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1.
Npj Ment Health Res ; 3(1): 36, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977903

RESUMEN

Mental fitness is a construct that goes beyond a simple focus on subjective emotional wellbeing to encompass more broadly our ability to think, feel, and act to achieve what we want in our daily lives. The measurement and monitoring of multiple (often interacting) domains is crucial to gain a holistic and complete insight into an individual's mental fitness. We aimed to demonstrate the capability of a new mobile app to characterise the mental fitness of a general population of Australians and to quantify the interrelationships among different domains of mental fitness. Cross-sectional data were collected from 4901 adults from the general population of Australians engaged in work or education who used a mobile app (Innowell) between September 2021 and November 2022. Individuals completed a baseline questionnaire comprised of 26 questions across seven domains of mental fitness (i.e., physical activity, sleep and circadian rhythms, nutrition, substance use, daily activities, social connection, psychological distress). Network analysis was applied at both a domain-level (e.g., 7 nodes representing each cluster of items) and an individual item-level (i.e., 26 nodes representing all questionnaire items). Only 612 people (12%) were functioning well across all domains. One quarter (n = 1204, 25%) had only one problem domain and most (n = 3085, 63%) had multiple problem domains. The two most problematic domains were physical activity (n = 2631, 54%) and social connection (n = 2151, 44%), followed closely by daily activity (n = 1914, 39%). At the domain-level, the strongest association emerged between psychological distress and daily activity (r = 0.301). Psychological distress was the most central node in the network (as measured by strength and expected influence), followed closely by daily activity, sleep and circadian rhythms and then social connection. The item-level network revealed that the nodes with the highest centrality in the network were: hopelessness, depression, functional impairment, effortfulness, subjective energy, worthlessness, and social connectedness. Social connection, sleep and circadian rhythms, and daily activities may be critical targets for intervention due to their widespread associations in the overall network. While psychological distress was not among the most common problems, its centrality may indicate its importance for indicated prevention and early intervention. We showcase the capability of a new mobile app to monitor mental fitness and identify the interrelationships among multiple domains, which may help people develop more personalised insights and approaches.

2.
Eur J Neurosci ; 59(12): 3322-3336, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38650167

RESUMEN

Protecting brain health is a goal of early intervention. We explored whether sleep quality or chronotype could predict white matter (WM) integrity in emerging mental disorders. Young people (N = 364) accessing early-intervention clinics underwent assessments for chronotype, subjective sleep quality, and diffusion tensor imaging. Using machine learning, we examined whether chronotype or sleep quality (alongside diagnostic and demographic factors) could predict four measures of WM integrity: fractional anisotropy (FA), and radial, axial, and mean diffusivities (RD, AD and MD). We prioritised tracts that showed a univariate association with sleep quality or chronotype and considered predictors identified by ≥80% of machine learning (ML) models as 'important'. The most important predictors of WM integrity were demographics (age, sex and education) and diagnosis (depressive and bipolar disorders). Subjective sleep quality only predicted FA in the perihippocampal cingulum tract, whereas chronotype had limited predictive importance for WM integrity. To further examine links with mood disorders, we conducted a subgroup analysis. In youth with depressive and bipolar disorders, chronotype emerged as an important (often top-ranking) feature, predicting FA in the cingulum (cingulate gyrus), AD in the anterior corona radiata and genu of the corpus callosum, and RD in the corona radiata, anterior corona radiata, and genu of corpus callosum. Subjective quality was not important in this subgroup analysis. In summary, chronotype predicted altered WM integrity in the corona radiata and corpus callosum, whereas subjective sleep quality had a less significant role, suggesting that circadian factors may play a more prominent role in WM integrity in emerging mood disorders.


