Oral ketamine effects on dynamics of functional network connectivity in patients treated for chronic suicidality.

The underlying brain mechanisms of ketamine in treating chronic suicidality and the characteristics of patients who will benefit from ketamine treatment remain unclear. To address these gaps, we investigated temporal variations of brain functional synchronisation in patients with suicidality treated with ketamine in a 6-week open-label oral ketamine trial. The trial's primary endpoint was the Beck Scale for Suicide Ideation (BSS). Patients who experienced greater than 50% improvement in BSS scores or had a BSS score less than 6 at the post-treatment and follow-up (10 weeks) visits were considered responders and persistent responders, respectively. The reoccurring and transient connectivity pattern (termed brain state) from 29 patients (45.6 years ± 14.5, 15 females) were investigated by dynamic functional connectivity analysis of resting-state functional MRI at the baseline, post-treatment, and follow-up. Post-treatment patients showed significantly more (FDR-Q = 0.03) transitions among whole brain states than at baseline. We also observed increased dwelling time (FDR-Q = 0.04) and frequency (FDR-Q = 0.04) of highly synchronised brain state at follow-up, which were significantly correlated with BSS scores (both FDR-Q = 0.008). At baseline, persistent responders had higher fractions (FDR-Q = 0.03, Cohen's d = 1.39) of a cognitive control network state with high connectivities than non-responders. These findings suggested that ketamine enhanced brain changes among different synchronisation patterns and enabled high synchronisation patterns in the long term, providing a possible biological pathway for its suicide-prevention effects. Moreover, differences in cognitive control states at baseline may be used for precise ketamine treatment planning.

Hippocampal subfield volumes predict treatment response to oral ketamine in people with suicidality.

Ongoing stress results in hippocampal neuro-structural alterations which produce pathological consequences, including depression and suicidality. Ketamine may ameliorate stress related illnesses, including suicidality, via neuroplasticity processes. This novel study sought to determine whether oral ketamine treatment specifically affects hippocampal (whole and subfield) volumes in patients with chronic suicidality and MDD. It was hypothesised that oral ketamine treatment would differentially alter hippocampal volumes in trial participants categorised as ketamine responders, versus those who were non-responders. Twenty-eight participants received 6 single, weekly doses of oral ketamine (0.5-3 mg/kg) and underwent MRI scans at pre-ketamine (week 0), post-ketamine (week 6), and follow up (week 10). Hippocampal subfield volumes were extracted using the longitudinal pipeline in FreeSurfer. Participants were grouped according to ketamine response status and then compared in terms of grey matter volume (GMV) changes, among 10 hippocampal regions, over 6 and 10 weeks. Mixed ANOVAs were used to analyse interactions between time and group. Post treatment analysis revealed a significant main effect of group for three left hippocampal GMVs as well in the left and right whole hippocampus. Ketamine acute responders (Week 6) showed increased GMVs in both left and right whole hippocampus and in three subfields compared to acute non-responders, across all three timepoints, suggesting that pre-treatment increased hippocampal GMVs (particularly left hemisphere) may be predictive biomarkers of acute treatment response. Future studies should further investigate the potential of hippocampal volumes as a biomarker of ketamine treatment response.

Oral ketamine may offer a solution to the ketamine conundrum.

Ketamine has received considerable attention for its rapid and robust antidepressant response over the past decade. Current evidence, in clinical populations, predominantly relates to parenterally administered ketamine, which is reported to produce significant undesirable side effects, with additional concerns regarding long-term safety and abuse potential. Attempts to produce a similar drug to ketamine, without the psychotomimetic side effects, have proved elusive. Orally administered ketamine has a different pharmacological profile to parentally administered ketamine, suggesting it may be a viable alternative. Emerging evidence regarding the efficacy and tolerability of oral ketamine suggests that it may be a favourable route of administration, as it appears to obtain similarly beneficial treatment effects, but without the cost and medical resources required in parenteral dosing. The pharmacological effects may be due to the active metabolite norketamine, which has been found to be at substantially higher levels via oral dosing, most likely due to first-pass clearance. Despite bioavailability and peak plasma concentrations both being lower than when administered parenterally, evidence suggests that low-dose oral ketamine is clinically effective in treating pain. This may also be due to the actions of norketamine and therefore, its relevance to the mental health context is explored in this narrative review.

