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1.
J Psychiatr Pract ; 30(3): 227-233, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38819247

ABSTRACT

OBJECTIVE: Prescriptions for atypical antipsychotics in children and adolescents are increasing globally. However, a precise understanding of the clinical variables and evidence that prescribers consider before using these agents is lacking. While empirical literature on the long-term safety and efficacy of these medications is available, the literature concerning their use in these younger age groups is relatively sparse. In this study, we examined the current prescribing patterns of medical professionals employed by a public health service in Australia. METHODS: A survey examining their current practice when prescribing atypical antipsychotics to children and adolescents was completed by 103 physicians. Questions were asked about commonly prescribed atypical antipsychotics, indications, dose ranges, target symptoms, duration of treatment, and the evidence base(s) used when making treatment decisions. RESULTS: Physicians prescribed atypical antipsychotics for a wide range of indications in this age group, with the most common agents being risperidone, quetiapine, and olanzapine. Adverse effects were reported as the main reason for treatment discontinuation. More than half of the respondents indicated that the most common source of guidance/evidence they referred to when initiating prescriptions were peers or expert opinion. CONCLUSIONS: Children and adolescents were prescribed a number of atypical antipsychotics for a variety of indications, with variable perceived confidence and a relatively heavy reliance on "own or peer experience" as opposed to good quality evidence. Challenges exist for both prescribers and policymakers, and further "head-to-head" studies are needed in this age group to ensure that a balance is maintained between therapeutic benefit and safety.


Subject(s)
Antipsychotic Agents , Practice Patterns, Physicians' , Humans , Antipsychotic Agents/therapeutic use , Adolescent , Practice Patterns, Physicians'/statistics & numerical data , Australia , Child , Male , Female , Drug Prescriptions/statistics & numerical data , Drug Prescriptions/standards , Risperidone/therapeutic use , Surveys and Questionnaires , Olanzapine/therapeutic use
2.
J Psychiatr Res ; 173: 200-209, 2024 May.
Article in English | MEDLINE | ID: mdl-38547742

ABSTRACT

Iron deficiency may play a role in the pathophysiology of Attention Deficit/Hyperactivity Disorder (ADHD). Due to its preponderant function in monoamine catecholamine and myelin synthesis, brain iron concentration may be of primary interest in the investigation of iron dysregulation in ADHD. This study reviewed current evidence of brain iron abnormalities in children and adolescents with ADHD using magnetic resonance imaging methods, such as relaxometry and quantitative susceptibility mapping, to assess brain iron estimates. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed for studies published between January 1, 2008 and July 7, 2023 in Medline, Scopus and Proquest. Regions of interest, brain iron index values and phenotypical information were extracted from the relevant studies. Risk of bias was assessed using a modified version of the National Heart, Lung, and Blood Institute quality assessment tool. Seven cross-sectional studies comparing brain iron estimates in children with ADHD with neurotypical children were included. Significantly reduced brain iron content in medication-naïve children with ADHD was a consistent finding. Two studies found psychostimulant use may increase and normalize brain iron concentration in children with ADHD. The findings were consistent across the studies despite differing methodologies and may lay the early foundation for the recognition of a potential biomarker in ADHD, although longitudinal prospective neuroimaging studies using larger sample sizes are required. Lastly, the effects of iron supplementation on brain iron concentration in children with ADHD need to be elucidated.