Asunto(s)
Imagen de Difusión Tensora , Calidad del Sueño , Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Masculino , Femenino , Adolescente , Imagen de Difusión Tensora/métodos , Adulto Joven , Trastorno Bipolar/diagnóstico por imagen , Trastorno Bipolar/fisiopatología , Aprendizaje Automático , Trastorno Depresivo/diagnóstico por imagen , Trastorno Depresivo/fisiopatología , Cronotipo
3.
Asia Pac Psychiatry ; 15(4): e12550, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37932015

RESUMEN

BACKGROUND: Major depressive disorder (MDD) can have severe impacts on function and quality of life. Up to one third of patients will have an inadequate response to their first line of treatment, with subsequent lines of therapy associated with lower remission rates and higher relapse rates. Recently esketamine has become available for Australian patients, and this agent provides an additional treatment option for those with MDD who have had an inadequate response to two or more antidepressant therapies during the current moderate to severe depressive episode. This paper provides an expert panel's practical recommendations and clinical guidance for establishing esketamine clinics in Australia. METHODS: An expert panel (n = 11) comprising psychiatrists, mental health care nurses, pharmacists, and individuals with experience establishing esketamine clinics was convened in Sydney. The panel developed practical recommendations and clinical guidance, which were then further refined. RESULTS: Five key areas were identified: practical considerations for esketamine clinic set-up, including multidisciplinary care considerations; patient selection; administering esketamine; adverse event management and long-term follow-up. CONCLUSIONS: Guidance presented in this paper should assist Australian clinicians to set up an esketamine clinic, and provide practical advice on the infrastructure and clinical requirements for treatment of patients with this agent.


Asunto(s)
Trastorno Depresivo Mayor , Trastorno Depresivo Resistente al Tratamiento , Humanos , Antidepresivos/uso terapéutico , Antidepresivos/efectos adversos , Trastorno Depresivo Mayor/tratamiento farmacológico , Calidad de Vida , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Australia
4.
BMJ Open ; 13(10): e072082, 2023 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-37821139

RESUMEN

OBJECTIVES: Many adolescents and young adults with emerging mood disorders do not achieve substantial improvements in education, employment, or social function after receiving standard youth mental health care. We have developed a new model of care referred to as 'highly personalised and measurement-based care' (HP&MBC). HP&MBC involves repeated assessment of multidimensional domains of morbidity to enable continuous and personalised clinical decision-making. Although measurement-based care is common in medical disease management, it is not a standard practice in mental health. This clinical effectiveness trial tests whether HP&MBC, supported by continuous digital feedback, delivers better functional improvements than standard care and digital support. METHOD AND ANALYSIS: This controlled implementation trial is a PROBE study (Prospective, Randomised, Open, Blinded End-point) that comprises a multisite 24-month, assessor-blinded, follow-up study of 1500 individuals aged 15-25 years who present for mental health treatment. Eligible participants will be individually randomised (1:1) to 12 months of HP&MBC or standardised clinical care. The primary outcome measure is social and occupational functioning 12 months after trial entry, assessed by the Social and Occupational Functioning Assessment Scale. Clinical and social outcomes for all participants will be monitored for a further 12 months after cessation of active care. ETHICS AND DISSEMINATION: This clinical trial has been reviewed and approved by the Human Research Ethics Committee of the Sydney Local Health District (HREC Approval Number: X22-0042 & 2022/ETH00725, Protocol ID: BMC-YMH-003-2018, protocol version: V.3, 03/08/2022). Research findings will be disseminated through peer-reviewed journals, presentations at scientific conferences, and to user and advocacy groups. Participant data will be deidentified. TRIAL REGISTRATION NUMBER: ACTRN12622000882729.


Asunto(s)
Salud Mental , Trastornos del Humor , Adolescente , Adulto Joven , Humanos , Trastornos del Humor/terapia , Estudios de Seguimiento , Estudios Prospectivos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
JMIR Form Res ; 7: e45161, 2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37682588

