Unveiling Assessment Gaps in Parkinson's Disease Psychosis: A Scoping Review.

BACKGROUND: Parkinson's disease psychosis (PDP) is a multidimensional construct that is challenging to measure. Accurate assessment of PDP requires comprehensive and reliable clinical outcome assessment (COA) measures. OBJECTIVE: To identify PDP measurement gaps in available COAs currently used in clinical and research settings. METHODS: We conducted a scoping review using Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) guidelines. We implemented a three-step search strategy in international databases with keywords related to Parkinson's disease (PD), psychosis, and COA. We analyzed studies using COA to assess PDP, classifying their items according to domains and subdomains. RESULTS: From 5673 identified studies, we included 628 containing 432 PDP core items from 32 COAs. Among the 32 COAs, 19 were PD-specific, containing 266 items, constructed as clinician-reported outcomes (ClinRO) (148 items), patient-reported outcomes (PRO) (112 items), and observer-reported outcomes (ObsRO) (six items). Across all PD-specific COAs, regardless of structure, 89.4% of the items from 27 COAs focused primarily on assessing PDP symptoms' severity, and only 9.7% of items probed the impact of PDP on a person's daily functioning. CONCLUSIONS: Symptom-based domains are currently prioritized for measuring the severity of PDP, with limited coverage of the functional impact of PDP on patients' lives. Whereas the International Parkinson and Movement Disorder Society has traditionally developed a "Unified" COA that culls items from prior COAs to form a new one, a new COA will largely need newly developed items if the functional impact of PDP is prioritized. © 2024 International Parkinson and Movement Disorder Society.

Assessment of Psychotic Symptoms in Individuals Exposed to Very High or Extreme Altitude: A Field Study.

Hüfner, Katharina, Fabio Caramazza, Agnieszka E. Stawinoga, Evelyn R. Pircher Nöckler, Paolo Fusar-Poli, Sanjeeb S. Bhandari, Buddha Basnyat, Monika Brodmann Maeder, Giacomo Strapazzon, Iztok Tomazin, Barbara Sperner-Unterweger, and Hermann Brugger. Assessment of psychotic symptoms in individuals exposed to very high or extreme altitude: A field study. High Alt Med Biol. 22:369-378, 2021. Background: Symptoms of psychosis such as hallucinations can occur at high or extreme altitude and have been linked to accidents on the mountain. No data are available on how to assess such symptoms in the field and what their prevalence or predisposing factors might be. Methods: In this field study at Everest Base Camp (5,365 m) in Nepal, 99 participants of organized expeditions underwent 279 assessments: The High Altitude Psychosis Questionnaire (HAPSY-Q), the Prodromal Questionnaire, 16-items (PQ-16), and the Mini International Neuropsychiatric Interview (M.I.N.I., psychosis section) were collected together with further clinical data. Statistical analysis was done for each phase, that is, altitude range of the climb, and overall data. Results: One of 97 climbers fulfilled the M.I.N.I. diagnostic criteria for psychosis during one acclimatization climb. At least one endorsed item on the HAPSY-Q and the PQ-16, indicating the presence of symptoms of psychosis in the absence of a psychotic disorders, were identified in 10/97 (10.3%) and 18/87 (20.7%) participants respectively. The scores of the HAPSY-Q and the PQ-16 were correlated (r = 0.268, p < 0.001). Odds ratio analysis identified an increased risk for accidents in individuals with endorsed items on the HAPSY-Q. Conclusions: The diagnosis of high altitude psychosis is rare in climbers during organized expeditions. Nevertheless, subdiagnostic symptoms of psychosis occurred in a significant proportion of climbers. Future research is needed to validate these pilot findings.

Comparative pharmacovigilance assessment of mortality with pimavanserin in Parkinson disease-related psychosis.

