The proteomic fingerprint in infants with single ventricle heart disease in the interstage period: evidence of chronic inflammation and widespread activation of biological networks.

Introduction: Children with single ventricle heart disease (SVHD) experience significant morbidity across systems and time, with 70% of patients experiencing acute kidney injury, 33% neurodevelopmental impairment, 14% growth failure, and 5.5% of patients suffering necrotizing enterocolitis. Proteomics is a method to identify new biomarkers and mechanisms of injury in complex physiologic states. Methods: Infants with SVHD in the interstage period were compared to similar-age healthy controls. Serum samples were collected, stored at -80°C, and run on a panel of 1,500 proteins in single batch analysis (Somalogic Inc., CO). Partial Least Squares-Discriminant Analysis (PLS-DA) was used to compare the proteomic profile of cases and controls and t-tests to detect differences in individual proteins (FDR <0.05). Protein network analysis with functional enrichment was performed in STRING and Cytoscape. Results: PLS-DA readily discriminated between SVHD cases (n = 33) and controls (n = 24) based on their proteomic pattern alone (Accuracy = 0.96, R2 = 0.97, Q2 = 0.80). 568 proteins differed between groups (FDR <0.05). We identified 25 up-regulated functional clusters and 13 down-regulated. Active biological systems fell into six key groups: angiogenesis and cell proliferation/turnover, immune system activation and inflammation, altered metabolism, neural development, gastrointestinal system, and cardiac physiology and development. Conclusions: We report a clear differentiation in the circulating proteome of patients with SVHD and healthy controls with >500 circulating proteins distinguishing the groups. These proteomic data identify widespread protein dysregulation across multiple biologic systems with promising biological plausibility as drivers of SVHD morbidity.

Understanding the mental health needs of Scotland's prison population: a health needs assessment.

Introduction: This study reports on an assessment of mental health needs among Scotland's prison population which aimed to describe the scale and nature of need as well as identify opportunities to improve upon the services available. The project was commissioned by the Scottish Government to ensure that future changes to the services available to support the mental health and wellbeing of people in prison would be evidence-based and person-centered. Methods: A standardized approach to health needs assessments was employed. The study was comprised of four phases. In phase I a rapid literature review was undertaken to gather evidence on the prevalence of mental health needs experienced by people in prison in the UK. In Phase II a multi-method and multi-informant national mapping exercise involving providers to all Scottish prisons was undertaken to describe the mental health services available, and any gaps in these services, for people in and leaving prison. In Phase III prevalence estimates of several mental health needs were derived for Scotland's current prison population, modeled from a national survey dataset of Scotland's community population using logistic regression. Finally in Phase IV, professional stakeholders and individuals with lived experience were interviewed to understand their experiences and insights on challenges to supporting the mental health and wellbeing of people in prison, and ideas on how these challenges could be overcome. Results: Evidence across the four phases of this needs assessment converged indicating that existing provision to support the mental health of people in prison in Scotland was considered inadequate to meet these needs. Barriers to effective partnership working for justice, health, social work and third sector providers appear to have led to inadequate and fragmented care, leaving prisoners without the support they need during and immediately following imprisonment. Conclusions: Joint and coordinated action from justice, health and social care, and third sector providers is needed to overcome enduring and structural challenges to supporting the mental health of people in prison. Eighteen evidence-based recommendations were proposed to the Scottish Government relating to the high-level and operational-level changes required to adequately meet the prison population's mental health needs.

Long-term outcomes of the recovery approach in a high-security mental health setting: a 20 year follow-up study.

