Publications by authors named "Philip Hazell"

123 Publications

Neural correlates of irritability in a community sample of children.

J Affect Disord 2021 Sep 5;292:223-226. Epub 2021 Jun 5.

Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; School of Psychology, Deakin University, Geelong, Australia.

Irritability has been associated with aberrant patterns of neural activation, yet little is known about structural brain correlates of irritability. As such, we aimed to investigate associations between irritability and gray matter volume (GMV) in a community sample of children enriched for irritability. The sample comprised children (n=162) aged 9-11 years with and without Attention-Deficit/Hyperactivity Disorder (ADHD), participating in a cohort study with magnetic resonance imaging data available. Mixed effects linear regression analyses tested the associations between irritability symptoms and regional GMV (extracted using Freesurfer). Irritability was associated with smaller gray matter volume across multiple brain regions implicated in executive functioning, and emotion and reward processing including frontal regions and the cingulate.
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http://dx.doi.org/10.1016/j.jad.2021.05.093DOI Listing
September 2021

Weight perception and symptoms of depression in rural Australian adolescents.

Australas Psychiatry 2021 May 16:10398562211009250. Epub 2021 May 16.

The University of Sydney Discipline of Child and Adolescent Health, Westmead, NSW, Australia.

Objective: To investigate associations between measured and perceived weight, and symptoms of depression in rural Australian adolescents.

Method: At baseline a prospective rural adolescent cohort study collected demographic data, measured weight and height, weight self-perception, and presence of depression (Short Mood and Feelings Questionnaire). Using World Health Organisation's (WHO) age and gender body mass index (BMI) standardisations, participants were classified into four perceptual groups: PG1 healthy/perceived healthy; PG2 overweight/perceived overweight; PG3 healthy/perceived overweight; and PG4 overweight/perceived healthy. Logistic regression analyses explored relationships between these groups and symptoms of depression.

Results: Data on adolescents ( = 339) aged 9-14. PG1 contained 63% of participants, PG2 18%, PG3 4% and PG4 14%. Across the cohort, 32% were overweight and 13% had symptoms of depression. PG2 (overweight/perceived overweight) were more likely to experience symptoms of depression than PG1 (healthy/perceived healthy; Adjusted Odds Ratio [AOR] 3.1, 95% CI 1.5-6.7). Females in PG3 (healthy/perceived overweight) were more likely to experience symptoms of depression (38%) than males (14%) and females in PG1 (10%, AOR 5.4, 95% CI 1.1-28.2).

Conclusions: Results suggest that perceptions of being overweight may be a greater predictor for symptoms of depression than actual weight. This has public health implications for youth mental health screening and illness prevention.
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http://dx.doi.org/10.1177/10398562211009250DOI Listing
May 2021

Weight perception and symptoms of depression in rural Australian adolescents.

Australas Psychiatry 2021 May 16:10398562211009250. Epub 2021 May 16.

The University of Sydney Discipline of Child and Adolescent Health, Westmead, NSW, Australia.

Objective: To investigate associations between measured and perceived weight, and symptoms of depression in rural Australian adolescents.

Method: At baseline a prospective rural adolescent cohort study collected demographic data, measured weight and height, weight self-perception, and presence of depression (Short Mood and Feelings Questionnaire). Using World Health Organisation's (WHO) age and gender body mass index (BMI) standardisations, participants were classified into four perceptual groups: PG1 healthy/perceived healthy; PG2 overweight/perceived overweight; PG3 healthy/perceived overweight; and PG4 overweight/perceived healthy. Logistic regression analyses explored relationships between these groups and symptoms of depression.

Results: Data on adolescents ( = 339) aged 9-14. PG1 contained 63% of participants, PG2 18%, PG3 4% and PG4 14%. Across the cohort, 32% were overweight and 13% had symptoms of depression. PG2 (overweight/perceived overweight) were more likely to experience symptoms of depression than PG1 (healthy/perceived healthy; Adjusted Odds Ratio [AOR] 3.1, 95% CI 1.5-6.7). Females in PG3 (healthy/perceived overweight) were more likely to experience symptoms of depression (38%) than males (14%) and females in PG1 (10%, AOR 5.4, 95% CI 1.1-28.2).

Conclusions: Results suggest that perceptions of being overweight may be a greater predictor for symptoms of depression than actual weight. This has public health implications for youth mental health screening and illness prevention.
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http://dx.doi.org/10.1177/10398562211009250DOI Listing
May 2021

Debate: Inpatient units must enhance the system of care.

Authors:
Philip Hazell

Child Adolesc Ment Health 2021 May 28;26(2):176-177. Epub 2021 Mar 28.

Specialty of Psychiatry, The University of Sydney School of Medicine, Concord West, NSW, Australia.

Child or adolescent psychiatric inpatient units are expensive; therefore, a lot is expected of them. Short stay units are best used for diagnostic clarification, the initiation and supervision of complex treatment, and acute containment of risk. Longer stay units provide a recovery-focused programme to address mental health problems that have not responded to intensive treatment in other settings. Both types of unit form part of the wider system of care that supports young people with mental health problems. The operational characteristics of such units will ensure timely, safe and effective interventions to young people who will likely go on to receive most of their clinical care in the community.
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http://dx.doi.org/10.1111/camh.12459DOI Listing
May 2021

Debate: Inpatient units must enhance the system of care.