BACKGROUND: Pimavanserin is approved for treatment of Parkinson disease (PD)-related psychosis, but its use has been associated with an increased risk of death during clinical trials, as well as during postmarketing surveillance. Previous reports on the association between pimavanserin and mortality have not taken into account limitations of data sources nor included comparable populations or comparisons to relevant treatment alternatives. OBJECTIVE: To conduct a comparative pharmacovigilance assessment of pimavanserin vs treatment alternatives and by restricting surveillance data to more representative populations. METHODS: This was a retrospective analysis of adverse event case reports submitted to the FDA's Adverse Event Reporting System (FAERS) from 2016 through 2019 quarter 3 (Q3). FAERS data are collected from the full population, were further restricted to only those with PD, and were based on PD medication use. Reports were assessed for exposure to pimavanserin, clozapine, quetiapine, haloperidol, and other atypical antipsychotics. The outcome of interest was all-cause death. A proportional reporting ratio (PRR) and 95% confidence limits were calculated for each 2 by 2 contingency of outcome (death) and exposure (pimavanserin and others). For each outcome/exposure pair, the baseline population was altered to include the full FAERS sample, only reports with PD, reports with PD treated with levodopa, and reports with PD treated with multiple PD medications. The sample was also stratified by time period before April 2018 and after September 2018 to capture periods of public knowledge and federal response. A lower 95% CI (Lower95CI) ≥ 2 for the PRR was considered as the accepted threshold for a drug safety signal. RESULTS: As of 2019 Q3, there were 2,287 reports of death associated with pimavanserin. Compared within the full FAERS base population, pimavanserin yielded a PRR Lower95CI = 2.08 but was smaller when restricted to comparison among only a base population with PD (Lower95CI = 1.09), PD treated with levodopa (Lower95CI = 1.15), or PD treated with multiple PD medications (Lower95CI = 1.63). Metrics for quetiapine, clozapine, and other atypical antipsychotics were similar in magnitude. Stratification by time showed a possible reporting bias associated with pimavanserin, since no safety signal was detected before April 2018; however, a signal was present thereafter. CONCLUSIONS: Compared in context with treatment alternatives for patients with PD, pimavanserin was not associated with excess reports of death in the FAERS data. This information should be used in shared decision making between physicians and PD patients to balance the risks and benefits of pimavanserin and other treatments for PD psychosis. DISCLOSURES: No outside funding supported this study. The authors report no disclosures or conflicts of interest relevant to this study. Armstrong receives research support from the NIA (P30AG047266, R01AG068128) and the Florida Department of Health (grant 20A08). She is the local principal investigator of a Lewy Body Dementia Association Research Center of Excellence. She also receives compensation from the American Academy of Neurology for work as an evidence-based medicine methodology consultant. She is on the level of evidence editorial board for Neurology and related publications (uncompensated), receives publishing royalties for Parkinson's Disease: Improving Patient Care (Oxford University Press, 2014), and has received an honorarium for presenting for Medscape CME in 2018. Okun serves as a consultant for the Parkinson's Foundation and has received research grants from NIH, Parkinson's Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. Okun has participated as a site principal investigator and/or co-investigator for several NIH-, foundation-, and industry-sponsored trials over the years but has not received honoraria. Malaty has participated in research funded by the Parkinson Foundation, Tourette Association, Dystonia Coalition, Abbvie, Boston Scientific, Eli Lilly, Neuroderm, Pfizer, Revance, and Teva. She has received travel compensation and/or honoraria from the Tourette Association of America, NeuroChallenge Foundation and NIH/Neurobiology of Disease in Children, Parkinson Foundation, Medscape, International Association of Parkinsonism and Related Disorders, and Cleveland Clinic, and royalties from Robert Rose publishers. The other authors have no disclosures.

Cost-Effectiveness of Routine Screening for Autoimmune Encephalitis in Patients With First-Episode Psychosis in the United States.

