Publications by authors named "Ian B Hickie"

464 Publications

Perceptions of social and work functioning are related to social anxiety and executive function in autistic adults.

Autism 2021 Jul 16:13623613211013664. Epub 2021 Jul 16.

The University of Sydney, Australia.

Lay Abstract: Many autistic adults have trouble in social situations and at work. Researchers do not know exactly why autistic people might find it difficult in these environments, and no studies to date have looked the way anxiety or other cognitive processes might affect autistic peoples' ability to socialise and succeed in getting and keeping jobs. Anxiety (how much you worry) and difficulty with getting stuff done or switching attention (known as executive function) can be concerns for autistic people and may contribute to social and work difficulties. This study looked at the relationships between the way autistic people perceived their anxiety and executive functioning and their ability to socialise and work. Sixty-two autistic participants completed questionnaires related to their ability to socialise and work, their social anxiety and their executive function. We found that participants who thought that they had poorer ability to work also found themselves to have more difficulties with executive function and they were more socially anxious. Our results showed that how autistic participants perceived their social anxiety and executive function were important in their perception of their social skills and work ability. This study supports the idea that anxiety and executive function could be targeted in interventions to support autistic people and their social and work outcomes.
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http://dx.doi.org/10.1177/13623613211013664DOI Listing
July 2021

Genetic risk for chronic pain is associated with lower antidepressant effectiveness: Converging evidence for a depression subtype.

Aust N Z J Psychiatry 2021 Jul 16:48674211031491. Epub 2021 Jul 16.

Department of Genetics & Computational Biology, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.

Introduction: Chronic pain and depression are highly comorbid and difficult-to-treat disorders. We previously showed this comorbidity is associated with higher depression severity, lower antidepressant treatment effectiveness and poorer prognosis in the Australian Genetics of Depression Study.

Objective: The current study aimed to assess whether a genetic liability to chronic pain is associated with antidepressant effectiveness over and above the effect of genetic factors for depression in a sample of 12,863 Australian Genetics of Depression Study participants.

Methods: Polygenic risk scores were calculated using summary statistics from genome-wide association studies of multisite chronic pain and major depression. Cumulative linked regressions were employed to assess the association between polygenic risk scores and antidepressant treatment effectiveness across 10 different medications.

Results: Mixed-effects logistic regressions showed that individual genetic propensity for chronic pain, but not major depression, was significantly associated with patient-reported chronic pain (Pain OR = 1.17 [1.12, 1.22]; MD OR = 1.01 [0.98, 1.06]). Significant associations were also found between lower antidepressant effectiveness and genetic risk for chronic pain or for major depression. However, a fully adjusted model showed the effect of Pain (adjOR = 0.93 [0.90, 0.96]) was independent of MD (adjOR = 0.96 [0.93, 0.99]). Sensitivity analyses were performed to assess the robustness of these results. After adjusting for depression severity measures (i.e. age of onset; number of depressive episodes; interval between age at study participation and at depression onset), the associations between Pain and patient-reported chronic pain with lower antidepressant effectiveness remained significant (0.95 [0.92, 0.98] and 0.84 [0.78, 0.90], respectively).

Conclusion: These results suggest genetic risk for chronic pain accounted for poorer antidepressant effectiveness, independent of the genetic risk for major depression. Our results, along with independent converging evidence from other studies, point towards a difficult-to-treat depression subtype characterised by comorbid chronic pain. This finding warrants further investigation into the implications for biologically based nosology frameworks in pain medicine and psychiatry.
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http://dx.doi.org/10.1177/00048674211031491DOI Listing
July 2021

Using Monozygotic Twins to Dissect Common Genes in Posttraumatic Stress Disorder and Migraine.

Front Neurosci 2021 22;15:678350. Epub 2021 Jun 22.

Centre for Genomics and Personalised Health, School of Biomedical Science, Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD, Australia.

Epigenetic mechanisms have been associated with genes involved in Posttraumatic stress disorder (PTSD). PTSD often co-occurs with other health conditions such as depression, cardiovascular disorder and respiratory illnesses. PTSD and migraine have previously been reported to be symptomatically positively correlated with each other, but little is known about the genes involved. The aim of this study was to understand the comorbidity between PTSD and migraine using a monozygotic twin disease discordant study design in six pairs of monozygotic twins discordant for PTSD and 15 pairs of monozygotic twins discordant for migraine. DNA from peripheral blood was run on Illumina EPIC arrays and analyzed. Multiple testing correction was performed using the Bonferroni method and 10% false discovery rate (FDR). We validated 11 candidate genes previously associated with PTSD including , , and 1. In the epigenome-wide scan, seven novel CpGs were significantly associated with PTSD within/near , , , , , and , with all CpGs except the CpG hypermethylated in PTSD. These results were significantly enriched for genes whose DNA methylation was previously associated with migraine (-value = 0.036). At 10% FDR, 132 CpGs in 99 genes associated with PTSD were also associated with migraine in the migraine twin samples. Genes associated with PTSD were overrepresented in vascular smooth muscle, axon guidance and oxytocin signaling pathways, while genes associated with both PTSD and migraine were enriched for AMPK signaling and longevity regulating pathways. In conclusion, these results suggest that common genes and pathways are likely involved in PTSD and migraine, explaining at least in part the co-morbidity between the two disorders.
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http://dx.doi.org/10.3389/fnins.2021.678350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258453PMC
June 2021

Repetitive transcranial magnetic stimulation (rTMS) in autism spectrum disorder: protocol for a multicentre randomised controlled clinical trial.

BMJ Open 2021 Jul 7;11(7):e046830. Epub 2021 Jul 7.

Central Clinical School, Monash University, Melbourne, Victoria, Australia.

Introduction: There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD.

Methods And Analysis: This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14-40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024.

Ethics And Dissemination: The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia's National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication.

Trial Registration Number: Australian New Zealand Clinical Trials Registry (ACTRN12620000890932).
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http://dx.doi.org/10.1136/bmjopen-2020-046830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264904PMC
July 2021

Effect of an online healthy lifestyle psychoeducation programme to improve cardiometabolic outcomes and affective symptoms in youth receiving mental health care: study protocol for a pilot clinical trial.

BMJ Open 2021 Jun 29;11(6):e044977. Epub 2021 Jun 29.

Youth Mental Health and Technology Team, The University of Sydney Brain and Mind Centre, Sydney, New South Wales, Australia.

Introduction: Worsened cardiometabolic profiles in youth with mental ill health have been associated with a number of modifiable lifestyle risk factors. It is becoming increasingly evident that clinical interventions need to be multimodal in focus to improve mental health symptoms and the physical health symptoms in this already at-risk cohort.