RESUMEN

BACKGROUND: As the demand for youth mental health care continues to rise, managing wait times and reducing treatment delays are key challenges to delivering timely and quality care. Clinical staging is a heuristic model for youth mental health that can stratify care allocation according to individuals' risk of illness progression. The application of staging has been traditionally limited to trained clinicians yet leveraging digital technologies to apply clinical staging could increase the scalability and usability of this model in services. OBJECTIVE: The aim of this study was to validate a digital algorithm to accurately differentiate young people at lower and higher risk of developing mental disorders. METHODS: We conducted a study with a cohort comprising 131 young people, aged between 16 and 25 years, who presented to youth mental health services in Australia between November 2018 and March 2021. Expert psychiatrists independently assigned clinical stages (either stage 1a or stage 1b+), which were then compared to the digital algorithm's allocation based on a multidimensional self-report questionnaire. RESULTS: Of the 131 participants, the mean age was 20.3 (SD 2.4) years, and 72% (94/131) of them were female. Ninety-one percent of clinical stage ratings were concordant between the digital algorithm and the experts' ratings, with a substantial interrater agreement (κ=0.67; P<.001). The algorithm demonstrated an accuracy of 91% (95% CI 86%-95%; P=.03), a sensitivity of 80%, a specificity of 93%, and an F1-score of 73%. Of the concordant ratings, 16 young people were allocated to stage 1a, while 103 were assigned to stage 1b+. Among the 12 discordant cases, the digital algorithm allocated a lower stage (stage 1a) to 8 participants compared to the experts. These individuals had significantly milder symptoms of depression (P<.001) and anxiety (P<.001) compared to those with concordant stage 1b+ ratings. CONCLUSIONS: This novel digital algorithm is sufficiently robust to be used as an adjunctive decision support tool to stratify care and assist with demand management in youth mental health services. This work could transform care pathways and expedite care allocation for those in the early stages of common anxiety and depressive disorders. Between 11% and 27% of young people seeking care may benefit from low-intensity, self-directed, or brief interventions. Findings from this study suggest the possibility of redirecting clinical capacity to focus on individuals in stage 1b+ for further assessment and intervention.

6.
Aust N Z J Psychiatry ; 57(12): 1562-1569, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37641519

RESUMEN

OBJECTIVE: To evaluate the potential impact of the recently announced 'Safeguards' initiative on mental health-related emergency department presentation rates for children and adolescents (0-17 years). This state-funded initiative aims to establish 25 Child and Adolescent Acute Response Teams across New South Wales. METHODS: We estimated the effects of the 'Safeguards' initiative using a state-level dynamic model of child and adolescent acute mental health care. Potential reductions in total numbers of mental health-related emergency department presentations and re-presentations (i.e. presentations within 3 months of an initial presentation) were assessed via a series of simulation experiments in which we systematically varied the total number of Child and Adolescent Acute Response Teams and the mean duration of care per patient. RESULTS: Assuming a mean treatment duration of 6 weeks per patient, 25 Child and Adolescent Acute Response Teams are projected to reduce total numbers of mental health-related emergency department presentations and re-presentations over the period 2022-2031 by 15.0% (95% interval, 12.0-18.2%) and 31.7% (26.2-37.8%), respectively. Increasing the total number of Child and Adolescent Acute Response Teams above 25 has minimal additional impact on projected reductions in numbers of emergency department presentations and re-presentations, provided the mean duration of care is no more than 8 weeks. However, where the mean duration of care is greater than 4 weeks, a decrease in the number of Child and Adolescent Acute Response Teams below 25 reduces the potential effectiveness of the 'Safeguards' initiative significantly. CONCLUSION: Our simulation results indicate that full and timely implementation will be critical if the potentially substantial impact of the 'Safeguards' initiative on demand for hospital-based emergency mental health care is to be realised.


Asunto(s)
Servicios de Salud Comunitaria , Servicios Comunitarios de Salud Mental , Niño , Humanos , Adolescente , Salud Mental , Nueva Gales del Sur , Servicio de Urgencia en Hospital
7.
Compr Psychiatry ; 126: 152404, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37524044