OBJECTIVE: Autoimmune encephalitis (AE) is a highly treatable neurologic condition that can cause psychosis. Screening for AE is not currently recommended in routine workup for first-episode psychosis (FEP), owing partly to the high cost of testing for AE-associated neuronal autoantibodies. METHODS: This study used a decision-analytic model to estimate the cost-effectiveness of routine serum screening for AE compared with clinically targeted screening in patients with FEP. Model parameters drawn from prior published literature included the prevalence of neuronal autoantibodies in FEP (4.5%), serum autoantibody panel cost (US $291), remission probability with antipsychotics (0.58), and remission probability with immunotherapy for patients diagnosed with AE (0.85). Outcomes included quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs), assessed over a 5-year horizon from the US health care sector and societal perspectives. ICER thresholds of $50,000/QALY to $150,000/QALY were used to define cost-effectiveness. The analysis was conducted between June 2018 and January 2020. RESULTS: Routine screening led to mean QALY gains of 0.008 among all patients and 0.174 among the subgroup of patients with neuronal autoantibodies. Mean costs increased by $780 from a societal perspective and $1,150 from a health care sector perspective, resulting in ICERs of $99,330/QALY and $147,460/QALY, respectively. Incorporating joint input data uncertainty, the likelihood routine screening has an ICER ≤ $150,000/QALY was 55% from a societal perspective and 37% from a health care sector perspective. The model parameter with the greatest contribution to overall uncertainty was the effectiveness of immunotherapy relative to antipsychotics. CONCLUSIONS: Routine screening for AE in patients with FEP may be cost-effective in the United States. As further immunotherapy effectiveness data become available, a more definitive recommendation to perform routine screening could be warranted.

Blinded SAPS-PD Assessment After 10 Weeks of Pimavanserin Treatment for Parkinson's Disease Psychosis.

BACKGROUND: Parkinson's disease psychosis (PDP) is a common nonmotor symptom that affects up to 60% of patients. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, is approved for treating hallucinations and delusions associated with PDP. OBJECTIVE: Evaluate the efficacy and tolerability of pimavanserin in an open-label extension (OLE) study. METHODS: Patients completing a pivotal 6-week placebo-controlled trial (Core Study) could enroll in the OLE. All patients pimavanserin 34 mg once daily, blinded to previous treatment allocation. Prespecified blinded assessments at Week 4 were the Scale for the Assessment of Positive Symptoms (SAPS) PD version and SAPS H + D scales, Caregiver Burden Scale (CBS), and Clinical Global Impression (CGI) Improvement and Severity scales. RESULTS: Of 171 who entered the OLE, 148 (87%) completed Week 4. Among patients who received placebo in the Core Study, mean (SD) change from OLE baseline to OLE Week 4 for the SAPS-PD was - 3.4 (6.3); p < 0.0001. Mean change from Core Study baseline to OLE Week 4 for SAPS-PD was similar among prior pimavanserin- and placebo-treated patients (-6.9 vs. -6.3). Improvement was similar with CGI-I, CGI-S, CBS, and SAPS-H + D in patients previously treated with placebo. Adverse events occurred in 92 (53.8%) patients during the 4-week OLE. CONCLUSION: Improvements at OLE Week 4 from pretreatment baseline were similar with placebo and pimavanserin in the Core Study. The beneficial effects observed with pimavanserin in the 6-week Core Study were maintained for 4 weeks in the blinded OLE, supporting the durability of response with pimavanserin 34 mg for PDP over 10 weeks.

[Suicidal behavior in light of COVID-19 outbreak: Clinical challenges and treatment perspectives]. / Épidémie de COVID-19 et prise en charge des conduites suicidaires : challenge et perspectives.

OBJECTIVE: The COVID-19 pandemic affected today more than 3,000,000 worldwide, and more than half of humanity has been placed in quarantine. The scientific community and the political authorities fear an epidemic of suicide secondary to this crisis. The aim of this review is to analyze the impact of the COVID-19 pandemic on the dimensions of the suicidal process and its interaction with the various risk factors. We also propose innovative strategies to manage suicidal behavior in the context of pandemic. METHODS: We carried out a narrative review of international publications dealing with major pandemics (COVID-19, SARS) and their influence on suicidal vulnerability. RESULTS: Many factors are likely to increase the emergence of suicidal ideation and suicide attempts during this crisis. Social distancing and quarantine could increase the feeling of disconnection and the perception of social pain in vulnerable individuals. Some populations at high suicidal risk could be further impacted by the current pandemic: the elderly, medical staff and individuals exposed to economic insecurity. Several innovative tools adapted to the constraints of social distancing and quarantine may prevent suicide risk: e-health, VigilanS, buddhist-derived practices and art engagement. CONCLUSIONS: This unprecedented crisis may interact with certain dimensions of the suicidal process. However, it is time to innovate. Several suicide prevention tools all have their place in new modes of care and should be tested on a large scale.

