapped on to this syndrome triad. These results were robust across data reduction but not component retention methods, suggesting that discrepancies in the literature regarding the component structure of the SAPS/SANS partly reflect the level of analysis and component retention method used. Further, they support a hierarchical symptom model, the implications of which are discussed

Disrupted reward processing in Parkinson's disease and its relationship with dopamine state and neuropsychiatric syndromes: a systematic review and meta-analysis

Background: Neuropsychiatric symptoms are common in Parkinson’s disease (PD) and predict poorer outcomes. Reward processing dysfunction is a candidate mechanism for the development of psychiatric symptoms including depression and impulse control disorders (ICDs). We aimed to determine whether reward processing is impaired in PD and its relationship with neuropsychiatric syndromes and dopamine replacement therapy. // Methods: The Ovid MEDLINE/PubMed, Embase and PsycInfo databases were searched for articles published up to 5 November 2020. Studies reporting reward processing task performance by patients with PD and healthy controls were included. Summary statistics comparing reward processing between groups were converted to standardised mean difference (SMD) scores and meta-analysed using a random effects model. // Results: We identified 55 studies containing 2578 participants (1638 PD and 940 healthy controls). Studies assessing three subcomponent categories of reward processing tasks were included: option valuation (n=12), reinforcement learning (n=37) and reward response vigour (n=6). Across all studies, patients with PD on medication exhibited a small-to-medium impairment versus healthy controls (SMD=0.34; 95% CI 0.14 to 0.53), with greater impairments observed off dopaminergic medication in within-subjects designs (SMD=0.43, 95% CI 0.29 to 0.57). Within-subjects subcomponent analysis revealed impaired processing off medication on option valuation (SMD=0.57, 95% CI 0.39 to 0.75) and reward response vigour (SMD=0.36, 95% CI 0.13 to 0.59) tasks. However, the opposite applied for reinforcement learning, which relative to healthy controls was impaired on-medication (SMD=0.45, 95% CI 0.25 to 0.65) but not off-medication (SMD=0.28, 95% CI −0.03 to 0.59). ICD was the only neuropsychiatric syndrome with sufficient studies (n=13) for meta-analysis, but no significant impairment was identified compared tonon-ICD patients (SMD=−0.02, 95% CI −0.43 to 0.39). // Conclusion: Reward processing disruption in PD differs according to subcomponent and dopamine medication state, and warrants further study as a potential treatment target and mechanism underlying associated neuropsychiatric syndromes

Role Stress, Role Reward, and Mental Health in a Multiethnic Sample of Midlife Women: Results from the Study of Women's Health Across the Nation (SWAN)

Abstract Background: Little is known about the independent associations of reward and stress within specific roles with multiple measures of mental health in an ethnically diverse community sample of midlife women. The objective of this study is to examine if (1) role reward (within each role and across roles) contributes directly to mental health and buffers the negative impact of role stress and (2) associations among role occupancy, role stress, and role reward and mental health vary by race/ethnicity. Methods: With separate logistic regression analysis, we investigated cross-sectional relationships between role stress and role reward with presence/absence of high depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D≥16]), anxiety symptoms (feeling tense or nervous, irritable or grouchy, fearful for no reason, and heart pounding or racing total score≥4), or low social functioning (bottom 25th percentile of the Short-Form-36 [SF-36] social functioning subscale) in 2549 women participating in the third visit of the Study of Women's Health Across the Nation (SWAN), a longitudinal population-based study of menopause. Results: High reward across roles attenuated the negative impact of role stress on social functioning but not on anxiety or depression. High reward marriage buffered the impact of marital stress on depression, and high reward mothering buffered the effect of maternal stress on depression and social functioning. Compared to Caucasians, Hispanics and Chinese with high stress across roles had better social functioning, and African American mothers had lower odds of high depressive symptoms. Conclusions: Role reward buffers the negative impact of stress on social functioning and depression, but not on anxiety. Minorities may respond to role stress by seeking social support.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98462/1/jwh%2E2011%2E3180.pd