Negative symptoms are a key feature of several psychiatric disorders. Difficulty identifying common neurobiological mechanisms that cut across diagnostic boundaries might result from equifinality (i.e., multiple mechanistic pathways to the same clinical profile), both within and across disorders. This study used a data-driven approach to identify unique subgroups of participants with distinct reward processing profiles to determine which profiles predicted negative symptoms.

Participants were a transdiagnostic sample of youth from a multisite study of psychosis risk, including 110 individuals at clinical high-risk for psychosis (CHR; meeting psychosis-risk syndrome criteria), 88 help-seeking participants who failed to meet CHR criteria and/or who presented with other psychiatric diagnoses, and a reference group of 66 healthy controls. Participants completed clinical interviews and behavioral tasks assessing four reward processing constructs indexed by the RDoC Positive Valence Systems: hedonic reactivity, reinforcement learning, value representation, and effort–cost computation.

k-means cluster analysis of clinical participants identified three subgroups with distinct reward processing profiles, primarily characterized by: a value representation deficit (54%), a generalized reward processing deficit (17%), and a hedonic reactivity deficit (29%). Clusters did not differ in rates of clinical group membership or psychiatric diagnoses. Elevated negative symptoms were only present in the generalized deficit cluster, which also displayed greater functional impairment and higher psychosis conversion probability scores.

Contrary to the equifinality hypothesis, results suggested one global reward processing deficit pathway to negative symptoms independent of diagnostic classification. Assessment of reward processing profiles may have utility for individualized clinical prediction and treatment.

Stigma of mental health conditions hinders recovery and well-being. The Honest, Open, Proud (HOP) program shows promise in reducing stigma but there is uncertainty about the feasibility of a randomized trial to evaluate a peer-delivered, individual adaptation of HOP for psychosis (Let's Talk).

A multi-site, Prospective Randomized Open Blinded Evaluation (PROBE) design, feasibility randomised controlled trial (RCT) comparing the peer-delivered intervention (Let's Talk) to treatment as usual (TAU). Follow-up was 2.5 and 6 months. Randomization was via a web-based system, with permuted blocks of random size. Up to 10 sessions of the intervention over 10 weeks were offered. The primary outcome was feasibility data (recruitment, retention, intervention attendance). Primary outcomes were analyzed by intention to treat. Safety outcomes were reported by as treated status. The study was prospectively registered: https://doi.org/10.1186/ISRCTN17197043.

149 patients were referred to the study and 70 were recruited. 35 were randomly assigned to intervention + TAU and 35 to TAU. Recruitment was 93% of the target sample size. Retention rate was high (81% at 2.5 months primary endpoint), and intervention attendance rate was high (83%). 21% of 33 patients in Let's talk + TAU had an adverse event and 16% of 37 patients in TAU. One serious adverse event (pre-randomization) was partially related and expected.

This is the first trial to show that it is feasible and safe to conduct a RCT of HOP adapted for people with psychosis and individual delivery. An adequately powered trial is required to provide robust evidence.

An accurate accounting of prior sport-related concussion (SRC) is critical to optimizing the clinical care of athletes with SRC. Yet, obtaining such a history via medical records or lifetime monitoring is often not feasible necessitating the use of self-report histories. The primary objective of the current project is to determine the degree to which athletes consistently report their SRC history on serial assessments throughout their collegiate athletic career.

Data were obtained from the NCAA-DoD CARE Consortium and included 1621 athletes (914 male) from a single Division 1 university who participated in athletics during the 2014-2017 academic years. From this initial cohort, 752 athletes completed a second-year assessment and 332 completed a third-year assessment. Yearly assessments included a brief self-report survey that queried SRC history of the previous year. Consistency of self-reported SRC history was defined as reporting the same number of SRC on subsequent yearly evaluation as had been reported the previous year.

For every year of participation, the number of SRC reported on the baseline exam (Reported) and the number of SRC recorded by athletes and medical staff during the ensuing season (Recorded) were tabulated. In a subsequent year, the expected number of SRC (Expected) was computed as the sum of Reported and Recorded. For participation years in which Expected could be computed, the reporting deviation (RepDev) gives the difference between the number of SRCs which were expected to be reported at a baseline exam based on previous participation year data and the number of SRCs which was actually reported by the athlete or medical record during the baseline exam. The reporting deviation was computed only for those SRC that occurred while the participant was enrolled in the current study (RepDevSO). Oneway intraclass correlations (ICC) were computed between the expected and reported numbers of SRC.

341 athletes had a history of at least one SRC and 206 of those (60.4%) had a RepDev of 0. The overall ICC for RepDev was 0.761 (95% CI 0.73-0.79). The presence of depression (ICC 0.87, 95% CI 0.79-0.92) and loss of consciousness (ICC 0.80, 95% CI 0.720.86) were associated with higher ICCs compared to athletes without these variables. Female athletes demonstrated higher self-report consistency (ICC 0.82, 95% CI 0.79-0.85) compared to male athletes (ICC 0.72, 95% CI 0.68-0.76). Differences in the classification of RepDev according to sex and sport were found to be significant (x2=77.6, df=56, p=0.03). The sports with the highest consistency were Women’s Tennis, Men’s Diving, and Men’s Tennis with 100% consistency between academic years. Sports with the lowest consistency were Women’s Gymnastics (69%), Men’s Lacrosse (70%), and Football (72%). 96 athletes had at least one study-only SRC in the previous year and 69 of those (71.9%) had a RepDevSO of 0 (ICC 0.673, 95% CI 0.64-0.71).