Methods And Analysis: This 12-week pilot clinical trial examines the efficacy, feasibility and acceptability of an adjunctive online psychoeducation programme for improving cardiometabolic risk parameters and affective symptoms in a transdiagnostic sample of at least 44 young people aged 16-25 years presenting for mental healthcare for mood and/or psychotic syndromes (including anxiety, depression, bipolar disorder and psychosis). Individuals will be invited to participate in a pilot clinical trial for a structured online psychoeducation programme incorporating nutritional, physical activity, sleep-wake and healthy lifestyle information, delivered fortnightly over six online modules. Participants will undergo a series of assessments including: (1) self-report and clinician administered assessments determining mental health symptomatology; (2) fasting blood tests to assess cardiometabolic markers (fasting insulin, fasting glucose and blood lipids); (3) anthropometric assessments (height, weight, waist circumference and blood pressure); and (4) sleep-wake behaviours and circadian rhythm assessments. Changes in scores for all cardiometabolic and affective measures will be assessed via paired samples t-tests, and correlations between change scores will be assessed via Pearson's or Spearman's correlations. Feasibility will be assessed via completion rates, and the acceptability of the programme will be assessed via programme satisfaction measures.

Ethics And Dissemination: This pilot clinical trial has been approved by the Sydney Local Health District Research Ethics and Governance Office (X20-0228 & 2020/ETH01201). The results of this pilot clinical trial 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: ACTRN12620000772943, Date 28 August 2020.
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http://dx.doi.org/10.1136/bmjopen-2020-044977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245471PMC
June 2021

Effect of an online healthy lifestyle psychoeducation programme to improve cardiometabolic outcomes and affective symptoms in youth receiving mental health care: study protocol for a pilot clinical trial.

BMJ Open 2021 Jun 29;11(6):e044977. Epub 2021 Jun 29.

Youth Mental Health and Technology Team, The University of Sydney Brain and Mind Centre, Sydney, New South Wales, Australia.

Introduction: Worsened cardiometabolic profiles in youth with mental ill health have been associated with a number of modifiable lifestyle risk factors. It is becoming increasingly evident that clinical interventions need to be multimodal in focus to improve mental health symptoms and the physical health symptoms in this already at-risk cohort.

Methods And Analysis: This 12-week pilot clinical trial examines the efficacy, feasibility and acceptability of an adjunctive online psychoeducation programme for improving cardiometabolic risk parameters and affective symptoms in a transdiagnostic sample of at least 44 young people aged 16-25 years presenting for mental healthcare for mood and/or psychotic syndromes (including anxiety, depression, bipolar disorder and psychosis). Individuals will be invited to participate in a pilot clinical trial for a structured online psychoeducation programme incorporating nutritional, physical activity, sleep-wake and healthy lifestyle information, delivered fortnightly over six online modules. Participants will undergo a series of assessments including: (1) self-report and clinician administered assessments determining mental health symptomatology; (2) fasting blood tests to assess cardiometabolic markers (fasting insulin, fasting glucose and blood lipids); (3) anthropometric assessments (height, weight, waist circumference and blood pressure); and (4) sleep-wake behaviours and circadian rhythm assessments. Changes in scores for all cardiometabolic and affective measures will be assessed via paired samples t-tests, and correlations between change scores will be assessed via Pearson's or Spearman's correlations. Feasibility will be assessed via completion rates, and the acceptability of the programme will be assessed via programme satisfaction measures.

Ethics And Dissemination: This pilot clinical trial has been approved by the Sydney Local Health District Research Ethics and Governance Office (X20-0228 & 2020/ETH01201). The results of this pilot clinical trial 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: ACTRN12620000772943, Date 28 August 2020.
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http://dx.doi.org/10.1136/bmjopen-2020-044977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245471PMC
June 2021

Autism spectrum disorder: An examination of sex differences in neuropsychological and self-report measures of executive and non-executive cognitive function.

Autism 2021 Jun 25:13623613211014991. Epub 2021 Jun 25.

The University of Sydney, Australia.

Lay Abstract: Research comparing females and males with a diagnosis of autism suggests that there are sex differences in some characteristics such as behaviour regulation. One area not studied in detail is whether females and males with autism perform differently in tests of cognitive ability. The results of previous research are quite mixed. One explanation may be that some research comparing females and males with autism did not include a neurotypical control group for comparison. As a result, it is not clear whether the sex differences in cognitive ability observed in people with autism are similar to differences between neurotypical males and females. To better understand whether there are unique differences between males and females with autism, it is important to also compare them with neurotypical males and females. In our research, we included a neurotypical group and compared males and females with and without a diagnosis of autism. We found that the sex differences in autism are similar to what we observe in males and females without autism. Our study showed that compared with males, females (with and without autism) do better in assessments of processing speed, cognitive flexibility, verbal learning and memory and semantic fluency. Our results suggest that although females show different cognitive performance to males, these sex differences were not specific to the group with a diagnosis of autism.
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http://dx.doi.org/10.1177/13623613211014991DOI Listing
June 2021

Innovative preclinic triage system to guide Australians to the right mental health care first time.

Aust Health Rev 2021 Jun 24. Epub 2021 Jun 24.

This paper presents a case study of an innovative direct-to-consumer preclinic triage system designed to reduce predicted peak demand for Australian mental health services as a result of COVID-19 and its associated socioeconomic consequences by guiding Australians to the right mental health care first time. Our innovative, digital health solution comprises two components: (1) a highly personalised and measurement-based model of care (Brain and Mind Centre model of care) that considers both the heterogeneity of mental disorders and other underlying comorbidities, as well as clinical staging; and (2) a health information technology (i.e. the InnoWell Platform). This digital health solution has been embedded as part of standard service delivery into a community-based intake service, thus resulting in a redesigned service model. The service model is currently being implemented as part of a pilot feasibility study, the marker of acceptability at the health professional and service level, and is now under active evaluation to determine its effect on outcomes for consumers, health professionals and the service. For the purposes of this paper, this model served as a prototype for the preclinic triage system that was conceptualised for national scalability at the primary health network level. When implemented at a national level, our direct-to-consumer preclinic triage system is expected to be an effective population health demand management strategy to address the rapidly emerging mental health demand crisis in Australia, and is aligned with the recent recommendation from the Productivity Commission to develop a sustainable national digital platform to facilitate the assessment and referral process to ensure access to mental health care matched to an individual's level of need.What is known about the topic?Although there is increased recognition of the mental health demand crisis in Australia as a result of the COVID-19 pandemic, little has been done to 'flatten' the curve. The Australian Government committed additional funding to support the Better Access Pandemic Support measure; however, this approach to care fails to appreciate both the disparities in service availability across Australia and the gap fees that are prohibitive to some of those seeking help. Furthermore, the expansion of this program may only result in those in care remaining in care, thus further delaying access to those in need.What does this paper add?This paper describes a digital health solution, comprised of a highly personalised and measurement-based model of care coupled with a health information technology, that has been embedded as part of standard service delivery. Consumers seeking mental health care complete a multidimensional self-report assessment via the technology, the results of which are available in real-time and used to facilitate triage to pathways of care as indicated by the severity of the consumer's illness and level of need to more effectively and efficiently allocate consumers to care. The redesigned service model is now under active evaluation to determine its effects on outcomes at consumer, health professional and service levels.What are the implications for practitioners?The redesigned local service model served as a prototype for our innovative direct-to-consumer preclinic triage system specifically designed to allocate consumers to self-management, ambulatory care or acute care based on clinical stage and level of need. It is our hypothesis that the preclinic triage system will be an effective population health demand management strategy. Importantly, the proposed preclinic triage system aligns with the recent recommendation from the Productivity Commission for the Australian Government to fund the development and sustained implementation of a digital platform to facilitate assessment and referral to evidence-based interventions matched to a consumer's level of need.
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http://dx.doi.org/10.1071/AH20233DOI Listing
June 2021

