OBJECTIVES Lurasidone is a new second generation (atypical) antipsychotic agent with unique recep... more OBJECTIVES Lurasidone is a new second generation (atypical) antipsychotic agent with unique receptor affinity and side-effect profiles, but limited literature is available on its use in adolescent populations. Contrasting with research treatment trials which typically recruit patients by stringent selection criteria, this case series examined the effects and tolerability of using lurasidone in adolescents within real-life clinical settings in treating complex cases who had not responded to other therapy options. METHODS We conducted a retrospective case-note audit of 6 adolescents aged 14 to 17 years old attending community child and adolescent mental health services (CAMHS) who were prescribed lurasidone. RESULTS Lurasidone had been prescribed for a range of "hard-to-manage" conditions with complex comorbidities, in adolescents in relation to specific use of lurasidone on the basis of clinical and pharmacological indications after exhausting more conventional treatment op...
Research suggests an overrepresentation of autism spectrum diagnoses (ASD) or autistic traits in ... more Research suggests an overrepresentation of autism spectrum diagnoses (ASD) or autistic traits in gender diverse samples, particularly in children and adolescents. Using data from the GENTLE (GENder identiTy Longitudinal Experience) Cohort at the Gender Diversity Service at the Perth Children’s Hospital, the primary objective of the current retrospective chart review was to explore psychopathology and quality of life in gender diverse children with co-occurring ASD relative to gender diverse children and adolescents without ASD. The Social Responsiveness Scale (Second Edition) generates a Diagnostic and Statistical Manual of Mental Disorders (DSM-5) score indicating a likely clinical ASD diagnosis, which was used to partition participants into two groups (indicated ASD, n = 19) (no ASD indicated, n = 60). Indicated ASD was far higher than would be expected compared to general population estimates. Indicated ASD on the Social Responsiveness Scale 2 (SRS 2) was also a significant predi...
Selective serotonin reuptake inhibitors (SSRIs) are amongst the most prescribed antidepressants f... more Selective serotonin reuptake inhibitors (SSRIs) are amongst the most prescribed antidepressants for adolescents with depressive symptoms and major depressive disorder. However, SSRIs have significant shortcomings as a first-line treatment considering that not all patients respond to these antidepressants. Amongst paediatric populations, meta-analyses indicate that up to approximately 40% of patients do not respond, and for those who do show benefit, there is substantial heterogeneity in response onset. The neurotransmitter serotonin (5-HT) plays a role in the clinical effectiveness and mechanisms of action of SSRIs. However, the exact and complete mechanism of action and reasons for the low response rate to SSRIs in some adolescent populations remains unknown. To examine SSRI response and the role of 5-HT, this study will employ a randomised double-blind within subject, repeated measures design, recruiting adolescent patients with major depressive disorder. Participants will be subj...
The ability to maintain attention to simple tasks (i.e., vigilant attention, VA) is often impaire... more The ability to maintain attention to simple tasks (i.e., vigilant attention, VA) is often impaired in attention-deficit/hyperactivity disorder (ADHD), but the underlying pathophysiological mechanisms at the brain network level are not clear yet. We therefore investigated ADHD-related differences in resting-state functional connectivity within a meta-analytically defined brain network of 14 distinct regions subserving VA (comprising 91 connections in total), as well as the association of connectivity with markers of behavioural dysfunction in 17 children (age range: 9-14 years) with a diagnosis of ADHD and 21 age-matched neurotypical controls. Our analyses revealed selective, rather than global, differences in the intrinsic coupling between nodes of the VA-related brain network in children with ADHD, relative to controls. In particular, ADHD patients showed substantially diminished intrinsic coupling for 7 connections and increased coupling for 4 connections, with many differences in...
The first line of pharmacological treatment for severe depressive disorders in young people is se... more The first line of pharmacological treatment for severe depressive disorders in young people is selective serotonin reuptake inhibitors (SSRIs). However, beneficial clinical effects are rarely observed before several weeks into treatment. Nitrous oxide (N2O) has a long-standing safety record for pain relief and has been used in adults and young people. In adults with severe treatment-resistant depression, a single dose of N2O had significant antidepressant effects, with maximum antidepressant effects observed 24 h after administration. However, the antidepressant effects of N2O have never been investigated in adolescents with a confirmed diagnosis of depression in a prospective trial. The aims of this study are to (1) investigate whether a single inhaled N2O administration leads to antidepressant effects in adolescents with depression at 24 h, (2) determine whether combined N2O and SSRI administration (commenced after N2O intervention) provides a clinically significant improvement in...
