Prostate Radiotherapy in Low-volume Metastatic Hormone-sensitive Prostate Cancer: A Network Meta-analysis.

BACKGROUND AND OBJECTIVE: The utility of prostate radiotherapy (RT) is unclear in men with metastatic hormone-sensitive prostate cancer (mHSPC) receiving intensified systemic therapy with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs). We performed a network meta-analysis of randomized controlled trials (RCTs) to investigate the role of prostate RT in low-volume mHSPC. METHODS: Bibliographic databases and conference proceedings were searched through July 2023 for RCTs evaluating the addition of ARPIs or prostate RT to standard of care (SOC) systemic therapy, defined as ADT or ADT plus docetaxel, for the initial treatment of mHSPC. We focused exclusively on aggregate data from the low-volume mHSPC subpopulation in these trials. We pooled the treatment arms into four groups: SOC, SOC plus ARPI, SOC plus RT, and SOC plus ARPI plus RT. The primary outcome was overall survival (OS). To compare treatment strategies, a fixed-effects Bayesian network meta-analysis was undertaken, while a Bayesian network meta-regression was performed to account for across-trial differences in docetaxel use as part of SOC and in proportions of patients with de novo presentation. KEY FINDINGS AND LIMITATIONS: Ten RCTs comprising 4423 patients were eligible. The Surface Under the Cumulative Ranking Curve scores were 0.0006, 0.45, 0.62, and 0.94 for SOC, SOC plus RT, SOC plus ARPI, and SOC plus ARPI plus RT, respectively. On a meta-regression, in a population with de novo mHSPC and no docetaxel use, we did not find sufficient evidence of a difference in OS between SOC plus ARPI plus RT versus SOC plus ARPI (hazard ratio [HR]: 0.76; 95% credible interval: 0.51-1.16) and SOC plus RT versus SOC plus ARPI (HR: 1.10; 95% credible interval: 0.92-1.42). CONCLUSIONS AND CLINICAL IMPLICATIONS: There was some evidence that SOC plus ARPI plus RT reduced mortality compared with the next best strategy of SOC plus ARPI in patients with low-volume de novo mHSPC. A meta-analysis with individual patient data or an RCT is needed to confirm these findings.

Benefit of Neoadjuvant Cisplatin-based Chemotherapy for Invasive Bladder Cancer Patients Treated with Radiation-based Therapy in a Real-world Setting: An Inverse Probability Treatment Weighted Analysis.

BACKGROUND: Neoadjuvant chemotherapy (NAC) improves survival for patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy. Studies on the potential benefit of NAC before radiation-based therapy (RT) are conflicting. OBJECTIVE: To evaluate the effect of NAC on patients with MIBC treated with curative-intent RT in a real-world setting. DESIGN, SETTING, AND PARTICIPANTS: The study cohort consisted of 785 patients with MIBC (cT2-4aN0-2M0) who underwent RT at academic centers across Canada. Patients were classified into two treatment groups based on the administration of NAC before RT (NAC vs no NAC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The inverse probability of treatment weighting (IPTW) with absolute standardized differences (ASDs) was used to balance covariates across treatment groups. The impact of NAC on complete response, overall, and cancer-specific survival (CSS) after RT in the weighted cohort was analyzed. RESULTS AND LIMITATIONS: After applying the exclusion criteria, 586 patients were included; 102 (17%) received NAC before RT. Patients in the NAC subgroup were younger (mean age 65 vs 77 yr; ASD 1.20); more likely to have Eastern Cooperative Oncology Group performance status 0-1 (87% vs 78%; ASD 0.28), lymphovascular invasion (32% vs 20%; ASD 0.27), higher cT stage (cT3-4 in 29% vs 20%; ASD 0.21), and higher cN stage (cN1-2 in 32% vs 4%; ASD 0.81); and more commonly treated with concurrent chemotherapy (79% vs 67%; ASD 0.28). After IPTW, NAC versus no NAC cohorts were well balanced (ASD <0.20) for all included covariates. NAC was significantly associated with improved CSS (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.14-0.56; p < 0.001) and overall survival (HR 0.56; 95% CI 0.38-0.84; p = 0.005). This study was limited by potential occult imbalances across treatment groups. CONCLUSIONS: If tolerated, NAC might be associated with improved survival and should be considered for eligible patients with MIBC planning to undergo bladder preservation with RT. Prospective trials are warranted. PATIENT SUMMARY: In this study, we showed that neoadjuvant chemotherapy might be associated with improved survival in patients with muscle-invasive bladder cancer who elect for curative-intent radiation-based therapy.

