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1.
Health Soc Care Deliv Res ; 12(5): 1-194, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38511977

ABSTRACT

Background: Falls are the most common safety incident reported by acute hospitals. The National Institute of Health and Care Excellence recommends multifactorial falls risk assessment and tailored interventions, but implementation is variable. Aim: To determine how and in what contexts multifactorial falls risk assessment and tailored interventions are used in acute National Health Service hospitals in England. Design: Realist review and multisite case study. (1) Systematic searches to identify stakeholders' theories, tested using empirical data from primary studies. Review of falls prevention policies of acute Trusts. (2) Theory testing and refinement through observation, staff interviews (n = 50), patient and carer interviews (n = 31) and record review (n = 60). Setting: Three Trusts, one orthopaedic and one older person ward in each. Results: Seventy-eight studies were used for theory construction and 50 for theory testing. Four theories were explored. (1) Leadership: wards had falls link practitioners but authority to allocate resources for falls prevention resided with senior nurses. (2) Shared responsibility: a key falls prevention strategy was patient supervision. This fell to nursing staff, constraining the extent to which responsibility for falls prevention could be shared. (3) Facilitation: assessments were consistently documented but workload pressures could reduce this to a tick-box exercise. Assessment items varied. While individual patient risk factors were identified, patients were categorised as high or low risk to determine who should receive supervision. (4) Patient participation: nursing staff lacked time to explain to patients their falls risks or how to prevent themselves from falling, although other staff could do so. Sensitive communication could prevent patients taking actions that increase their risk of falling. Limitations: Within the realist review, we completed synthesis for only two theories. We could not access patient records before observations, preventing assessment of whether care plans were enacted. Conclusions: (1) Leadership: There should be a clear distinction between senior nurses' roles and falls link practitioners in relation to falls prevention; (2) shared responsibility: Trusts should consider how processes and systems, including the electronic health record, can be revised to better support a multidisciplinary approach, and alternatives to patient supervision should be considered; (3) facilitation: Trusts should consider how to reduce documentation burden and avoid tick-box responses, and ensure items included in the falls risk assessment tools align with guidance. Falls risk assessment tools and falls care plans should be presented as tools to support practice, rather than something to be audited; (4) patient participation: Trusts should consider how they can ensure patients receive individualised information about risks and preventing falls and provide staff with guidance on brief but sensitive ways to talk with patients to reduce the likelihood of actions that increase their risk of falling. Future work: (1) Development and evaluation of interventions to support multidisciplinary teams to undertake, and involve patients in, multifactorial falls risk assessment and selection and delivery of tailored interventions; (2) mixed method and economic evaluations of patient supervision; (3) evaluation of engagement support workers, volunteers and/or carers to support falls prevention. Research should include those with cognitive impairment and patients who do not speak English. Study registration: This study is registered as PROSPERO CRD42020184458. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR129488) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 5. See the NIHR Funding and Awards website for further award information.


Many accidental falls by older people in hospitals could be avoided. There are guidelines to prevent falls, but some hospitals are better at following them than others. This study aimed to find out why. First, we looked at research and hospitals' falls policies for ideas about what stops falls. With advice from service users, we tested these ideas in four hospitals in England, watching how falls were prevented on wards for older people and people who need bone care, and talking to 50 staff, 28 patients and 3 carers. We found the following: Falls leadership: wards had staff called falls link practitioners who supported falls prevention, but senior nurses, not link practitioners, made the most important decisions. Sharing responsibility: patients with falls risks were monitored to try to stop falls. Because only nursing teams were always present to monitor patients, they had most responsibility for preventing falls. This limited sharing responsibility with other staff. Computer tools: nurses used computers to record prevention work, but high workloads could make this a 'tick-box' exercise. Computer tools reminded them to do this, although tools varied. Patients had individual falls plans, but they were also ranked more generally as high or low risk of falling, with 'high-risk' patients being monitored. Patient involvement: nursing staff did not have time to explain to patients how to prevent falls, but other staff could have such conversations. Many patients had problems like dementia and found it difficult to follow safety advice, although some could take steps to keep safe, with sensitive staff support. We need to involve patients, carers and different staff in falls prevention. Hospitals could develop computer systems to support this, think how to involve more ward staff, and provide guidance on helpful ways to talk with patients about falls.