Neurobiology Youth Follow-up Study: protocol to establish a longitudinal and prospective research database using multimodal assessments for current and past mental health treatment-seeking young people within an early intervention service.

BMJ Open 2021 06 18;11(6):e044731. Epub 2021 Jun 18.

Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.

Introduction: Approximately 75% of major mental illness occurs before the age of 25 years. Despite this, our capacity to provide effective, early and personalised interventions is limited by insufficient evidence for characterising early-stage, and less specific, presentations of major mental disorders in youth populations. This article describes the protocol for setting up a large-scale database that will collect longitudinal, prospective data that incorporate clinical, social and occupational function, neuropsychological, circadian, metabolic, family history and genetic metrics. By collecting data in a research-purposed, standardised manner, the 'Neurobiology Youth Follow-up Study' should improve identification, characterisation and profiling of youth attending mental healthcare, to better inform diagnosis and treatment at critical time points. The overall goal is enhanced long-term clinical and functional outcomes.

Methods And Analysis: This longitudinal clinical cohort study will invite participation from youth (12-30 years) who seek help for mental health-related issues at an early intervention service (headspace Camperdown) and linked services. Participants will be prospectively tracked over 3 years with a series of standardised multimodal assessments at baseline, 6, 12, 24 and 36 months. Evaluations will include: (1) clinician-administered and self-report assessments determining clinical stage, pathophysiological pathways to illness, diagnosis, symptomatology, social and occupational function; (2) neuropsychological profile; (3) sleep-wake patterns and circadian rhythms; (4) metabolic markers and (5) genetics. These data will be used to: (1) model the impact of demographic, phenomenological and treatment variables, on clinical and functional outcomes; (2) map neurobiological profiles and changes onto a transdiagnostic clinical stage and pathophysiological mechanisms framework.

Ethics And Dissemination: This study protocol has been approved by the Human Research Ethics Committee of the Sydney Local Health District (2020/ETH01272, protocol V.1.3, 14 October 2020). Research findings will be disseminated through peer-reviewed journals and presentations at scientific conferences and to user and advocacy groups. Participant data will be de-identified.
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http://dx.doi.org/10.1136/bmjopen-2020-044731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215251PMC
June 2021

Supporting Clinicians to Use Technology to Deliver Highly Personalized and Measurement-Based Mental Health Care to Young People: Protocol for an Evaluation Study.

JMIR Res Protoc 2021 Jun 14;10(6):e24697. Epub 2021 Jun 14.

Brain and Mind Centre, University of Sydney, Camperdown, Australia.

Background: Australia's mental health care system has long been fragmented and under-resourced, with services falling well short of demand. In response, the World Economic Forum has recently called for the rapid deployment of smarter, digitally enhanced health services to facilitate effective care coordination and address issues of demand. The University of Sydney's Brain and Mind Centre (BMC) has developed an innovative digital health solution that incorporates 2 components: a highly personalized and measurement-based (data-driven) model of youth mental health care and a health information technology (HIT) registered on the Australian Register of Therapeutic Goods. Importantly, research into implementation of such solutions considers education and training of clinicians to be essential to adoption and optimization of use in standard clinical practice. The BMC's Youth Mental Health and Technology Program has subsequently developed a comprehensive education and training program to accompany implementation of the digital health solution.

Objective: This paper describes the protocol for an evaluation study to assess the effectiveness of the education and training program on the adoption and optimization of use of the digital health solution in service delivery. It also describes the proposed tools to assess the impact of training on knowledge and skills of mental health clinicians.

Methods: The evaluation study will use the Kirkpatrick Evaluation Model as a framework with 4 levels of analysis: Reaction (to education and training), Learning (knowledge acquired), Behavior (practice change), and Results (client outcomes). Quantitative and qualitative data will be collected using a variety of tools, including evaluation forms, pre- and postknowledge questionnaires, skill development and behavior change scales, as well as a real-time clinical practice audit.

Results: This project is funded by philanthropic funding from Future Generation Global. Ethics approval has been granted via Sydney Local Health District's Human Research Ethics Committee. At the time of this publication, clinicians and their services were being recruited to this study. The first results are expected to be submitted for publication in 2021.

Conclusions: The education and training program teaches clinicians the necessary knowledge and skills to assess, monitor, and manage complex needs; mood and psychotic syndromes; and trajectories of youth mental ill-health using a HIT that facilitates a highly personalized and measurement-based model of care. The digital health solution may therefore guide clinicians to help young people recover low functioning associated with subthreshold diagnostic presentations and prevent progression to more serious mental ill-health.

International Registered Report Identifier (irrid): PRR1-10.2196/24697.
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http://dx.doi.org/10.2196/24697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240796PMC
June 2021

Increased spindle density correlates with sleep continuity improvements following an eight-week course of a melatonin agonist in people with depression: A proof-of-concept study with agomelatine.

Eur J Neurosci 2021 Jun 5. Epub 2021 Jun 5.

Sleep Research Unit, University of Ottawa Institute of Mental Health Research at The Royal, Ottawa, ON, Canada.