Authors:
Philip Hazell

Child Adolesc Ment Health 2021 May 28;26(2):176-177. Epub 2021 Mar 28.

Specialty of Psychiatry, The University of Sydney School of Medicine, Concord West, NSW, Australia.

Child or adolescent psychiatric inpatient units are expensive; therefore, a lot is expected of them. Short stay units are best used for diagnostic clarification, the initiation and supervision of complex treatment, and acute containment of risk. Longer stay units provide a recovery-focused programme to address mental health problems that have not responded to intensive treatment in other settings. Both types of unit form part of the wider system of care that supports young people with mental health problems. The operational characteristics of such units will ensure timely, safe and effective interventions to young people who will likely go on to receive most of their clinical care in the community.
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http://dx.doi.org/10.1111/camh.12459DOI Listing
May 2021

Guideline adherence in the management of attention deficit hyperactivity disorder in children: An audit of selected medical records in three Australian states.

PLoS One 2021 8;16(2):e0245916. Epub 2021 Feb 8.

Centre for Healthcare Resilience and Implementation Science, Australian Institute of Health Innovation, Macquarie University, Sydney, New South Wales, Australia.

Objective: To assess General Practitioner (GP) and pediatrician adherence to clinical practice guidelines (CPGs) for diagnosis, treatment and management of attention deficit hyperactivity disorder (ADHD).

Method: Medical records for 306 children aged ≤15 years from 46 GP clinics and 20 pediatric practices in Australia were reviewed against 34 indicators derived from CPG recommendations. At indicator level, adherence was estimated as the percentage of indicators with 'Yes' or 'No' responses for adherence, which were scored 'Yes'. This was done separately for GPs, pediatricians and overall; and weighted to adjust for sampling processes.

Results: Adherence with guidelines was high at 83.6% (95% CI: 77.7-88.5) with pediatricians (90.1%; 95% CI: 73.0-98.1) higher than GPs (68.3%; 95% CI: 46.0-85.8; p = 0.02). Appropriate assessment for children presenting with signs or symptoms of ADHD was undertaken with 95.2% adherence (95% CI: 76.6-99.9), however ongoing reviews for children with ADHD prescribed stimulant medication was markedly lower for both pediatricians (51.1%; 95% CI: 9.6-91.4) and GPs (18.7%; 95% CI: 4.1-45.5).

Conclusion: Adherence to CPGs for ADHD by pediatricians was generally high. Adherence by GPs was lower across most domains; timely recognition of medication side effects is a particular area for improvement.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245916PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869992PMC
February 2021

A longitudinal analysis of puberty-related cortical development.

Neuroimage 2021 03 29;228:117684. Epub 2020 Dec 29.

School of Psychology, Deakin University, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia; Developmental Imaging, Murdoch Children's Research Institute, Parkville, Australia.

The brain undergoes extensive structural changes during adolescence, concurrent to puberty-related physical and hormonal changes. While animal research suggests these biological processes are related to one another, our knowledge of brain development in humans is largely based on age-related processes. Thus, the current study characterized puberty-related changes in human brain structure, by combining data from two longitudinal neuroimaging cohorts. Beyond normative changes in cortical thickness, we examined whether individual differences in the rate of pubertal maturation (or "pubertal tempo") was associated with variations in cortical trajectories. Participants (N = 192; scans = 366) completed up to three waves of MRI assessments between 8.5 and 14.5 years of age, as well as questionnaire assessments of pubertal stage at each wave. Generalized additive mixture models were used to characterize trajectories of cortical development. Results revealed widespread linear puberty-related changes across much of the cortex. Many of these changes, particularly within the frontal and parietal cortices, were independent of age-related development. Males exhibiting faster pubertal tempo demonstrated greater thinning in the precuneus and frontal cortices than same-aged and -sex peers. Findings suggest that the unique influence of puberty on cortical development may be more extensive than previously identified, and also emphasize important individual differences in the coupling of these developmental processes.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117684DOI Listing
March 2021

Investigating neural circuits of emotion regulation to distinguish euthymic patients with bipolar disorder and major depressive disorder.

Bipolar Disord 2021 05 9;23(3):284-294. Epub 2021 Jan 9.

Brain Dynamics Centre, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.

Background: Up to 40% of patients with bipolar disorder (BD) are initially diagnosed as having major depressive disorder (MDD), and emotional lability is a key aspect of both sets of mood disorders. However, it remains unknown whether differences in the regulation of emotions through cognitive reappraisal may serve to distinguish BD and MDD. Therefore, we examined this question in euthymic BD and MDD patients.

Methods: Thirty-eight euthymic BD, 33 euthymic MDD and 37 healthy control (HC) participants, matched for age, gender and depression severity, engaged in an emotion regulation (ER) cognitive reappraisal task during an fMRI scan were examined. Participants either reappraised (Think condition) or passively watched negative (Watch condition) or neutral (Neutral condition) pictures and rated their affect. Activation and connectivity analyses were used to examine group differences in reappraisal (Think vs Watch) and reactivity (Watch vs Neutral) conditions in ER-specific neural circuits.

Results: Irrespective of group, participants rated most negatively the images during the Watch condition relative to Think and Neutral conditions, and more negatively to Think relative to Neutral. Notably, BD participants exhibited reduced subgenual anterior cingulate activation (sgACC) relative to MDD during reappraisal, but exhibited greater sgACC activation relative to MDD during reactivity, whereas MDD participants elicited greater activation in right amygdala relative to BD during reactivity. We found no group differences in task-related connectivity.