Familial and socioeconomic contributions to premorbid functioning in psychosis: Impact on age at onset and treatment response.

BACKGROUND: Premorbid adjustment (PA) abnormalities in psychotic disorders are associated with an earlier age at onset (AAO) and unfavorable clinical outcomes, including treatment resistance. Prior family studies suggest that familial liability, likely reflecting increased genetic risk, and socioeconomic status (SES) contribute to premorbid maladjustment. However, their joint effect possibly indicating gene-environment interaction has not been evaluated. METHODS: We examined whether family history of psychosis (FHP) and parental SES may predict PA and AAO in unrelated cases with first-episode psychosis (n = 108) and schizophrenia (n = 104). Premorbid academic and social functioning domains during childhood and early adolescence were retrospectively assessed. Regression analyses were performed to investigate main effects of FHP and parental SES, as well as their interaction. The relationships between PA, AAO, and response to antipsychotic medication were also explored. RESULTS: Positive FHP associated with academic PA difficulties and importantly interacted with parental SES to moderate social PA during childhood (interaction p = 0.024). Positive FHP and parental SES did not predict differences in AAO. Nevertheless, an earlier AAO was observed among cases with worse social PA in childhood (ß = -0.20; p = 0.005) and early adolescence (ß = -0.19; p = 0.007). Further, confirming evidence emerged for an association between deficient childhood social PA and poor treatment response (p = 0.04). CONCLUSIONS: Familial risk for psychosis may interact with parental socioeconomic position influencing social PA in childhood. In addition, this study supports the link between social PA deviations, early psychosis onset, and treatment resistance, which highlights premorbid social functioning as a promising clinical indicator.

Increases in institutionalization, healthcare resource utilization, and mortality risk associated with Parkinson disease psychosis: Retrospective cohort study.

INTRODUCTION: Patients with Parkinson disease (PD) often develop psychosis (P). The association of PDP with death and long-term custodial care (CC) has not been well studied. METHODS: Medicare Parts A, B, and D data, 2007-2015, were used to define cohorts of PD and PDP patients. PD was defined by ≥ 2 ICD-9-CM codes (332.0x) at least 30, but no more than 365, days apart, and PDP by ≥ 2 codes for psychotic symptoms. Outcomes were CC use, defined as nursing home stays of >100 consecutive days, and death. To compare the association of PDP with outcomes, PDP patients were matched to PD patients without psychosis. RESULTS: Within 1 year of PDP diagnosis, 12.1% of PDP patients used CC, versus 3.5% of non-PDP patients 1 year after the matching date; corresponding percentages at 5 years were 25.8% and 10.0%. Cumulative incidence curves for CC and for death differed significantly (P < 0.0001). PDP was associated with RRs of 3.38 (95% CI, 2.93-3.90) for CC and 1.34 (1.23-1.45) for death. Other factors associated with CC were age (3.57, 2.08-6.14, age ≥90 versus ≤70 years) and female sex (1.37, 1.18-1.58). Female sex was associated with a lower RR for death (0.76, 0.70-0.82). Health care utilization and costs were substantially higher for PDP than for non-PDP patients. CONCLUSION: In PD patients, psychosis was associated with a more than 3-fold increased risk of CC and a nearly one-third increased risk of death. Women entered CC more often than men, likely because they lived longer in the setting of PD.

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.

Blindness and Visual Impairment in the Medicare Population: Disparities and Association with Hip Fracture and Neuropsychiatric Outcomes.