Sleep fragmentation and reductions in sleep spindles have been observed in individuals with depression. Sleep spindles are known to play a protective role for sleep, and there are indications that melatonin agents can enhance spindles in healthy people. Whether agomelatine, a melatonin agonist indicated for the treatment of depression, may increase spindle density sufficiently to impact sleep continuity in people with depression remains unknown. This proof-of-concept study investigated changes in spindles following agomelatine intake in young adults with depression and assessed how they may relate to potential changes in sleep continuity and depressive symptoms. This study was based on an open-label design. Fifteen participants between 17 and 28 years of age (mean = 22.2; standard deviation [SD] = 3.4) with a diagnosis of a depressive disorder underwent polysomnography before and after an intervention including a 1 hr psychoeducation session centered on sleep and circadian rhythms, and an 8-week course of agomelatine (25-50 mg) with a guided sleep phase advance. Fast spindle density significantly increased from pre- to post-intervention. This increase in spindle density significantly correlated with a reduction in wake after sleep onset, and a similar trend was found with increased sleep efficiency. There was no significant correlation between spindle parameters and depressive symptoms. These findings suggest that agomelatine may contribute to enhanced sleep consolidation, possibly in part through the modulation of spindle production. This should be confirmed by larger randomized control trials.
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http://dx.doi.org/10.1111/ejn.15340DOI Listing
June 2021

Early expressions of psychopathology and risk associated with trans-diagnostic transition to mood and psychotic disorders in adolescents and young adults.

PLoS One 2021 4;16(6):e0252550. Epub 2021 Jun 4.

Brain and Mind Centre, The University of Sydney, Sydney, Australia.

Objectives: The heterogeneity and comorbidity of major mental disorders presenting in adolescents and young adults has fostered calls for trans-diagnostic research. This study examines early expressions of psychopathology and risk and trans-diagnostic caseness in a community cohort of twins and non-twin siblings.

Methods: Using data from the Brisbane Longitudinal Twin Study, we estimated median number of self-rated psychiatric symptoms, prevalence of subthreshold syndromes, family history of mood and/or psychotic disorders, and likelihood of subsequent trans-diagnostic caseness (individuals meeting diagnostic criteria for mood and/or psychotic syndromes). Next, we used cross-validated Chi-Square Automatic Interaction Detector (CHAID) analyses to identify the nature and relative importance of individual self-rated symptoms that predicted trans-diagnostic caseness. We examined the positive and negative predictive values (PPV; NPV) and accuracy of all classifications (Area under the Curve and 95% confidence intervals: AUC; 95% CI).

Results: Of 1815 participants (Female 1050, 58%; mean age 26.40), more than one in four met caseness criteria for a mood and/or psychotic disorder. Examination of individual factors indicated that the AUC was highest for subthreshold syndromes, followed by family history then self-rated psychiatric symptoms, and that NPV always exceeded PPV for caseness. In contrast, the CHAID analysis (adjusted for age, sex, twin status) generated a classification tree comprising six trans-diagnostic symptoms. Whilst the contribution of two symptoms (need for sleep; physical activity) to the model was more difficult to interpret, CHAID analysis indicated that four self-rated symptoms (sadness; feeling overwhelmed; impaired concentration; paranoia) offered the best discrimination between cases and non-cases. These four symptoms showed different associations with family history status.

Conclusions: The findings need replication in independent cohorts. However, the use of CHAID might provide a means of identifying specific subsets of trans-diagnostic symptoms representing clinical phenotypes that predict transition to caseness in individuals at risk of onset of major mental disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252550PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177455PMC
June 2021

Early expressions of psychopathology and risk associated with trans-diagnostic transition to mood and psychotic disorders in adolescents and young adults.

PLoS One 2021 4;16(6):e0252550. Epub 2021 Jun 4.

Brain and Mind Centre, The University of Sydney, Sydney, Australia.

Objectives: The heterogeneity and comorbidity of major mental disorders presenting in adolescents and young adults has fostered calls for trans-diagnostic research. This study examines early expressions of psychopathology and risk and trans-diagnostic caseness in a community cohort of twins and non-twin siblings.

Methods: Using data from the Brisbane Longitudinal Twin Study, we estimated median number of self-rated psychiatric symptoms, prevalence of subthreshold syndromes, family history of mood and/or psychotic disorders, and likelihood of subsequent trans-diagnostic caseness (individuals meeting diagnostic criteria for mood and/or psychotic syndromes). Next, we used cross-validated Chi-Square Automatic Interaction Detector (CHAID) analyses to identify the nature and relative importance of individual self-rated symptoms that predicted trans-diagnostic caseness. We examined the positive and negative predictive values (PPV; NPV) and accuracy of all classifications (Area under the Curve and 95% confidence intervals: AUC; 95% CI).

Results: Of 1815 participants (Female 1050, 58%; mean age 26.40), more than one in four met caseness criteria for a mood and/or psychotic disorder. Examination of individual factors indicated that the AUC was highest for subthreshold syndromes, followed by family history then self-rated psychiatric symptoms, and that NPV always exceeded PPV for caseness. In contrast, the CHAID analysis (adjusted for age, sex, twin status) generated a classification tree comprising six trans-diagnostic symptoms. Whilst the contribution of two symptoms (need for sleep; physical activity) to the model was more difficult to interpret, CHAID analysis indicated that four self-rated symptoms (sadness; feeling overwhelmed; impaired concentration; paranoia) offered the best discrimination between cases and non-cases. These four symptoms showed different associations with family history status.

Conclusions: The findings need replication in independent cohorts. However, the use of CHAID might provide a means of identifying specific subsets of trans-diagnostic symptoms representing clinical phenotypes that predict transition to caseness in individuals at risk of onset of major mental disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252550PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177455PMC
June 2021

Early expressions of psychopathology and risk associated with trans-diagnostic transition to mood and psychotic disorders in adolescents and young adults.

PLoS One 2021 4;16(6):e0252550. Epub 2021 Jun 4.

Brain and Mind Centre, The University of Sydney, Sydney, Australia.

Objectives: The heterogeneity and comorbidity of major mental disorders presenting in adolescents and young adults has fostered calls for trans-diagnostic research. This study examines early expressions of psychopathology and risk and trans-diagnostic caseness in a community cohort of twins and non-twin siblings.

Methods: Using data from the Brisbane Longitudinal Twin Study, we estimated median number of self-rated psychiatric symptoms, prevalence of subthreshold syndromes, family history of mood and/or psychotic disorders, and likelihood of subsequent trans-diagnostic caseness (individuals meeting diagnostic criteria for mood and/or psychotic syndromes). Next, we used cross-validated Chi-Square Automatic Interaction Detector (CHAID) analyses to identify the nature and relative importance of individual self-rated symptoms that predicted trans-diagnostic caseness. We examined the positive and negative predictive values (PPV; NPV) and accuracy of all classifications (Area under the Curve and 95% confidence intervals: AUC; 95% CI).

Results: Of 1815 participants (Female 1050, 58%; mean age 26.40), more than one in four met caseness criteria for a mood and/or psychotic disorder. Examination of individual factors indicated that the AUC was highest for subthreshold syndromes, followed by family history then self-rated psychiatric symptoms, and that NPV always exceeded PPV for caseness. In contrast, the CHAID analysis (adjusted for age, sex, twin status) generated a classification tree comprising six trans-diagnostic symptoms. Whilst the contribution of two symptoms (need for sleep; physical activity) to the model was more difficult to interpret, CHAID analysis indicated that four self-rated symptoms (sadness; feeling overwhelmed; impaired concentration; paranoia) offered the best discrimination between cases and non-cases. These four symptoms showed different associations with family history status.