Insights into the neurobiology of suicidality: explicating the role of glutamatergic systems through the lens of ketamine.

Suicidality is a prevalent mental health condition, and managing suicidal patients is one of the most challenging tasks for health care professionals due to the lack of rapid-acting, effective psychopharmacological treatment options. According to the literature, suicide has neurobiological underpinnings that are not fully understood, and current treatments for suicidal tendencies have considerable limitations. To treat suicidality and prevent suicide, new treatments are required; to achieve this, the neurobiological processes underlying suicidal behavior must be thoroughly investigated. Although multiple neurotransmitter systems, particularly serotonergic systems, have been studied in the past, less has been reported in relation to disruptions in glutamatergic neurotransmission, neuronal plasticity, and neurogenesis that result from stress-related abnormalities of the hypothalamic-pituitary-adrenal system. Informed by the literature, which reports robust antisuicidal and antidepressive properties of subanaesthetic doses of ketamine, this review aims to provide an examination of the neurobiology of suicidality (and relevant mood disorders) with implications of pertinent animal, clinical, and postmortem studies. We discuss dysfunctions in the glutamatergic system, which may play a role in the neuropathology of suicidality and the role of ketamine in restoring synaptic connectivity at the molecular levels.

Treatment response with ketamine in chronic suicidality: An open label functional connectivity study.

BACKGROUND: Ketamine has recently been proposed as a treatment option for suicidality. Whilst its mechanism of action has been explored at molecular levels, the effect on the brain at the organ level remains unclear. Here we investigate immediate post-treatment and prolonged large-scale resting-state neural network changes to elucidate the neuronal underpinnings associated with ketamine's therapeutic effects. METHODS: Twenty-eight adults (aged 22-72 years) participated in the Oral Ketamine Trial On Suicidality, which is an open-label trial of weekly sub-anaesthetic doses of oral ketamine over 6 weeks. MRI was acquired at baseline, post-treatment, and follow-up. Functional connectivity changes at post-treatment and follow-up were examined using seed based and independent component analysis. RESULTS: The seed-based connectivity analysis revealed significantly reduced connectivity at post-treatment from the right hippocampus to both right and left superior frontal gyrus, from the left anterior parahippocampus to right superior frontal gyrus, left superior frontal gyrus, right middle frontal gyrus, and left frontal operculum cortex. Compared with baseline, the ICA showed reduced anterior default mode network connectivities to bilateral posterior cingulate cortex, middle and anterior cingulate cortex, lingual gyrus, and cuneus and increased connectivity of the frontoparietal network to the right superior parietal lobule at post-treatment. LIMITATIONS: Open label pilot study. CONCLUSIONS: We have shown sub-anaesthetic doses of ketamine alters connectivity in networks which have been shown to be aberrantly hyper-connected in numerous psychiatric conditions. These neurocircuitry changes are supported by significant reductions in suicide ideation. Our results provide support for the use of ketamine as a treatment for suicidality.

Electrophysiological phenotypes of suicidality predict prolonged response to oral ketamine treatment.

