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Choline contributes to the biogenesis of methyl groups, neurotransmitters, and cell membranes. Our genome-wide association study (GWAS) of circulating choline in 2228 college students found that alleles in SLC25A48 (rs6596270) influence choline concentrations in men (p = 9.6 × 10-8), but not women. Previously, the subcellular location and function of SLC25A48 were unknown. Using super-resolution immunofluorescence microscopy, we localized SLC25A48 to the inner mitochondrial membrane. Our results suggest that SLC25A48 transports choline across the inner mitochondrial membrane.
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BACKGROUND: There has been increasing interest in examining the potential moderating effects that cognitive functioning has on treatment outcome in bipolar disorder (BD) and major depressive disorder (MDD). Therefore, the aim of this exploratory study was to examine the relationship between baseline cognitive function and treatment outcome in individuals with mood disorders who completed 12 months of interpersonal and social rhythm therapy (IPSRT), and were randomised to receive adjunctive cognitive remediation (CR) or no additional intervention. METHODS: Fifty-eight patients with mood disorders (BD, n = 36, MDD, n = 22), who were randomised to IPSRT-CR or IPSRT, underwent cognitive testing at baseline and completed follow-up mood measures after 12 months. General linear modelling was used to examine the relationship between baseline cognitive function (both objective and subjective) and change in mood symptom burden, and functioning, from baseline to treatment-end. RESULTS: Poorer baseline attention/executive function was associated with less change in mood symptom burden, particularly depressive symptoms, at treatment-end. Additionally, slower psychomotor speed at baseline was associated with less improvement in mania symptom burden. Subjective cognitive function at baseline was not related to change in mood symptom burden at treatment-end, and neither objective nor subjective cognitive function was associated with functional outcome. LIMITATIONS: Due to the exploratory nature of the study, there was no correction for multiple comparisons. CONCLUSION: Aspects of objective cognitive function were associated with treatment outcomes following psychotherapy. Further large-scale research is required to examine the role that cognitive function may have in determining various aspects of mood disorder recovery.
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INTRODUCTION: Although short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral ketamine, high relapse rates following ketamine dosing and the uncertain role of psychotherapy. This randomised controlled trial (RCT) seeks to establish the feasibility of evaluating repeated oral doses of ketamine and behavioural activation therapy (BAT), compared with ketamine treatment alone, for TR-MDD. We also aim to compare relapse rates between treatment arms to determine the effect size of adding BAT to oral ketamine. METHODS AND ANALYSIS: This is a prospectively registered, two-centre, single-blind RCT. We aim to recruit 60 participants with TR-MDD aged between 18 and 65 years. Participants will be randomised to 8 weeks of oral ketamine and BAT, or 8 weeks of oral ketamine alone. Feasibility will be assessed by tracking attendance for ketamine and BAT, acceptability of treatment measures and retention to the study follow-up protocol. The primary efficacy outcome measure is the Montgomery-Asberg Depression Rating Scale (MADRS) measured weekly during treatment and fortnightly during 12 weeks of follow-up. Other outcome measures will assess the tolerability of ketamine and BAT, cognition and activity (using actigraphy). Participants will be categorised as non-responders, responders, remitters and relapsed during follow-up. MADRS scores will be analysed using a linear mixed model. For a definitive follow-up RCT study to be recommended, the recruitment expectations will be met and efficacy outcomes consistent with a >20% reduction in relapse rates favouring the BAT and ketamine arm will be achieved. ETHICS AND DISSEMINATION: Ethics approval was granted by the New Zealand Central Health and Disability Ethics Committee (reference: 2023 FULL18176). Study findings will be reported to participants, stakeholder groups, conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER: UTN: U1111-1294-9310, ACTRN12623000817640p.