Research has implicated that changes in zinc (Zn) metabolism may be associated with the biologica... more Research has implicated that changes in zinc (Zn) metabolism may be associated with the biological underpinnings of eating disorders, in particular anorexia nervosa. However, to date research on the role of Zn in patients with bulimia nervosa (BN) is scarce. We aimed to explore serum Zn concentrations in young patients with BN, with a focus on the stage of the disorder, comparing acutely ill and recovered patients with BN with healthy controls. Serum Zn concentrations were obtained from healthy controls and from acutely ill and remitted young patients with BN. Mean duration of remission was 4.0±3.5 years. Remitted patients showed elevated serum Zn concentrations when compared to controls (Cohen's d=2.022), but concentrations were still in the normal range. Acutely ill patients also had higher serum Zn levels when compared to controls (all values still being within the reference range, Cohen's d=0.882). There was no difference between acutely ill and remitted patients with BN...
The lancet. Diabetes & endocrinology, Jan 22, 2017
The World Professional Association for Transgender Health's standards of care recommend suspe... more The World Professional Association for Transgender Health's standards of care recommend suspending puberty, preferably with the use of gonadotropin-releasing hormone agonists, in certain gender non-conforming minors (aged under 18 years) who have undergone a psychiatric assessment and have reached at least Tanner stage II of puberty. This approach seeks to lessen the discordance between assigned natal sex and gender identity by temporarily halting the development of secondary sexual characteristics, essentially widening the temporal window for gender clarification. Despite promising preliminary evidence on the clinical utility of this approach, there is a dearth of research to inform evidence-based practice. In view of these challenges, we review the available empirical evidence on the cognitive, physical, and surgical implications of puberty suppression in gender-incongruent children and adolescents. We also explore the historical underpinnings and clinical impetus for suspendi...
Concentrations of different adipokines in human breast milk are thought to be able to affect ener... more Concentrations of different adipokines in human breast milk are thought to be able to affect energy intake of the infant. Leptin is a hormone synthesized by adipose tissue and the human placenta and favors satiety. The availability of leptin in breast milk is influenced by epithelial cells of the mammary gland that are known to be able to produce leptin, as well as leptin from maternal circulation that is transported to the breast milk, and which can thus in turn reach neonatal blood after absorption. Research so far as mainly focused on leptin concentrations in breast milk. However, evidence suggests that in addition to leptin concentrations levels of the so-called soluble leptin receptor (sOb-R), the main high-affinity binding protein for leptin in humans, are necessary in order to calculate the free leptin index (FLI) and to assess function of the leptin axis. FLI is calculated from the ratio of leptin to the sOb-R, and serves as the main parameter for assessing function of the leptin axis throughout maturation and development. Here we propose that assessing sOb-R levels in addition to leptin concentrations in breast milk could serve as a valuable tool to investigate effects of the leptin axis in breast milk because sOb-R concentrations can impact available leptin levels, and which in turn can have significant implications for infant energy intake and related development.
European child & adolescent psychiatry, Jan 17, 2015
important aspect in the light of the ongoing discussion on DMDD and ODD. ODD as a diagnostic cate... more important aspect in the light of the ongoing discussion on DMDD and ODD. ODD as a diagnostic category has been around for many years, but DMDD as a diagnosis is new. However, this does not mean that ODD is either correct or ideal as a diagnostic category, and that it does not need any further revision. Indeed, there may yet be unintentional benefits of the controversy over DMDD. There is reason to believe the current conceptualisation of ODD conflates two commonly co-occurring but distinct phenotypes, irritability and noncompliance/oppositional behaviours. Studied as distinct phenomena, these constructs, respectively, show prospective associations with depressive/anxiety problems, and with conduct disorder and ADHD [3–5]. We believe that these findings suggest that both the disorders, DMDD and ODD, require an equal amount of scrutiny as diagnostic categories as regards their validity. Another relevant related area is the issue of hierarchy in diagnosis. As the authors have pointed out, DSM-5 mandates a preferential diagnosis of DMDD over ODD, when features of both are deemed to be present. This could, potentially, be construed as meaning that DMDD is a more severe form of ODD. But there are no empirical data, to date, to suggest that this is the case. Further research is therefore needed to clarify constructs that constitute valid individual diagnostic categories as well as potential overlap between categories. At this stage it is not possible to determine in advance which of the different views on this important clinical topic is correct. As reflected in the US National Institute of Mental Health Research Domain Criteria Initiative, a close examination of particular constructs in mental illness may fruitfully inform better taxonomies and diagnoses [6]. We believe the controversy over DMDD, and in particular its phenotypic overlap with ODD, may be an impetus for a To the Editor,
Background To describe the rates, indications, and adverse effects of psychotropic drug prescript... more Background To describe the rates, indications, and adverse effects of psychotropic drug prescription in a specialist tertiary hospital child and adolescent eating disorder service. Methods Retrospective case note study of all active eating disorder patients (N = 115) over the period of treatment from referral to time of study (M = 2 years), covering patient demographics, clinical characteristics, drug prescriptions, indications, and adverse effects. Results Psychotropic drugs were prescribed in 45% of cases, most commonly antidepressants (41%), followed by anxiolytics (29%) and antipsychotics (22%), with 8% initiated before referral to the specialist eating disorder program. Common indications were depressed mood, agitation, anxiety, and insomnia. Patient clinical severity and complexity was associated with prescribing. Adverse effects, mostly minor, were recorded in 23% of antidepressant prescriptions, 39% of antipsychotic prescriptions, and 13% of anxiolytic prescriptions. Second ...
