Athlete External Load Measures Across a Competitive Season in High School Basketball.

ABSTRACT: Askow, AT, Jennings, W, Jagim, AR, Fields, JB, Beaudoin, RG, Sanchez, GM, Weeks, JE, Oliver, JM, and Jones, MT. Athlete external load measures across a competitive season in high school basketball. J Strength Cond Res 37(11): 2206-2212, 2023-The purpose of this retrospective analysis was to quantify in-season external load and to determine if relationships existed between load metrics and basketball performance. Eleven male high school varsity basketball athletes (n = 11; mass 80.5 ± 9.6 kg, height 190.2 ± 9.4 cm, age 17.6 ± 0.7 years) were monitored across a season. PlayerLoad (PL), PL per minute (PL·min -1 ), total jumps, and explosive movements (EMs) were quantified using a commercially available local positioning unit. Basketball-specific performance metrics, including points scored, points allowed, point differentials, and shooting percentages for each quarter and game, were compiled. Data were analyzed using repeated-measure analysis of variance to evaluate differences in load by starting status, session type, game outcome, and game type. Pearson's correlation coefficients were used to assess relationships between load metrics and basketball performance. Statistical significance was set at p < 0.05. The mean values across 23 games for PL, PL·min -1 , total jumps, and EMs were 457 ± 104 AU, 10.9 ± 1.6 AU, 42.6 ± 9.6, and 46.7 ± 7.2, respectively. Relationships were observed ( p < 0.05) between PL and points scored ( r = 0.38) and free throw percentage ( r = 0.21). Further relationships were observed between PL·min -1 and free throw shooting percentage ( r = -0.27), and between points scored and total jumps ( r = 0.28), and EMs ( r = 0.26). Notable differences in game demands were observed for playing status. Meaningful differences in measures of external load were observed between each quarter of play, with the highest measures evident in quarters 1 and 3. Guards and forwards experienced minimal differences in external load during gameplay, and game outcome did not result in differences. Higher point totals corresponded with higher PL, total jumps, and EM.

Adherence to clozapine vs. other antipsychotics in schizophrenia.

BACKGROUND: To date, there have been no studies evaluating adherence to clozapine with electronic adherence monitoring (EAM) such as the Medication Event Monitoring System (MEMS® ). METHODS: In outpatients with schizophrenia, we conducted a 3-month prospective study investigating antipsychotic adherence with EAM (eCAP® ). Participants were treated with different oral antipsychotics, including clozapine, and blind to EAM monitoring; all were on antipsychotic monotherapy administered once daily. Outcome measures included adherence rate, missed dose, and medication gap. Adherence trajectory patterns were also analyzed for clozapine vs. other antipsychotics collectively. RESULTS: A total of 111 patients were included in the study; 33 and 78 patients received clozapine or other antipsychotics, respectively. Adherence rates, defined as proportion of days that the subject took the medication at the prescribed time ± 3 h and proportion of subjects with ≥80% adherence, were numerically higher in patients receiving clozapine vs. other antipsychotics (72.0% vs. 65.1%, P = 0.10; 49.5% vs. 35.7%, P = 0.11, respectively). Along similar lines, some of the missed dose and medication gap outcomes were significantly better in patients receiving clozapine vs. other antipsychotics. Three adherence trajectory patterns were identified for both clozapine and other antipsychotics, with two shared by both groups (i.e., low adherence with a slight decrease over time; high and stable adherence). CONCLUSION: Findings suggest that in patients with schizophrenia clozapine adherence is at least comparable, if not slightly better, compared with other antipsychotics.

Clozapine administration in clinical practice: once-daily versus divided dosing.

OBJECTIVE: While it is recommended that clozapine be administered in a divided dosing regimen, it is unclear whether this recommendation is followed in real-world clinical practice. In two large datasets, we examined clozapine dosing frequency and patient characteristics across different dosing regimens. METHOD: We conducted a cross-sectional survey, collecting data on patients receiving clozapine in August/September 2015 from the Centre for Addiction and Mental Health (CAMH) in Toronto, Canada, and The Zucker Hillside Hospital (ZHH) in New York, United States. RESULTS: Of 676 and 308 patients included in CAMH and ZHH datasets, clozapine was prescribed once daily in 75.1% and 74.4%, even though doses exceeding 200 mg/day were administered in 88.6% and 84.4% of the respective samples. No significant difference was found in the rates of positive symptom remission between once-daily vs. divided dosing (79.7% vs. 80.5%, P = 1.00). Higher clozapine dose and use of anticholinergic medications were significantly associated with divided dosing in both datasets. Older age or male gender was related to divided dosing in CAMH or ZHH dataset respectively. CONCLUSION: Despite the product monograph recommendation, clozapine is frequently prescribed once daily in North America. Further studies are needed to compare clinical outcomes between once-daily vs. divided clozapine dosing.