Conclusions: The findings need replication in independent cohorts. However, the use of CHAID might provide a means of identifying specific subsets of trans-diagnostic symptoms representing clinical phenotypes that predict transition to caseness in individuals at risk of onset of major mental disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252550PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177455PMC
June 2021

Days out of role and somatic, anxious-depressive, hypo-manic, and psychotic-like symptom dimensions in a community sample of young adults.

Transl Psychiatry 2021 05 13;11(1):285. Epub 2021 May 13.

Youth Mental Health & Technology Team, Brain and Mind Centre, University of Sydney, Sydney, Australia.

Improving our understanding of the causes of functional impairment in young people is a major global challenge. Here, we investigated the relationships between self-reported days out of role and the total quantity and different patterns of self-reported somatic, anxious-depressive, psychotic-like, and hypomanic symptoms in a community-based cohort of young adults. We examined self-ratings of 23 symptoms ranging across the four dimensions and days out of role in >1900 young adult twins and non-twin siblings participating in the "19Up" wave of the Brisbane Longitudinal Twin Study. Adjusted prevalence ratios (APR) and 95% confidence intervals (95% CI) quantified associations between impairment and different symptom patterns. Three individual symptoms showed significant associations with days out of role, with the largest association for impaired concentration. When impairment was assessed according to each symptom dimension, there was a clear stepwise relationship between the total number of somatic symptoms and the likelihood of impairment, while individuals reporting ≥4 anxious-depressive symptoms or five hypomanic symptoms had greater likelihood of reporting days out of role. Furthermore, there was a stepwise relationship between the total number of undifferentiated symptoms and the likelihood of reporting days out of role. There was some suggestion of differences in the magnitude and significance of associations when the cohort was stratified according to sex, but not for age or twin status. Our findings reinforce the development of early intervention mental health frameworks and, if confirmed, support the need to consider interventions for subthreshold and/or undifferentiated syndromes for reducing disability among young people.
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http://dx.doi.org/10.1038/s41398-021-01390-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119948PMC
May 2021

Implementing a digital health model of care in Australian youth mental health services: protocol for impact evaluation.

BMC Health Serv Res 2021 May 12;21(1):452. Epub 2021 May 12.

The University of Sydney, Brain and Mind Centre, 94 Mallett St, Camperdown, Sydney, NSW, 2050, Australia.

Background: The World Economic Forum has recently highlighted substantial problems in mental health service provision and called for the rapid deployment of smarter, digitally-enhanced health services as a means to facilitate effective care coordination and address issues of demand. In mental health, the biggest enabler of digital solutions is the implementation of an effective model of care that is facilitated by integrated health information technologies (HITs); the latter ensuring the solution is easily accessible, scalable and sustainable. The University of Sydney's Brain and Mind Centre (BMC) has developed an innovative digital health solution - delivered through the Youth Mental Health and Technology Program - which incorporates two components: 1) a highly personalised and measurement-based (data-driven) model of youth mental health care; and 2) an industrial grade HIT registered on the Australian Register of Therapeutic Goods. This paper describes a research protocol to evaluate the impact of implementing the BMC's digital health solution into youth mental health services (i.e. headspace - a highly accessible, youth-friendly integrated service that responds to the mental health, physical health, alcohol or other substance use, and vocational concerns of young people aged 12 to 25 years) within urban and regional areas of Australia.

Methods: The digital health solution will be implemented into participating headspace centres using a naturalistic research design. Quantitative and qualitative data will be collected from headspace health professionals, service managers and administrators, as well as from lead agency and local Primary Health Network (PHN) staff, via service audits, Implementation Officer logs, online surveys, and semi-structured interviews, at baseline and then three-monthly intervals over the course of 12 months.

Discussion: At the time of publication, six headspace centres had been recruited to this study and had commenced implementation and impact evaluation. The first results are expected to be submitted for publication in 2021. This study will focus on the impact of implementing a digital health solution at both a service and staff level, and will evaluate digital readiness of service and staff adoption; quality, usability and acceptability of the solution by staff; staff self-reported clinical competency; overall impact on headspace centres as well as their lead agencies and local PHNs; and social return on investment.
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http://dx.doi.org/10.1186/s12913-021-06394-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113792PMC
May 2021

Comorbid Chronic Pain and Depression: Shared Risk Factors and Differential Antidepressant Effectiveness.

Front Psychiatry 2021 12;12:643609. Epub 2021 Apr 12.

Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

The bidirectional relationship between depression and chronic pain is well-recognized, but their clinical management remains challenging. Here we characterize the shared risk factors and outcomes for their comorbidity in the Australian Genetics of Depression cohort study ( = 13,839). Participants completed online questionnaires about chronic pain, psychiatric symptoms, comorbidities, treatment response and general health. Logistic regression models were used to examine the relationship between chronic pain and clinical and demographic factors. Cumulative linked logistic regressions assessed the effect of chronic pain on treatment response for 10 different antidepressants. Chronic pain was associated with an increased risk of depression (OR = 1.86 [1.37-2.54]), recent suicide attempt (OR = 1.88 [1.14-3.09]), higher use of tobacco (OR = 1.05 [1.02-1.09]) and misuse of painkillers (e.g., opioids; OR = 1.31 [1.06-1.62]). Participants with comorbid chronic pain and depression reported fewer functional benefits from antidepressant use and lower benefits from sertraline (OR = 0.75 [0.68-0.83]), escitalopram (OR = 0.75 [0.67-0.85]) and venlafaxine (OR = 0.78 [0.68-0.88]) when compared to participants without chronic pain. Furthermore, participants taking sertraline (OR = 0.45 [0.30-0.67]), escitalopram (OR = 0.45 [0.27-0.74]) and citalopram (OR = 0.32 [0.15-0.67]) specifically for chronic pain (among other indications) reported lower benefits compared to other participants taking these same medications but not for chronic pain. These findings reveal novel insights into the complex relationship between chronic pain and depression. Treatment response analyses indicate differential effectiveness between particular antidepressants and poorer functional outcomes for these comorbid conditions. Further examination is warranted in targeted interventional clinical trials, which also include neuroimaging genetics and pharmacogenomics protocols. This work will advance the delineation of disease risk indicators and novel aetiological pathways for therapeutic intervention in comorbid pain and depression as well as other psychiatric comorbidities.
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http://dx.doi.org/10.3389/fpsyt.2021.643609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072020PMC
April 2021

The Feasibility of Magnetic Resonance Imaging in a Non-Selective Comprehensive Clinical Trial in Pediatric Autism Spectrum Disorder.