Bipolar disorder (BD) is a severe mental condition with neurodevelopmental features that clinical... more Bipolar disorder (BD) is a severe mental condition with neurodevelopmental features that clinically results in pathological fluctuations of mood. Whereas it was classically or traditionally considered as an adult-onset disorder, recent findings suggest that BD may occur very early in the life course, thus, determining what is now called Juvenile bipolar disorder (JBD). One of the reasons for which JBD has been so difficult to identify is that JBD primary symptoms vary much from the typical adulthood BD clinical expression. Euphoric mood is rare in JBD, while irritability mood, aggressive temper, mixed manic state onset, rapid cycling, anger outbursts and chronic course of symptoms are much more frequent. This specific clinical presentation makes JBD difficult to differentiate from other diagnoses related to pathological externalizing behaviours, including conduct disorder, oppositional provocative disorder, and attention deficit-hyperactivity disorder.
OBJECTIVES Lurasidone is a new second generation (atypical) antipsychotic agent with unique recep... more OBJECTIVES Lurasidone is a new second generation (atypical) antipsychotic agent with unique receptor affinity and side-effect profiles, but limited literature is available on its use in adolescent populations. Contrasting with research treatment trials which typically recruit patients by stringent selection criteria, this case series examined the effects and tolerability of using lurasidone in adolescents within real-life clinical settings in treating complex cases who had not responded to other therapy options. METHODS We conducted a retrospective case-note audit of 6 adolescents aged 14 to 17 years old attending community child and adolescent mental health services (CAMHS) who were prescribed lurasidone. RESULTS Lurasidone had been prescribed for a range of "hard-to-manage" conditions with complex comorbidities, in adolescents in relation to specific use of lurasidone on the basis of clinical and pharmacological indications after exhausting more conventional treatment op...
Research suggests an overrepresentation of autism spectrum diagnoses (ASD) or autistic traits in ... more Research suggests an overrepresentation of autism spectrum diagnoses (ASD) or autistic traits in gender diverse samples, particularly in children and adolescents. Using data from the GENTLE (GENder identiTy Longitudinal Experience) Cohort at the Gender Diversity Service at the Perth Children’s Hospital, the primary objective of the current retrospective chart review was to explore psychopathology and quality of life in gender diverse children with co-occurring ASD relative to gender diverse children and adolescents without ASD. The Social Responsiveness Scale (Second Edition) generates a Diagnostic and Statistical Manual of Mental Disorders (DSM-5) score indicating a likely clinical ASD diagnosis, which was used to partition participants into two groups (indicated ASD, n = 19) (no ASD indicated, n = 60). Indicated ASD was far higher than would be expected compared to general population estimates. Indicated ASD on the Social Responsiveness Scale 2 (SRS 2) was also a significant predi...