Radiation-based Therapy for Muscle-invasive Bladder Cancer: Contemporary Outcomes Across Tertiary Centers.

BACKGROUND: Radiation therapy (RT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To analyze predictors of complete response (CR) and survival after RT for MIBC. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter retrospective study of 864 patients with nonmetastatic MIBC who underwent curative-intent RT from 2002 to 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Regression models were used to explore prognostic factors associated with CR, cancer-specific survival (CSS), and overall survival (OS). RESULTS AND LIMITATIONS: The median patient age was 77 yr and median follow-up was 34 mo. Disease stage was cT2 in 675 patients (78%) and cN0 in 766 (89%). Neoadjuvant chemotherapy (NAC) was given to 147 patients (17%) and concurrent chemotherapy to 542 (63%). A CR was experienced by 592 patients (78%). cT3-4 stage (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.29-0.63; p < 0.001) and hydronephrosis (OR 0.50, 95% CI 034-0.74; p = 0.001) were significantly associated with lower CR. The 5-yr survival rates were 63% for CSS and 49% for OS. Higher cT stage (HR 1.93, 95% CI 1.46-2.56; p < 0.001), carcinoma in situ (HR 2.10, 95% CI 1.25-3.53; p = 0.005), hydronephrosis (HR 2.36, 95% CI 1.79-3.10; p < 0.001), NAC use (HR 0.66, 95% CI 0.46-0.95; p = 0.025), and whole-pelvis RT (HR 0.66, 95% CI 0.51-0.86; p = 0.002) were independently associated with CSS; advanced age (HR 1.03, 95% CI 1.01-1.05; p = 0.001), worse performance status (HR 1.73, 95% CI 1.34-2.22; p < 0.001), hydronephrosis (HR 1.50, 95% CI 1.17-1.91; p = 0.001), NAC use (HR 0.69, 95% CI 0.49-0.97; p = 0.033), whole-pelvis RT (HR 0.64, 95% CI 0.51-0.80; p < 0.001), and being surgically unfit (HR 1.42, 95% CI 1.12-1.80; p = 0.004) were associated with OS. The study is limited by the heterogeneity of different treatment protocols. CONCLUSIONS: RT for MIBC yields a CR in most patients who elect for curative-intent bladder preservation. The benefit of NAC and whole-pelvis RT require prospective trial validation. PATIENT SUMMARY: We investigated outcomes for patients with muscle-invasive bladder cancer treated with curative-intent radiation therapy as an alternative to surgical removal of the bladder. The benefit of chemotherapy before radiotherapy and whole-pelvis radiation (bladder plus the pelvis lymph nodes) needs further study.

Do larger cuff sizes with artificial urinary sphincter placement increase the risk of leakage after placement?