3.
Clin Nutr ESPEN ; 52: 78-85, 2022 12.
Article in English | MEDLINE | ID: mdl-36513489

ABSTRACT

Attention Deficit/Hyperactivity Disorder (ADHD) is the most common mental health disorder in the paediatric population. ADHD is highly comorbid with obesity, and has also been associated with poor dietary patterns such as increased consumption of refined carbohydrates and saturated fats. Although ADHD in children was associated with high consumption of saturated fats, so far there has been no evidence-based attempt to integrate dietary strategies controlling for intake of saturated fats into the etiological framework of the disorder. Evidence from human studies and animal models has shown that diets high in saturated fats are detrimental for the development of dopaminergic neurocircuitries, synthesis of neurofactors (e.g. brain derived neurotrophic factor) and may promote brain inflammatory processes. Notably, animal models provide evidence that early life consumption of a high saturated fats diet may impair the development of central dopamine pathways. In the present paper, we review the impact of high saturated fats diets on neurobiological processes in human studies and animal models, and how these associations may be relevant to the neuropathophysiology of ADHD in children. The validation of this relationship and its underlying mechanisms through future investigative studies could have implications for the prevention or exacerbation of ADHD symptoms, improve the understanding of the pathogenesis of the disorder, and help design future dietary studies in patients with ADHD.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Child , Animals , Humans , Attention Deficit Disorder with Hyperactivity/etiology , Attention Deficit Disorder with Hyperactivity/epidemiology , Diet/adverse effects , Comorbidity , Brain , Dopamine
4.
J Pharm Pract ; 35(5): 800-804, 2022 Oct.
Article in English | MEDLINE | ID: mdl-33757374

ABSTRACT

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 options. Case-note review suggested response to lurasidone was clinically positive in 3 cases, equivocal/marginal in 2 cases, and ineffective in 1 case. There were no cases of poor tolerance or adverse effects. Notably, positive responses for depressive and irritable mood symptoms were specifically recorded by prescribing clinicians, indicative of benefits on symptom improvement. No lurasidone attributed weight gain, galactorrhoea, metabolic abnormalities, sexual dysfunction or intolerance were reported. Pro-cognitive effects were not detected; but our findings were constrained by the non-systematic and incomplete information ascertainment, typical in retrospective case-note review. CONCLUSION: This case series provides preliminary data supporting lurasidone's potential use in adolescents of complex clinical needs (but without a clinical diagnosis of bipolar disorder) within real-life clinical settings. Lurasidone appears to show a weight-sparing effect, in addition to improving mood symptoms in some cases. Lurasidone deserves further study for its use in the adolescent population (outside the remit of FDA) given its potential more favorable risk-benefit profile in young people. The favorable tolerability appear to be borne out by the pharmacodynamic predictions in our complex patients who would be excluded in formal clinical trial studies.


Subject(s)
Antipsychotic Agents , Bipolar Disorder , Mental Disorders , Adolescent , Antipsychotic Agents/adverse effects , Bipolar Disorder/drug therapy , Humans , Lurasidone Hydrochloride/therapeutic use , Mental Disorders/drug therapy , Retrospective Studies
5.
Nutr Neurosci ; 25(11): 2269-2278, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34369315

ABSTRACT

BACKGROUND: Vigilant Attention (VA) is a critical cognitive function allowing to maintain our attention, particularly in redundant or intellectually unchallenging situations. Evidence has shown that, as the brain develops, VA abilities rapidly improve throughout childhood and adolescence. Dietary omega-3 polyunsaturated fats (PUFA), playing a critical role for proper brain development and maturation of cortical regions, may contribute to variations in VA abilities. OBJECTIVE: The present study investigated the effect of dietary omega-3 PUFA intake (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) on resting-state functional connectivity (rsFC) of a meta-analytically defined VA network in 24 neurotypical children and adolescents (7.3-17.2 years) from the Healthy Brain Network databank. METHODS: Functional MRI and phenotypical information were collected from the Healthy Brain Network databank. Intake of omega-3 DHA and EPA was assessed using a food frequency questionnaire and was adjusted for total calorie intake. Out of scanner VA-related performance was assessed using the VA condition of the Adaptive Cognitive Evaluation tool. RESULTS: Overall, reported intake of omega-3 PUFA was not significantly associated with VA-related performance. Furthermore, energy-adjusted omega-3 intake was not significantly correlated with rsFC within the VA network. A complementary whole-brain analysis revealed that energy-adjusted omega-3 intake was correlated with decreased rsFC between parieto-occipital brain regions. CONCLUSION: The present study was not able to detect a relationship between dietary omega-3 and rsFC or VA performance.