Oral ketamine has shown to be a rapid-acting antidepressant and a potential treatment option for suicidality, however, repeated doses are often required. Objective markers of prolonged treatment response are needed to help individuals and clinicians make informed treatment decisions. This secondary analysis sought to identify objective electrophysiological predictors of both prolonged response and dose sensitivity to low-dose oral ketamine in people with chronic suicidality. Individuals with a Beck Scale for Suicide Ideation total score (BSS) ≥ 6 (N = 29) completed a six-week ketamine treatment, pre-treatment electroencephalography and follow-up assessment of suicidality (four weeks from the final ketamine dose). Prolonged response was observed in 52% of participants (follow-up BSS reduced by 50% or ≤6); nearly half were prolonged non-responders. There was decisive evidence for a predictive Bayesian linear regression model with follow-up BSS score as the response variable and pre-treatment auditory evoked power bands as predictors (theta, alpha and beta frequencies, BF10 = 17,948, R2 = 0.70). A Bayesian one-way ANOVA indicated strong evidence for a model of positive association between auditory evoked power and ketamine dose sensitivity (theta-alpha BF+0 = 108, effect size δ = 1.3, 95% CI 0.5-2.1; high-beta BF+0 = 7.4, δ = 0.8, 95% CI 0.1-1.6). Given auditory evoked power may index serotonin neurotransmission, these results suggest that a prolonged response to ketamine may, in part, be mediated by pre-treatment serotonergic functioning. In addition, the observed beta power differences may arise from GABAergic functioning. These suicidality phenotypes, identifiable by pre-treatment electrophysiology, may aid diagnosis, treatment selection and prediction of prolonged treatment outcome.

Stress, mental disorder and ketamine as a novel, rapid acting treatment.

The experience of stress is often utilised in models of emerging mental illness and neurobiological systems are implicated as the intermediary link between the experience of psychological stress and the development of a mental disorder. Chronic stress and prolonged glucocorticoid exposure have potent effects on neuronal architecture particularly in regions that modulate the hypothalamic-pituitary-adrenal (HPA) axis and are commonly associated with psychiatric disorders. This review provides an overview of stress modulating neurobiological and neurochemical systems which underpin stress-related structural and functional brain changes. These changes are thought to contribute not only to the development of disorders, but also to the treatment resistance and chronicity seen in some of our most challenging mental disorders. Reports to date suggest that stress-related psychopathology is the aetiological mechanism of these disorders and thus we review the rapid acting antidepressant ketamine as an effective emerging treatment. Ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, is shown to induce a robust treatment effect in mental disorders via enhanced synaptic strength and connectivity in key brain regions. Whilst ketamine's glutamatergic effect has been previously examined, we further consider ketamine's capacity to modulate the HPA axis and associated pathways.

Oral ketamine reduces the experience of stress in people with chronic suicidality.

BACKGROUND: Stress is prevalent in people experiencing suicidality and is a major contributor to the development of mental disorders. Evidence suggests ketamine shows capacity to reverse stress-induced brain changes. Though stress and ketamine have been explored individually for suicidality, this study is the first to examine ketamine treatment for self-reported stress in adults with chronic suicidality, building on pre-clinical evidence of ketamine's capacity to normalize stress-induced responses and contributing to our understanding of oral ketamine in clinical populations. METHODS: Thirty two adult participants (22-72 years; 17 female) with chronic suicidality completed 6 weeks of active treatment, receiving low (0.5 mg/kg - 3.0 mg/kg) doses of oral ketamine once per week, with a 4-week follow-up phase, to assess the effect of ketamine on their perceived stress. Stress was measured via self-report utilizing the Depression Anxiety Stress Scale-21(DASS-21), and analysed at pre-treatment (week 0), post-treatment (week 6) and at follow-up (week 10). RESULTS: Repeated measures ANOVA showed a significant reduction in stress (p<.001) post-treatment and Reliable Change Index calculations confirmed this to be clinically significant. Furthermore, those classified as 'prolonged responders' demonstrated a sustained reduction in stress at follow-up (i.e. after 4 weeks of nil ketamine). LIMITATIONS: Small sample size, open label design, expectancy, secondary analysis CONCLUSIONS: Ketamine showed the capacity to produce a robust and sustained improvement in stress symptoms, in people with chronic suicidality. Future larger, controlled studies examining treatment suitability in a range of stress related disorders are warranted.

Overhead throwing biomechanics in cricketers: The effect of a run-up approach.