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Transtorno Depressivo Resistente a Tratamento , Ketamina , Humanos , Ketamina/administração & dosagem , Ketamina/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/terapia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Adulto , Método Simples-Cego , Pessoa de Meia-Idade , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/tratamento farmacológico , Masculino , Feminino , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia Comportamental/métodos , Adulto Jovem , Adolescente , Resultado do Tratamento , Estudos Prospectivos , IdosoRESUMO
Bipolar disorder (BD) is a serious mental health condition that is clinically complex to monitor and manage. While best practice guidelines exist, they vary internationally lacking consensus. Indigenous peoples, including Maori in New Zealand, experience higher community rates of BD. While New Zealand practice guidelines recommend providing culturally responsive care to Maori, studies show that Maori do not receive best practice. This qualitative study aimed to share the evidence about patterns of health service use and Maori patient experiences with focus group participants involved in the design and delivery of BD services, to discuss and develop guidelines for best practice for Maori with BD and address areas of unmet need. Three focus groups were conducted with 22 participants involved in the delivery of services to Maori with BD across three sites. Willing participants were sent background information and three focus group questions framed to elicit priority solutions to improve clinical, structural and organisational features of mental health service delivery for Maori patients with BD and their whanau (family). The nominal group technique was used to synthesise responses, and then develop a prioritised list of proposed solutions. Results identified system-level changes required at the clinical, structural and organisational levels of healthcare. Findings further evidence the need for healthcare reform in New Zealand, to be responsive to Maori with BD.
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The international migration of health professionals has been an ongoing issue with the medical workforce in Aotearoa New Zealand. There are many reasons why New Zealand-trained doctors choose to leave. Often it has been to gain overseas experience, with many eventually returning to New Zealand; however, this has now changed, with increasing numbers not returning. Little has been done to combat this developing problem, amidst an increasingly competitive global market for health professionals. There is public and political concern about the current shortage and uneven distribution of doctors, particularly because this has fostered unsustainable working conditions, which diminishes the provision of safe healthcare in this country. This article examines the context behind the migration of New Zealand-trained doctors and proposes several strategies for retention as potential solutions to the underlying problem.
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Médicos , Humanos , Nova Zelândia , Atitude do Pessoal de SaúdeRESUMO
BACKGROUND: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. METHODS: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. RESULTS: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. CONCLUSIONS: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno Bipolar , Estimulantes do Sistema Nervoso Central , Disfunção Cognitiva , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Uso Off-Label , Metilfenidato/efeitos adversos , Metilfenidato/uso terapêuticoRESUMO
Introduction: Emotion processing is an essential part of interpersonal relationships and social interactions. Changes in emotion processing have been found in both mood disorders and in aging, however, the interaction between such factors has yet to be examined in detail. This is of interest due to the contrary nature of the changes observed in existing research - a negativity bias in mood disorders versus a positivity effect with aging. It is also unclear how changes in non-emotional cognitive function with aging and in mood disorders, interact with these biases. Methods and results: In individuals with mood disorders and in healthy control participants, we examined emotional processing and its relationship to age in detail. Data sets from two studies examining facial expression recognition were pooled. In one study, 98 currently depressed individuals (either unipolar or bipolar) were compared with 61 healthy control participants, and in the other, 100 people with bipolar disorder (in various mood states) were tested on the same facial expression recognition task. Repeated measures analysis of variance was used to examine the effects of age and mood disorder diagnosis alongside interactions between individual emotion, age, and mood disorder diagnosis. A positivity effect was associated with increasing age which was evident irrespective of the presence of mood disorder or current mood episode. Discussion: Results suggest a positivity effect occurring at a relatively early age but with no evidence of a bias toward negative emotions in mood disorder or specifically, in depressed episodes. The positivity effect in emotional processing in aging appears to occur even within people with mood disorders. Further research is needed to understand how this fits with negative biases seen in previous studies in mood disorders.
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Recruiting participants for research from highly traumatised ethnic and faith communities requires a participatory and trauma-informed approach that considers logistic barriers, as well as trauma-related and culture-specific issues. Active community engagement through every stage of the project and employing community members in research roles can help build trust, identify and mitigate concerns early, prevent re-traumatization, and ensure that findings will be of value to the community. Some of these research challenges are discussed in the context of the Christchurch mosque terror attacks. These insights may be helpful for researchers and clinicians working in similarly challenging environments.