Selective serotonin reuptake inhibitors (SSRIs) are amongst the most prescribed antidepressants f... more Selective serotonin reuptake inhibitors (SSRIs) are amongst the most prescribed antidepressants for adolescents with depressive symptoms and major depressive disorder. However, SSRIs have significant shortcomings as a first-line treatment considering that not all patients respond to these antidepressants. Amongst paediatric populations, meta-analyses indicate that up to approximately 40% of patients do not respond, and for those who do show benefit, there is substantial heterogeneity in response onset. The neurotransmitter serotonin (5-HT) plays a role in the clinical effectiveness and mechanisms of action of SSRIs. However, the exact and complete mechanism of action and reasons for the low response rate to SSRIs in some adolescent populations remains unknown. To examine SSRI response and the role of 5-HT, this study will employ a randomised double-blind within subject, repeated measures design, recruiting adolescent patients with major depressive disorder. Participants will be subj...
The ability to maintain attention to simple tasks (i.e., vigilant attention, VA) is often impaire... more The ability to maintain attention to simple tasks (i.e., vigilant attention, VA) is often impaired in attention-deficit/hyperactivity disorder (ADHD), but the underlying pathophysiological mechanisms at the brain network level are not clear yet. We therefore investigated ADHD-related differences in resting-state functional connectivity within a meta-analytically defined brain network of 14 distinct regions subserving VA (comprising 91 connections in total), as well as the association of connectivity with markers of behavioural dysfunction in 17 children (age range: 9-14 years) with a diagnosis of ADHD and 21 age-matched neurotypical controls. Our analyses revealed selective, rather than global, differences in the intrinsic coupling between nodes of the VA-related brain network in children with ADHD, relative to controls. In particular, ADHD patients showed substantially diminished intrinsic coupling for 7 connections and increased coupling for 4 connections, with many differences in...
The first line of pharmacological treatment for severe depressive disorders in young people is se... more The first line of pharmacological treatment for severe depressive disorders in young people is selective serotonin reuptake inhibitors (SSRIs). However, beneficial clinical effects are rarely observed before several weeks into treatment. Nitrous oxide (N2O) has a long-standing safety record for pain relief and has been used in adults and young people. In adults with severe treatment-resistant depression, a single dose of N2O had significant antidepressant effects, with maximum antidepressant effects observed 24 h after administration. However, the antidepressant effects of N2O have never been investigated in adolescents with a confirmed diagnosis of depression in a prospective trial. The aims of this study are to (1) investigate whether a single inhaled N2O administration leads to antidepressant effects in adolescents with depression at 24 h, (2) determine whether combined N2O and SSRI administration (commenced after N2O intervention) provides a clinically significant improvement in...
Research has implicated that changes in zinc (Zn) metabolism may be associated with the biologica... more Research has implicated that changes in zinc (Zn) metabolism may be associated with the biological underpinnings of eating disorders, in particular anorexia nervosa. However, to date research on the role of Zn in patients with bulimia nervosa (BN) is scarce. We aimed to explore serum Zn concentrations in young patients with BN, with a focus on the stage of the disorder, comparing acutely ill and recovered patients with BN with healthy controls. Serum Zn concentrations were obtained from healthy controls and from acutely ill and remitted young patients with BN. Mean duration of remission was 4.0±3.5 years. Remitted patients showed elevated serum Zn concentrations when compared to controls (Cohen's d=2.022), but concentrations were still in the normal range. Acutely ill patients also had higher serum Zn levels when compared to controls (all values still being within the reference range, Cohen's d=0.882). There was no difference between acutely ill and remitted patients with BN...
The lancet. Diabetes & endocrinology, Jan 22, 2017
The World Professional Association for Transgender Health's standards of care recommend suspe... more The World Professional Association for Transgender Health's standards of care recommend suspending puberty, preferably with the use of gonadotropin-releasing hormone agonists, in certain gender non-conforming minors (aged under 18 years) who have undergone a psychiatric assessment and have reached at least Tanner stage II of puberty. This approach seeks to lessen the discordance between assigned natal sex and gender identity by temporarily halting the development of secondary sexual characteristics, essentially widening the temporal window for gender clarification. Despite promising preliminary evidence on the clinical utility of this approach, there is a dearth of research to inform evidence-based practice. In view of these challenges, we review the available empirical evidence on the cognitive, physical, and surgical implications of puberty suppression in gender-incongruent children and adolescents. We also explore the historical underpinnings and clinical impetus for suspendi...