Conclusions: Euthymic BD and MDD patients engage differential brain regions to process and regulate emotional information. These differences could serve to distinguish the clinical groups and provide novel insights into the underlying pathophysiology of BD.
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http://dx.doi.org/10.1111/bdi.13042DOI Listing
May 2021

The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders.

Aust N Z J Psychiatry 2021 01;55(1):7-117

Centre for Mental Health, Swinburne University of Technology, Hawthorn, VIC, Australia.

Objectives: To provide advice and guidance regarding the management of mood disorders, derived from scientific evidence and supplemented by expert clinical consensus to formulate s that maximise clinical utility.

Methods: Articles and information sourced from search engines including PubMed, EMBASE, MEDLINE, PsycINFO and Google Scholar were supplemented by literature known to the mood disorders committee (e.g. books, book chapters and government reports) and from published depression and bipolar disorder guidelines. Relevant information was appraised and discussed in detail by members of the mood disorders committee, with a view to formulating and developing consensus-based recommendations and clinical guidance. The guidelines were subjected to rigorous consultation and external review involving: expert and clinical advisors, key stakeholders, professional bodies and specialist groups with interest in mood disorders.

Results: The Royal Australian and New Zealand College of Psychiatrists mood disorders clinical practice guidelines 2020 (MDcpg) provide up-to-date guidance regarding the management of mood disorders that is informed by evidence and clinical experience. The guideline is intended for clinical use by psychiatrists, psychologists, primary care physicians and others with an interest in mental health care.

Conclusion: The MDcpg builds on the previous 2015 guidelines and maintains its joint focus on both depressive and bipolar disorders. It provides up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus.

Mood Disorders Committee: Gin S Malhi (Chair), Erica Bell, Darryl Bassett, Philip Boyce, Richard Bryant, Philip Hazell, Malcolm Hopwood, Bill Lyndon, Roger Mulder, Richard Porter, Ajeet B Singh and Greg Murray.
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http://dx.doi.org/10.1177/0004867420979353DOI Listing
January 2021

The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders: Major depression summary.

Bipolar Disord 2020 12;22(8):788-804

Centre for Mental Health, Swinburne University of Technology, Hawthorn, VIC, Australia.

Objectives: To provide a succinct, clinically useful summary of the management of major depression, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg ).

Methods: To develop the MDcpg , the mood disorders committee conducted an extensive review of the available literature to develop evidence-based recommendations (EBR) based on National Health and Medical Research Council (NHMRC) guidelines. In the MDcpg , these recommendations sit alongside consensus-based recommendations (CBR) that were derived from extensive deliberations of the mood disorders committee, drawing on their expertise and clinical experience. This guideline summary is an abridged version that focuses on major depression. In collaboration with international experts in the field, it synthesises the key recommendations made in relation to the diagnosis and management of major depression.

Results: The depression summary provides a systematic approach to diagnosis, and a logical clinical framework for management. The latter begins with Actions, which include important strategies that should be implemented from the outset. These include lifestyle changes, psychoeducation and psychological interventions. The summary advocates the use of antidepressants in the management of depression as Choices and nominates seven medications that can be trialled as clinically indicated before moving to Alternatives for managing depression. Subsequent strategies regarding Medication include Increasing Dose, Augmenting and Switching (MIDAS). The summary also recommends the use of electroconvulsive therapy (ECT), and discusses how to approach non-response.

Conclusions: The major depression summary provides up to date guidance regarding the management of major depressive disorder, as set out in the MDcpg . The recommendations are informed by research evidence in conjunction with clinical expertise and experience. The summary is intended for use by psychiatrists, psychologists and primary care physicians, but will be of interest to all clinicians and carers involved in the management of patients with depressive disorders.
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http://dx.doi.org/10.1111/bdi.13035DOI Listing
December 2020

The 2020 Royal Australian and New Zealand College of psychiatrists clinical practice guidelines for mood disorders: Bipolar disorder summary.

Bipolar Disord 2020 12;22(8):805-821

Centre for Mental Health, Swinburne University of Technology, Hawthorn, VIC, Australia.

Objectives: To provide a succinct, clinically useful summary of the management of bipolar disorder, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg ).

Methods: To develop the MDcpg , the mood disorders committee conducted an extensive review of the available literature to develop evidence-based recommendations (EBR) based on National Health and Medical Research Council (NHMRC) guidelines. In the MDcpg , these recommendations sit alongside consensus-based recommendations (CBR) that were derived from extensive deliberations of the mood disorders committee, drawing on their expertise and clinical experience. This guideline summary is an abridged version that focuses on bipolar disorder. In collaboration with international experts in the field, it synthesises the key recommendations made in relation to the diagnosis and management of bipolar disorder.

Results: The bipolar disorder summary provides a systematic approach to diagnosis, and a logical clinical framework for management. It addresses the acute phases of bipolar disorder (mania, depression and mixed states) and its longer-term management (maintenance and prophylaxis). For each phase it begins with Actions, which include important strategies that should be implemented from the outset wherever possible. These include for example, lifestyle changes, psychoeducation and psychological interventions. In each phase, the summary advocates the use of Choice medications for pharmacotherapy, which are then used in combinations along with additional Alternatives to manage acute symptoms or maintain mood stability and provide prophylaxis. The summary also recommends the use of electroconvulsive therapy (ECT) for each of the acute phases but not for maintenance therapy. Finally, it briefly considers bipolar disorder in children and its overlap in adults with borderline personality disorder.