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Cachexia syndrome, leading to reduced skeletal muscle and fat mass, is highly prevalent in cancer patients, resulting in further negative implications for these patients. To date, there is no approved therapy for cachexia syndrome. The objective of this study was to establish an in vitro model of cancer cachexia in mature human skeletal muscle myotubes, with the intention of exploiting the cell model to assess potential cachexia therapeutics, specifically cannabinoid related drugs. Having cultured and differentiated primary human muscle myoblasts to mature myotubes, we successfully established two cancer cachexia models using conditioned media (CM) from human colon adenocarcinoma (SW480) and from non-small-cell lung carcinoma (H1299) cultured cells. The cancer-CM-induced extensive myotube degeneration, demonstrated by a significant reduction in mature myotube diameter, which progressed over the period studied. Myotube degeneration is a characteristic feature of cancer cachexia and was used in this study as an index of cachexia. Expression of cannabinoid 1 and 2 receptors (CB1R and CB2R) was confirmed in the mature human skeletal muscle myotubes. Subsequently, the effect of cannabinoid compounds on this myotube degeneration were assessed. Tetrahydrocannabinol (THC), a partial CB1R/CB2R agonist, and JWH133, a selective CB2R agonist, proved efficacious in protecting mature human myotubes from the deleterious effects of both (SW480 and H1299) cancer cachexia conditions. ART27.13, a full, peripherally selective CB1R/CB2R agonist, currently being trialled in cancer cachexia (IRAS ID 278450, REC 20/NE/0198), was also significantly protective against myotube degeneration in both (SW480 and H1299) cancer cachexia conditions. Furthermore, the addition of the CB2R antagonist AM630, but not the CB1R antagonist Rimonabant, abolished the protective effect of ART27.13. In short, we have established a convenient and robust in vitro model of cancer-induced human skeletal muscle cachexia. The data obtained using the model demonstrate the therapeutic potential of ART27.13 in cancer-induced cachexia prevention and provides evidence indicating that this effect is via CB2R, and not CB1R.
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BACKGROUND: Depression and anxiety are common and debilitating mental disorders with severe negative repercussions at both individual and societal levels. Although virtual reality (VR) has emerged as a safe and effective tool for the treatment of anxiety disorders, studies of the therapeutic application of VR to treat depression are more limited. OBJECTIVE: The purpose of this study was to test whether a novel type of individualized VR (iVR) can be used to improve self-compassion and decrease depressive symptoms and to evaluate the usability and acceptability of this approach, as rated by participants. The iVR system was designed and developed based on the feedback obtained from a previous study, with improved appearance and feel of the avatar and enhanced graphical quality. METHODS: A total of 36 young adult participants were recruited from a university community social media site. Participants were aware that the study was investigating a treatment for depression but were not recruited based on depression diagnosis. Participants were asked to complete 2 iVR sessions, spaced 2 weeks apart. At baseline and upon completion of each iVR session, participants were asked to complete validated measures of self-compassion and depression. Upon completion of both iVR sessions, additional measures were administered to assess participants' perceptions about the perceived usability and system acceptability of the iVR approach. RESULTS: Self-compassion was assessed at the beginning of session 1 (preintervention baseline) and at the end of session 1 (postintervention assessment). Owing to COVID-19 constraints, 36% (13/36) of the participants were unable to complete the follow-up iVR session. Self-compassion was assessed again for the remaining 64% (23/36) of the participants at the end of session 2 (postintervention assessment). Within-group analyses revealed that self-compassion was significantly increased at the end of both session 1 (P=.01) and session 2 (P=.03) relative to baseline. There was also a nonsignificant trend for depressive symptoms to be low at the end of session 2 relative to baseline. Both quantitative and qualitative participant data supported the iVR approach as being acceptable and usable. CONCLUSIONS: Although these data must be treated as preliminary owing to the small sample size and potential selection bias, the data provide encouraging initial evidence that iVR might be a useful tool to enhance self-compassion and reduce depressive symptoms, highlighting the need for randomized controlled trials in the future.