Subject(s)
Eicosapentaenoic Acid , Fatty Acids, Omega-3 , Child , Humans , Adolescent , Docosahexaenoic Acids , Diet , Attention
6.
Brain Cogn ; 154: 105791, 2021 11.
Article in English | MEDLINE | ID: mdl-34509772

ABSTRACT

The development of Vigilant Attention (VA), the ability to focus and maintain our attention to repetitive and cognitively unchallenging tasks over time, has been investigated for more than a decade. The development of this critical executive function across the lifespan has been characterised by a rapid improvement in VA performance throughout childhood and adolescence, a steady improvement in adulthood and a slow decline in older adulthood. However, the development of the neural correlates of VA in children and adolescents remains poorly understood. Using a cross-sectional design, the present study used a meta-analytically defined VA network in children and adolescents to explore the developmental trend of the resting-state functional connectivity (rsFC) within the VA network across two independent cohorts. The results showed a linear and non-linear decrease of rsFC between the left and right VA brain regions across age. However, the results could not be reproduced in the replication cohort, potentially due to a smaller sample size. Based on previous findings from behavioural studies, the present findings suggest that changes in rsFC may underlie a developmental shift in cognitive strategies in neurotypical children and adolescents.


Subject(s)
Brain , Magnetic Resonance Imaging , Adolescent , Brain Mapping , Child , Cross-Sectional Studies , Humans , Neural Pathways , Wakefulness
7.
Cortex ; 132: 374-385, 2020 11.
Article in English | MEDLINE | ID: mdl-33035933

ABSTRACT

Vigilant Attention (VA), defined as the ability to maintain attention to cognitively unchallenging activities over a prolonged period of time, is critical to support higher cognitive functions and many behaviours in our everyday life. Evidence has shown that VA rapidly improves throughout childhood and adolescence until young adulthood and tends to decline in older adulthood. Although neuroimaging studies have extensively investigated this cognitive function in adults, the neural correlates of VA in neurotypical children and adolescents remain unclear. The current meta-analysis reviewed and examined functional neuroimaging studies in paediatric populations that used behavioural tasks involving VA. The selected studies (N = 25) were analyzed using the activation likelihood estimation method. Findings showed convergence of activation in mainly right-lateralized brain areas, including dorsomedial frontal cortex and parieto-temporal areas, and are consistent with previous literature on the neural correlates of VA. Results are discussed in terms of their functional and developmental implications for VA in children and adolescents.


Subject(s)
Brain , Magnetic Resonance Imaging , Adolescent , Adult , Aged , Brain/diagnostic imaging , Brain Mapping , Child , Functional Neuroimaging , Humans , Likelihood Functions , Neuroimaging , Wakefulness , Young Adult
8.
Brain Cogn ; 131: 56-65, 2019 04.
Article in English | MEDLINE | ID: mdl-29150311

ABSTRACT

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 involving connectivity with the anterior insula. Moreover, connectivity strength of several aberrant connections was found to be associated with core aspects of ADHD symptomatology, such as poor attention, difficulties with social functioning, and impaired cognitive control, attesting to the behavioural relevance of specific connectivity differences observed in the resting state.


Subject(s)
Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Attention/physiology , Brain/diagnostic imaging , Nerve Net/diagnostic imaging , Adolescent , Attention Deficit Disorder with Hyperactivity/physiopathology , Brain/physiopathology , Brain Mapping , Child , Female , Humans , Magnetic Resonance Imaging , Male , Nerve Net/physiopathology
9.
World J Biol Psychiatry ; 20(5): 416-423, 2019 06.
Article in English | MEDLINE | ID: mdl-29353534