Conclusions: The bipolar disorder summary provides up to date guidance regarding the management of bipolar disorder, as set out in the MDcpg . The recommendations are informed by evidence and clinical expertise and experience. The summary is intended for use by psychiatrists, psychologists and primary care physicians but will be of interest to anyone involved in the management of patients with bipolar disorder.
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http://dx.doi.org/10.1111/bdi.13036DOI Listing
December 2020

Associations Between Limbic System White Matter Structure and Socio-Emotional Functioning in Children with ADHD + ASD.

J Autism Dev Disord 2021 Aug;51(8):2663-2672

School of Psychology, Deakin University, Geelong, VIC, Australia.

Children with attention deficit/hyperactivity disorder (ADHD) combined with autism spectrum disorder (ASD) symptoms (ADHD + ASD) have poorer social and emotional functioning than those with ADHD alone. However, no studies have specifically examined the associations between ASD symptoms, measures of social and emotional functioning and limbic system white matter microstructure. Tractography on the cingulum, uncinate fasciculus and fornix were performed for 151 children with (N = 78) and without (N = 73) ADHD. Participants in the ADHD group who scored 11 or above on the Social Communication Questionnaire were classified as the ADHD + ASD group (N = 16). Significant differences in mean cingulum FA were present between the control group and the ADHD (all) group, however, no significant differences were seen between the ADHD and ADHD + ASD groups. Despite this, significant associations were seen between mean FA of the left cingulum and emotional problems for the ADHD + ASD group. Results give greater insights into the specific biological basis of emotional problems in the ADHD + ASD group, indicating that the cingulum may play a role.
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http://dx.doi.org/10.1007/s10803-020-04738-3DOI Listing
August 2021

ADHD at Age 7 and Functional Impairments at Age 10.

Pediatrics 2020 11 6;146(5). Epub 2020 Oct 6.

Murdoch Children's Research Institute, Parkville, Victoria, Australia.

Background And Objectives: Attention-deficit/hyperactivity disorder (ADHD) cohort studies have typically involved clinical samples and have usually recruited children across wide age ranges, limiting generalizability across complexity and developmental stage. We compared academic, emotional-behavioral and social functioning at age 10, and predictors of outcomes, in a nonreferred cohort of children recruited at age 7, between those with full-syndrome (FS) ADHD and controls with no ADHD.

Methods: This was a prospective cohort study with a 3-year follow-up period. Children were recruited from 43 socioeconomically diverse schools in Melbourne, Australia. Multi-informant outcomes at age 10 were academic functioning (Wide Range Achievement Test 4; Social Skills Improvement System), emotional-behavioral functioning (Strengths and Difficulties Questionnaire total), and social functioning (Strengths and Difficulties Questionnaire peer problems). Outcomes were compared across the groups by using adjusted random-effects linear regression analyses.

Results: In total, 477 children (62% male) were recruited at a mean (SD) age of 7.3 years (0.4). There were 179 participants with FS ADHD, 86 with ST ADHD, and 212 controls. Sample retention was 78.2% at 3-year follow-up. Both the FS and ST groups were functioning worse than controls on almost all outcome measures. The best predictors of outcome for children with ADHD were working memory (academic outcome, < .001), ADHD symptom severity (emotional-behavioral outcome, parent: < .001; teacher: < .01), and autism spectrum disorder symptoms (emotional-behavioral outcome, parent = .003; social outcome, parent = .001).

Conclusions: Children with FS and ST ADHD at age 7 experience persisting functional impairments across domains at age 10. The predictors identified at age 7 present potential targets for intervention to ameliorate impairments.
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http://dx.doi.org/10.1542/peds.2020-1061DOI Listing
November 2020

Persistence of disruptive mood dysregulation disorder in children with attention-deficit/hyperactivity disorder.

J Affect Disord 2021 01 28;278:502-505. Epub 2020 Sep 28.

Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; School of Psychology, Deakin University, Geelong, Australia.

Disruptive mood dysregulation disorder (DMDD) is common in children with ADHD yet it is not known how persistent DMDD is in this population. As such we aimed to investigate the persistence of disruptive mood dysregulation disorder (DMDD) in a community sample of children with ADHD. The sample comprised children (n = 136) participating in a cohort study with data available at age 7 and age 10. DMDD status was ascertained using proxy items from the Diagnostic Interview Schedule for Children, Version IV. Of those with DMDD at age 7 (n = 30), eight (21.1%) had DMDD that persisted at age 10. In the first study investigating the longitudinal course of DMDD in ADHD one in five children with ADHD+DMDD at age 7 continued to meet diagnostic criteria for DMDD three years later.
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http://dx.doi.org/10.1016/j.jad.2020.09.109DOI Listing
January 2021

Mindful Parenting Behaviors and Emotional Self-Regulation in Children With ADHD and Controls.

J Pediatr Psychol 2020 10;45(9):1074-1083

School of Psychology, Deakin University.

Objective: Mindfulness is defined as paying attention in a particular way: on purpose, in the present moment, and nonjudgmentally and these behaviors can be applied to parenting. Thus far, it is not understood whether mindful parenting (MP) differs in parents of children with and without attention-deficit/hyperactivity disorder (ADHD), and how MP relates to other parenting practices and children's self-regulation.