INTRODUCTION: To determine whether larger artificial urinary sphincters (AUS) cuff sizes of ≥ 5.0 cm have an impact on urinary incontinence after AUS implantation as compared to cuff sizes ≤ 4.5 cm. MATERIALS AND METHODS: A retrospective chart review of AUS implants performed at our institution from 1991 to 2021. Medical records were reviewed for demographics including body mass index (BMI), cause of incontinence, pelvic radiation, valsalva leak point pressure (VLPP), degree of leakage preoperatively and at 1-year post-AUS surgery, AUS revisions, erosion rate and the need for adjunct medication postoperatively. RESULTS: A total of 110 patients were included in the analysis. Of these, 44 patients had an AUS cuff size of ≥ 5.0 cm and 66 patients had a cuff size ≤ 4.5 cm. After AUS implantation at 1 year both groups had a median pad use of 1 pad per day. Lastly, the erosion rate was higher in the ≤ 4.5 cm cuff group (7.7% vs. 2.4%) but this was not statically significant. In all cases (6 patients) of cuff erosion, each patient had been radiated. CONCLUSION: AUS cuff sizes of ≥ 5.0 cm do not appear to have a negative impact on the degree of incontinence at 1-year post AUS as compared to those with cuff sizes ≤ 4.5 cm. The erosion rate was higher in those with cuffs ≤ 4.5 cm but was not statistically significant. This would suggest that at AUS implantation, the surgeon should choose a larger cuff if there is any doubt especially in those with radiation.

A Canadian national survey: Perspectives on routine pathological examination of hernia sacs after inguinal hernia and hydrocele repair among pediatric urologists, surgeons, and pathologists.

BACKGROUND/OBJECTIVE: This study aims to understand perspectives on routine pathological examination of hernia sacs following pediatric inguinal hernia and hydrocele repair among Canadian pediatric urologists, surgeons, and pathologists. STUDY DESIGN: All active members of Pediatric Urologists of Canada (PUC), Canadian Association of Pediatric Surgeons (CAPS), and the divisional heads of anatomical pathology at the Canadian children's hospitals (AP) were invited to participate between June 2019 and January 2021 in an anonymous multiple-choice-based questionnaire. RESULTS: The response rates were 71% from PUC (24/34), 20% from CAPS (25/130), and 64% from AP (7/11). The majority of the surgeons (PUC:54%, CAPS:68%) did not routinely send hernia sacs for pathological examination after inguinal hernia repair. Most felt there was a little value in such examination (PUC:96%, CAPS:72%). Among those who submit hernia sacs, the majority did not receive reports that were clinically significant impacting patient management (PUC:82%, CAPS:50%). On the other hand, the pathologists had mixed opinion on the value of examining hernia sacs. Most of them only did gross examination (86%), unless requested by surgeons or concerning features were noted on gross examination. The majority have found clinically meaningful abnormal findings (71%), including vas deferens and portions of the spermatic cord. DISCUSSION: Currently, there are no evidence-based clinical guidelines on pathological assessment of hernia sacs after pediatric inguinal hernia and hydrocele repair. Instead of making it mandatory, future guidelines should highlight specimens that should be submitted for further investigations (e.g., challenging cases where inadvertent surgical injuries might have occurred). Future studies should also address whether patients who may be at higher risk of having clinically significant pathology can be identified pre- or perioperatively to more efficiently triage specimens that would benefit from pathological examination. Limitation of the study includes low response rate from the CAPS members during the COVID-19 pandemic. CONCLUSIONS: While most of the pediatric urologists and surgeons felt there is a little value of pathological examination of hernia sacs following inguinal hernia and hydrocele repair, half of the anatomical pathologists felt there is value. Future studies should aim to establish evidence-based clinical guidelines taking stakeholders perspectives into consideration.

Anti-vaccination attitudes are associated with less analytical and more intuitive reasoning.

Online anti-vaccination rhetoric has produced far reaching negative health consequences. Persons who endorse anti-vaccination attitudes may employ less analytical reasoning when problem solving. Considering limitations in previous research, we used an online web-based survey (n = 760; mean age = 47.69; 388 males, 372 females) to address this question. Analytical reasoning was negatively correlated with anti-vaccination attitudes (r = -.18, p < .0001). This relationship remained significant after statistically controlling for potential confounders, including age, sex, education, and religiosity (r = -.16, p < .0001). We hope that elucidating the cognitive, non-information-based aspects of anti-vaccination attitudes will help to guide effective educational interventions aimed at improving public health in the future.

Psychological morbidity associated with prostate cancer: Rates and predictors of depression in the RADICAL PC study.