Background: This study examined the outcomes of a descriptive, longitudinal cohort consisting of 241 patients initially examined in a population study at the high secure State Hospital for Scotland and Northern Ireland in 1992-93. A partial follow-up focusing on patients with schizophrenia was conducted in 2000-01, followed by a comprehensive 20 year follow-up that began in 2014. Aims: To explore what happens to patients who required high secure care during a 20 year follow-up period. Method: Previously collected data were amalgamated with newly collected information to examine the recovery journey since baseline. Various sources were employed, including patient and keyworker interviews, case note reviews, and extraction from health and national records, and Police Scotland datasets. Results: Over half of the cohort (56.0%) with available data resided outside secure services at some point during the follow-up period (mean 19.2 years), and only 12% of the cohort were unable to transition out of high secure care. The symptoms of psychosis improved, with statistically significant reductions observed in reported delusions, depression, and flattened affect. Reported sadness [according to the Montgomery-Åsberg Depression Rating Scale (MADRS)] at baseline, first, and 20 year follow-up interviews was negatively correlated with the questionnaire about the process of recovery (QPR) scores at the 20 year follow-up. However, qualitative data depicted progress and personal development. According to societal measures, there was little evidence of sustained social or functional recovery. The overall conviction rate post-baseline was 22.7%, with 7.9% violent recidivism. The cohort exhibited poor morbidity and mortality, with 36.9% of the cohort dying, primarily from natural causes (91%). Conclusions: Overall, the findings showed positive outcomes in terms of movement out of high-security settings, symptom improvement, and low levels of recidivism. Notably, this cohort experienced a high rate of deaths and poor physical morbidity, along with a lack of sustained social recovery, particularly among those who had negotiated a path through services and who were current residents in the community. Social engagement, enhanced during residence in low secure or open ward settings, diminished significantly during the transition to the community. This is likely a result of self-protective measures adopted to mitigate societal stigma and the shift from a communal environment. Subjective depressive symptoms may impact broader aspects of recovery.

Randomised controlled trial of the short-term effects of osmotic-release oral system methylphenidate on symptoms and behavioural outcomes in young male prisoners with attention deficit hyperactivity disorder: CIAO-II study.

BACKGROUND: Research has shown that 20-30% of prisoners meet the diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Methylphenidate reduces ADHD symptoms, but effects in prisoners are uncertain because of comorbid mental health and substance use disorders. AIMS: To estimate the efficacy of an osmotic-release oral system methylphenidate (OROS-methylphenidate) in reducing ADHD symptoms in young adult prisoners with ADHD. METHOD: We conducted an 8-week parallel-arm, double-blind, randomised placebo-controlled trial of OROS-methylphenidate versus placebo in male prisoners (aged 16-25 years) meeting the DSM-5 criteria for ADHD. Primary outcome was ADHD symptoms at 8 weeks, using the investigator-rated Connors Adult ADHD Rating Scale (CAARS-O). Thirteen secondary outcomes were measured, including emotional dysregulation, mind wandering, violent attitudes, mental health symptoms, and prison officer and educational staff ratings of behaviour and aggression. RESULTS: In the OROS-methylphenidate arm, mean CAARS-O score at 8 weeks was estimated to be reduced by 0.57 points relative to the placebo arm (95% CI -2.41 to 3.56), and non-significant. The responder rate, defined as a 20% reduction in CAARS-O score, was 48.3% for the OROS-methylphenidate arm and 47.9% for the placebo arm. No statistically significant trial arm differences were detected for any of the secondary outcomes. Mean final titrated dose was 53.8 mg in the OROS-methylphenidate arm. CONCLUSIONS: ADHD symptoms did not respond to OROS-methylphenidate in young adult prisoners. The findings do not support routine treatment with OROS-methylphenidate in this population. Further research is needed to evaluate effects of higher average dosing and adherence to treatment, multi-modal treatments and preventative interventions in the community.

Epidemiology of knife carrying among young British men.

PURPOSE: Knife carrying has caused considerable public concern in the UK. But little is known of the epidemiology and characteristics of men who carry knives. We investigated associations with socioeconomic deprivation, area-level factors, and psychiatric morbidity. METHODS: Cross-sectional surveys of 5005 British men, 18-34 years, oversampling Black and Minority Ethnic (BME) men, lower social grades, and in London Borough of Hackney and Glasgow East. Participants completed questionnaires covering violent behaviour and psychiatric morbidity using standardised self-report instruments. Socioeconomic deprivation measured at small area level. RESULTS: Prevalence of knife carrying was 5.5% (4.8-6.9) and similar among white and BME subgroups. However, prevalence was twice the national rate in Glasgow East, and four times higher among Black men in Hackney, both areas with high levels of background violence and gang activity. Knife carrying was associated with multiple social problems, attitudes encouraging violence, and psychiatric morbidity, including antisocial personality disorder (AOR 9.94 95% CI 7.28-13.56), drug dependence (AOR 2.96 95% CI 1.90-4.66), and paranoid ideation (AOR 6.05 95% CI 4.47-8.19). There was no evidence of a linear relationship with socioeconomic deprivation. CONCLUSION: Men who carry knives represent an important public health problem with high levels of health service use. It is not solely a criminal justice issue. Rates are increased in areas where street gangs are active. Contact with the criminal justice system provides opportunity for targeted violence prevention interventions involving engagement with integrated psychiatric, substance misuse, and criminal justice agencies.