RESUMEN

OBJECTIVES: There is an ongoing necessity to match clinical interventions with the multidimensional needs of young people. A key step toward better service planning and the design of optimal models of care is to use multidimensional assessment to understand the clinical needs of those presenting to primary mental health care. METHODS: 1284 people aged 12-25 years presenting to primary youth mental health services completed an online assessment at service entry. Latent class analysis was conducted for seven scales assessing anxiety, depression, psychosis, mania, functioning (indexed by Work and Social Adjustment Scale), and suicidality. RESULTS: A three-class solution was identified as the optimal solution. Class 1 (n = 305, 23.75%), an early illness stage group, had low and mixed symptomatology with limited functional impairment, class 2 (n = 353, 27.49%) was made up of older persons with established depression and functional impairment, and class 3 (n = 626, 48.75%) had very high and complex needs, with functional impairment, suicidality, and at-risk mental states (psychosis or mania). Additional differentiating characteristics included psychological distress, circadian disturbances, social support, mental health history, eating disorder behaviours, and symptoms of post-traumatic stress disorder. CONCLUSIONS: A large proportion of help-seeking young people present with symptoms and functional impairment that may exceed the levels of care available from basic primary care or brief intervention services. These subgroups highlight the importance of multidimensional assessments to determine appropriate service pathways and care options.


Asunto(s)
Salud Mental , Trastornos Psicóticos , Adolescente , Humanos , Anciano , Anciano de 80 o más Años , Manía , Ansiedad , Trastornos de Ansiedad
8.
Chronobiol Int ; 40(6): 699-709, 2023 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-37132360

RESUMEN

There is significant interest in the possible influence of chronotype on clinical states in young people with emerging mental disorders. We apply a dynamic approach (bivariate latent change score modelling) to examine the possible prospective influence of chronotype on depressive and hypo/manic symptoms in a youth cohort with predominantly depressive, bipolar, and psychotic disorders (N = 118; 14-30-years), who completed a baseline and follow-up assessment of these constructs (mean interval = 1.8-years). Our primary hypotheses were that greater baseline eveningness would predict increases in depressive but not hypo/manic symptoms. We found moderate to strong autoregressive effects for chronotype (ß = -0.447 to -0.448, p < 0.001), depressive (ß = -0.650, p < 0.001) and hypo/manic symptoms (ß = -0.819, p < 0.001). Against our predictions, baseline chronotypes did not predict change in depressive (ß = -0.016, p = 0.810) or hypo/manic symptoms (ß = 0.077, p = 0.104). Similarly, the change in chronotype did not correlate with the change in depressive symptoms (ß = -0.096, p = 0.295) nor did the change in chronotype and the change in hypo/manic symptoms (ß = -0.166, p = 0.070). These data suggest that chronotypes may have low utility for predicting future hypo/manic and depressive symptoms in the short term, or that more frequent assessments over longer periods are needed to observe these associations. Future studies should test whether other circadian phenotypes (e.g. sleep-wake variability) are better indicators of illness course.


Asunto(s)
Depresión , Trastornos Mentales , Humanos , Depresión/diagnóstico , Cronotipo , Estudios Prospectivos , Ritmo Circadiano
9.
BJPsych Open ; 9(3): e76, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37092680

RESUMEN

BACKGROUND: Understanding premature mortality risk from suicide and other causes in youth mental health cohorts is essential for delivering effective clinical interventions and secondary prevention strategies. AIMS: To establish premature mortality risk in young people accessing early intervention mental health services and identify predictors of mortality. METHOD: State-wide data registers of emergency departments, hospital admissions and mortality were linked to the Brain and Mind Research Register, a longitudinal cohort of 7081 young people accessing early intervention care, between 2008 and 2020. Outcomes were mortality rates and age-standardised mortality ratios (SMR). Cox regression was used to identify predictors of all-cause mortality and deaths due to suicide or accident. RESULTS: There were 60 deaths (male 63.3%) during the study period, 25 (42%) due to suicide, 19 (32%) from accident or injury and eight (13.3%) where cause was under investigation. All-cause SMR was 2.0 (95% CI 1.6-2.6) but higher for males (5.3, 95% CI 3.8-7.0). The mortality rate from suicide and accidental deaths was 101.56 per 100 000 person-years. Poisoning, whether intentional or accidental, was the single greatest primary cause of death (26.7%). Prior emergency department presentation for poisoning (hazard ratio (HR) 4.40, 95% CI 2.13-9.09) and psychiatric admission (HR 4.01, 95% CI 1.81-8.88) were the strongest predictors of mortality. CONCLUSION: Premature mortality in young people accessing early intervention mental health services is greatly increased relative to population. Prior health service use and method of self-harm are useful predictors of future mortality. Enhanced care pathways following emergency department presentations should not be limited to those reporting suicidal ideation or intent.