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BACKGROUND: The evidence base for racemic ketamine treatment for treatment-resistant major depressive disorder (TRD) continues to expand, but there are major challenges translating this evidence base into routine clinical care. AIM: To prepare guidelines for ketamine treatment of TRD that are suitable for routine use by publicly funded specialist mental health services. METHOD: We consulted with senior leadership, clinical pharmacy, psychiatrists, nursing, service users and Maori mental health workers on issues relating to ketamine treatment. We prepared treatment guidelines taking the evidence base for ketamine treatment and the consultation into account. RESULTS: Ketamine treatment guidance is reported. This offers two treatment pathways, including a test of ketamine responsiveness with intramuscular ketamine and the dominant use of oral ketamine for a 3-month course to maximise the opportunity for the short-term benefits of ketamine to accumulate. CONCLUSIONS: We have responded to the challenges of translating the evidence base for ketamine treatment into a form suitable for routine care.
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BACKGROUND: There is evidence of Indigenous and ethnic minority inequities in the incidence and outcomes of early psychosis. Racism has been implicated as having an important role. AIM: To use Indigenous experiences to develop a more detailed understanding of how racism operates to impact early psychosis outcomes. METHODS: Critical Race Theory informed the methodology used. Twenty-three Indigenous participants participated in four family focus group interviews and thirteen individual interviews, comprising of 9 Maori youth with early psychosis, 10 family members and 4 Maori mental health professionals. An analysis of the data was undertaken using deductive structural coding to identify descriptions of racism, followed by inductive descriptive and pattern coding. RESULTS: Participant experiences revealed how racism operates as a socio-cultural phenomenon that interacts with institutional policy and culture across systems pertaining to social responsiveness, risk discourse, and mental health service structures. This is described across three major themes: 1) selective responses based on racial stereotypes, 2) race related risk assessment bias and 3) institutional racism in the mental health workforce. The impacts of racism were reported as inaction in the face of social need, increased use of coercive practices and an under resourced Indigenous mental health workforce. CONCLUSION: The study illustrated the inter-related nature of interpersonal, institutional and structural racism with examples of interpersonal racism in the form of negative stereotypes interacting with organizational, socio-cultural and political priorities. These findings indicate that organizational cultures may differentially impact Indigenous and minority people and that social responsiveness, risk discourse and the distribution of workforce expenditure are important targets for anti-racism efforts.
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Disparidades em Assistência à Saúde , Povo Maori , Transtornos Psicóticos , Racismo , Adolescente , Humanos , Etnicidade , Povo Maori/psicologia , Grupos Minoritários/psicologia , Transtornos Psicóticos/economia , Transtornos Psicóticos/etnologia , Transtornos Psicóticos/psicologia , Transtornos Psicóticos/terapia , Racismo/economia , Racismo/etnologia , Racismo/psicologia , Racismo/estatística & dados numéricos , Disparidades em Assistência à Saúde/economia , Disparidades em Assistência à Saúde/ética , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Serviços de Saúde Mental/economia , Serviços de Saúde Mental/ética , Serviços de Saúde Mental/provisão & distribuição , Serviços de Saúde do Indígena/economia , Serviços de Saúde do Indígena/ética , Serviços de Saúde do Indígena/provisão & distribuição , Necessidades e Demandas de Serviços de Saúde/economia , Mão de Obra em Saúde/economia , Ética Institucional , Responsabilidade SocialRESUMO
INTRODUCTION: Our previous research has demonstrated significant cognitive effects of earthquake exposure 2-3 years following the Canterbury earthquake sequence of 2011. Such impairment has major implications for a population trying to recover, and to rebuild, a devastated city. This study aims to examine psychological, cognitive and biological factors that may contribute to subjective cognitive difficulties in a large group of individuals exposed to the Canterbury earthquake sequence. METHODS AND ANALYSIS: Two-hundred earthquake-exposed participants from an existing large cohort study (Christchurch Health and Development Study, CHDS) will be recruited. Inclusion is based on results of online screening of the CHDS cohort, using the Cognitive Failures Questionnaire. Individuals scoring the highest (n=100) and lowest (n=100), representing the highest and lowest levels of subjective cognitive impairment, are selected. Exclusions are: psychotic/bipolar disorders, serious substance/alcohol dependence, chronic medical conditions, pregnancy and previous serious head injury. Participants will undergo a half-day assessment including clinician-rated interviews, self-report measures, objective and subjective cognitive assessments, blood sample collection and physical measurements. The primary analysis will compare cognitive, psychological and biological measures in 'high' and 'low' subjective cognitive impairment groups. The study will have power (p<0.05, α=0.8) to show a difference between groups of 0.4 SD on any variable. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by the New Zealand Health and Disability Ethics Committee. The online screening component of the study received ethical approval on 1 April 2021 (16/STH/188, PAF 7), and the main study (subsequent to screening) received approval on 16 August 2021 (Northern A 21/NTA/68). All participants provide written informed consent. Findings will be disseminated initially to the CHDS cohort members, the wider Canterbury community, and then by publication in scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05090046).