Exploration of morbidity, suicide and all-cause mortality in a Scottish forensic cohort over 20 years.

BACKGROUND: Premature mortality among patients experiencing forensic care is high. This paper examines the morbidity and mortality of all Scottish high secure patients in 1992/1993 and followed up 20 years later through the context of recovery. AIMS: To explore morbidity and delineate which patients are at greatest risk of premature mortality. To assess the extent of suicide and unnatural deaths. To establish which factors, if any, appear protective. METHOD: Health and mortality data were extracted from national data-sets and death categorised as premature or post-expected age. Standardised mortality ratios were calculated to explore natural, unnatural and suicide deaths with Cox regression conducted to explore baseline demographics and premature death. RESULTS: During a mean follow-up of 21.1 years, 36.9% (n = 89) died, at an average age of 55.6 years. Of these, 70.8% (n = 63) died prematurely. Men lost on average 14.9 years and women 24.1 years of potential life. Five lives (5.6%) were lost by suicide and three (3.4%) by unnatural means. CONCLUSIONS: In contrast to other mainstream and forensic cohorts, high rates of suicide and accidental deaths were not apparent. Risk of premature mortality is high. A greater focus upon physical health by community and in-patient services is essential.

Rethinking Rideshares: A Transportation Assistance Pilot for Pediatric Patients with Sickle Cell Disease.

OBJECTIVE: Transportation barriers can limit health care access. This is particularly problematic for patients with chronic medical conditions such as sickle cell disease (SCD) who require frequent medical visits. This study assesses the efficacy of health care-directed rideshare services for overcoming these barriers at an urban pediatric specialty clinic. METHODS: A pilot study was conducted at Boston Medical Center's Pediatric Hematology Clinic from January to April 2019. Patients whose caregivers reported transportation difficulties were offered rides. Primary outcomes were no-show rates and cost. Secondary outcomes included timeliness and patient experience. RESULTS: Implementation of rideshare services led to an 8.5% decrease in the no-show rate among patients with SCD. The intervention cost $2,175 over three months and generated $40,262 in charges. No adverse experiences were reported. CONCLUSIONS: In an urban, underserved pediatric hematology clinic, the use of rideshare services is a feasible and relatively low-cost strategy for improving health care access.

Randomised controlled trial of the short-term effects of OROS-methylphenidate on ADHD symptoms and behavioural outcomes in young male prisoners with attention-deficit/hyperactivity disorder (CIAO-II).

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder, seen in 20-30% of young adult prisoners. Pharmacoepidemiological studies, a small randomised controlled trial and open trial data of methylphenidate suggest clinically significant reductions in ADHD symptoms, emotional dysregulation, disruptive behaviour and increased engagement with educational activities. Yet, routine treatment of ADHD in offenders is not yet established clinical practice. There is continued uncertainty about the clinical response to methylphenidate (MPH), a first-line treatment for ADHD, in offenders, who often present with an array of complex mental health problems that may be better explained by states of inattentive, overactive, restless and impulsive behaviours. To address this problem, we will conduct an efficacy trial to establish the short-term effects of osmotic-controlled release oral delivery system (OROS)-methylphenidate (Concerta XL), an extended release formulation of MPH, on ADHD symptoms, emotional dysregulation and behaviour. METHODS: This study is a parallel-arm, randomised, placebo-controlled trial of OROS-MPH on ADHD symptoms, behaviour and functional outcomes in young male prisoners aged 16-25, meeting Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria for ADHD. Participants are randomised to 8 weeks of treatment with OROS-MPH or placebo, titrated over 5 weeks to balance ADHD symptom improvement against side effects. Two hundred participants will be recruited with a 1:1 ratio of drug to placebo. The primary outcome is change in level of ADHD symptoms after 8 weeks of trial medication. DISCUSSION: Potential benefits include improvement in ADHD symptoms, emotional dysregulation, attitudes towards violence and critical incidents and increased engagement with educational and rehabilitation programmes. Demonstrating the efficacy and safety of MPH on ADHD symptoms and associated impairments may provide the data needed to develop effective healthcare pathways for a significant group of young offenders. Establishing efficacy of MPH in this population will provide the foundation needed to establish long-term effectiveness studies with the potential for demonstrating significant reductions in criminal behaviour and improved health-economic outcomes. TRIAL REGISTRATION: ISRCTN registry, ISRCTN16827947, 31st May 2016; EudraCT number, 2015-004271-78, 31st May 2016. Last particpant last visit 6 June 2019. Data lock 27 August 2019.