Purpose: Vision loss has been associated with negative health outcomes, but population-level data on vision loss are lacking, and there are limited data on low vision-associated outcomes among women, minorities, and older age groups. The objective of this study was to determine the prevalence of vision loss in a nationally representative sample of older US adults and examine its association with hip fracture, depression, anxiety, and dementia. Methods: Cross-sectional analysis of Medicare claims data from 2014. Blindness and low vision, hip fracture, depression, anxiety, and dementia were identified using Chronic Condition Warehouse indicator variables based on ICD-9 and CPT codes. Multivariable logistic regression models were built to examine whether sociodemographic factors were associated with vision loss and to determine the relationships between vision loss and hip fracture and neuropsychiatric outcomes. Results: The prevalence of low vision in the Medicare population was 994/100,000 and increased significantly with age, Black (1,854/100,000) or Hispanic (2,862/100,000) race/ethnicity, female gender (1,181/100,000), and Medicaid eligibility (2,975/100,000). After adjusting for relevant comorbidities, low vision was significantly associated with hip fracture (adjusted odds ratio [AOR] 2.54, 95% CI: 2.52-2.57), depression (AOR 3.99, 95% CI: 3.97-4.01), anxiety (AOR 2.93, 95% CI: 2.91-2.95), and dementia (AOR 3.91, 95% CI: 3.88-3.93). Conclusion: Blindness and low vision are common in older Americans, especially among racial and ethnic minorities and lower income individuals, and associated with hip fracture, depression, anxiety, and dementia. The prevention and treatment of vision loss may reduce health disparities and negative health outcomes in the aging population.

Negative social comparisons and psychosis proneness in a healthy adolescent population.

There is growing evidence of an association between negative social comparisons (NSC) and both psychosis, and psychosis proneness. The majority of the work thus far, however, has focused largely on one type of NSC, namely, social rank. Whilst social rank is clearly an important factor, an individual's perception of belonging is likely also of importance; particularly, when considering individuals from collectivistic cultures such as China, where greater emphasis is placed on fitting into the group. There is also limited research investigating what factors may contribute towards the relationship between NSC and psychosis proneness, and to what extent this relationship may be due to common familial factors. To address these issues, we examined whether (1) Social rank and perceived belonging predict negative, positive and depressive psychotic experiences in a Chinese, adolescent, twin and sibling population, (2) coping styles moderate the impact of these relationships and (3), there is a familial association between NSC and psychosis proneness. Both social rank and perceived belonging were found to predict the negative and depressive dimensions of psychosis. These relationships were moderated by problem-focused coping styles. Interestingly, the association between perception of belonging, and negative psychotic experiences was familial-and stronger in Monozygotic twins-indicating perhaps shared aetiology due to common genes. Our findings highlight NSC as potential vulnerability markers for negative and depressive psychotic experiences, and suggest potentially different aetiological pathways amongst different NSC and different psychotic experiences. On a clinical level, our findings emphasize the need to consider coping styles when treating at-risk individuals.

Parkinson's disease and Parkinson's disease psychosis: a perspective on the challenges, treatments, and economic burden.

Parkinson's disease (PD) is a progressive neurodegenerative disease associated with a decrease in the neurotransmitter dopamine and characterized by the cardinal motor hallmarks of resting tremor, rigidity, bradykinesia/akinesia, and postural instability. Lesser-known features of PD revolve around nonmotor concerns including psychosis, dementia, sleep disturbances, autonomic dysfunction, and sensory abnormalities. Parkinson's disease psychosis (PDP) contributes significantly to morbidity, mortality, nursing home placement, and quality of life (QOL). PDP management suffers from a lack of safe, effective pharmacological agents and the opposing nature of atypical antipsychotics and dopaminergic therapies. Pimavanserin, the only atypical antipsychotic currently approved by the FDA for treating PDP-related hallucinations and delusions, has no appreciable affinity for dopaminergic receptors, and a controlled clinical study demonstrated its efficacy in treating PDP-associated hallucinations and delusions without affecting motor function. A recent analysis of all health resource utilization (HRU) and total costs attributable to PD and PDP found that mean 12-month HRU services per patient were 2.3 times higher and costs were 2.1 times higher in the PDP cases, while falls were 3.4 times higher and fractures 2.3 times higher, respectively. Products or services that prevent, delay, or lessen the severity of PDP may contribute to reduced healthcare system costs and improve the QOL of patients with PDP and of their caregivers.