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Transtorno Bipolar , Disfunção Cognitiva , Terremotos , Transtornos Relacionados ao Uso de Substâncias , Humanos , Estudos de Coortes , Nova Zelândia/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Estudos Observacionais como AssuntoRESUMO
This paper reports on the development and validation of the COVID Psychosocial Impacts Scale (CPIS), a self-report measure that comprehensively examines both positive and negative psychosocial impacts from the COVID-19 pandemic. This is the first part of the program of work in which the CPIS was administered and compared with a measure of psychological distress (Kessler Psychological Distress Scale, K-10) and wellbeing (World Health Organization Well-Being Index, WHO-5). The data were obtained online in 2020 and 2022 at two distinct time points to capture different exposures to the pandemic in the New Zealand population to a non-representative sample of 663 and 687 adults, respectively. Two hundred seventy-one participants took part in both surveys. Findings indicate a unidimensional structure within CPIS subscales and inter-relatedness among CPIS stress-related subscales. The scatter plots and correlation matrix indicate CPIS having a positive moderate correlation with K10 and a negative moderate correlation with WHO-5, indicative of construct validity. The paper outlines contextual factors surrounding CPIS development and makes suggestions for future iterations of CPIS. Further work will examine its psychometric properties across cultures.
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COVID-19 , Adulto , Humanos , COVID-19/epidemiologia , Pandemias , Inquéritos e Questionários , Autorrelato , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologiaRESUMO
OBJECTIVE: Temporal lobe epilepsy (TLE) is characterized by recurrent seizures generated in the limbic system, particularly in the hippocampus. In TLE, recurrent mossy fiber sprouting from dentate gyrus granule cells (DGCs) crea an aberrant epileptogenic network between DGCs which operates via ectopically expressed GluK2/GluK5-containing kainate receptors (KARs). TLE patients are often resistant to anti-seizure medications and suffer significant comorbidities; hence, there is an urgent need for novel therapies. Previously, we have shown that GluK2 knockout mice are protected from seizures. This study aims at providing evidence that downregulating KARs in the hippocampus using gene therapy reduces chronic epileptic discharges in TLE. METHODS: We combined molecular biology and electrophysiology in rodent models of TLE and in hippocampal slices surgically resected from patients with drug-resistant TLE. RESULTS: Here, we confirmed the translational potential of KAR suppression using a non-selective KAR antagonist that markedly attenuated interictal-like epileptiform discharges (IEDs) in TLE patient-derived hippocampal slices. An adeno-associated virus (AAV) serotype-9 vector expressing anti-grik2 miRNA was engineered to specifically downregulate GluK2 expression. Direct delivery of AAV9-anti grik2 miRNA into the hippocampus of TLE mice led to a marked reduction in seizure activity. Transduction of TLE patient hippocampal slices reduced levels of GluK2 protein and, most importantly, significantly reduced IEDs. INTERPRETATION: Our gene silencing strategy to knock down aberrant GluK2 expression demonstrates inhibition of chronic seizure in a mouse TLE model and IEDs in cultured slices derived from TLE patients. These results provide proof-of-concept for a gene therapy approach targeting GluK2 KARs for drug-resistant TLE patients. ANN NEUROL 2023;94:745-761.