Subject(s)
Group Processes , State Medicine , Humans , Aged , Risk Assessment , Leadership , Academies and Institutes
2.
Article in English | MEDLINE | ID: mdl-38375970

ABSTRACT

INTRODUCTION: This study aimed to analyze the real-time variability of suicidal ideation intensity and the relationship between real-time and retrospective reports of suicidal ideation made on the Beck Scale for Suicidal Ideation (BSS), among young people with borderline personality disorder (BPD). METHODS: Young people (15-25-year olds) with BPD (N = 46), recruited from two government-funded mental health services, rated the intensity of their suicidal ideation six times per day for 7 days before completing the BSS. RESULTS: For 70% of participants, suicidal ideation changed in intensity approximately five times across the week, both within and between days. BSS ratings were most highly correlated with the highest real-time ratings of suicidal ideation. However, this was not significantly different from the relationship between the BSS and both the average and most recent ratings. Median ratings of suicidal ideation intensity were higher on the BSS compared with an equivalent question asked in real time. CONCLUSION: Findings suggest that young people with BPD experience high levels of fluctuation in their intensity of suicidal ideation across a week and that retrospective reports of suicidal ideation might be more reflective of the most intense experience of suicidal ideation across the week.

3.
Transl Psychiatry ; 14(1): 62, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38272868

ABSTRACT

Major depressive disorder (MDD) is marked by altered processing of emotional stimuli, including facial expressions. Recent neuroimaging research has attempted to investigate how these stimuli alter the directional interactions between brain regions in those with MDD; however, methodological heterogeneity has made identifying consistent effects difficult. To address this, we systematically examined studies investigating MDD-associated differences present in effective connectivity during the processing of emotional facial expressions. We searched five databases: PsycINFO, EMBASE, PubMed, Scopus, and Web of Science, using a preregistered protocol (registration number: CRD42021271586). Of the 510 unique studies screened, 17 met our inclusion criteria. These studies identified that compared with healthy controls, participants with MDD demonstrated (1) reduced connectivity from the dorsolateral prefrontal cortex to the amygdala during the processing of negatively valenced expressions, and (2) increased inhibitory connectivity from the ventromedial prefrontal cortex to amygdala during the processing of happy facial expressions. Most studies investigating the amygdala and anterior cingulate cortex noted differences in their connectivity; however, the precise nature of these differences was inconsistent between studies. As such, commonalities observed across neuroimaging modalities warrant careful investigation to determine the specificity of these effects to particular subregions and emotional expressions. Future research examining longitudinal connectivity changes associated with treatment response may provide important insights into mechanisms underpinning therapeutic interventions, thus enabling more targeted treatment strategies.


Subject(s)
Depressive Disorder, Major , Facial Recognition , Humans , Depressive Disorder, Major/drug therapy , Magnetic Resonance Imaging , Emotions/physiology , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiology , Brain/diagnostic imaging , Brain Mapping/methods
4.
Psychiatry Res ; 333: 115745, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38271886