Childhood adversity and psychosis in detained inpatients from medium to high secured units: Results from the Scottish census survey.

BACKGROUND: There is limited data available regarding the most common forms of psychiatric illness, the occurrence of childhood adversity, and the link between childhood adversity and criminal and psychiatric outcomes amongst forensic inpatients. AIMS: Using census data for all Scottish forensic inpatients, we investigated the most common primary psychiatric diagnoses in forensic settings, the occurrence of childhood adversity amongst forensic inpatients, and whether childhood adversity experiences significantly predict a range of criminal and psychiatric outcomes. METHOD: Data for the current study were drawn from 'The Scottish Forensic Network Inpatient Census' (N = 422). The Responsible Medical Officers and other members of the clinical team collected all data from official patient records. All forensic inpatients across high, medium, and low security sites were surveyed. RESULTS: The majority of patients had a psychotic disorder as their primary diagnosis (86.4%), with schizophrenia being the most common (70.0%). Childhood adversity was highly prevalent (79.2%), with physical abuse being the most common adverse experience (40.1%). Increased levels of childhood adversity were significantly associated with an increased risk of criminal convictions, self-reported abuse of animals, suicidal and self-injurious behaviour, and problematic use of drugs or alcohol. CONCLUSIONS: Considering the association between adversity and psychosis, trauma informed care is essential for the mental health and forensic needs of this population.

Night-time confinement and the practice of realistic medicine.

SummaryNight-time confinement is the practice of routinely locking patients in their rooms at night unless there is a contrary clinical indication. It is used in high-secure psychiatric hospitals. This article argues in favour of this practice on the basis of realistic medicine, an individual human rights based approach, the principles of mental health legislation in Scotland and England and cost effectiveness. This is not an academic debate. There is a real danger that those advocating against night-time confinement, if successful, will at best make little difference to the lives of our patients as they sleep, and at worst may hugely impoverish their lives because of reduced daytime activities.Declaration of interestL.T. is Medical Director at The State Hospital. Night-time confinement is used within this setting.

Changes in tissue oxygen tension, venous saturation, and Fick-based assessments of cardiac output during hyperoxia.

BACKGROUND: Hyperoxemia (arterial oxygen tension >100 mm Hg) may occur in critically ill patients and have effects on mixed venous saturation (SvO2 ) and on Fick-based estimates of cardiac output (CO). We investigated the effect of hyperoxemia on SvO2 and on assessments of CO using the Fick equation. METHODS: Yorkshire swine (n = 14) were anesthetized, intubated, and paralyzed for instrumentation. SvO2 (co-oximetry) and tissue oxygen tension (tPO2 , implantable electrodes) in brain and myocardium were measured during systematic manipulation of arterial oxygen tension (PaO2 ) using graded hyperoxia (fraction of inspired oxygen 0.21 → 0.8). Secondarily, oxygen- and carbon dioxide-based estimates of CO (FickO2 and FickCO2 , respectively) were compared with measurements from a flow probe placed on the aortic root. RESULTS: Independent of changes in measured oxygen delivery, cerebral and myocardial tPO2 increased in proportion to PaO2 , as did SvO2 (P < 0.001 for all). Based on mixed model analysis, each 100 mm Hg increase in PaO2 resulted in a 4.8 ± 0.9% increase in SvO2 under the conditions tested. Because neither measured oxygen consumption, arterial oxyhemoglobin saturation or cardiac output varied significantly during hyperoxia, changes in SvO2 resulted in successively increasing errors in FickO2 during hyperoxia (34% during normoxia, 72% during FiO2 0.8). FickCO2 lacked the progressively worsening errors present in FickO2 , but correlated poorly with CO. CONCLUSION: SvO2 acutely changes following changes in PaO2 even absent changes in measured DO2 . This may lead to errors in FickO2 estimates of CI. Further work is necessary to understand the impact of this phenomenon in disease states.

On the Road to Recovery psychological therapy versus treatment as usual for forensic mental health patients: study protocol for a randomized controlled feasibility trial.