J Autism Dev Disord 2021 Apr 26. Epub 2021 Apr 26.

Faculty of Medicine and Health, Brain and Mind Centre, Children's Hospital Westmead Clinical School, Autism Clinic for Translational Research, University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia.

There is an increasing interest in using magnetic resonance imaging (MRI) as a tool for precision medicine in autism spectrum disorder (ASD). This study investigated the feasibility of MRI scanning in a large comprehensive, inclusive and test heavy clinical trial for children (aged 3-12 years) with ASD, without functioning constraints for participation. Of the 71 participants enrolled who consented to the MRI, 24 participants (38%) successfully completed an MRI scan at baseline along with other assessments. This scanning followed a familiarization procedure at two preceding visits. At post-treatment, 21 participants successfully completed the MRI scan. This study highlights the challenge of completing MRI assessments in ASD populations when conducted as one of a number of tests in a clinical trial.
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http://dx.doi.org/10.1007/s10803-021-05028-2DOI Listing
April 2021

Evaluation of the Usability and Acceptability of the InnoWell Platform as Rated by Older Adults: Survey Study.

JMIR Aging 2021 Apr 21;4(2):e25928. Epub 2021 Apr 21.

Brain and Mind Centre, The University of Sydney, Camperdown, Australia.

Background: As the global population ages, there is increased interest in developing strategies to promote health and well-being in later life, thus enabling continued productivity, social engagement, and independence. As older adults use technologies with greater frequency, proficiency, and confidence, health information technologies (HITs) now hold considerable potential as a means to enable broader access to tools and services for the purposes of screening, treatment, monitoring, and ongoing maintenance of health for this group. The InnoWell Platform is a digital tool co-designed with lived experience to facilitate better outcomes by enabling access to a comprehensive multidimensional assessment, the results of which are provided in real time to enable consumers to make informed decisions about clinical and nonclinical care options independently or in collaboration with a health professional.

Objective: This study aims to evaluate the usability and acceptability of a prototype of the InnoWell Platform, co-designed and configured with and for older adults, using self-report surveys.

Methods: Participants were adults 50 years and older who were invited to engage with the InnoWell Platform naturalistically (ie, at their own discretion) for a period of 90 days. In addition, they completed short web-based surveys at baseline regarding their background, health, and mental well-being. After 90 days, participants were asked to complete the System Usability Scale to evaluate the usability and acceptability of the prototyped InnoWell Platform, with the aim of informing the iterative redesign and development of this digital tool before implementation within a health service setting.

Results: A total of 19 participants consented to participate in the study; however, only the data from the 16 participants (mean age 62.8 years, SD 7.5; range 50-72) who completed at least part of the survey at 90 days were included in the analyses. Participants generally reported low levels of psychological distress and good mental well-being. In relation to the InnoWell Platform, the usability scores were suboptimal. Although the InnoWell Platform was noted to be easy to use, participants had difficulty identifying the relevance of the tool for their personal circumstances. Ease of use, the comprehensive nature of the assessment tools, and the ability to track progress over time were favored features of the InnoWell Platform, whereas the need for greater personalization and improved mobile functionality were cited as areas for improvement.

Conclusions: HITs such as the InnoWell Platform have tremendous potential to improve access to cost-effective and low-intensity interventions at scale to improve and maintain mental health and well-being in later life. However, to promote adoption of and continued engagement with such tools, it is essential that these HITs are personalized and relevant for older adult end users, accounting for differences in background, clinical profiles, and levels of need.
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http://dx.doi.org/10.2196/25928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100885PMC
April 2021

Participatory Design of an Activities-Based Collective Mentoring Program in After-School Care Settings: Connect, Promote, and Protect Program.

JMIR Pediatr Parent 2021 Apr 12;4(2):e22822. Epub 2021 Apr 12.

Brain and Mind Centre, University of Sydney, Camperdown, Australia.

Background: Out of school hours care (OSHC) services provide a unique opportunity to deliver early intervention programs to enhance primary school-aged children's social, emotional, physical, and cognitive well-being; however, such programs are currently lacking.

Objective: This study aims to address the lack of well-being programs for children accessing OSHC services in the research literature by using participatory design (PD) to collaboratively develop and test an OSHC well-being program-the connect, promote, and protect program (CP3).

Methods: The study employed methods of PD, user (acceptance) testing, and iterative knowledge translation to develop a novel well-being program framework-CP3-with key stakeholders (eg, children, OSHC staff, volunteers, families, clinicians, educators, and researchers). Thematic techniques were used to interpret and translate the qualitative information obtained during the research and design cycles.

Results: The co-design process generated the CP3 model, which comprises a group-based mentoring approach to facilitate enhanced activities in OSHC settings. Activities are underpinned by 4 key principles of program delivery: build well-being and resilience, broaden horizons, inspire and engage, and connect communities.

Conclusions: To our knowledge, the CP3 program is the first co-designed well-being program developed specifically for OSHC services. This co-design process is key to ensuring local community needs-particularly those of young people accessing OSHC-are met and that these individuals are meaningfully and actively involved in all stages of the research and design process, from conception to implementation, evaluation, and continuous improvement.
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http://dx.doi.org/10.2196/22822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076982PMC
April 2021

Evaluating the quality and safety of health-related apps and e-tools: Adapting the Mobile App Rating Scale and developing a quality assurance protocol.

Internet Interv 2021 Apr 17;24:100379. Epub 2021 Mar 17.

Brain and Mind Centre, The University of Sydney. Sydney, NSW, Australia.

Background: Whilst apps and e-tools have tremendous potential as low-cost, scalable mental health intervention and prevention tools, it is essential that consumers and health professionals have a means by which to evaluate their quality and safety.

Objective: This study aimed to: 1) adapt the original Mobile App Rating Scale (MARS) in order to be appropriate for the evaluation of both mobile phone applications as well as e-tools; 2) test the reliability of the revised scale; and 3) develop a quality assurance protocol for identifying and rating new apps and e-tools to determine appropriateness for use in clinical practice.

Methods: The MARS was adapted to include items specific to health-related apps and e-tools, such as the availability of resources, strategies for self-management, and quality information. The 41 apps and e-tools in the standard youth configuration of the InnoWell Platform, a digital tool designed to support or enhance mental health service delivery, were independently rated by two expert raters using the A-MARS. Cronbach's alpha was used to calculate the internal consistency and interclass correlation coefficients were used to calculate interrater reliability.

Results: The A-MARS was shown to be a reliable scale with acceptable to excellent internal consistency and moderate to excellent interrater reliability across the subscales. Given the ever-increasing number of health information technologies on the market, a protocol to identify and rate new apps and e-tools for potential clinical use is presented.