ABSTRACT

A set of clinical criteria, the Clinical High At-Risk Mental State (CHARMS) criteria, have been developed to identify symptomatic young people who are at-risk of disorder progression. The current study aimed to validate the CHARMS criteria by testing whether they prospectively identify individuals at-risk of progressing from attenuated symptomatology to a first episode of serious mental disorder, namely first episode psychosis, first episode mania, severe major depression, and borderline personality disorder. 121 young people completed clinical evaluations at baseline, 6- and 12-month follow-up. The Kaplan-Meier method was used to assess transition rates. Cox regression and LASSO were used to examine baseline clinical predictors of transition. Linear mixed effects modelling was used to examine symptom severity. 28 % of CHARMS+ individuals transitioned to a Stage 2 disorder by 12-month follow-up. The CHARMS+ group had more severe symptoms at follow-up than the CHARMS- group. 96 % of Stage 2 transitions were initially to severe depression. Meeting criteria for multiple CHARMS subgroups was associated with higher transition risk: meeting one at-risk group = 24 %; meeting two at-risk groups = 17 %, meeting three at-risk groups = 55 %, meeting four at-risk groups = 50 %. The strongest baseline predictor of transition was severity of depressive symptoms. The CHARMS criteria identified a group of individuals at-risk of imminent onset of severe mental disorder, particularly severe depression. Larger scale studies and longer follow-up periods are required to validate and extend these findings.


Subject(s)
Borderline Personality Disorder , Depressive Disorder, Major , Psychotic Disorders , Humans , Adolescent , Psychotic Disorders/diagnosis , Depressive Disorder, Major/diagnosis , Borderline Personality Disorder/diagnosis , Mania
5.
Sci Rep ; 14(1): 1084, 2024 01 11.
Article in English | MEDLINE | ID: mdl-38212349

ABSTRACT

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.


Subject(s)
Depressive Disorder, Major , Humans , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/psychology , Benchmarking , Brain/diagnostic imaging , Neuroimaging/methods , Machine Learning , Magnetic Resonance Imaging/methods
6.
Neuroimage Clin ; 41: 103564, 2024.
Article in English | MEDLINE | ID: mdl-38218081

ABSTRACT

Dysfunctional activity of the rostral anterior cingulate cortex (rACC) - an extensively connected hub region of the default mode network - has been broadly linked to cognitive and affective impairments in depression. However, the nature of aberrant task-related rACC suppression in depression is incompletely understood. In this study, we sought to characterize functional connectivity of rACC activity suppression ('deactivation') - an essential feature of rACC function - during external task engagement in depression. Specifically, we aimed to explore neural patterns of functional decoupling and coupling with the rACC during its task-driven suppression. We enrolled 81 15- to 25-year-old young people with moderate-to-severe major depressive disorder (MDD) before they commenced a 12-week clinical trial that assessed the effectiveness of cognitive behavioral therapy plus either fluoxetine or placebo. Ninety-four matched healthy controls were also recruited. Participants completed a functional magnetic resonance imaging face matching task known to elicit rACC suppression. To identify brain regions associated with the rACC during its task-driven suppression, we employed a seed-based functional connectivity analysis. We found MDD participants, compared to controls, showed significantly reduced 'decoupling' of the rACC with extended task-specific regions during task performance. Specifically, less decoupling was observed in the occipital and fusiform gyrus, dorsal ACC, medial prefrontal cortex, cuneus, amygdala, thalamus, and hippocampus. Notably, impaired decoupling was apparent in participants who did not remit to treatment, but not treatment remitters. Further, we found MDD participants showed significant increased coupling with the anterior insula cortex during task engagement. Our findings indicate that aberrant task-related rACC suppression is associated with disruptions in adaptive neural communication and dynamic switching between internal and external cognitive modes that may underpin maladaptive cognitions and biased emotional processing in depression.


Subject(s)
Depressive Disorder, Major , Gyrus Cinguli , Humans , Adolescent , Young Adult , Adult , Gyrus Cinguli/diagnostic imaging , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/therapy , Depression , Brain , Cognition , Magnetic Resonance Imaging/methods
10.
Psychother Res ; 34(1): 41-53, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37963351