BACKGROUND: On the Road to Recovery (OTRTR) is a brief low intensity group psychological therapy that aims to improve patients' insight into their mental disorder and develop adaptive coping skills to help manage distress. OTRTR is currently delivered in forensic mental health services in Scotland. However, to date, this therapy has not been evaluated as to its effectiveness or safety for forensic patients. METHODS: This is a parallel-group feasibility randomized controlled trial with single-blind assessments comparing OTRTR therapy to treatment as usual (TAU) for forensic mental health patients. Fifty participants will be recruited from high, medium, and low secure forensic mental health services in Scotland. Participants will receive OTRTR for approximately 12 weeks or continue treatment as usual for 12 weeks. The trial's primary aims relate to testing the acceptability and feasibility of key trial procedures that would be necessary for a definitive RCT of OTRTR. The secondary aims include estimating therapeutic effect sizes on clinical outcomes including insight and coping skills. The study design also features an adverse event monitoring plan to estimate the safety of OTRTR for participants, as well as use of intensive longitudinal methods to identify "key ingredients" to the OTRTR therapy protocol. DISCUSSION: This study will inform the design and sample size for a future full-scale randomized controlled trial (RCT), which will be conducted to determine the effectiveness of the On the Road to Recovery intervention in improving forensic mental health patients' clinical insight and coping skills. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN75126867 registered 27 July 2017.

A protocol in action: Recovery approach for patients within high secure care: A 20+ year follow-up.

OBJECTIVES: A person-centred approach to recovery is increasingly represented within mainstream mental health literature. Little examination of recovery among forensic mental health patients is evidenced. This study plans to address that insufficiency. METHODS: This protocol paper details a novel approach to exploring recovery among a cohort of 241 patients detained under conditions of high secure care in Scotland during August 1992 to August 1993. Under discussion is the repurposing of previous research to circumnavigate length of inpatient stay commonly associated with forensic mental health care. The methodology adopted, while considering data leakage given the vulnerable participant group, will be discussed. RESULTS: Repurposing and extending previous research attempts to address the file cabinet effect with 85% of health care research being wasted and future uncertainty regarding research funding in a post-Brexit era. This is an ongoing study. Ethical, confidentiality, privacy issues, and permissions are considered within the methodology. CONCLUSIONS: Ethical arguments can be made for tracing and attempting contact with vulnerable groups under-represented in the literature. A well-considered methodology putting the focus on participant welfare and confidentiality at every step is essential. The reported methodology provides an opportunity to expand and re-examine previously collected data through a contemporary lens.

Signatures of selection in mammalian clock genes with coding trinucleotide repeats: Implications for studying the genomics of high-pace adaptation.

Climate change is predicted to affect the reproductive ecology of wildlife; however, we have yet to understand if and how species can adapt to the rapid pace of change. Clock genes are functional genes likely critical for adaptation to shifting seasonal conditions through shifts in timing cues. Many of these genes contain coding trinucleotide repeats, which offer the potential for higher rates of change than single nucleotide polymorphisms (SNPs) at coding sites, and, thus, may translate to faster rates of adaptation in changing environments. We characterized repeats in 22 clock genes across all annotated mammal species and evaluated the potential for selection on repeat motifs in three clock genes (NR1D1,CLOCK, and PER1) in three congeneric species pairs with different latitudinal range limits: Canada lynx and bobcat (Lynx canadensis and L. rufus), northern and southern flying squirrels (Glaucomys sabrinus and G. volans), and white-footed and deer mouse (Peromyscus leucopus and P. maniculatus). Signatures of positive selection were found in both the interspecific comparison of Canada lynx and bobcat, and intraspecific analyses in Canada lynx. Northern and southern flying squirrels showed differing frequencies at common CLOCK alleles and a signature of balancing selection. Regional excess homozygosity was found in the deer mouse at PER1 suggesting disruptive selection, and further analyses suggested balancing selection in the white-footed mouse. These preliminary signatures of selection and the presence of trinucleotide repeats within many clock genes warrant further consideration of the importance of candidate gene motifs for adaptation to climate change.

Responsive monitoring of mitochondrial redox states in heart muscle predicts impending cardiac arrest.