10.
Australas Psychiatry ; 31(3): 295-301, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37035873

RESUMEN

OBJECTIVE: This study utilised digital technology to assess the clinical needs of young people presenting for care at headspace centres across Australia. METHOD: 1490 young people (12-25 years) who presented to one of 11 headspace services from four geographical locations (urban New South Wales, urban South Australia, regional New South Wales, and regional Queensland) completed a digital multidimensional assessment at initial presentation. Characteristics were compared between services and geographical locations. RESULTS: We identified major variation in the demographics, and the type and severity of needs across different services. Individuals from regional services were more likely to be younger, of Aboriginal and Torres Strait Islander origin, and present with psychotic-like symptoms and suicidality, while those in urban areas were more likely to have previously sought help and have problematic alcohol use. Further differences in age, distress, depressive symptoms, psychotic-like experiences, trauma, family history, alcohol use, education/employment engagement, and days out of role were identified between different urban sites. CONCLUSIONS: The variability between services provides insight into the heterogeneity of youth mental health populations which has implications for appropriate early intervention and prevention service provisions. We propose that integrating digital technologies has the potential to provide insights for smarter service planning and evaluation.


Asunto(s)
Servicios de Salud del Indígena , Trastornos Mentales , Servicios de Salud Mental , Humanos , Adolescente , Tecnología Digital , Australia , Queensland
11.
BMJ Open ; 13(2): e064682, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36810174

RESUMEN

INTRODUCTION: Metformin is a medication likely to improve measures of cardiometabolic disturbance in young people with mental illness. Evidence also suggests metformin may improve depressive symptoms. This 52-week double-blind randomised control trial (RCT) aims to investigate the efficacy of metformin pharmacotherapy as an adjunct to a healthy lifestyle behavioural intervention in improving cardiometabolic outcomes, and depressive, anxiety and psychotic symptoms in youth with clinically diagnosed major mood syndromes. METHODS AND ANALYSIS: At least 266 young people aged 16-25 presenting for mental healthcare for major mood syndromes who are also at risk for poor cardiometabolic outcomes will be invited to participate in this study. All participants will engage in a 12-week sleep-wake, activity and metabolically focused behavioural intervention programme. As an adjunctive intervention, participants will receive either metformin (500-1000 mg) or placebo pharmacotherapy for 52 weeks.Participants will undergo a series of assessments including: (1) self-report and clinician-administered assessments; (2) blood tests; (3) anthropometric assessments (height, weight, waist circumference and blood pressure); and (4) actigraphy. Univariate and multivariate tests (generalised mixed-effects models) will be used to examine changes in primary and secondary outcomes (and associations with predetermined predictor variables). ETHICS AND DISSEMINATION: This study has been approved by the Sydney Local Health District Research Ethics and Governance Office (X22-0017). The results of this double-blind RCT will be disseminated into the scientific and broader community through peer-reviewed journals, conference presentations, social media and university websites. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR) Number: ACTRN12619001559101p, 12 November 2019.


Asunto(s)
Enfermedades Cardiovasculares , Metformina , Humanos , Adolescente , Síndrome , Australia , Sueño , Ensayos Clínicos Controlados Aleatorios como Asunto
12.
Early Interv Psychiatry ; 17(9): 893-900, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-36682384

RESUMEN

AIM: This retrospective cohort study aimed to identify the cardiometabolic characteristics, cross-sectionally and longitudinally, associated with clinical stage in youth accessing early intervention mental health services. METHODS: Cardiometabolic data we collected in 511 young people (aged 12-25 years at entry) receiving mental health care at the early intervention services in Sydney, Australia. RESULTS: The majority of young people (N = 448, 87.67%) were classified in stage 1a or 1b at entry. At entry to care, there was no cross-sectional relationship between clinical stage and age, gender, fasting insulin, fasting glucose, updated homeostatic model assessment for insulin resistance (HOMA2-IR) score, BMI or waist circumference. Of the 111 (21.7%) young people initially classified at stage 1a ('non-specific symptoms') and the 337 (65.9%) classified in stage 1b ('attenuated syndromes'), 40 individuals transitioned to stage 2+ (7.8%) ("full-threshold disorders") longitudinally. No cardiometabolic factors predicted clinical stage transitions. However, those with an increase in BMI over the course of care (n = 54) were 1.46 (OR; 95% CI: 1.02-2.17) times more likely to progress to stage 2+ at follow up. CONCLUSIONS: Whilst no relationships were found between demographic or cardiometabolic variables and clinical stage at entry to care, an increased BMI over time was associated with clinical stage transition longitudinally. Further longitudinal research is needed to understand the demographic, clinical, illness progression or treatment factors associated with changes in cardiometabolic status.