ABSTRACT

OBJECTIVE: Prior studies of Cognitive Behavioral Therapy (CBT) have focused on the quantity and quality of clients' homework completion and only rarely have considered the role of therapist competence. METHODS: The present study examined (a) therapist competence across the entire process of integrating homework into CBT, including the review, design, and planning of tasks; (b) homework engagement, including client appraisals of the difficulty and obstacles encountered in task completion using the Homework Rating Scale - Revised (HRS-II); (c) pre-post symptom reduction as the index of outcome; and (d) considered client factors such as suicide risk in a community-based trial for adolescent depression. Trained independent observers assessed therapist competence and engagement with homework at two consecutive sessions of CBT for N = 80 young people (Mage = 19.61, SD = 2.60). RESULTS: Significant complementary mediation effects were obtained; there was an indirect mediation effect of HRS-II Beliefs (b = 1.03, SE B = 0.42, 95% BCa CI [0.35, 2.03]) and HRS-II Perceived Consequences on the Competence-Engagement relationship (b = 0.85, SE B = 0.31, 95% BCa CI [0.39, 1.61]). High levels of suicidal ideation were also shown to moderate this relationship. CONCLUSIONS: The present findings contribute to the growing body of CBT process research designed to examine the complex interrelationships of client and therapist variables, in a manner that reflects the actual process of therapy, and advances beyond studies of isolated predictors of symptom change.


Subject(s)
Cognitive Behavioral Therapy , Depression , Humans , Adolescent , Young Adult , Adult , Suicidal Ideation , Treatment Outcome
11.
Early Interv Psychiatry ; 18(2): 153-164, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37394278

ABSTRACT

AIM: Basic self disturbance is a putative core vulnerability marker of schizophrenia spectrum disorders. The primary aims of the Self, Neuroscience and Psychosis (SNAP) study are to: (1) empirically test a previously described neurophenomenological self-disturbance model of psychosis by examining the relationship between specific clinical, neurocognitive, and neurophysiological variables in UHR patients, and (2) develop a prediction model using these neurophenomenological disturbances for persistence or deterioration of UHR symptoms at 12-month follow-up. METHODS: SNAP is a longitudinal observational study. Participants include 400 UHR individuals, 100 clinical controls with no attenuated psychotic symptoms, and 50 healthy controls. All participants complete baseline clinical and neurocognitive assessments and electroencephalography. The UHR sample are followed up for a total of 24 months, with clinical assessment completed every 6 months. RESULTS: This paper presents the protocol of the SNAP study, including background rationale, aims and hypotheses, design, and assessment procedures. CONCLUSIONS: The SNAP study will test whether neurophenomenological disturbances associated with basic self-disturbance predict persistence or intensification of UHR symptomatology over a 2-year follow up period, and how specific these disturbances are to a clinical population with attenuated psychotic symptoms. This may ultimately inform clinical care and pathoaetiological models of psychosis.


Subject(s)
Psychotic Disorders , Schizophrenia , Humans , Risk Factors , Psychotic Disorders/psychology , Schizophrenia/diagnosis , Longitudinal Studies , Attention , Psychiatric Status Rating Scales
12.
Biol Psychiatry ; 95(5): 426-433, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37355004

ABSTRACT

BACKGROUND: Clinical trials suggest that long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) (fish oil) may reduce depressive symptoms in adults with major depressive disorder. Therefore, n-3 PUFAs may be a potential treatment for depression in youth. METHODS: Participants were 15- to-25 year-old individuals with major depressive disorder who sought care in one of three government-funded mental health services for young people in metropolitan Melbourne, Perth, or Sydney, Australia. Participants were randomly assigned in a double-blind, parallel-arm design to receive either fish oil (840 mg of eicosapentaenoic acid and 560 mg of docosahexaenoic acid) or placebo capsules as adjunct to cognitive behavioral case management. All participants were offered 50-minute cognitive behavioral case management sessions every 2 weeks delivered by qualified therapists (treatment as usual) at the study sites during the intervention period. The primary outcome was change in the interviewer-rated Quick Inventory of Depressive Symptomatology, Adolescent Version, score at 12 weeks. Erythrocyte n-3 PUFA levels were assessed pre-post intervention. RESULTS: A total of 233 young people were randomized to the treatment arms: 115 participants to the n-3 PUFA group and 118 to the placebo group. Mean change from baseline in the Quick Inventory of Depressive Symptomatology score was -5.8 in the n-3 PUFA group and -5.6 in the placebo group (mean difference, 0.2; 95% CI, -1.1 to 1.5; p = .75). Erythrocyte PUFA levels were not associated with depression severity at any time point. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS: This placebo-controlled trial and biomarker analysis found no evidence to support the use of fish oil for treatment in young people with major depressive disorder.