Concentrations of different adipokines in human breast milk are thought to be able to affect ener... more Concentrations of different adipokines in human breast milk are thought to be able to affect energy intake of the infant. Leptin is a hormone synthesized by adipose tissue and the human placenta and favors satiety. The availability of leptin in breast milk is influenced by epithelial cells of the mammary gland that are known to be able to produce leptin, as well as leptin from maternal circulation that is transported to the breast milk, and which can thus in turn reach neonatal blood after absorption. Research so far as mainly focused on leptin concentrations in breast milk. However, evidence suggests that in addition to leptin concentrations levels of the so-called soluble leptin receptor (sOb-R), the main high-affinity binding protein for leptin in humans, are necessary in order to calculate the free leptin index (FLI) and to assess function of the leptin axis. FLI is calculated from the ratio of leptin to the sOb-R, and serves as the main parameter for assessing function of the leptin axis throughout maturation and development. Here we propose that assessing sOb-R levels in addition to leptin concentrations in breast milk could serve as a valuable tool to investigate effects of the leptin axis in breast milk because sOb-R concentrations can impact available leptin levels, and which in turn can have significant implications for infant energy intake and related development.
European child & adolescent psychiatry, Jan 17, 2015
important aspect in the light of the ongoing discussion on DMDD and ODD. ODD as a diagnostic cate... more important aspect in the light of the ongoing discussion on DMDD and ODD. ODD as a diagnostic category has been around for many years, but DMDD as a diagnosis is new. However, this does not mean that ODD is either correct or ideal as a diagnostic category, and that it does not need any further revision. Indeed, there may yet be unintentional benefits of the controversy over DMDD. There is reason to believe the current conceptualisation of ODD conflates two commonly co-occurring but distinct phenotypes, irritability and noncompliance/oppositional behaviours. Studied as distinct phenomena, these constructs, respectively, show prospective associations with depressive/anxiety problems, and with conduct disorder and ADHD [3–5]. We believe that these findings suggest that both the disorders, DMDD and ODD, require an equal amount of scrutiny as diagnostic categories as regards their validity. Another relevant related area is the issue of hierarchy in diagnosis. As the authors have pointed out, DSM-5 mandates a preferential diagnosis of DMDD over ODD, when features of both are deemed to be present. This could, potentially, be construed as meaning that DMDD is a more severe form of ODD. But there are no empirical data, to date, to suggest that this is the case. Further research is therefore needed to clarify constructs that constitute valid individual diagnostic categories as well as potential overlap between categories. At this stage it is not possible to determine in advance which of the different views on this important clinical topic is correct. As reflected in the US National Institute of Mental Health Research Domain Criteria Initiative, a close examination of particular constructs in mental illness may fruitfully inform better taxonomies and diagnoses [6]. We believe the controversy over DMDD, and in particular its phenotypic overlap with ODD, may be an impetus for a To the Editor,
Background To describe the rates, indications, and adverse effects of psychotropic drug prescript... more Background To describe the rates, indications, and adverse effects of psychotropic drug prescription in a specialist tertiary hospital child and adolescent eating disorder service. Methods Retrospective case note study of all active eating disorder patients (N = 115) over the period of treatment from referral to time of study (M = 2 years), covering patient demographics, clinical characteristics, drug prescriptions, indications, and adverse effects. Results Psychotropic drugs were prescribed in 45% of cases, most commonly antidepressants (41%), followed by anxiolytics (29%) and antipsychotics (22%), with 8% initiated before referral to the specialist eating disorder program. Common indications were depressed mood, agitation, anxiety, and insomnia. Patient clinical severity and complexity was associated with prescribing. Adverse effects, mostly minor, were recorded in 23% of antidepressant prescriptions, 39% of antipsychotic prescriptions, and 13% of anxiolytic prescriptions. Second ...
Bipolar disorder (BD) is a severe mental condition with neurodevelopmental features that clinical... more Bipolar disorder (BD) is a severe mental condition with neurodevelopmental features that clinically results in pathological fluctuations of mood. Whereas it was classically or traditionally considered as an adult-onset disorder, recent findings suggest that BD may occur very early in the life course, thus, determining what is now called Juvenile bipolar disorder (JBD). One of the reasons for which JBD has been so difficult to identify is that JBD primary symptoms vary much from the typical adulthood BD clinical expression. Euphoric mood is rare in JBD, while irritability mood, aggressive temper, mixed manic state onset, rapid cycling, anger outbursts and chronic course of symptoms are much more frequent. This specific clinical presentation makes JBD difficult to differentiate from other diagnoses related to pathological externalizing behaviours, including conduct disorder, oppositional provocative disorder, and attention deficit-hyperactivity disorder.
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