Asunto(s)
Servicios de Salud Mental , Salud Mental , Adolescente , Humanos , Estudios Retrospectivos , Circunferencia de la Cintura , Intervención Educativa Precoz , Índice de Masa Corporal , Factores de Riesgo
13.
Bipolar Disord ; 25(3): 191-199, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36661342

RESUMEN

OBJECTIVES: Emerging evidence suggests a role of circadian dysrhythmia in the switch between "activation" states (i.e., objective motor activity and subjective energy) in bipolar I disorder. METHODS: We examined the evidence with respect to four relevant questions: (1) Are natural or environmental exposures that can disrupt circadian rhythms also related to the switch into high-/low-activation states? (2) Are circadian dysrhythmias (e.g., altered rest/activity rhythms) associated with the switch into activation states in bipolar disorder? (3) Do interventions that affect the circadian system also affect activation states? (4) Are associations between circadian dysrhythmias and activation states influenced by other "third" factors? RESULTS: Factors that naturally or experimentally alter circadian rhythms (e.g., light exposure) have been shown to relate to activation states; however future studies need to measure circadian rhythms contemporaneously with these natural/experimental factors. Actigraphic measures of circadian dysrhythmias are associated prospectively with the switch into high- or low-activation states, and more studies are needed to establish the most relevant prognostic actigraphy metrics in bipolar disorder. Interventions that can affect the circadian system (e.g., light therapy, lithium) can also reduce the switch into high-/low-activation states. Whether circadian rhythms mediate these clinical effects is an unknown but valuable question. The influence of age, sex, and other confounders on these associations needs to be better characterised. CONCLUSION: Based on the reviewed evidence, our view is that circadian dysrhythmia is a plausible driver of transitions into high- and low-activation states and deserves prioritisation in research in bipolar disorders.


Asunto(s)
Trastorno Bipolar , Humanos , Trastorno Bipolar/tratamiento farmacológico , Ritmo Circadiano , Litio/uso terapéutico , Descanso , Fototerapia , Sueño/fisiología
14.
bioRxiv ; 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38318207

RESUMEN

Primary cilia have been involved in the development and mechanosensation of various tissue types, including bone. In this study, we explored the mechanosensory role of primary cilia in bone growth and adaptation by examining two cilia specific genes, IFT88 and MKS5, required for proper cilia assembly and function. To analyze the role of primary cilia in osteoblasts, Osx1-GFP:Cre mice were bred with IFT88 LoxP/LoxP to generate mice with a conditional knockout of primary cilia in osteoblasts. A significant decrease in body weight was observed in both male (p=0.0048) and female (p=0.0374) conditional knockout (cKO) mice compared to the wild type (WT) controls. The femurs of cKO mice were significantly shorter than that of the WT mice of both male (p=0.0003) and female (p=0.0019) groups. Histological analysis revealed a significant difference in MAR (p=0.0005) and BFR/BS (p<0.0001) between female cKO and WT mice. The BFR/BS of male cKO mice was 58.03% lower compared to WT mice. To further investigate the role of primary cilia in osteocytes, Dmp1-8kb-Cre mice were crossed with MKS5 LoxP/LoxP to generate mice with defective cilia in osteocytes. In vivo axial ulnar loading was performed on 16-week-old mice for 3 consecutive days. The right ulnae were loaded for 120 cycles/day at a frequency of 2Hz with a peak force of 2.9N for female mice and 3.2N for male mice. Load-induced bone formation was measured using histomorphometry. The relative values of MS/BS, MAR and BFR/BS (loaded ulnae minus nonloaded ulnae) in male MKS5 cKO mice were decreased by 24.88%, 46.27% and 48.24%, respectively, compared to the controls. In the female groups, the rMS/BS was 52.5% lower, the rMAR was 27.58% lower, and the rBFR/BS was 41.54% lower in MKS5 cKO mice than the WT group. Histological analysis indicated that MKS5 cKO mice showed significantly decreased response to mechanical loading compared to the controls. Taken together, these data highlight a critical role of primary cilia in bone development and mechanotransduction, suggesting that the presence of primary cilia in osteoblasts play an important role in skeletal development, and primary cilia in osteocytes mediate mechanically induced bone formation.