Subject(s)
Depressive Disorder, Major , Fatty Acids, Omega-3 , Humans , Adolescent , Adult , Young Adult , Fish Oils/therapeutic use , Depressive Disorder, Major/drug therapy , Depression , Case Management , Fatty Acids, Omega-3/therapeutic use , Double-Blind Method , Cognition
13.
Aust N Z J Psychiatry ; 58(2): 109-116, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37830221

ABSTRACT

In this paper, the case study of ketamine as a new treatment for severe depression is used to outline the challenges of repurposing established medicines and we suggest potential solutions. The antidepressant effects of generic racemic ketamine were identified over 20 years ago, but there were insufficient incentives for commercial entities to pursue its registration, or support for non-commercial entities to fill this gap. As a result, the evaluation of generic ketamine was delayed, piecemeal, uncoordinated, and insufficient to gain approval. Meanwhile, substantial commercial investment enabled the widespread registration of a patented, intranasal s-enantiomeric ketamine formulation (Spravato®) for depression. However, Spravato is priced at $600-$900/dose compared to ~$5/dose for generic ketamine, and the ~AUD$100 million annual government investment requested in Australia (to cover drug costs alone) has been rejected twice, leaving this treatment largely inaccessible for Australian patients 2 years after Therapeutic Goods Administration approval. Moreover, emerging evidence indicates that generic racemic ketamine is at least as effective as Spravato, but no comparative trials were required for regulatory approval and have not been conducted. Without action, this story will repeat regularly in the next decade with a new wave of psychedelic-assisted psychotherapy treatments, for which the original off-patent molecules could be available at low-cost and reduce the overall cost of treatment. Several systemic reforms are required to ensure that affordable, effective options become accessible; these include commercial incentives, public and public-private funding schemes, reduced regulatory barriers and more coordinated international public funding schemes to support translational research.


Subject(s)
Depressive Disorder, Major , Ketamine , Humans , Ketamine/pharmacology , Ketamine/therapeutic use , Depression/drug therapy , Depressive Disorder, Major/drug therapy , Australia
14.
Sensors (Basel) ; 23(24)2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38139691

ABSTRACT

Wireless communications systems are traditionally designed by independently optimising signal processing functions based on a mathematical model. Deep learning-enabled communications have demonstrated end-to-end design by jointly optimising all components with respect to the communications environment. In the end-to-end approach, an assumed channel model is necessary to support training of the transmitter and receiver. This limitation has motivated recent work on over-the-air training to explore disjoint training for the transmitter and receiver without an assumed channel. These methods approximate the channel through a generative adversarial model or perform gradient approximation through reinforcement learning or similar methods. However, the generative adversarial model adds complexity by requiring an additional discriminator during training, while reinforcement learning methods require multiple forward passes to approximate the gradient and are sensitive to high variance in the error signal. A third, collaborative agent-based approach relies on an echo protocol to conduct training without channel assumptions. However, the coordination between agents increases the complexity and channel usage during training. In this article, we propose a simpler approach for disjoint training in which a local receiver model approximates the remote receiver model and is used to train the local transmitter. This simplified approach performs well under several different channel conditions, has equivalent performance to end-to-end training, and is well suited to adaptation to changing channel environments.