Overhead throwing by cricketers when fielding with different approaches has been described using two-dimensional analysis. Currently, the three-dimensional kinematic and kinetic characteristics of an overhead throw performed by cricketers following a run-up are unknown. Fifteen South African cricketers performed six overhead throws, from a stationary position and with a run-up over 15-20 m prior to fielding a ball, respectively. Kinematic data and ground reaction forces were collected throughout the throwing trials. Joint kinetics were calculated using inverse dynamics. An independent t-test or Mann-Whitney U-test was used to determine joint kinetic differences between throwing approaches. Differences between the kinematic waveforms for stationary and run-up throwing approaches were assessed using one-dimensional statistical parametric mapping ANOVA (P < 0.05). The shoulder, elbow and thoraco-lumbar joints displayed similar kinematics between throwing approaches. The run-up approach displayed increased hip flexion between 0-34% and 57-100% (F(1, 28) = 6.726; P = 0.01) of the throwing cycle; and lumbo-pelvic flexion between 57 and 65% (F(1, 28) = 6.823; P = 0.02) of the throwing cycle; greater shoulder compression (F(1, 28) = 1.036; P = 0.02) and posterior force (F(1, 28) = 1.052; P = 0.009) at maximum external rotation; yet less superior shoulder force (F(1, 28) = 1.744; P = 0.005) and elbow compression (F(1, 28) = 4.331; P = 0.03), superior (F(1, 28) = 1.212; P = 0.002) and medial (F(1, 28) = 1.370; P = 0.03) elbow forces at ball release, when compared to a stationary position. Cricketers maintain similar upper limb kinematics between overhead throwing approaches. However, throwing with a run-up approximately doubles the forces exerted on the shoulder at maximum external rotation, which is most likely caused by the greater dominant hip and lumbo-pelvic flexion noted. This may amplify the potential risk for shoulder injury when throwing.HighlightsThrowing arm motion is similar irrespective of the approach used by cricketers to throw.Throwing with a run-up produced increased angles of lumbo-pelvic and dominant hip flexion in various phases of the throwing cycle.Throwing with a run-up resulted in greater shoulder compression and posterior force at maximum external rotation.

Relationships between reduction in symptoms and restoration of function and wellbeing: Outcomes of the Oral Ketamine Trial on Suicidality (OKTOS).

Recovery of functioning is integral to successful treatment outcomes in depressive illness. Optimal antidepressant treatment results in both symptomatic remission and functional recovery. Oral ketamine rapidly reduces suicidality and depression; however, reports of functional and wellbeing outcomes are lacking. This study examines participants' social and occupational functioning and wellbeing outcomes in the Oral Ketamine Trial on Suicidality (OKTOS). Thirty adults with chronic suicidality participated in the trial over 10 weeks. Functional recovery and wellbeing were assessed using the Social and Occupational Functioning Scale (SOFAS) and World Health Organization Well-Being Index (WHO-5). Suicidality and depressive symptoms were assessed using the Beck Scale for Suicidal ideation (BSS) and Montgomery-Asberg Depression Rating Scale (MADRS). Relationships between the four treatment outcomes were analysed. Forty-three percent of participants achieved healthy function (SOFAS ≥ 80) and 27% reported healthy wellbeing (WHO-5 > 60%) at the four-week post-treatment follow-up. Wellbeing was revealed as the data-derived treatment endpoint for the sample. Effect sizes for functioning and wellbeing outcomes were smaller than for suicidality and depression outcomes. Results suggest that reduction in depressive symptoms and suicidal ideation may be necessary but not sufficient for full restoration of function and wellbeing in antisuicidal and antidepressant therapy, including clinical trials.

Six-week oral ketamine treatment for chronic suicidality is associated with increased grey matter volume.