Methods: This study examined the relationships between MP, parenting behaviors and children's self-regulation in 120 families with child ADHD (85% male; mean age = 11.93) and 105 control families (62% male; mean age = 11.98). Parents completed measures of MP (Interpersonal Mindfulness in Parenting Scale), parenting behaviors (parenting warmth, consistency, and anger assessed with the Longitudinal Study of Australian Children measures), psychological distress (Kessler 6), and children's self-regulation (Social Skills Improvement System-self-control subscale).

Results: When compared with controls, parents of children with ADHD reported significantly lower MP. Higher MP was associated with lower levels of parent psychological distress, higher levels of parenting warmth and consistency, lower levels of parenting anger, and higher child emotion self-regulation in both groups. In mediation analyses, MP was indirectly associated with child emotion self-regulation through lower parenting anger, with the model accounting for 55% of the variance in child self-regulation.

Conclusions: MP is a useful construct for understanding parent behaviors, and children's emotion self-regulation.
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http://dx.doi.org/10.1093/jpepsy/jsaa073DOI Listing
October 2020

Longitudinal Trajectories of Sustained Attention Development in Children and Adolescents with ADHD.

J Abnorm Child Psychol 2020 12;48(12):1529-1542

Department of Paediatrics, The University of Melbourne, Melbourne, Australia.

The present study characterizes changes in sustained attention ability over ages 9-14, and whether longitudinal trajectories of attention development differ between persistent ADHD, remitted ADHD and control groups. The Sustained Attention to Response Task (SART) was administered to 120 children with ADHD and 123 controls on three occasions between ages 9 and 14. Trajectories of sustained attention development, indicated by changes in SART performance (standard deviation of response time [SDRT], omission errors, and ex-Gaussian parameters sigma and tau), were examined using generalized additive mixed models. For all measures there was a significant main effect of age; response time variability and number of omission errors improved linearly as children aged. However, children with ADHD had significantly greater SDRT, tau and omission errors than controls across waves. There were no significant group differences in sigma, indicating that the greater overall response time variability (SDRT) observed in ADHD was likely driven by more intermittent long responses (larger tau). Trajectories of sustained attention performance did not differ between children with persistent ADHD or ADHD in remission. Longitudinal trajectories of sustained attention development are comparable between ADHD and controls, however children with ADHD (regardless of remission status) display a performance deficit equivalent to typical controls 1-3 years younger. Findings highlight the need for continued clinical support for children in remission from ADHD and provide support for tau as an endophenotype of ADHD.
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http://dx.doi.org/10.1007/s10802-020-00698-5DOI Listing
December 2020

Video Consultation Consumer Home-based Assessment Tool (VC-CHAT).

Aust N Z J Psychiatry 2020 12 22;54(12):1229-1231. Epub 2020 Jul 22.

Discipline of Psychiatry, The University of Sydney School of Medicine, Sydney, NSW, Australia.

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http://dx.doi.org/10.1177/0004867420941595DOI Listing
December 2020

Neurophysiological markers of attention distinguish bipolar disorder and unipolar depression.

J Affect Disord 2020 09 21;274:411-419. Epub 2020 May 21.

Brain Dynamics Centre, Westmead Institute for Medical Research, The University of Sydney, Westmead, Sydney, Australia; Discipline of Psychiatry, Sydney Medical School, The University of Sydney, Sydney, Australia. Electronic address:

Background: Attentional deficits are common in both symptomatic and symptom-remitted patients with bipolar disorder (BP) and major depressive disorder (MDD). However, whether the level of neurocognitive impairment in attentional processing is different between these two disorders, or not, is still unclear. Thus, we investigated the P300 event-related potential component as a biomarker of cognitive dysfunction to differentiate BP and MDD.

Methods: Twenty-three age and gender matched BP, 20 MDD and 23 healthy controls (HC) were part of a discovery cohort to identify neurophysiological differences between groups and build a classification model of these disorders. The replication of this model was then tested in an independent second cohort of 17 BP, 19 MDD and 19 HC. All participants were symptom-remitted for at least two weeks. We compared neural responses to target stimuli during an auditory oddball task, computing peak amplitude and latency of the P300 component extracted from the midline centro-parietal electrode.

Results: BP had significantly smaller P300 amplitudes compared to both MDD and HC, whereas there were no differences between MDD and HC. The differences between groups were replicated in the second cohort, however the accuracy level of the classification model was only 53.5%.

Limitations: Small sample sizes may have led to low accuracy levels of the classification model.

Conclusion: Specific neural mechanisms of attention and context updating seem not to recover with symptom remission in BP. These findings contribute to the detection of a potential electrophysiological marker for BP, which may allow its differentiation from unipolar major depressive disorder.
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http://dx.doi.org/10.1016/j.jad.2020.05.048DOI Listing
September 2020

Lithium should be borne in mind: Five key reasons.

Aust N Z J Psychiatry 2020 07;54(7):659-663

Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia.

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http://dx.doi.org/10.1177/0004867420934189DOI Listing
July 2020

Make lithium great again!

Bipolar Disord 2020 06;22(4):325-327

Emeritus Professor Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

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http://dx.doi.org/10.1111/bdi.12942DOI Listing
June 2020

Serial measurement of mood via text messaging in young people.

Child Adolesc Psychiatry Ment Health 2020 29;14. Epub 2020 Jan 29.

1University of Sydney School of Medicine, Sydney, Australia.