Clozapine's critical role in treatment resistant schizophrenia: ensuring both safety and use.

INTRODUCTION: Clozapine was first introduced as an antipsychotic in the 1970's but a cluster of deaths, later linked to the drug's risk of agranulocytosis, led to its withdrawal in most countries. However, work in the 1980's established its unique efficacy in treatment resistant schizophrenia (TRS), which constitutes as many as 30% of those with the illness. Clozapine was reintroduced with this indication shortly thereafter, but because of this risk its use requires routine hematologic monitoring. AREAS COVERED: An update is provided regarding clozapine's risk of neutropenia, agranulocytosis, and associated mortality. In addition, updates are provided on other side effects, specifically myocarditis and bowel obstruction, as evidence suggests these are more common than agranulocytosis and associated with higher mortality rates. EXPERT OPINION: Clozapine remains the only treatment indicated in TRS, but it is dramatically underutilized. Clearly there are serious side effects associated with its use, and while the focus has historically been on hematologic concerns, we highlight other side effects that also demand systematic monitoring. Because it is the only effective treatment option we have for TRS, though, efforts must be implemented that ensure its use in this population while maximizing safety.

The adrenergic α2 antagonist atipamezole alters the behavioural effects of pramipexole and increases pramipexole concentration in blood plasma.

Pramipexole is a dopaminergic agonist used in Parkinson's disease treatment. It is thought to exert its therapeutic and side effects through actions on dopamine D3 receptors. In a recent study, we found that at doses occupying D3 but not D2 receptors pramipexole reduced locomotion and operant responding for primary and conditioned reinforcement. These effects, however, were not blocked by a D3 receptor antagonist and were present in D3 knockout mice, suggesting non-D3 receptor mechanisms. Among the next highest affinity binding sites of pramipexole are adrenergic α2 receptors. Here we explored α2 receptor involvement in the behavioural effects of pramipexole. We found that the α2 antagonist atipamezole, which was itself behaviourally silent, counteracted pramipexole's reduction of locomotion, but not operant responding for water or a conditioned reinforcer. The resulting behavioural profile was similar to that of a higher dose of pramipexole, leading to the hypothesize that atipamezole mediates its behavioural effects by increasing pramipexole effective dose. In support of this hypothesis, we found that atipamezole increased pramipexole concentration in blood plasma. This is not likely due to an effect on drug metabolism since pramipexole is not known to undergo metabolic transformation. Future work should examine two alternative hypotheses; that pramipexole plasma concentration is elevated as the result of 1) competition with atipamezole for renal excretion, or 2) atipamezole blockade of peripheral α2 binding sites, thereby preventing pramipexole distribution to α2-rich tissues. The suggestion of adrenergic effects of pramipexole is important in light of recent interest in adrenergic pathophysiology in Parkinson's disease.

Schizophrenia and the influence of male gender.

Adolescent boys are the demographic group most likely to receive a diagnosis of schizophrenia. Before adulthood, boys accumulate more potential brain hazards than girls, and this may predispose them to disordered neurodevelopment during adolescence. Hormonal and immune gender differences that emerge at this time likely play an additional and significant role. Very recently, gender differences can be examined even before the onset of full-blown illness, in individuals at "clinically high risk."

Motivated to do well: an examination of the relationships between motivation, effort, and cognitive performance in schizophrenia.

The uncertain relationship between negative symptoms, and specifically motivational deficits, with cognitive dysfunction in schizophrenia is in need of further elucidation as it pertains to the interpretation of cognitive test results. Findings to date have suggested a possible mediating role of motivational deficits on cognitive test measures, although findings from formal examinations of effort using performance validity measures have been inconsistent. The aim of this study was to examine the relationships between motivation, effort exerted during cognitive testing, and cognitive performance in schizophrenia. Sixty-nine outpatients with schizophrenia or schizoaffective disorder were evaluated for psychopathology, severity of motivational deficits, effort exerted during cognitive testing, and cognitive performance. Motivation and degree of effort exerted during cognitive testing were significantly related to cognitive performance, specifically verbal fluency, verbal and working memory, attention and processing speed, and reasoning and problem solving. Further, effort accounted for 15% of the variance in cognitive performance, and partially mediated the relationship between motivation and cognitive performance. Examining cognitive performance profiles for individuals exerting normal or reduced effort revealed significant differences in global cognition, as well as attention/processing speed and reasoning and problem solving. These findings suggest that cognitive domains may be differentially affected by impairments in motivation and effort, and highlight the importance of understanding the interplay between motivation and cognitive performance deficits, which may guide the appropriate selection of symptom targets for promoting recovery in patients.