INTRODUCTION: Across all cancer sites and stages, prostate cancer has one of the greatest median five-year survival rates, highlighting the important focus on survivorship issues following diagnosis and treatment. In the current study, we sought to evaluate the prevalence and predictors of depression in a large, multicenter, contemporary, prospectively collected sample of men with prostate cancer. METHODS: Data from the current study were drawn from the baseline visit of men enrolled in the RADICAL PC study. Men with a new diagnosis of prostate cancer or patients initiating androgen deprivation therapy for prostate cancer for the first time were recruited. Depressive symptoms were evaluated using the nine-item version of the Patient Health Questionnaire (PHQ-9). To evaluate factors associated with depression, a multivariable logistic regression model was constructed, including biological, psychological, and social predictor variables. RESULTS: Data from 2445 patients were analyzed. Of these, 201 (8.2%) endorsed clinically significant depression. Younger age (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.16-1.60 per 10-year decrease), being a current smoker (OR 2.77, 95% CI 1.66-4.58), former alcohol use (OR 2.63, 95% CI 1.33-5.20), poorer performance status (OR 5.01, 95% CI 3.49-7.20), having a pre-existing clinical diagnosis of depression or anxiety (OR 3.64, 95% CI 2.42-5.48), and having high-risk prostate cancer (OR 1.49, 95% CI 1.05-2.12) all conferred independent risk for depression. CONCLUSIONS: Clinically significant depression is common in men with prostate cancer. Depression risk is associated with a host of biopsychosocial variables. Clinicians should be vigilant to screen for depression in those patients with poor social determinants of health, concomitant disability, and advanced disease.

Quality of life, depression, and psychosocial mechanisms of suicide risk in prostate cancer.

INTRODUCTION: Prostate cancer (PCa) is the most common non-cutaneous cancer in men and is usually identified at a stage at which prolonged survival is expected. Therefore, strategies to address survivorship and promote well-being are crucial. This study's aim was to better understand suicidal behavior in PCa patients by examining psychosocial mediators (i.e., depression, psychache, perceived burdensomeness [PB], thwarted belongingness [TB]) in the relationship between quality of life (PCa-QoL) and suicide risk. METHODS: Four hundred and six men with PCa (Median age 69.35 years, standard deviation 7.79) completed an online survey on various psychosocial variables associated with suicide risk. A combined serial/parallel mediation model tested whether depression, in serial with both psychache and PB/TB, mediated the relationship between PCa-QoL and suicide risk. RESULTS: Over 14% of participants' self-reports indicated clinically significant suicide risk. Poorer PCa-QoL was related to greater depression, which was related to both greater psychache and PB/TB, which was associated with greater suicide risk. The serial mediation effect of depression and psychache was significantly stronger than that of depression and PB/TB. PCa-QoL did not predict suicide risk through depression alone, showing that depressive symptoms affect suicide risk through psychache and PB/TB. CONCLUSIONS: Given the alarming estimate of individuals at risk for suicide in this study, clinicians should consider patients with poorer PCa-QoL and elevated depression for psychosocial referral or management. Psychache (i.e., psychological pain) and PB/TB (i.e., poor social fit) may be important targets for reducing suicide risk intervention beyond the impact of depression alone.

Assessing analytic and intuitive reasoning using the cognitive reflection test in young patients with schizophrenia.