Background: To support longitudinal research into mood in adolescents we sought to assess the feasibility of collecting mood data via Short Message Service (SMS) over 3 years, and to investigate the relationship between SMS data and self-report measures of depression.

Methods: Prospective cohort study of young people aged 9 to 14 years at baseline. Participants completed Short Mood and Feelings Questionnaire (SMFQ) and the Youth Self Report Anxious/Depressed ((YSR)/AD) and Withdrawn/Depressed (YSR/WD) scales at baseline and annually for 3 years. In addition, at 3 monthly intervals they responded to an SMS asking them to rate their mood from 0 to 9 (9 highest).

Results: 277 young people (43% female) completed all four waves of the survey. There was a 87% response rate to requests for SMS Mood ratings. Mean SMS Mood decreased over time for females (p = 0.006) but not males (p = 0.45). We found an inverse association between SMS Mood and the SMFQ, YSR/AD and YSR/WD, scales in females and the SMFQ and YSR/WD scales in males. 45% of participants reported at least one SMS Mood rating score below 5, while 5% reported clusters of low SMS scores. Clusters of low SMS Mood scores were associated with SMFQ scores in the clinical range at 24 (OR = 4.45) and 36 months (OR = 4.72), and YSR/WD in the clinical range at 36 months (OR = 4.61).

Conclusions: SMS Mood ratings represent a feasible means to augment but not replace assessment of mood obtained using standard instruments.
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http://dx.doi.org/10.1186/s13034-020-0313-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988358PMC
January 2020

The Association Between Autism Symptoms and Child Functioning in a Sample With ADHD Recruited From the Community.

J Atten Disord 2021 06 11;25(8):1129-1134. Epub 2019 Nov 11.

Deakin University, Melbourne, Victoria, Australia.

Although autism spectrum disorder (ASD) symptoms are associated with poorer functioning in children with attention-deficit/hyperactivity disorder (ADHD), it is unclear which ASD symptom domains are most impairing. This study investigated whether specific ASD symptom domains were associated with child functioning in children with ADHD. Parents of 164 children with ADHD completed a diagnostic interview to assess ADHD and comorbidities. Parents reported on ASD symptoms (Social Communication Questionnaire) and child quality of life (Pediatric Quality of Life Inventory 4.0). Parents and teachers completed the Strengths and Difficulties Questionnaire (emotional, conduct, and peer problems). Repetitive and stereotyped behaviors were independently associated with emotional ( = .02) and conduct ( = .03) problems, and poorer quality of life ( = .004). Reciprocal social interaction deficits were independently associated with peer problems ( = .03). Reciprocal social interaction deficits and repetitive and stereotyped behaviors are important areas that should be focused on in ADHD assessment and treatment.
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http://dx.doi.org/10.1177/1087054719886352DOI Listing
June 2021

Effect of Fluoxetine on Obsessive-Compulsive Behaviors in Children and Adolescents With Autism Spectrum Disorders: A Randomized Clinical Trial.

JAMA 2019 10;322(16):1561-1569

University of Sydney School of Medicine, Sydney, New South Wales, Australia.

Importance: Selective serotonin receptor inhibitors are prescribed to reduce the severity of core behaviors of autism spectrum disorders, but their efficacy remains uncertain.

Objective: To determine the efficacy of fluoxetine for reducing the frequency and severity of obsessive-compulsive behaviors in autism spectrum disorders.

Design, Setting, And Participants: Multicenter, randomized, placebo-controlled clinical trial. Participants aged 7.5-18 years with autism spectrum disorders and a total score of 6 or higher on the Children's Yale-Brown Obsessive Compulsive Scale, modified for pervasive developmental disorder (CYBOCS-PDD) were recruited from 3 tertiary health centers across Australia. Enrollment began November 2010 and ended April 2017. Follow-up ended August 2017.

Interventions: Participants were randomized to receive fluoxetine (n = 75) or placebo (n = 71). Study medication was commenced at 4 or 8 mg/d for the first week, depending on weight, and then titrated to a maximum dose of 20 or 30 mg/d over 4 weeks. Treatment duration was 16 weeks.

Main Outcomes And Measures: The primary outcome was the total score on the CYBOCS-PDD (scores range from 0-20; higher scores indicate higher levels of maladaptive behaviors; minimal clinically important difference, 2 points) at 16 weeks postrandomization, analyzed with a linear regression model adjusted for stratification factors (site, age at baseline, and intellectual disability), with an additional prespecified model that included additional adjustment for baseline score, sex, communication level, and imbalanced baseline and demographic variables.

Results: Among the 146 participants who were randomized (85% males; mean age, 11.2 years), 109 completed the trial; 31 in the fluoxetine group and 21 in the placebo group dropped out or did not complete treatment. The mean CYBOCS-PDD score from baseline to 16 weeks decreased in the fluoxetine group from 12.80 to 9.02 points (3.72-point decrease; 95% CI, -4.85 to -2.60) and in the placebo group from 13.13 to 10.89 points (2.53-point decrease; 95% CI, -3.86 to -1.19). The between-group mean difference at 16 weeks was -2.01 (95% CI, -3.77 to -0.25; P = .03) (adjusted for stratification factors), and in the prespecified model with further adjustment, it was -1.17 (95% CI, -3.01 to 0.67; P = .21).