Low dose pramipexole causes D3 receptor-independent reduction of locomotion and responding for a conditioned reinforcer.

Pramipexole is a clinically important dopamine receptor agonist with reported selectivity for dopamine D3 receptors over other dopaminergic and non-dopaminergic sites. Many of its behavioural effects are therefore attributed to D3 receptor activity. Here we relate pramipexole's ex vivo D2 and D3 receptor binding (measured using [(3)H]-(+)-PHNO binding experiments) to its effects on locomotion and operant responding for primary and conditioned reinforcers. We show that pramipexole has inhibitory behavioural effects on all three behaviours at doses that occupy D3 but not D2 receptor. However, these effects are 1) not inhibited by a D3 selective dose of the antagonist SB-277011-A, and 2) present in D3 receptor knockout mice. These results suggest that a pharmacological mechanism other than D3 receptor activity must be responsible for these behavioural effects. Finally, our receptor binding results also suggest that these behavioural effects are independent of D2 receptor activity. However, firmer conclusions regarding D2 involvement would be aided by further pharmacological or receptor knock-out experiments. The implications of our findings for the understanding of pramipexole's behavioural and clinical effects are discussed.

Motivational and neurocognitive deficits are central to the prediction of longitudinal functional outcome in schizophrenia.

OBJECTIVE: Functional impairment is characteristic of most individuals with schizophrenia; however, the key variables that undermine community functioning are not well understood. This study evaluated the association between selected clinical variables and one-year longitudinal functional outcomes in patients with schizophrenia. METHOD: The sample included 754 patients with schizophrenia who completed both baseline and one-year follow-up visits in the CATIE study. Patients were evaluated with a comprehensive battery of assessments capturing symptom severity and cognitive performance among other variables. The primary outcome variable was functional status one-year postbaseline measured using the Heinrichs-Carpenter Quality of Life Scale. RESULTS: Factor analysis of negative symptom items revealed two factors reflecting diminished expression and amotivation. Multivariate regression modeling revealed several significant independent predictors of longitudinal functioning scores. The strongest predictors were baseline amotivation and neurocognition. Both amotivation and neurocognition also had independent predictive value for each of the domains of functioning assessed (e.g., vocational). CONCLUSION: Both motivational and neurocognitive deficits independently contribute to longitudinal functional outcomes assessed 1 year later among patients with schizophrenia. Both of these domains of psychopathology impede functional recovery; hence, it follows that treatments ameliorating each of these symptoms should promote community functioning among individuals with schizophrenia.

Impact of primary negative symptoms on functional outcomes in schizophrenia.

OBJECTIVE: Negative symptoms are known to undermine functional outcomes in people with schizophrenia; however, most studies have not accounted for whether these symptoms were primary or secondary to other psychopathological factors. The present study examined the impact of primary negative symptoms on functional outcomes in patients with schizophrenia. METHOD: The sample included 1427 patients with schizophrenia who completed the baseline visit in the CATIE study. Symptoms were assessed with the Positive and Negative Syndrome Scale and Calgary Depression Scale, extrapyramidal side effects with the Simpson-Angus scale, and functional status with the Heinrichs-Carpenter Quality of Life Scale. RESULTS: Negative symptoms were significantly and inversely related to each domain of functioning examined. These relationships remained after statistically controlling for the influence of potential sources of secondary negative symptoms. In addition, the relationships between negative symptoms and specific domains of functioning remained in patients who had mild/absent positive, depressive, anxiety and extrapyramidal symptoms. Negative symptoms were associated with functional outcomes even in antipsychotic-free patients. CONCLUSIONS: Primary negative symptoms significantly contribute to the functional impairment seen in people with schizophrenia. A better understanding of the etiology and pathobiology of these symptoms is required to guide the search for effective therapeutics that promote functional recovery.

Examining cognitive biases in patients with delusions of reference.

Cognitive biases may not be seen in all subtypes of delusions, and might be more involved in the etiology of some delusional subtypes than others. A sample of patients with delusions of reference did not show the jumping to conclusions (JTC) bias. JTC appears to be more closely related to paranoia than referential delusions.

Association study of cannabinoid receptor 1 (CNR1) gene in tardive dyskinesia.