15.
BMC Med ; 20(1): 479, 2022 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-36514113

RESUMEN

BACKGROUND: Clinical staging proposes that youth-onset mental disorders develop progressively, and that active treatment of earlier stages should prevent progression to more severe disorders. This retrospective cohort study examined the longitudinal relationships between clinical stages and multiple clinical and functional outcomes within the first 12 months of care. METHODS: Demographic and clinical information of 2901 young people who accessed mental health care at age 12-25 years was collected at predetermined timepoints (baseline, 3 months, 6 months, 12 months). Initial clinical stage was used to define three fixed groups for analyses (stage 1a: 'non-specific anxious or depressive symptoms', 1b: 'attenuated mood or psychotic syndromes', 2+: 'full-threshold mood or psychotic syndromes'). Logistic regression models, which controlled for age and follow-up time, were used to compare clinical and functional outcomes (role and social function, suicidal ideation, alcohol and substance misuse, physical health comorbidity, circadian disturbances) between staging groups within the initial 12 months of care. RESULTS: Of the entire cohort, 2093 young people aged 12-25 years were followed up at least once over the first 12 months of care, with 60.4% female and a baseline mean age of 18.16 years. Longitudinally, young people at stage 2+ were more likely to develop circadian disturbances (odds ratio [OR]=2.58; CI 1.60-4.17), compared with individuals at stage 1b. Additionally, stage 1b individuals were more likely to become disengaged from education/employment (OR=2.11, CI 1.36-3.28), develop suicidal ideations (OR=1.92; CI 1.30-2.84) and circadian disturbances (OR=1.94, CI 1.31-2.86), compared to stage 1a. By contrast, we found no relationship between clinical stage and the emergence of alcohol or substance misuse and physical comorbidity. CONCLUSIONS: The differential rates of emergence of poor clinical and functional outcomes between early versus late clinical stages support the clinical staging model's assumptions about illness trajectories for mood and psychotic syndromes. The greater risk of progression to poor outcomes in those who present with more severe syndromes may be used to guide specific intervention packages.


Asunto(s)
Salud Mental , Trastornos Relacionados con Sustancias , Adolescente , Humanos , Femenino , Niño , Adulto Joven , Adulto , Masculino , Estudios Retrospectivos , Ideación Suicida , Comorbilidad
16.
BMJ Open ; 12(8): e061734, 2022 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-35948386

RESUMEN

OBJECTIVES: The aim of this study was to determine the prevalence of disordered eating in young people attending a headspace centre, an enhanced primary care centre providing early intervention services for mental health disorders for young people aged 12-25 years, in metropolitan Sydney. DESIGN: Cross-sectional assessment of disordered eating symptoms and behaviours. SETTING: An enhanced primary care youth mental health service in inner urban Sydney, Australia. PARTICIPANTS: A sequential cohort of 530 young people aged 14-26 years presenting to headspace Camperdown for support with mental health concerns. OUTCOME MEASURES: Participants completed a series of questionnaires online which included items assessing the presence of eating disorder symptoms and behaviours. RESULTS: Over one-third of young people aged 14-26 years presenting to headspace Camperdown in a 22-month period reported symptoms of disordered eating. Of these, 32% endorsed overeating behaviours, 25% endorsed dietary restriction and 8% reported purging behaviours. In total, 44% reported engaging in one of more of these behaviours on a regular basis. Almost half reported experiencing significant shape and weight concerns. Eating disorder behaviours were particularly prevalent among female and gender-diverse participants (48% of females and 46% of gender-diverse participants compared with 35% of males) and overall scores across all of the eating disorder and body image items assessed were significantly higher for female participants compared with males. CONCLUSIONS: Disordered eating behaviours and symptoms are common among those presenting to youth mental health primary care services. Proactive screening for these behaviours presents opportunities for early detection and specific interventions. TRIAL REGISTRATION NUMBER: ACTRN12618001676202; Results.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos , Salud Mental , Adolescente , Australia/epidemiología , Estudios Transversales , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Femenino , Humanos , Masculino , Prevalencia , Encuestas y Cuestionarios
17.
Australas Psychiatry ; 30(6): 689-693, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35852822