Cognitive biases may contribute to the formation and maintenance of positive symptoms in patients with schizophrenia. However, cognitive reflection (i.e., the ability to use analytical thinking to override intuitive responses) has not been explicitly examined in schizophrenia patients using the cognitive reflection test (CRT). Using the CRT, we examined the degree of analytical and intuitive reasoning employed during problem solving in patients with schizophrenia versus healthy controls. Fifty-eight outpatients with schizophrenia and fifty-eight age- and sex-matched healthy controls (18-35 years of age) participated in this study. In addition to CRT performance, neurocognition, apathy, impulsivity, depression, insight, and clinical symptoms were evaluated. Patients with schizophrenia produced significantly fewer analytical responses (U = 1167.00, p<0.05) and more intuitive responses (U = 1273.50, p<0.05) compared to healthy controls. Patients without significant cognitive impairment also produced fewer analytical responses compared to controls (U = 894.50, p<0.05). Among patients, analytical thinking was positively correlated with working memory (r = 0.27, p<0.05), and affective symptoms (r = 0.31, p<0.05). Analytical reasoning was not significantly correlated with positive symptoms, avolition, or impulsivity. Patients with schizophrenia demonstrate less analytical and more intuitive reasoning while problem solving compared to healthy controls. This reduction in cognitive reflection is not significantly explained by global cognitive impairment or motivational deficits.

Depression and prostate cancer: A focused review for the clinician.

Prostate cancer is the most common malignancy among men. Given its prevalence and relatively low mortality rates, several biopsychosocial survivorship issues have garnered recent attention. This article reviews the literature on the association between depression and prostate cancer, emphasizing key practice points relevant for clinicians. Depression is prevalent among men with prostate cancer, with approximately 1 in 6 patients experiencing clinical depression. Suicidal ideation is also not uncommon in this population and does not always present in those with other depressive symptoms. While choice of definitive cancer treatment (radiation or surgery) does not seem to affect depressive symptoms, receipt of androgen deprivation therapy appears to have a negative effect. Not only are patients at increased risk for depression following a prostate cancer diagnosis, but depression itself seems to adversely affect oncologic outcomes. We were not able to identify any clinical trials examining the efficacy of antidepressant medications for depressive symptoms in these patients, however population-based studies suggest antidepressant prescriptions are commonly utilized. Taken together, the literature on the intersection between urologic oncology and psychology/psychiatry affirms the importance of depression among men with prostate cancer. Clinicians should consider assessment of this symptom domain and treat or refer judiciously. Clinical trials represent a priority for future research.

Goal-directed planning and action impairments in schizophrenia evaluated in a virtual environment.

Planning and executing goal-directed behaviours are critical final steps in translating motivation into action. Amotivation is a key feature of schizophrenia, but its impact on goal-directed functioning has not been extensively studied in an objective and ecologically valid manner. To address this, we investigated goal-directed planning and action in schizophrenia using a virtual reality task, the Multitasking in the City Test (MCT). The MCT was administered to 49 outpatients with schizophrenia and 55 healthy controls, and required participants to complete a series of errands in a virtual city. Ability to complete the task as directed was assessed by a performance score based on errands completed and errors committed. Task efficiency was evaluated by the total distance travelled, and an index of path efficiency comparing an optimal route with the traversed route. Schizophrenia participants had lower performance scores, travelled farther, and had reduced path efficiency compared to healthy controls. Greater distance travelled and lower path efficiency in schizophrenia were related to amotivation. Path efficiency in schizophrenia was also related to neurocognition, including planning ability; notably, this relationship appeared to be independent of the relationship with amotivation. Individuals with schizophrenia demonstrated impaired goal-directed planning and action in the context of a simulated everyday errands task, both in terms of reduced capacity to complete errands and reduced efficiency in doing so. The latter may manifest as diminished real-world motivated and functional behaviour in patients with schizophrenia and indicates a specific deficit in the execution of planned behaviour.

Does relapse contribute to treatment resistance? Antipsychotic response in first- vs. second-episode schizophrenia.