Tardive dyskinesia (TD) is a severe, debilitating movement disorder observed in 25-30% of the patients treated with typical antipsychotics. Cannabinoid receptor 1 (CNR1) activators tend to inhibit movement, an effect prevented by rimonabant and other selective CNR1 antagonists. Furthermore, CNR1 receptor is downregulated in Huntington's disease and upregulated in Parkinson's disease. Twenty tagSNPs spanning the CNR1 gene were analyzed in schizophrenia patients of European ancestry (n=191; 74 with TD). Significant genotypic (P=0.012) and allelic (P=0.012) association was observed with rs806374 (T>C). Carriers of the CC genotype were more likely to be TD positive (CC vs TT+TC, odds ratio=3.4 (1.5-7.8), P=0.003) and had more severe TD (CC vs TT+TC; 9.52±9.2 vs 5.62±6.9, P=0.046). These results indicate a possible role of CNR1 in the development of TD in our patient population. However, these observations are marginal after correcting for multiple testing and need to be replicated in a larger patient population.

Prediction of longitudinal functional outcomes in schizophrenia: the impact of baseline motivational deficits.

Emerging evidence suggests that motivational deficits are a central component of negative symptoms in schizophrenia, and linked to functional impairment characterizing this illness. This study extends previous cross-sectional findings by examining the concurrent contributions of baseline motivational deficits, other negative symptoms, and other symptom domains on longitudinal functional outcomes in schizophrenia. Results of this longitudinal examination of 18 patients from our previous pilot study reveal that amotivation accounts for 74% and 72% of the variance in functional outcomes at baseline and 6-month follow-up, respectively. These findings further suggest a fundamental role for motivational deficits in predicting functional outcomes in schizophrenia.

Motivational deficits as the central link to functioning in schizophrenia: a pilot study.

Negative symptoms have consistently been found to contribute to functional impairment in schizophrenia. In this pilot study, we sought to delineate the core negative symptoms that contribute to this functional impairment. Adult outpatients with schizophrenia were evaluated for the severity of positive, negative, cognitive, and depressive symptoms. The Quality of Life Scale was used to assess current functioning. Results from 21 participants revealed that a motivation was the sole predictor of functioning, accounting for 74% of the variance in current functioning. This suggests that motivational deficits are the central link between negative symptoms and functional impairment in schizophrenia.

Association study of tardive dyskinesia and five DRD4 polymorphisms in schizophrenia patients.

Tardive dyskinesia (TD) is a side effect of chronic antipsychotic medication exposure. Abnormalities in dopaminergic activity in the nigro-striatal system have been most often suggested to be involved because the agents that cause TD share in common potent antagonism of dopamine D(2) receptors (DRD2). Thus, a number of studies have focused on the association of dopamine system gene polymorphisms and TD, with the most consistent findings being an association between TD and the Ser9Gly polymorphism of the DRD3 gene and the TaqIA site 3' of the DRD2 gene. The DRD4 gene codes for the third member of the D(2)-like dopamine receptor family, and the variable number tandem-repeat polymorphism in exon 3 of DRD4 has been associated with TD. However, other polymorphisms have not been thoroughly examined. In this study, we investigated five polymorphisms spanning the DRD4 gene and their association with TD in our European Caucasian sample (N=171). Although the exon 3 variable number tandem repeat was not associated with TD, haplotypes consisting of four tag polymorphisms were associated with TD in males. This study suggests that DRD4 may be involved in TD in the Caucasian population, although further replication studies are needed.

Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy.

OBJECTIVE: Natalizumab is a humanized recombinant monoclonal antibody against very late activation antigen-4 approved for the treatment of patients with multiple sclerosis (MS). A phase II study failed to demonstrate a difference between natalizumab treatment groups and the placebo group with regard to gadolinium enhancing lesions on MRI 3 months after discontinuation of therapy. The objective of this study was to assess clinical MS disease activity, surrogate disease markers on MRI, immunologic parameters in peripheral blood and CSF, as well as safety in patients with MS after discontinuation of natalizumab therapy. METHODS: This study is a longitudinal and serial cross-sectional assessment, in which 23 patients who were treated with natalizumab in the context of two phase III clinical trials were originally enrolled. A subgroup of patients was followed over 14 months. The annual relapse rate, neurologic disease progression assessed by the Expanded Disability Status Scale, disease surrogate markers on MRI, cellular and humoral immune markers in peripheral blood and CSF, and adverse events of the drug were monitored. RESULTS: With regard to clinical disease activity, neuroimaging, and immune responses, the majority of patients in our cohort were stable. Decreased lymphocyte cell numbers and altered cell ratios returned to normal 14 months after cessation of natalizumab. No infectious complications were observed. CONCLUSION: This is the first long-term follow-up of patients who discontinued natalizumab. We did not observe a clinical, radiographic, or immunologic rebound phenomenon after discontinuation of natalizumab therapy.