Chronic suicidality has been associated with neuronal atrophy in cortico-striato-limbic regions and is thought to be mediated via a glutamatergic imbalance. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been posited to exert anti-suicidal effects by promoting neurogenesis via modulation of glutamatergic transmission. This voxel-based morphometry study examined the effect of ketamine on whole brain grey matter in adults with chronic suicidality. Grey matter in the periaqueductal grey, nucleus accumbens, putamen, caudate, and thalamus was significantly increased following 6 weeks of low dose oral ketamine treatment. These results support the notion that ketamine rapidly enhances synaptic plasticity within striato-limbic regions.

The association between gird and overhead throwing biomechanics in cricket.

The development of GIRD is a well-documented adaptation associated with repetitive overhead throwing in numerous sports. In occurrence with total rotational range of motion deficit, GIRD is considered pathological and increases shoulder injury risk. While cricketers demonstrate these deficits in rotational range; the association between GIRD and overhead throwing has yet to be explored. Therefore, the aim of this study was to determine the relationship between GIRD and overhead throwing biomechanics in cricketers. Passive shoulder rotational range of motion was measured in 15 cricketers (elite = 8, amateur = 7). Kinetic and kinematic data were obtained during overhead throws from a stationary and run-up approach. Linear regression was used to determine potential relationships between GIRD and discrete shoulder kinetics for both throwing approaches. One-dimensional statistical parametric mapping regression was conducted to assess relationships between GIRD and throwing kinematics. When throwing overhead from a stationary position, GIRD was associated with reduced hip abduction during the preparatory arc (p = 0.002); superior shoulder (p = 0.003) and elbow compressive (p = 0.009) forces, at cocking. In addition, GIRD was associated with increased posterior shoulder force during arm deceleration for both stationary (p = 0.013) and run-up approaches (p = 0.03) to overhead throwing. Cricketers with GIRD utilise a shorter stride, creating early pelvic rotation and a slow throwing arm with an associated reduction in forces about the shoulder and elbow at cocking, when throwing from a stationary position. Further, overload of the posterior shoulder occurs during arm deceleration, irrespective of throwing approach. These findings highlight potential shoulder injury risk.

Low dose oral ketamine treatment in chronic suicidality: An open-label pilot study.

Recently, low-dose ketamine has been proposed as a rapid-acting treatment option for suicidality. The majority of studies to date have utilised intravenous (IV) ketamine, however, this route of administration has limitations. On the other hand, oral ketamine can be administered in a range of settings, which is important in treating suicidality, although studies as to safety and feasibility are lacking. n = 32 adults (aged 22-72 years; 53% female) with chronic suicidal thoughts participated in the Oral Ketamine Trial on Suicidality (OKTOS), an open-label trial of sub-anaesthetic doses of oral ketamine over 6 weeks. Participants commenced with 0.5 mg/kg of ketamine, which was titrated to a maximum 3.0 mg/kg. Follow-up assessments occurred at 4 weeks after the final dose. The primary outcome measure was the Beck Scale for Suicide Ideation (BSS) and secondary measures included scales for suicidality and depressive symptoms, and measures of functioning and well-being. Mean BSS scores significantly reduced from a high level of suicidal ideation at the pre-ketamine (week 0) timepoint to below the clinical threshold at the post-ketamine (week 6) timepoint. The proportion of participants that achieved clinical improvement within the first 6 weeks was 69%, whereas 50% achieved a significant improvement by the follow-up (week 10) timepoint. Six weeks of oral ketamine treatment in participants with chronic suicidality led to significant reduction in suicidal ideation. The response observed in this study is consistent with IV ketamine trials, suggesting that oral administration is a feasible and tolerable alternative treatment for chronic suicidality.

Predicting therapeutic response to oral ketamine for chronic suicidal ideation: a Bayesian network for clinical decision support.