Although some studies have suggested that relapse may be associated with antipsychotic treatment resistance in schizophrenia, the number and quality of studies is limited. The current analysis included patients with a diagnosis of first-episode schizophrenia or schizoaffective disorder who met the following criteria: (1) referral to the First-Episode Psychosis Program between 2003 and 2013; (2) treatment with an oral second-generation antipsychotic according to a standardized treatment algorithm; (3) positive symptom remission; (4) subsequent relapse (i.e., second episode) in association with non-adherence; and (5) reintroduction of antipsychotic treatment with the same agent used to achieve response in the first episode. The following outcomes were used as an index of antipsychotic treatment response: changes in the brief psychiatric rating scale (BPRS) total and positive symptom scores and number of patients who achieved positive symptom remission and 20 and 50% response. A total of 130 patients were included in the analyses. Although all patients took the same antipsychotic in both episodes, there were significant episode-by-time interactions for all outcomes of antipsychotic treatment response over 1 year in favor of the first episode compared to the second episode (50% response rate: 48.7 vs. 10.4% at week 7; 88.2 vs. 27.8% at week 27, respectively). Although antipsychotic doses in the second episode were significantly higher than those in the first episode, results remained unchanged after adjusting for antipsychotic dose. The present findings suggest that antipsychotic treatment response is reduced or delayed in the face of relapse following effective treatment of the first episode of schizophrenia.

Objective investigation of activity preference in schizophrenia: A pilot study.

Amotivation and reduced goal-directed activity engagement are prominent features of schizophrenia. Previous investigations of patients' activities have relied on accounts of daily living activities, rather than objective measures. This study used wireless motion capture to objectively evaluate activity preference when individuals are provided an explicit choice between an active versus passive engagement option. Twenty outpatients with schizophrenia and twenty matched healthy controls completed the Activity Preference Task, in which participants play a motion-based game (active) or watch a film (passive), and were administered clinical and cognitive assessments. Schizophrenia participants' duration, intensity, and persistence of active engagement were associated with apathy and community functioning. No group differences emerged from comparisons of task measures; however, exploratory cluster analysis identified a distinct subgroup of schizophrenia patients with reduced engagement and increased apathy compared to other patients and controls. The Task provides a means of quantifying activity engagement, which may be particularly valuable given the lack of objective measures for intrinsically motivated behaviours. Our initial findings suggest that schizophrenia patients as a group are equally inclined as healthy individuals towards actively engaging activities when presented an explicit choice, but such provision may be insufficient for initiation and maintenance of functional behaviours among amotivated patients.

A new wave of urologists? Graduating urology residents' practices of and attitudes toward social media.

INTRODUCTION: Social media (SoMe) have revolutionized healthcare, but physicians remain hesitant to adopt SoMe in their practices. We sought to assess graduating urology residents' practices of and attitudes toward SoMe. METHODS: A close-ended questionnaire, employing five-point Likert scales, was distributed to all final-year residents (n=100) in Canadian urology training programs in 2012, 2014, and 2016 to assess SoMe usage and perceived usefulness. RESULTS: All (100%) questionnaires were completed. Respondents frequently used online services for personal (100%) and professional (96%) purposes. Most (92%) used SoMe. Many (73%) frequently used SoMe for personal purposes, but few (12%) frequently used SoMe for professional purposes. While a majority (59%) opposed direct patient interaction online, most supported using SoMe to provide patients with static information (76%) and collaborate with colleagues (65%). Many (70-73%) were optimistic that novel solutions to privacy issues in online communications will arise, making SoMe and email contact with patients conceivable. Few (2-8%) were aware and had read guidelines and legislations regarding physician online practices; however, awareness of medical associations' and institutional SoMe policies significantly increased over time (p<0.05). CONCLUSIONS: Despite their active online use, graduating urology residents rarely used SoMe in professional settings and were wary of using it in patient care. Nevertheless, they were optimistic toward its integration in urology and supported its use in physician-physician communication. Considering SoMe's increased influence on urology and graduating residents' limited awareness of guidelines and legislations, postgraduate medical educators should encourage residents to become more familiar with current online communication recommendations.

Reward motivation in humans and its relationship to dopamine D2/3 receptor availability: A pilot study with dual [11C]-raclopride and [11C]-(+)-PHNO imaging.