RESUMEN

OBJECTIVE: Youth with early-onset mood or psychotic disorders are occasionally prescribed metformin to manage cardiometabolic risk. This retrospective study explores the demographic, clinical and metabolic factors associated with metformin prescription youth with mood or psychotic disorders. METHOD: Participants included 72 youth with mood or psychotic disorders from a young adult mental health inpatient unit, of which 18 (33%) were newly prescribed metformin, and 54 (66%) were not prescribed metformin. Demographic and clinical information were extracted from the patients' medical files along with body mass index (BMI), fasting serum bloods and calculated updated homeostatic model of insulin resistance assessment (HOMA2-IR) scores to compare profiles between groups. RESULTS: Of those prescribed metformin, 83% were overweight or obese and 72% had elevated HOMA2-IR scores. Of those not receiving metformin treatment, 41% were overweight or obese and 22% had elevated HOMA2-IR scores. Youth prescribed metformin had significantly higher BMI, and elevated markers of insulin resistance, but did not differ to those not prescribed metformin on other demographic, clinical or metabolic factors. CONCLUSIONS: While metformin is prescribed to some youth with mood or psychotic disorders displaying markers of cardiometabolic disturbance, there is a need to develop clearer treatment guidelines for metformin in these youth.


Asunto(s)
Enfermedades Cardiovasculares , Resistencia a la Insulina , Metformina , Trastornos Psicóticos , Adolescente , Adulto Joven , Humanos , Metformina/uso terapéutico , Sobrepeso , Pacientes Internos , Estudios Retrospectivos , Obesidad/complicaciones , Índice de Masa Corporal , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/complicaciones
19.
Psychiatry Clin Neurosci ; 76(10): 481-489, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35730893

RESUMEN

AIMS: Patients with depression and bipolar disorder have previously been shown to have impaired white matter (WM) integrity compared with healthy controls. This study aimed to investigate potential sex differences that may provide further insight into the pathophysiology of these highly debilitating mood disorders. METHODS: Participants aged 17 to 30 years (168 with depression [60% females], 107 with bipolar disorder [74% females], and 61 controls [64% females]) completed clinical assessment, self-report measures, and a neuropsychological assessment battery. Participants also underwent magnetic resonance imaging from which diffusion tensor imaging data were collected among five fronto-limbic WM tracts: cingulum bundle (cingulate gyrus and hippocampus subsections), fornix, stria terminalis, and the uncinate fasciculus. Mean fractional anisotropy (FA) scores were compared between groups using analyses of variance with sex and diagnosis as fixed factors. RESULTS: Among the nine WM tracts analyzed, one revealed a significant interaction between sex and diagnosis, controlling for age. Male patients with bipolar disorder had significantly lower FA scores in the fornix compared with the other groups. Furthermore, partial correlations revealed a significant positive association between FA scores for the fornix and psychomotor speed. CONCLUSIONS: Our findings suggest that males with bipolar disorder may be at increased risk of disruptions in WM integrity, especially in the fornix, which is thought to be responsible for a range of cognitive functions. More broadly, our findings suggest that sex differences may exist in WM integrity and thereby alter our understanding of the pathophysiology of mood disorders.


Asunto(s)
Sustancia Blanca , Adolescente , Anisotropía , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Masculino , Trastornos del Humor/diagnóstico por imagen , Caracteres Sexuales , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología
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