Conclusions: Whilst the A-MARS is a useful tool to guide health professionals as they explore available apps and e-tools for potential clinical use, the training, time, and skill required to use it effectively may be prohibitive. As such, health professionals and services are likely to benefit from including a digital navigator as part of the care team to assist in selecting and rating apps and e-tools, increasing the usability of the data, and technology troubleshooting. When selecting, evaluating and/or recommending apps and e-tools to consumers, it is important to consider: 1) the availability of explicit strategies to set, monitor and review SMART goals; 2) the accessibility of credible, user friendly information and resources from reputable sources; 3) evidence of effectiveness; and 4) interoperability with other health information technologies.
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http://dx.doi.org/10.1016/j.invent.2021.100379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985461PMC
April 2021

Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders.

Genome Biol 2021 Mar 26;22(1):90. Epub 2021 Mar 26.

Centre for Clinical Research, The University of Queensland, Brisbane, QLD, 4019, Australia.

Background: People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm) provides a way to explore this overlap and heterogeneity as it is determined by the combined effects of genetic variation and the environment. In this study, we aim to identify shared blood DNAm differences between controls and people with Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease.

Results: We use a mixed-linear model method (MOMENT) that accounts for the effect of (un)known confounders, to test for the association of each DNAm site with each disorder. While only three probes are found to be genome-wide significant in each MOMENT association analysis of amyotrophic lateral sclerosis and Parkinson's disease (and none with Alzheimer's disease), a fixed-effects meta-analysis of the three disorders results in 12 genome-wide significant differentially methylated positions. Predicted immune cell-type proportions are disrupted across all neurodegenerative disorders. Protein inflammatory markers are correlated with profile sum-scores derived from disease-associated immune cell-type proportions in a healthy aging cohort. In contrast, they are not correlated with MOMENT DNAm-derived profile sum-scores, calculated using effect sizes of the 12 differentially methylated positions as weights.

Conclusions: We identify shared differentially methylated positions in whole blood between neurodegenerative disorders that point to shared pathogenic mechanisms. These shared differentially methylated positions may reflect causes or consequences of disease, but they are unlikely to reflect cell-type proportion differences.
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http://dx.doi.org/10.1186/s13059-021-02275-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004462PMC
March 2021

Using Staged Care to Provide "Right Care First Time" to People With Common Affective Disorders.

Psychiatr Serv 2021 Jun 26;72(6):691-703. Epub 2021 Mar 26.

Brain and Mind Centre, University of Sydney, Sydney, Australia (Sawrikar, Stewart, LaMonica, Iorfino, Davenport, Cross, Naismith, Mowszowski, Guastella, Hickie); School of Health in Social Science, University of Edinburgh, Edinburgh (Sawrikar); School of Medicine, University of Notre Dame Australia, Sydney (Scott).

An ongoing need exists for innovation in service delivery to ensure that mental health services deliver high-quality treatment and prevention in the population. This Special Article proposes the adoption of "staged care" as a population health-oriented service delivery model for packages of specialized services delivered largely in ambulatory care settings for individuals with common affective disorders. Staged care integrates measures of clinical need alongside clinical stage and personal choice to select hierarchically arranged service packages for individuals. Packages then vary according to the intensity, duration, and mix of treatment options. This Special Article describes five levels of care in staged care: self- or family-directed monitoring and management, low-intensity services, moderate-intensity services, high-intensity services, and acute and specialist community mental health services. The care environment, treatment team, and length of treatment are also described, and provisional criteria are specified for assigning individuals to different care levels on the basis of current clinical need and clinical stage. Staged care is presented as a model that guides treatment selection and health service delivery to ensure that the high-quality care aims of "right care first time" and prevention are achieved and optimal use of available resources is considered.
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http://dx.doi.org/10.1176/appi.ps.202000145DOI Listing
June 2021

Association between lifetime depression history, hippocampal volume and memory in non-amnestic mild cognitive impairment.

Eur J Neurosci 2021 Mar 25. Epub 2021 Mar 25.

Healthy Brain Ageing Program, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.

Hippocampal subfield volume loss in older adults with amnestic mild cognitive impairment (aMCI) and depression history are associated with amyloid beta and tau pathology, thereby increasing the risk for Alzheimer's disease (AD). However, no studies have exclusively examined distinct alterations in hippocampal subfields in non-amnestic MCI (naMCI) in relation to depression history. Here, we used both longitudinal and transverse hippocampal segmentation methods using the automated FreeSurfer software to examine whether a lifetime depression history is associated with differences in hippocampal head/body/tail (H/B/T) and key subfield volumes (CA1, subiculum, dentate gyrus) in older adults with naMCI. Further, we explored whether differences in hippocampal H/B/T and subfield volumes were associated with structured and unstructured verbal encoding and retention, comparing those with and without a depression history. The naMCI with a depression history group demonstrated larger or relatively preserved right CA1 volumes, which were associated with better unstructured verbal encoding and as well as structured verbal memory retention. This association between memory encoding and hippocampal CA1 and total head volume was significantly different to those with no depression history. The relationship between right CA1 volume and memory retention was also moderated by depression history status F (5,143) = 7.84, p < 0.001, R  = 0.22. Those participants taking antidepressants had significantly larger hippocampal subiculum (p = 0.008), and right hippocampal body (p = 0.004) and better performance on structured encoding (p = 0.011) and unstructured memory retention (p = 0.009). These findings highlight the importance of lifetime depression history and antidepressant use on the hippocampus and encoding and memory retention in naMCI.
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http://dx.doi.org/10.1111/ejn.15207DOI Listing
March 2021

Circadian depression: A mood disorder phenotype.

Neurosci Biobehav Rev 2021 07 6;126:79-101. Epub 2021 Mar 6.

Youth Mental Health and Technology Team, Brain & Mind Centre, The University of Sydney, Camperdown, Australia. Electronic address:

Major mood syndromes are among the most common and disabling mental disorders. However, a lack of clear delineation of their underlying pathophysiological mechanisms is a major barrier to prevention and optimised treatments. Dysfunction of the 24-h circadian system is a candidate mechanism that has genetic, behavioural, and neurobiological links to mood syndromes. Here, we outline evidence for a new clinical phenotype, which we have called 'circadian depression'. We propose that key clinical characteristics of circadian depression include disrupted 24-h sleep-wake cycles, reduced motor activity, low subjective energy, and weight gain. The illness course includes early age-of-onset, phenomena suggestive of bipolarity (defined by bidirectional associations between objective motor and subjective energy/mood states), poor response to conventional antidepressant medications, and concurrent cardiometabolic and inflammatory disturbances. Identifying this phenotype could be clinically valuable, as circadian-targeted strategies show promise for reducing depressive symptoms and stabilising illness course. Further investigation of underlying circadian disturbances in mood syndromes is needed to evaluate the clinical utility of this phenotype and guide the optimal use of circadian-targeted interventions.
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http://dx.doi.org/10.1016/j.neubiorev.2021.02.045DOI Listing
July 2021

Age-related parietal GABA alterations in children with autism spectrum disorder.