Conclusions And Relevance: In this preliminary study of children and adolescents with autism spectrum disorders, treatment with fluoxetine compared with placebo resulted in significantly lower scores for obsessive-compulsive behaviors at 16 weeks. Interpretation is limited by the high dropout rate, null findings of prespecified analyses that accounted for potentially confounding factors and baseline imbalances, and CIs for the treatment effect that included the minimal clinically important difference.

Trial Registration: anzctr.org.au Identifier: ACTRN12608000173392.
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http://dx.doi.org/10.1001/jama.2019.14685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806436PMC
October 2019

Investigating the neural basis of cognitive control dysfunction in mood disorders.

Bipolar Disord 2020 05 22;22(3):286-295. Epub 2019 Oct 22.

Brain Dynamics Centre, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, Australia.

Objectives: Dysfunction of cognitive control is a feature of both bipolar disorder (BP) and major depression (MDD) and persists through to remission. However, it is unknown whether these disorders are characterized by common or distinct disruptions of cognitive control function and its neural basis. We investigated this gap in knowledge in asymptomatic BP and MDD participants, interpreted within a framework of normative function.

Methods: Participants underwent fMRI scans engaging cognitive control through a working memory task and completed a cognitive battery evaluating performance across multiple subdomains of cognitive control, including attention, impulsivity, processing speed, executive function, and memory. Analysis was performed in two stages: (i) cognitive control-related brain activation and deactivation were correlated with cognitive control performance in 115 healthy controls (HCs), then, (ii) significantly correlated regions from (i) were compared between 25 asymptomatic BP, 25 remitted MDD, and with 25 different HCs, matched for age and gender.

Results: Impulsivity and executive function performance were significantly worse in BP compared to both MDD and HCs. Both BP and MDD had significantly poorer memory performance compared to HCs. Greater deactivation of the medial prefrontal cortex (MPFC) during the fMRI task was associated with better executive function in healthy controls. Significantly less deactivation in this region was present in both BP and MDD compared to HCs.

Conclusions: Failure to deactivate the MPFC, a key region of the default mode network, during working memory processing is a shared neural feature present in both bipolar and major depression and could be a source of common cognitive dysfunction.
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http://dx.doi.org/10.1111/bdi.12844DOI Listing
May 2020

Investigating the neural basis of cognitive control dysfunction in mood disorders.

Bipolar Disord 2020 05 22;22(3):286-295. Epub 2019 Oct 22.

Brain Dynamics Centre, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, Australia.

Objectives: Dysfunction of cognitive control is a feature of both bipolar disorder (BP) and major depression (MDD) and persists through to remission. However, it is unknown whether these disorders are characterized by common or distinct disruptions of cognitive control function and its neural basis. We investigated this gap in knowledge in asymptomatic BP and MDD participants, interpreted within a framework of normative function.

Methods: Participants underwent fMRI scans engaging cognitive control through a working memory task and completed a cognitive battery evaluating performance across multiple subdomains of cognitive control, including attention, impulsivity, processing speed, executive function, and memory. Analysis was performed in two stages: (i) cognitive control-related brain activation and deactivation were correlated with cognitive control performance in 115 healthy controls (HCs), then, (ii) significantly correlated regions from (i) were compared between 25 asymptomatic BP, 25 remitted MDD, and with 25 different HCs, matched for age and gender.

Results: Impulsivity and executive function performance were significantly worse in BP compared to both MDD and HCs. Both BP and MDD had significantly poorer memory performance compared to HCs. Greater deactivation of the medial prefrontal cortex (MPFC) during the fMRI task was associated with better executive function in healthy controls. Significantly less deactivation in this region was present in both BP and MDD compared to HCs.

Conclusions: Failure to deactivate the MPFC, a key region of the default mode network, during working memory processing is a shared neural feature present in both bipolar and major depression and could be a source of common cognitive dysfunction.
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http://dx.doi.org/10.1111/bdi.12844DOI Listing
May 2020

Indications for psychiatric hospitalization of children and adolescents.

Aust N Z J Psychiatry 2019 08 15;53(8):729-731. Epub 2019 Mar 15.

3 Discipline of Psychiatry, Sydney Medical School, The University of Sydney, Concord West, NSW, Australia.

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http://dx.doi.org/10.1177/0004867419835930DOI Listing
August 2019

Debate: That which we call a rose.

Authors:
Philip Hazell

Child Adolesc Ment Health 2019 Feb 10;24(1):97-98. Epub 2019 Jan 10.

Thomas Walker Hospital, University of Sydney School of Medicine, Concord West, NSW, Australia.

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http://dx.doi.org/10.1111/camh.12317DOI Listing
February 2019

A network analysis approach to ADHD symptoms: More than the sum of its parts.

PLoS One 2019 18;14(1):e0211053. Epub 2019 Jan 18.

School of Psychology, Deakin University, Geelong, Australia.