BACKGROUND: The glutamatergic modulator ketamine has been shown to result in rapid reductions in both suicidal ideation (SI) and depressive symptoms in clinical trials. There is a practical need for identification of pre-treatment predictors of ketamine response. Previous studies indicate links between treatment response and body mass index (BMI), depression symptoms and previous suicide attempts. Our aim was to explore the use of clinical and demographic factors to predict response to serial doses of oral ketamine for chronic suicidal ideation. METHODS: Thirty-two participants completed the Oral Ketamine Trial on Suicidality (OKTOS). Data for the current study were drawn from pre-treatment and follow-up time-points of OKTOS. Only clinical and sociodemographic variables were included in this analysis. Data were used to create a proof of concept Bayesian network (BN) model of variables predicting prolonged response to oral ketamine, as defined by the Beck Scale for Suicide Ideation (BSS). RESULTS: The network of potential predictors of response was evaluated using receiver operating characteristic (ROC) curve analyses. A combination of nine demographic and clinical variables predicted prolonged ketamine response, with strong contributions from BMI, Social and Occupational Functioning Assessment Scale (SOFAS), Montgomery-Asberg Depression Rating Scale (MADRS), number of suicide attempts, employment status and age. We evaluated and optimised the proposed network to increase the area under the ROC curve (AUC). The performance evaluation demonstrated that the BN predicted prolonged ketamine response with 97% accuracy, and AUC = 0.87. CONCLUSIONS: At present, validated tools to facilitate risk assessment are infrequently used in psychiatric practice. Pre-treatment assessment of individuals' likelihood of response to oral ketamine for chronic suicidal ideation could be beneficial in making more informed decisions about likelihood of success for this treatment course. Clinical trials registration number ACTRN12618001412224, retrospectively registered 23/8/2018.

Anorexia nervosa, zinc deficiency and the glutamate system: The ketamine option.

Anorexia nervosa (AN) is a severe, biological brain disorder with significant medical risks and a tenacious development over time. Unfortunately, few treatments show efficacy in people with AN although numerous therapies including pharmacological have been explored. Zinc deficiency has been implicated in AN and zinc is important in a large range of processes in the brain. In particular, it is an allosteric modulator of NMDA receptors - the maintenance of zinc levels within a normal, narrow range is essential for glutamatergic functioning. Chronic zinc deficiency increases neuronal stores of calcium and reduces direct modulation of NMDA receptors which collectively lead to overactivation and upregulation of NMDA receptors. This may facilitate pathologically high levels of glutamate, calcium influx and subsequent excitotoxicity, which can disrupt synaptogenesis and synaptic plasticity. While studies of zinc supplementation in AN have shown some promise, the efficacy of this treatment is limited. This may be due to AN illness chronicity and the significant changes already made, as well as a reduced potency of zinc to inhibit NMDA receptors in a pathological state. Thus, we propose that the safe (at low doses) yet more potent NMDA receptor antagonist, ketamine, may act to normalise a perturbed glutamatergic system and increase synaptogenesis in the short term. This 'kickstart' via ketamine could then allow zinc supplementation and other forms of treatment to enhance recovery in AN.

Overhead throwing in cricketers: A biomechanical description and playing level considerations.

This study aimed to describe stationary overhead throwing biomechanics in South African cricketers, considering playing level, and relative to baseball. Kinematics and ground reaction forces were collected during throwing trials. Inverse dynamics was used to calculate joint kinetics. Inter-subject variability was calculated using the coefficient of variance. A one-dimensional statistical parametric mapping ANOVA was conducted to assess differences between the kinematic waveforms in elite and amateur cricketers (p < 0.05). Fifteen cricketers (elite = 8; amateur = 7) participated in this study. The basic parameters of a cricketer's throwing action are described. Substantial inter-subject variability was noted for all variables, except lumbopelvic movement. Cricketers presented with 74.9 ± 27.3° glenohumeral external rotation and 94.8 ± 23.7° elbow flexion, at maximum external rotation (MER). Amateur cricketers displayed decreased elbow flexion range of motion between 2-14% of the throwing cycle (F = 9.365;p = 0.01); greater shoulder (121.0vs85.9 N; F = 0.36,p = 0.021) and elbow compression (105.6vs72.8 N;F = 0.007,p = 0.043), and superior shoulder force (203.1vs115.5 N;F = 2.43,p = 0.022) at MER, when compared with elite cricketers. Cricketers display similarities to baseball pitchers when throwing overhead from a stationary position. The "preparatory arc" utilised is different to the wind-up noted for baseball. The forces exerted on the shoulder and elbow, in amateur cricketers specifically, are substantially greater at MER and may indicate the potential risk for injury.