Autism Res 2021 05 25;14(5):859-872. Epub 2021 Feb 25.

Brain and Mind Centre, Children's Hospital Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

GABA is the primary inhibitory neurotransmitter in the brain, and is essential to the balance of cortical excitation and inhibition. Reductions in GABA are proposed to result in an overly excitatory cortex that may cause, or contribute to, symptoms of autism spectrum disorder (ASD). This study employed a cross-sectional design to explore GABA+ differences in ASD and the impact of age, comparing 4-12 year olds with ASD (N = 24) to typically developing children (N = 35). GABA+ concentration was measured using edited magnetic resonance spectroscopy in the left parietal lobe. This study used a mixed model to investigate group differences between children with ASD and typically developing children. There was a significant difference in GABA+ levels between the groups, a significant effect of age and interaction between age and diagnostic group. The ASD group showed an association between GABA+ and age, with GABA+ levels gradually increasing with age (r = 0.59, p = 0.003). Typically developing children did not show age-related change in GABA+ concentration (r = 0.09, p = 0.60). By the age of 9, children with ASD showed GABA+ levels that were comparable to their typically developing peers. This study suggests that children with ASD have initially lower levels of GABA+ in the left parietal lobe compared to typically developing children, and that these initially lower levels of GABA+ increase with age in ASD within this region. It is suggested that this developmental shift of GABA+ levels within the left parietal lobe provides a possible explanation for the previously found reductions in childhood that does not persist in adults. LAY SUMMARY: This study measured levels of GABA in the left parietal lobe using magnetic resonance spectroscopy in children with ASD and typically developing children. GABA levels were initially lower in the ASD group, and increased with age, while GABA did not change with age in the typically developing group. This suggests that alterations in GABA signaling may be associated with ASD in childhood. Autism Res 2021, 14: 859-872. © 2021 International Society for Autism Research, Wiley Periodicals LLC.
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http://dx.doi.org/10.1002/aur.2487DOI Listing
May 2021

Schizophrenia polygenic risk scores in youth mental health: preliminary associations with diagnosis, clinical stage and functioning.

BJPsych Open 2021 Feb 22;7(2):e58. Epub 2021 Feb 22.

Youth Mental Health & Technology Team, Brain and Mind Centre, University of Sydney, Australia.

Background: The schizophrenia polygenic risk score (SCZ-PRS) is an emerging tool in psychiatry.

Aims: We aimed to evaluate the utility of SCZ-PRS in a young, transdiagnostic, clinical cohort.

Method: SCZ-PRSs were calculated for young people who presented to early-intervention youth mental health clinics, including 158 patients of European ancestry, 113 of whom had longitudinal outcome data. We examined associations between SCZ-PRS and diagnosis, clinical stage and functioning at initial assessment, and new-onset psychotic disorder, clinical stage transition and functional course over time in contact with services.

Results: Compared with a control group, patients had elevated PRSs for schizophrenia, bipolar disorder and depression, but not for any non-psychiatric phenotype (for example cardiovascular disease). Higher SCZ-PRSs were elevated in participants with psychotic, bipolar, depressive, anxiety and other disorders. At initial assessment, overall SCZ-PRSs were associated with psychotic disorder (odds ratio (OR) per s.d. increase in SCZ-PRS was 1.68, 95% CI 1.08-2.59, P = 0.020), but not assignment as clinical stage 2+ (i.e. discrete, persistent or recurrent disorder) (OR = 0.90, 95% CI 0.64-1.26, P = 0.53) or functioning (R = 0.03, P = 0.76). Longitudinally, overall SCZ-PRSs were not significantly associated with new-onset psychotic disorder (OR = 0.84, 95% CI 0.34-2.03, P = 0.69), clinical stage transition (OR = 1.02, 95% CI 0.70-1.48, P = 0.92) or persistent functional impairment (OR = 0.84, 95% CI 0.52-1.38, P = 0.50).

Conclusions: In this preliminary study, SCZ-PRSs were associated with psychotic disorder at initial assessment in a young, transdiagnostic, clinical cohort accessing early-intervention services. Larger clinical studies are needed to further evaluate the clinical utility of SCZ-PRSs, especially among individuals with high SCZ-PRS burden.
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http://dx.doi.org/10.1192/bjo.2021.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058892PMC
February 2021

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 17. Epub 2021 Feb 17.

Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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http://dx.doi.org/10.1002/hbm.25364DOI Listing
February 2021

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 11. Epub 2021 Feb 11.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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http://dx.doi.org/10.1002/hbm.25320DOI Listing
February 2021

Recommendations for Designing Health Information Technologies for Mental Health Drawn From Self-Determination Theory and Co-design With Culturally Diverse Populations: Template Analysis.

J Med Internet Res 2021 02 10;23(2):e23502. Epub 2021 Feb 10.

Brain and Mind Centre, The University of Sydney, Sydney, Australia.

Background: Culturally diverse populations (including Aboriginal and Torres Strait Islander people, people of diverse genders and sexualities, and culturally and linguistically diverse people) in nonurban areas face compounded barriers to accessing mental health care. Health information technologies (HITs) show promising potential to overcome these barriers.

Objective: This study aims to identify how best to improve a mental health and well-being HIT for culturally diverse Australians in nonurban areas.

Methods: We conducted 10 co-design workshops (N=105 participants) in primary youth mental health services across predominantly nonurban areas of Australia and conducted template analysis on the workshop outputs. Owing to local (including service) demographics, the workshop participants naturalistically reflected culturally diverse groups.

Results: We identified 4 main themes: control, usability, affirmation, and health service delivery factors. The first 3 themes overlap with the 3 basic needs postulated by self-determination theory (autonomy, competence, and relatedness) and describe participant recommendations on how to design an HIT. The final theme includes barriers to adopting HITs for mental health care and how HITs can be used to support care coordination and delivery. Hence, it describes participant recommendations on how to use an HIT.

Conclusions: Although culturally diverse groups have specific concerns, their expressed needs fall broadly within the relatively universal design principles identified in this study. The findings of this study provide further support for applying self-determination theory to the design of HITs and reflect the tension in designing technologies for complex problems that overlap multiple medical, regulatory, and social domains, such as mental health care. Finally, we synthesize the identified themes into general recommendations for designing HITs for mental health and provide concrete examples of design features recommended by participants.
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http://dx.doi.org/10.2196/23502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904400PMC
February 2021
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