In interpreting attention-deficit/hyperactivity disorder (ADHD) symptoms, categorical and dimensional approaches are commonly used. Both employ binary symptom counts which give equal weighting, with little attention to the combinations and relative contributions of individual symptoms. Alternatively, symptoms can be viewed as an interacting network, revealing the complex relationship between symptoms. Using a novel network modelling approach, this study explores the relationships between the 18 symptoms in the Diagnostic Statistical Manual (DSM-5) criteria and whether network measures are useful in predicting outcomes. Participants were from a community cohort, the Children's Attention Project. DSM ADHD symptoms were recorded in a face-to-face structured parent interview for 146 medication naïve children with ADHD and 209 controls (aged 6-8 years). Analyses indicated that not all symptoms are equal. Frequencies of endorsement and configurations of symptoms varied, with certain symptoms playing a more important role within the ADHD symptom network. In total, 116,220 combinations of symptoms within a diagnosis of ADHD were identified, with 92% demonstrating a unique symptom configuration. Symptom association networks highlighted the relative importance of hyperactive/impulsive symptoms in the symptom network. In particular, the 'motoric'-type symptoms as well as interrupts as a marker of impulsivity in the hyperactive domain, as well as loses things and does not follow instructions in the inattentive domain, had high measures of centrality. Centrality-measure weighted symptom counts showed significant association with clinical but not cognitive outcomes, however the relationships were not significantly stronger than symptom count alone. The finding may help to explain heterogeneity in the ADHD phenotype.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211053PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338383PMC
October 2019

Prevalence and Predictors of Medication Use in Children with Attention-Deficit/Hyperactivity Disorder: Evidence from a Community-Based Longitudinal Study.

J Child Adolesc Psychopharmacol 2019 02 1;29(1):50-57. Epub 2018 Dec 1.

3 Department of Health Services, Murdoch Children's Research Institute, Parkville, Australia.

Objectives: To determine, in a community-based sample of primary school-aged children meeting diagnostic criteria for attention-deficit/hyperactivity disorder (ADHD), (1) the proportion of children with ADHD treated with medication; (2) predictors of medication use; and (3) the association between medication use and psychological service utilization.

Methods: Grade 1 children with ADHD were recruited through 43 schools in Melbourne, Australia, using a two-stage screening and case confirmation procedure. Parent report of medication treatment, clinician diagnosis, and psychological service use were collected at ages 7 and 10 years. Medication use was analyzed by ADHD subtype. Predictors of medication treatment examined included ADHD symptom severity and persistence, externalizing comorbidities, poor academic performance, and social disadvantage. Unadjusted and adjusted logistic regression were used to identify the predictors of medication status.

Results: One hundred seventy-nine children with ADHD were recruited. At baseline, 17.3% had been clinically diagnosed with ADHD, increasing to 37.7% at age 10 years. At baseline, 13.6% were taking ADHD medications, increasing to 25.6% at age 10. Children with the combined and hyperactive-impulsive subtypes were more likely to be taking medication than those with inattentive subtype (age 7: p = 0.002; age 10: p = 0.03). ADHD symptom severity (Conners 3 ADHD Index) at baseline was concurrently and prospectively associated with medication use at both ages (both p = 0.01), and ADHD symptom severity at age 10 was also associated with medication use at age 10 (p = 0.01). Baseline area-level disadvantage was associated with medication use at age 7 (p = 0.04). At 10 years, children receiving medication were more likely, compared with those who were not, to be receiving psychological services (p = 0.001).

Conclusions: In this study, only a minority of children meeting diagnostic criteria for ADHD were diagnosed clinically or treated with ADHD medication by age 10. The strongest predictors of medication treatment were ADHD symptom severity and area disadvantage.
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http://dx.doi.org/10.1089/cap.2018.0095DOI Listing
February 2019

Amygdala Activation and Connectivity to Emotional Processing Distinguishes Asymptomatic Patients With Bipolar Disorders and Unipolar Depression.

Biol Psychiatry Cogn Neurosci Neuroimaging 2019 04 31;4(4):361-370. Epub 2018 Aug 31.

Discipline of Psychiatry, University of Sydney School of Medicine, New South Wales, Australia; Clinical Assessment Diagnostic Evaluation (CADE) Clinic, Department of Psychiatry, Royal North Shore Hospital, Sydney, New South Wales, Australia.

Background: Mechanistically based neural markers, such as amygdala reactivity, offer one approach to addressing the challenges of differentiating bipolar and unipolar depressive disorders independently from mood state and acute symptoms. Although emotion-elicited amygdala reactivity has been found to distinguish patients with bipolar depression from patients with unipolar depression, it remains unknown whether this distinction is traitlike and present in the absence of an acutely depressed mood. We addressed this gap by investigating patients with bipolar disorder (BP) and unipolar major depressive disorder (MDD) in remission.

Methods: Supraliminal and subliminal processing of faces exhibiting threat, sad, happy, and neutral emotions during functional magnetic resonance imaging was completed by 73 participants (23 BP patients and 25 MDD patients matched for age and gender, number of depressive episodes and severity; 25 age- and gender-matched healthy control subjects). We compared groups for activation and connectivity for the amygdala.

Results: BP patients had lower left amygdala activation than MDD patients during supraliminal and subliminal threat, sad, and neutral emotion processing and for subliminal happy faces. BP patients also exhibited lower amygdala connectivity to the insula and hippocampus for threat and to medial orbitofrontal cortex for happy supraliminal and subliminal processing. BP patients also demonstrated greater amygdala-insula connectivity for sad supraliminal and subliminal face processing. Both patient groups were distinct from control subjects across several measures for activation and connectivity.

Conclusions: Independent of valence or level of emotional awareness, amygdala activation and connectivity during facial emotion processing can distinguish BP patients and MDD patients. These findings provide evidence that this neural substrate could be a potential trait marker to differentiate these two disorders largely independent of illness state.
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http://dx.doi.org/10.1016/j.bpsc.2018.08.012DOI Listing
April 2019