Incidence and impact of time loss and non-time-loss shoulder injury in elite South African cricketers: A one-season, prospective cohort study.

OBJECTIVES: To determine the incidence, prevalence and impact of shoulder injury in elite South African cricketers. DESIGN: Prospective longitudinal cohort study. METHODS: One hundred and six senior national/franchise cricketers completed a pre-season Kerlan-Jobe Orthopaedic Clinic shoulder and elbow (KJOC) score. All injuries sustained during the 2016/2017 season were captured on an injury reporting system. Injuries were verified by the respective squad physiotherapist at the end of the season and post-season KJOC score was obtained from all the players. RESULTS: Eighteen percent (95% CI: 11-25%) of cricketers sustained a shoulder injury, at a rate of 0.19 injuries per player per year. Annual injury prevalence was 1.1%. Shoulder injury occurred primarily while throwing (58%). Fielding performance was maintained by adapting throwing technique (58%) or fielding position (21%). Thirty-two percent of shoulder injuries resulted in time lost to matches and/or training. A history of shoulder injury increased the risk of sustaining another injury by 1.91 times (95% CI: 1.73-2.15). Irrespective of injury, cricketers demonstrated consistently low pre- (78.5 ±â€¯15.6) and post-season (81.2 ±â€¯17.1) KJOC scores. Pre-season KJOC scores were significantly lower (r2 = 0.106, p = 0.001) in those cricketers with a history of shoulder injury. Cricketers who sustained a seasonal shoulder injury had significantly lower (r2 = 0.112, p < 0.001) post-season KJOC scores, indicating persistent shoulder pain or dysfunction. CONCLUSION: This is the first study to report both time- and non-time-loss shoulder injury in elite South African cricketers. All non-time-loss shoulder injuries compromised primary skill, while some resulted in changes to throwing technique and fielding position. Thus shoulder injury, whether it results in time loss or not, potentially impacts match performance.

The cricketer's shoulder: Not a classic throwing shoulder.

OBJECTIVES: To describe the musculoskeletal adaptations inherent to the cricketers' shoulder and determine potential predictors of shoulder injury in elite South African cricketers. DESIGN: Prospective longitudinal cohort study; SETTING: Non-clinical, at national cricket indoor training venues. PARTICIPANTS: One hundred and six elite cricketers, representing 82% of the South African national and franchise teams, consent. A total of 105 cricketers (27 ±â€¯4 years) were eligible for participation in this study. MAIN OUTCOME MEASURES: A pre-season shoulder screening battery including a shoulder function questionnaire, two ultrasonographic shoulder measurements and 14 musculoskeletal tests including pain provocation, range of motion, strength and flexibility was assessed. Non-contact dominant shoulder injuries were documented throughout the 2016/2017 season. RESULTS: The musculoskeletal profile of a cricketer's shoulder is described. 17% (95%CI: 9-24%) of cricketers sustained an injury during the 2016/2017 season. Two of the 17 screening tests predicted seasonal dominant shoulder injury (p < 0.05): a dominant supraspinatus tendon thickness ≥5.85 mm (sensitivity: 72%, specificity: 63%) and non-dominant pectoralis minor length ≤12.85 cm (sensitivity: 83%, specificity: 55%). CONCLUSION: The musculoskeletal adaptations inherent to cricketing shoulders are distinctly different to the classic "thrower's shoulder" described in baseball. A thickened dominant supraspinatus tendon and a shortened non-dominant pectoralis minor muscle are risk factors for developing shoulder injury in this group. This identifies the need to investigate preventative strategies (strengthening/flexibility) and throwing workload management in cricketers with shoulder injury.