Characteristics, correlates, and assessment of psychosis in Parkinson disease without dementia.

INTRODUCTION: Considering that psychosis in Parkinson disease (PD) is associated with worse outcomes, including dementia, we aimed to study the characteristics, correlates, and assessment of PD psychosis in those without dementia. METHODS: 101 PD subjects without dementia (Montreal Cognitive Assessment ≥21/30) were recruited to participate in a study of neuropsychiatric symptoms in PD. This study included a baseline standard neurological exam and common PD symptom assessments. Using the Scale for the Assessment of Positive Symptoms (SAPS) and separate assessment of visual illusions and sense of presence, NINDS-NIMH criteria for PD psychosis were applied. RESULTS: Of the 33 (32.7%) PD subjects who met diagnostic criteria for psychosis in PD, visual illusions were most common (72.7%), followed by visual hallucinations (39.4%). Adjusted for presence of REM sleep behavior disorder (RBD) (p = 0.097), use of dopamine agonists (OR = 3.7, p = 0.012) and greater autonomic symptom burden (OR = 1.1 (per 1-unit change in score on SCOPA-AUT), p = 0.012) were associated with greater risk of psychosis. Use of dopamine agonists (OR = 5.0, p = 0.007), higher MDS-UPDRS Part II score (OR = 1.1, p = 0.010), and presence of RBD (OR = 4.8, p = 0.012) were independent predictors of visual hallucinations and visual illusions. MDS-UPDRS item 1.2 score ≥1 had highly correlated with the SAPS score (r = 0.65, p < 0.0001), but was 42% sensitive and 96% specific for identifying psychosis. CONCLUSION: This study confirms the association between dopamine agonists and psychosis in PD patients without dementia. The association of RBD, autonomic symptoms, and MDS-UPDRS Part II scores with psychosis underscore its link to brainstem dysfunction and greater PD motor symptom severity.

Current developments and challenges in the assessment of negative symptoms.

Reliable and valid assessment of negative symptoms is crucial to further develop etiological models and improve treatments. Our understanding of the concept of negative symptoms has undergone significant advances since the introduction of quantitative assessments of negative symptoms in the 1980s. These include the conceptualization of cognitive dysfunction as separate from negative symptoms and the distinction of two main negative symptom factors (avolition and diminished expression). In this review we provide an overview of existing negative symptom scales, focusing on both observer-rated and self-rated measurement of negative symptoms. We also distinguish between measures that assess negative symptoms as part of a broader assessment of schizophrenia symptoms, those specifically developed for negative symptoms and those that assess specific domains of negative symptoms within and beyond the context of psychotic disorders. We critically discuss strengths and limitations of these measures in the light of some existing challenges, i.e. observed and subjective symptom experiences, the challenge of distinguishing between primary and secondary negative symptoms, and the overlap between negative symptoms and related factors (e.g. personality traits and premorbid functioning). This review is aimed to inform the ongoing development of negative symptom scales.

Secondary negative symptoms - A review of mechanisms, assessment and treatment.

Negative symptoms in schizophrenia may be classified as primary or secondary. Primary negative symptoms are thought to be intrinsic to schizophrenia, while secondary negative symptoms are caused by positive symptoms, depression, medication side-effects, social deprivation or substance abuse. Most of the research on secondary negative symptoms has aimed at ruling them out in order to isolate primary negative symptoms. However, secondary negative symptoms are common and can have a major impact on patient-relevant outcomes. Therefore, the assessment and treatment of secondary negative symptoms are clinically relevant. Furthermore, understanding the mechanisms underlying secondary negative symptoms can contribute to an integrated model of negative symptoms. In this review we provide an overview of concepts, evidence, assessment and treatment for the major causes of secondary negative symptoms. We also summarize neuroimaging research relevant to secondary negative symptoms. We emphasize the relevance of recent developments in psychopathological assessment of negative symptoms, such as the distinction between amotivation and diminished expression, which have only rarely been applied in research on secondary negative symptoms.