Rodent studies suggest that dopamine signaling at D2/3 receptors in the ventral striatum is critical for reward motivation. Whether this is also true in humans is unclear. Positron emission tomography studies in healthy humans have generally not observed a relationship between D2/3 receptor availability in the ventral striatum and motivation. We developed the "mounting-effort for reward task" to assess high motivational demand for (a) gaining money (CS+), (b) losing money or avoiding electric shock (CS-), and (c) non-reward (Neutral). Receipt was contingent on participants making sufficient button responses relative to a "reward-threshold" determined by prior motor performance. This reward-threshold was dynamically increased if surpassed, making the task increasingly more difficult on every trial. The mounting-effort for reward task was preliminarily validated in 29 healthy volunteers (mean age: 25.83±3.58; 15 female). In this sample, %CS+ and %CS- significantly correlated with different dimensions of self-reported apathy. In a sub-sample of eight healthy volunteers (mean age: 25.75±1.91; four female), the mounting-effort for reward task demonstrated good test-retest reliability (%variance: 0.20-2.61%). Seven healthy male volunteers (mean age: 31.14±5.43) completed the mounting-effort for reward task and provided both [11C]-raclopride and [11C]-(+)-PHNO PET scans to assess D2/3 receptor availability. %CS+ and %CS- were positively correlated with [11C]-raclopride binding in the dorsal striatum. %CS+, %Cs-, and %Neutral were positively correlated with [11C]-(+)-PHNO binding in the globus pallidus. Thus, increased expression of D2 receptors in the dorsal striatum, and D3 receptors in the globus pallidus, may be related to motivation for rewards. Larger positron emission tomography studies are required to formally validate the mounting-effort for reward task and replicate our pilot findings.

Achievement motivation in early schizophrenia: Relationship with symptoms, cognition and functional outcome.

BACKGROUND: Individuals with schizophrenia engage in goal-directed activities significantly less often compared to healthy individuals in the community. There is ample evidence documenting the presence of motivational deficits in schizophrenia using observer-based ratings; however, purely self-reported accounts of patients' motivation are less well understood. This study examined subjective accounts of trait achievement motivation among relatively young, clinically stable, early-course outpatients with schizophrenia. METHODS: Thirty-nine early-course patients and 39 healthy comparison subjects completed clinical and cognitive assessments in addition to a self-report inventory measuring achievement motivation. RESULTS: Patients were found to endorse significantly lower levels of motivation, a mean difference which translated to a large effect size (Cohen's d = 1.1). Patients' self-reported motivation was significantly related to clinician ratings of motivational deficits which were based on behavioural output, and to vocational functioning. Within the patient sample, 33.3% of individuals were found to experience prominent or clinically significant levels of amotivation based on patients' own self-report. Self-reported achievement motivation was not associated with other clinical variables such as positive symptom severity or expressive negative symptoms. CONCLUSIONS: Our results serve to highlight the occurrence and prevalence of motivational deficits in patients with schizophrenia who are in the early stages of their illness. Subjective accounts of motivation in this population were found to be related to important outcomes such as community functioning, highlighting the importance of this domain of illness. Targeting these deficits early in the course of the illness offers the potential to curb potential prospective poor outcomes and sets the stage for recovery.

Objective assessment of exploratory behaviour in schizophrenia using wireless motion capture.

Motivation deficits are a prominent feature of schizophrenia and have substantial consequences for functional outcome. The impact of amotivation on exploratory behaviour has not been extensively assessed by entirely objective means. This study evaluated deficits in exploratory behaviour in an open-field setting using wireless motion capture. Twenty-one stable adult outpatients with schizophrenia and twenty matched healthy controls completed the Novelty Exploration Task, in which participants explored a novel environment containing familiar and uncommon objects. Objective motion data were used to index participants' locomotor activity and tendency for visual and tactile object exploration. Clinical assessments of positive and negative symptoms, apathy, cognition, depression, medication side-effects, and community functioning were also administered. Relationships between task performance and clinical measures were evaluated using Spearman correlations, and group differences were evaluated using multivariate analysis of covariance tests. Although locomotor activity and tactile exploration were similar between the schizophrenia and healthy control groups, schizophrenia participants exhibited reduced visual object exploration (F(2,35)=3.40, p=0.045). Further, schizophrenia participants' geometric pattern of locomotion, visual exploration, and tactile exploration were correlated with overall negative symptoms (|ρ|=0.46-0.64, p<=0.039) and apathy (|ρ|=0.49-0.62, p<=0.028), and both visual and tactile exploration were also correlated with community functioning (|ρ|=0.46-0.48, p<=0.043). The Novelty Exploration Task may be a valuable tool to quantify exploratory behaviour beyond what is captured through standard clinical instruments and human observer ratings. Findings from this initial study suggest that locomotor activity and object interaction tendencies are impacted by motivation, and reveal deficits specifically in visual exploration in schizophrenia.