15.
Transl Psychiatry ; 13(1): 344, 2023 Nov 11.
Article in English | MEDLINE | ID: mdl-37951951

ABSTRACT

The brain's default mode network has a central role in the processing of information concerning oneself. Dysfunction in this self-referential processing represents a key component of multiple mental health conditions, particularly social anxiety disorder (SAD). This case-control study aimed to clarify alterations to network dynamics present during self-appraisal in SAD participants. A total of 38 adolescents and young adults with SAD and 72 healthy control participants underwent a self-referential processing fMRI task. The task involved two primary conditions of interest: direct self-appraisal (thinking about oneself) and reflected self-appraisal (thinking about how others might think about oneself). Dynamic causal modeling and parametric empirical Bayes were then used to explore differences in the effective connectivity of the default mode network between groups. We observed connectivity differences between SAD and healthy control participants in the reflected self-appraisal but not the direct self-appraisal condition. Specifically, SAD participants exhibited greater excitatory connectivity from the posterior cingulate cortex (PCC) to medial prefrontal cortex (MPFC) and greater inhibitory connectivity from the inferior parietal lobule (IPL) to MPFC. In contrast, SAD participants exhibited reduced intrinsic connectivity in the absence of task modulation. This was illustrated by reduced excitatory connectivity from the PCC to MPFC and reduced inhibitory connectivity from the IPL to MPFC. As such, participants with SAD showed changes to afferent connections to the MPFC which occurred during both reflected self-appraisal as well as intrinsically. The presence of connectivity differences in reflected and not direct self-appraisal is consistent with the characteristic fear of negative social evaluation that is experienced by people with SAD.


Subject(s)
Phobia, Social , Young Adult , Adolescent , Humans , Phobia, Social/diagnostic imaging , Diagnostic Self Evaluation , Case-Control Studies , Bayes Theorem , Magnetic Resonance Imaging , Gyrus Cinguli , Brain/diagnostic imaging , Brain Mapping
16.
Trials ; 24(1): 686, 2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37875938

ABSTRACT

BACKGROUND: Existing treatments for young people with severe depression have limited effectiveness. The aim of the Study of Ketamine for Youth Depression (SKY-D) trial is to determine whether a 4-week course of low-dose subcutaneous ketamine is an effective adjunct to treatment-as-usual in young people with major depressive disorder (MDD). METHODS: SKY-D is a double-masked, randomised controlled trial funded by the Australian Government's National Health and Medical Research Council (NHMRC). Participants aged between 16 and 25 years (inclusive) with moderate-to-severe MDD will be randomised to receive either low-dose ketamine (intervention) or midazolam (active control) via subcutaneous injection once per week for 4 weeks. The primary outcome is change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) after 4 weeks of treatment. Further follow-up assessment will occur at 8 and 26 weeks from treatment commencement to determine whether treatment effects are sustained and to investigate safety outcomes. DISCUSSION: Results from this trial will be important in determining whether low-dose subcutaneous ketamine is an effective treatment for young people with moderate-to-severe MDD. This will be the largest randomised trial to investigate the effects of ketamine to treat depression in young people. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ID: ACTRN12619000683134. Registered on May 7, 2019. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377513 .


Subject(s)
Depressive Disorder, Major , Ketamine , Humans , Adolescent , Infant , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/drug therapy , Ketamine/adverse effects , Depression/therapy , Australia , Treatment Outcome , Randomized Controlled Trials as Topic
17.
Mol Psychiatry ; 28(8): 3171-3181, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37580524

ABSTRACT

Most mental disorders have a typical onset between 12 and 25 years of age, highlighting the importance of this period for the pathogenesis, diagnosis, and treatment of mental ill-health. This perspective addresses interactions between risk and protective factors and brain development as key pillars accounting for the emergence of psychopathology in youth. Moreover, we propose that novel approaches towards early diagnosis and interventions are required that reflect the evolution of emerging psychopathology, the importance of novel service models, and knowledge exchange between science and practitioners. Taken together, we propose a transformative early intervention paradigm for research and clinical care that could significantly enhance mental health in young people and initiate a shift towards the prevention of severe mental disorders.