Why Are Children in Urban Neighborhoods at Increased Risk for Psychotic Symptoms? Findings From a UK Longitudinal Cohort Study.

BACKGROUND: Urban upbringing is associated with a 2-fold adulthood psychosis risk, and this association replicates for childhood psychotic symptoms. No study has investigated whether specific features of urban neighborhoods increase children's risk for psychotic symptoms, despite these early psychotic phenomena elevating risk for schizophrenia and other psychiatric disorders in adulthood. METHODS: Analyses were conducted on over 2000 children from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of UK-born twins. Neighborhood-level characteristics were assessed for each family via: a geodemographic discriminator indexing neighborhood-level deprivation, postal surveys of over 5000 residents living alongside the children, and in-home interviews with the children's mothers. Children were interviewed about psychotic symptoms at age 12. Analyses were adjusted for important family-level confounders including socioeconomic status (SES), psychiatric history, and maternal psychosis. RESULTS: Urban residency at age-5 (OR = 1.80, 95% CI = 1.16-2.77) and age-12 (OR = 1.76, 95% CI = 1.15-2.69) were both significantly associated with childhood psychotic symptoms, but not with age-12 anxiety, depression, or antisocial behavior. The association was not attributable to family SES, family psychiatric history, or maternal psychosis, each implicated in childhood mental health. Low social cohesion, together with crime victimization in the neighborhood explained nearly a quarter of the association between urbanicity and childhood psychotic symptoms after considering family-level confounders. CONCLUSIONS: Low social cohesion and crime victimization in the neighborhood partly explain why children in cities have an elevated risk of developing psychotic symptoms. Greater understanding of the mechanisms leading from neighborhood-level exposures to psychotic symptoms could help target interventions for emerging childhood psychotic symptoms.

Who "jumps to conclusions"? A comprehensive assessment of probabilistic reasoning in psychosis following traumatic brain injury (PFTBI), and comparison with TBI, schizophrenia, and nonclinical controls.

INTRODUCTION: The "jumping to conclusions" (JTC) bias has received significant attention in the schizophrenia and delusion literature as an important aspect of cognition characterising psychosis. The JTC bias has not been explored in psychosis following traumatic brain injury (PFTBI). METHODS: JTC was investigated in 10 patients with PFTBI using the beads task (ratios 85:15 and 60:40). Probabilistic predictions, draws-to-decision, self-rated decision confidence, and JTC bias were recorded. Responses from 10 patients with traumatic brain injury (TBI), 23 patients with schizophrenia, and 23 nonclinical controls were compared. Relationships were explored between draws-to-decision and current intelligence quotient, affective state, executive function, delusions (severity and type), and illness chronicity (duration). RESULTS: Groups were comparable on JTC measures. Delusion severity and type were not related to draws-to-decision for either trial. In the entire sample, executive function (reduced mental flexibility) was significantly related to more draws-to-decision on the 60:40 ratio trial. CONCLUSIONS: We found no evidence for an elevated JTC bias in patients with PFTBI or TBI alone. The influence of executive dysfunction should be considered by future studies using the beads tasks in patient populations. These findings need to be replicated in larger PFTBI and TBI samples.

Dimensional assessment of behavioral changes in the cuprizone short-term exposure model for psychosis.

Recent clinical studies have suggested a role for immune/inflammatory responses in the pathophysiology of psychosis. However, a mechanistic understanding of this process and its application for drug discovery is underdeveloped. Here we assessed our recently developed cuprizone short-term exposure (CSE) mouse model across behavioral domains targeting neurocognitive and neuroaffective systems. We propose that the CSE model may be useful for understanding the mechanism associating inflammation and psychosis, with applications for drug discovery in that context.