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Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , MicroRNAs , Humanos , Camundongos , Animais , Epilepsia do Lobo Temporal/terapia , Lobo Temporal , Hipocampo , Epilepsia Resistente a Medicamentos/genética , Epilepsia Resistente a Medicamentos/terapia , ConvulsõesRESUMO
There is evidence of Indigenous and ethnic minority inequities in the incidence and outcomes of early psychosis. racism has an important role. This study aimed to use Indigenous experiences to develop a more detailed understanding of how racism operates to impact early psychosis. Critical Race Theory informed the methods used. Twenty-three Indigenous participants participated in 4 family focus group interviews and 13 individual interviews, comprising of 9 youth, 10 family members and 4 mental health professionals. An analysis of the data was undertaken using deductive structural coding to identify descriptions of racism, followed by inductive descriptive and pattern coding. Participant experiences revealed how racism operates as a socio-cultural phenomenon that interacts with institutional policy and culture across systems. This is described across three themes: (1) selective responses based on racial stereotypes, (2) race related risk assessment bias and (3) institutional racism in the mental health workforce. The impacts of racism were reported as inaction in the face of social need, increased coercion and an under resourced Indigenous workforce. These findings indicate that organizational cultures may differentially impact Indigenous and minority people and that social responsiveness, risk discourse and the distribution of workforce expenditure are important targets for anti-racism efforts.
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Transtornos Psicóticos , Racismo , Adolescente , Humanos , Grupos Minoritários , Etnicidade , Racismo/psicologia , Pesquisa QualitativaRESUMO
Improving cattle feed efficiency through selection of residual feed intake (RFI) is a widely accepted approach to sustainable beef production. A greater understanding of the molecular control of RFI in various breeds offered contrasting diets is necessary for the accurate identification of feed efficient animals and will underpin accelerated genetic improvement of the trait. The aim of this study was to determine genes and biological processes contributing to RFI across varying breed type and dietary sources in skeletal muscle tissue. Residual feed intake was calculated in Charolais and Holstein-Friesian steers across multiple dietary phases (phase-1: high concentrate (growing-phase); phase-2: zero-grazed grass (growing-phase); phase-3: high concentrate (finishing-phase). Steers divergent for RFI within each breed and dietary phase were selected for muscle biopsy collection, and muscle samples subsequently subjected to RNAseq analysis. No gene was consistently differentially expressed across the breed and diet types examined. However, pathway analysis revealed commonality across breeds and diets for biological processes including fatty acid metabolism, immune function, energy production and muscle growth. Overall, the lack of commonality of individual genes towards variation in RFI both within the current study and compared to the published literature, suggests other genomic features warrant further evaluation in relation to RFI.
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Ração Animal , Transcriptoma , Bovinos/genética , Animais , Ração Animal/análise , Melhoramento Vegetal , Ingestão de Alimentos/genética , Dieta/veterináriaRESUMO
BACKGROUND: Ketamine is an effective short-term treatment for a range of psychiatric disorders. A key question is whether the addition of psychotherapy to ketamine treatment improves outcomes or delays relapse. AIM: To identify all studies combining psychotherapy with ketamine for the treatment of psychiatric disorders to summarise their effects and make recommendations for future research. METHOD: The review protocol was prospectively registered with PROSPERO (registration number CRD42022318120). Potential studies were searched for in MEDLINE, Embase, PsycINFO, SCOPUS, the Cochrane library and Google Scholar. Eligible studies combined ketamine and psychotherapy for the treatment of psychiatric disorders and did not use case reports or qualitative designs. Key findings relating to psychotherapy type, diagnosis, ketamine protocol, sequencing of psychotherapy and study design are reported. Risk of bias was assessed using modified Joanna Briggs critical appraisal tools. RESULTS: Nineteen studies evaluating 1006 patients were included in the systematic review. A variety of supportive individual and group, manualised and non-manualised psychotherapies were used. The majority of studies evaluated substance use disorders, post-traumatic stress disorder and treatment-resistant depression. Ketamine protocols and sequencing of ketamine/psychotherapy treatment varied substantially between studies. Outcomes were largely positive for the addition of psychotherapy to ketamine treatment. CONCLUSION: The combination of psychotherapy and ketamine offers promise for the treatment of psychiatric disorders, but study heterogeneity prevents definitive recommendations for their integration. Larger randomised controlled trials using manualised psychotherapies and standardised ketamine protocols are recommended to clarify the extent to which the addition of psychotherapy to ketamine improves outcomes over ketamine treatment alone.