Approximately 40% of athletes do not consistently report their SRC history, potentially further complicating the clinical management of SRC. These findings encourage clinicians to be aware of factors which could influence the reliability of self-reported SRC history.

Arachnoid cysts are fluid-filled sacs thought to be a developmental abnormality which form as a result of splitting or duplication of the arachnoid membrane. In most cases, arachnoid cysts are congenital and asymptomatic throughout an individual’s life. Rarely, arachnoid cysts develop because of head injury, intraventricular hemorrhage of prematurity, presence of a tumor, infection or surgery on the brain. Intracranial cysts are typically incidental brain imaging findings and most commonly located in the middle fossa, the suprasellar region, and the posterior fossa. In cases where the cyst enlarges significantly individuals may experience symptoms of increased intracranial pressure, mass effects, seizures, nausea and vomiting, focal neurological deficits, or hydrocephalus. This presentation compares the differing symptom presentation of two individuals with medically confirmed arachnoid cysts -- one in the middle cranial fossa region (Patient A) and the other in the posterior cranial fossa region (Patient B).

The 2 patients were referred to a private practice neuropsychological clinic for neuropsychological assessment. Patient A was a 39-year-old, right-handed, married Syrian male with 12 years if education, unemployed at the time of testing. Changes in cognition, behavior and personality were reported for Patient A approximately two years after a known cerebrovascular accident. Patient B was a 48-year-old, left-handed married Caucasian male with 16 years of education, on disability due to his medical condition. Patient B reported severe memory impairment, speech and language deficits, variable attention, executive dysfunction, impaired gait with falls, emotional dysregulation, and sleep difficulties. He was diagnosed with bipolar disorder and alcohol use disorder in remission for 9 years.

Neuropsychological testing results for Patient A were not valid, due to initiation difficulties, paranoia about the testing and consequent limited engagement in the process. Predominant symptoms were consistent with negative symptoms of schizophrenia, (i.e., avolition, abulia, and diminished emotional expression); no positive symptoms were observed or reported. His speech was limited -he lacked spontaneous speech and only responded to direct questions. His informant completed a measure assessing pre/post changes in frontal systems and there were significant increases in apathy and executive dysfunction reported. Neuropsychological results collected from Patient B revealed mild to severe impairment of aspects of executive functioning, memory, processing speed, visual attention, expressive language, and manual dexterity bilaterally and manual motor strength - more consistent with subcortical neurological disease. Self-report and informant data revealed significant difficulties with functional abilities, pre/post changes in frontal systems (apathy, disinhibition, and executive dysfunction), sleep efficiency and daytime fatigue, and psychological distress (anxiety and depressive symptoms).

The presenting case analysis illustrates the importance of neuropsychology in identifying and tracking the nature of symptoms associated with neuroimaging confirmed arachnoid cysts. This case analysis is unique as it highlights the complexities of differing symptom phenotypes of the same condition due to location of the cyst. Surgical intervention usually through draining the cyst directly or implantation of a shunt is typically recommended for symptomatic patients and that course of treatment was suggested to both patients. Treatment recommendations geared to target psychosocial and functional difficulties should also be considered.

Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.

In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.

Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.

Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Among patients with a history of ESBL infection, uncertainty remains regarding whether all of these patients require ESBL-targeted therapy when presenting with a subsequent infection. We sought to determine the risks associated with a subsequent ESBL infection to help inform empiric antibiotic decisions.

A retrospective cohort study of adult patients with positive index culture for Escherichia coli or Klebsiella pneumoniae (EC/KP) receiving medical care during 2017 was conducted. Risk assessments were performed to identify factors associated with subsequent infection caused by ESBL-producing EC/KP.

In total, 200 patients were included in the cohort, 100 with ESBL-producing EC/KP and 100 with ESBL-negative EC/KP. Of 100 patients (50%) who developed a subsequent infection, 22 infections were ESBL-producing EC/KP, 43 were other bacteria, and 35 had no or negative cultures. Subsequent infection caused by ESBL-producing EC/KP only occurred when the index culture was also ESBL-producing (22 vs 0). Among those with ESBL-producing index culture, the incidences of subsequent infection caused by ESBL-producing EC/KP versus other bacterial subsequent infection were similar (22 vs 18; P = .428). Factors associated with subsequent infection caused by ESBL-producing EC/KP include history of ESBL-producing index culture, time ≤180 days between index culture and subsequent infection, male sex, and Charlson comorbidity index score >3.

History of ESBL-producing EC/KP culture is associated with subsequent infection caused by ESBL-producing EC/KP, particularly within 180 days after the historical culture. Among patients presenting with infection and a history of ESBL-producing EC/KP, other factors should be considered in making empiric antibiotic decisions, and ESBL-targeted therapy may not always be warranted.

Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.

To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.

This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.

The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.

Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.