Subject(s)
Mental Disorders , Mental Health , Humans , Adolescent , Mental Disorders/therapy , Mental Disorders/diagnosis , Psychopathology
18.
Nat Neurosci ; 26(9): 1613-1629, 2023 09.
Article in English | MEDLINE | ID: mdl-37580620

ABSTRACT

The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive-compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience-ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Autism Spectrum Disorder , Bipolar Disorder , Obsessive-Compulsive Disorder , Humans , Magnetic Resonance Imaging , Gray Matter , Brain
19.
J Affect Disord ; 339: 633-639, 2023 10 15.
Article in English | MEDLINE | ID: mdl-37467794

ABSTRACT

BACKGROUND: Antipsychotic medications are increasingly used for difficult-to-treat depression in young people. However, the evidence-base for this is unclear. Our aim was to assess the evidence for the efficacy of atypical antipsychotics in treating unipolar and bipolar depression in adolescents and young adults. METHOD: We conducted a comprehensive systematic review and meta-analysis of randomized-control-trial studies (RCTs) of antipsychotic medications for 10- to 25-year-olds with unipolar and bipolar depression. The primary outcome of interest was change in depressive symptoms from baseline to trial endpoint. RESULTS: No studies were identified that evaluated the use of antipsychotics in the treatment of unipolar depression. However, we identified four studies, of quetiapine, lurasidone and olanzapine/fluoxetine combination, comprising a total of 866 randomized patients, that evaluated treatment of bipolar depression. All studies used the Children's Depression Rating Scale-Revised (CDRS-R). Our meta-analysis revealed the weighted mean difference (WMD) was -4.58 (95 % CI, -6.59 to -2.57) between antipsychotic and placebo-treated groups. Response and remission rates were also significantly in favor of antipsychotic treatment. LIMITATIONS: There were few studies, several did not address risk-of-bias domains and there was a lack of non-industry sponsored studies. CONCLUSION: There is an absence of evidence for the use of antipsychotic medications in treatment of youth unipolar depression, and no recommendations can be made. There is some evidence for the efficacy of antipsychotics, specifically lurasidone and olanzapine/fluoxetine combination, in the treatment of young people with bipolar depression. However, this evidence is limited and more studies investigating the use of these medications in young people are needed.


Subject(s)
Antipsychotic Agents , Bipolar Disorder , Child , Adolescent , Young Adult , Humans , Antipsychotic Agents/therapeutic use , Bipolar Disorder/diagnosis , Fluoxetine/therapeutic use , Olanzapine/therapeutic use , Lurasidone Hydrochloride/therapeutic use
20.
Front Plant Sci ; 14: 1155188, 2023.
Article in English | MEDLINE | ID: mdl-37346113

ABSTRACT

Miscanthus is a promising crop for bioenergy and biorefining in Europe. The improvement of Miscanthus as a crop relies on the creation of new varieties through the hybridization of germplasm collected in the wild with genetic variation and suitable characteristics in terms of resilience, yield and quality of the biomass. Local adaptation has likely shaped genetic variation for these characteristics and is therefore important to quantify. A key biomass quality parameter for biorefining is the ease of conversion of cell wall polysaccharides to monomeric sugars. Thus far, the variability of cell wall related traits in Miscanthus has mostly been explored in accessions from limited genetic backgrounds. Here we analysed the soil and climatic conditions of the original collection sites of 592 Miscanthus genotypes, which form eight distinct genetic groups based on discriminant analysis of principal components of 25,014 single-nucleotide polymorphisms. Our results show that species of the genus Miscanthus grow naturally across a range of soil and climate conditions. Based on a detailed analysis of 49 representative genotypes, we report generally minor differences in cell wall characteristics between different genetic groups and high levels of genetic variation within groups, with less investigated species like M. floridulus showing lower recalcitrance compared to the other genetic groups. The results emphasize that both inter- and intra- specific variation in cell wall characteristics and biomass recalcitrance can be used effectively in Miscanthus breeding programmes, while also reinforcing the importance of considering biomass yield when quantifying overall conversion efficiency. Thus, in addition to reflecting the complexity of the interactions between compositional and structural cell wall features and cell wall recalcitrance to sugar release, our results point to traits that could potentially require attention in breeding programmes targeted at improving the Miscanthus biomass crop.

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