Amotivation is associated with smaller ventral striatum volumes in older patients with schizophrenia.

OBJECTIVE: Motivational deficits are prevalent in patients with schizophrenia, persist despite antipsychotic treatment, and predict long-term outcomes. Evidence suggests that patients with greater amotivation have smaller ventral striatum (VS) volumes. We wished to replicate this finding in a sample of older, chronically medicated patients with schizophrenia. Using structural imaging and positron emission tomography, we examined whether amotivation uniquely predicted VS volumes beyond the effects of striatal dopamine D2/3 receptor (D2/3 R) blockade by antipsychotics. METHODS: Data from 41 older schizophrenia patients (mean age: 60.2 ± 6.7; 11 female) were reanalysed from previously published imaging data. We constructed multivariate linear stepwise regression models with VS volumes as the dependent variable and various sociodemographic and clinical variables as the initial predictors: age, gender, total brain volume, and antipsychotic striatal D2/3 R occupancy. Amotivation was included as a subsequent step to determine any unique relationships with VS volumes beyond the contribution of the covariates. In a reduced sample (n = 36), general cognition was also included as a covariate. RESULTS: Amotivation uniquely explained 8% and 6% of the variance in right and left VS volumes, respectively (right: ß = -.38, t = -2.48, P = .01; left: ß = -.31, t = -2.17, P = .03). Considering cognition, amotivation levels uniquely explained 9% of the variance in right VS volumes (ß = -.43, t = -0.26, P = .03). CONCLUSION: We replicate and extend the finding of reduced VS volumes with greater amotivation. We demonstrate this relationship uniquely beyond the potential contributions of striatal D2/3 R blockade by antipsychotics. Elucidating the structural correlates of amotivation in schizophrenia may help develop treatments for this presently irremediable deficit.

The neural correlates of apathy in schizophrenia: An exploratory investigation.

BACKGROUND: Motivational deficits represent a core negative symptom in patients with schizophrenia. Previous morphology studies have demonstrated that apathy in patients with schizophrenia is associated with reduced frontal grey matter (GM). We attempted to replicate this previous finding, and explored whether it was distinct from potential associations with a distinct subdomain of negative symptoms, namely Affective Flattening, and GM. METHODS: Twenty medicated patients with schizophrenia provided structural T1-weighted images acquired on a 3-Tesla MRI scanner and negative symptoms were evaluated using the Scale for the Assessment of Negative Symptoms. Voxel-based morphometry (VBM) was used to explore the correlations between whole-brain GM and i) Apathy, and ii) Affective Flattening, respectively. RESULTS: Apathy scores were negatively correlated with several GM clusters in frontal regions, including the frontal inferior operculum and the left dorsal anterior cingulate cortex. Only positive correlations with GM clusters were observed for Affective Flattening, particularly in the inferior temporal lobe. Notably, the regions associated with apathy scores were distinct from those associated with Affective Flattening, and these findings remained after controlling for antipsychotic medication dosage. CONCLUSIONS: We replicated previous associations between reduced frontal GM and apathy in patients with schizophrenia. Moreover, we demonstrated that these GM associations are distinct from those with Affective Flattening. The present findings set the stage for future larger-scale studies confirming the structural and neurochemical substrates of apathy in schizophrenia.