Assessing the adequacy of oxygen delivery to tissues is vital, particularly in the fields of intensive care medicine and surgery. As oxygen delivery to a cell becomes deficient, changes in mitochondrial redox state precede changes in cellular function. We describe a technique for the continuous monitoring of the mitochondrial redox state on the epicardial surface using resonance Raman spectroscopy. We quantify the reduced fraction of specific electron transport chain cytochromes, a metric we name the resonance Raman reduced mitochondrial ratio (3RMR). As oxygen deficiency worsens, heme moieties within the electron transport chain become progressively more reduced, leading to an increase in 3RMR. Myocardial 3RMR increased from baseline values of 18.1 ± 5.9 to 44.0 ± 16.9% (P = 0.0039) after inferior vena cava occlusion in rodents (n = 8). To demonstrate the diagnostic power of this measurement, 3RMR was continuously measured in rodents (n = 31) ventilated with 5 to 8% inspired oxygen for 30 min. A 3RMR value exceeding 40% at 10 min predicted subsequent cardiac arrest with 95% sensitivity and 100% specificity [area under the curve (AUC), 0.98], outperforming all current measures, including contractility (AUC, 0.51) and ejection fraction (AUC, 0.39). 3RMR correlated with indices of intracellular redox state and energy production. This technique may permit the real-time identification of critical defects in organ-specific oxygen delivery.

Hemodynamic Effects of Lipid-Based Oxygen Microbubbles via Rapid Intravenous Injection in Rodents.

PURPOSE: Low oxygen levels, or hypoxemia, is a common cause of morbidity and mortality in critically ill patients. Hypoxemia is typically addressed by increasing the fraction of inspired oxygen, the use of mechanical ventilation, or more invasive measures. Recently, the injection of oxygen gas directly into the bloodstream by packaging it within lipid-based oxygen microbubbles (LOMs) has been explored. The purpose of this work is to examine the acute hemodynamic effects of intravenous injections of LOMs. METHODS: LOMs composed of 1,2-distearoyl-sn-glycero-3-phosphocoline and cholesterol were manufactured using a process of shear homogenization under an oxygen headspace. A 5 mL aliquot of either PlasmaLyte A, or low (37%) or high (55%) concentration LOMs (n = 10 per group) was injected over a 1 min period into Sprague Dawley rats instrumented for measurement of cardiac index and pulmonary (PVR) and systemic (SVR) vascular resistance during a 60 min observation period. Hemodynamics were compared between groups by linear mixed modeling. RESULTS: Approximately 1011 LOMs with mean diameter 3.77 ± 1.19 µm were injected over the 1 min period. Relative to controls, rodents treated with high concentration LOMs exhibited a higher pulmonary artery pressure (20 ± 0.4 mmHg vs 18 ± 0.4 mmHg, P < 0.001) and higher PVR (0.31 ± 0.01 vs 0.23 ± 0.01 mmHg/mL*min*kg, P < 0.001. Despite a stable cardiac index (62.2 ± 3.5 vs 62.3 ± 3.4 mL/min*kg, P < 0.001), mean arterial blood pressure decreased significantly in LOM-treated animals (46 ± 2 vs 60 ± 2 mmHg, P < 0.001) due to a decrease in SVR. Injections with aged LOM emulsions (>48 h since manufacture) resulted in a higher incidence of hemodynamic collapse during the observation period (P = 0.02). CONCLUSIONS: LOMs may be injected in quantities sufficient to deliver clinically meaningful volumes of oxygen but cause significant decrements in blood pressure and elevations in PVR.

Improving our understanding of the in vivo modelling of psychotic disorders: A protocol for a systematic review and meta-analysis.

Psychosis represents a set of symptoms against which current available treatments are not universally effective and are often accompanied by adverse side effects. Clinical management could potentially be improved with a greater understanding of the underlying biology and subsequently with the introduction of novel treatments. Since many clinical drug candidates are identified through in vivo modelling, a deeper understanding of the pre-clinical field, might help us understand why translation of results from animal models to inform mental health clinical practice has so far been weak. We set out to give a shallow, but broad unbiased overview of experiments looking at the in vivo modelling of psychotic disorders using a systematic review and meta-analysis. This protocol describes the exact methodology we propose to follow in order to quantitatively review both studies characterizing a model and those experiments that investigate the effects of novel therapeutic options. We are interested in assessing the prevalence of the reporting of measures to reduce risk of bias, and the internal and external validity of the animal models and outcome measures used to validate these models. This generation of strong empirical evidence has the potential to identify areas for improvement, make suggestions for future research avenues, and ultimately inform what we think we know to improve the current attrition rate between bench and bedside in psychosis research. A review like this will also support the reduction of animal numbers used in research and the refinement of experiments to maximize their value in informing the field.