ABSTRACT

Objectives: Recent research suggested an influence of diminished central nervous serotonin (5-HT) synthesis on the leptin axis via immunological mechanisms in healthy adult females. However, studies assessing immunological parameters in combination with dietary challenge techniques that impact brain 5-HT synthesis in humans are lacking. Methods: In the present trial, a pilot analysis was conducted on data obtained in healthy adult humans receiving either different dietary acute tryptophan depletion (ATD) challenge or tryptophan (TRP)-balanced control conditions (BAL) to study the effects of reduced central nervous 5-HT synthesis on serum tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 concentrations. The data of N = 35 healthy adults were analysed who were randomly subjected to one of the following two dietary conditions in a double-blind between-subject approach: (1) The Moja-De ATD challenge (ATD), or (2) TRP-balanced control condition for ATD Moja-De (BAL). Serum concentrations for the assessment of relevant parameters (TNF-α, IL-1ß and IL-6) and relevant TRP-related characteristics after the respective challenge procedures were assessed at baseline (T0) and in hourly intervals after administration over a period of 6 h (T1-T6). Results: The ATD condition did not result in significant changes to cytokine concentrations for the entire study sample, or in male and female subgroups. Depletion of CNS 5-HT via dietary TRP depletion appears to have no statistically significant short-term impact on cytokine concentrations in healthy adults. Conclusions: Future research on immunological stressors in combination with challenge techniques will be of value in order to further disentangle the complex interplay between brain 5-HT synthesis and immunological pathways.


Subject(s)
Cytokines/blood , Immune System/drug effects , Tryptophan/administration & dosage , Tryptophan/blood , Adolescent , Adult , Body Mass Index , Brain/drug effects , Brain/metabolism , Double-Blind Method , Female , Healthy Volunteers , Humans , Male , Serotonin/metabolism , Sex Factors , Young Adult
10.
Early Interv Psychiatry ; 13(1): 151-158, 2019 02.
Article in English | MEDLINE | ID: mdl-30187642

ABSTRACT

BACKGROUND: Multiple services are often needed to address the needs of young people with complex emotional or behavioural needs. The Youth Wraparound model of service aims to provide all health and supportive services from one coordinating agency. While this has been researched overseas, there are currently few examples of this described in the Australian psychiatric context. AIM: To document the implementation and evaluation of a Youth Wraparound service which was provided to a young person with exceptionally complex and challenging needs for 6 months. A single-case study design is presented with an evaluation of the clinical outcome and economic costs. METHODS: We present a description of the service context, principles of the model of care, implementation process, and an evaluation of service utilization data from health and child protection services and mental health records. A single-case longitudinal design compared service utilization data obtained up to 3 years prior to treatment with data collected one and a half years since treatment commenced. RESULTS: There were significant reductions in the number of admissions to emergency departments, mental health wards and secure units, and improvements in mental health and well-being. Yearly average time in institutional settings reduced from 69% to 7%. Cost savings in health utilization were estimated at $2 326 790. CONCLUSIONS: The Youth Wraparound model has the potential to offer improved clinical outcomes, significant cost savings over time, improved coordination between care providers, and an alternative to detention or incarceration.


Subject(s)
Adolescent Health Services , Community Mental Health Services , Adolescent , Adolescent Health Services/economics , Community Mental Health Services/economics , Cost Savings , Feasibility Studies , Health Services Research , Hospitalization , Humans , Male , Patient Acceptance of Health Care , Program Development , Time Factors , Treatment Outcome , Western Australia
11.
Front Psychiatry ; 10: 1007, 2019.
Article in English | MEDLINE | ID: mdl-32210845

ABSTRACT

Serotonin (5-HT) is widely implicated as a key neurotransmitter relevant to a range of psychiatric disorders and psychological processes. The role of central nervous 5-HT function underlying these processes can be examined through serotonergic challenge methodologies. Acute tryptophan depletion (ATD) is a key challenge method whereby a diminished dietary intake of tryptophan-the amino acid precursor to brain 5-HT synthesis-results in temporary diminished central nervous 5-HT synthesis. While this particular methodology has been used in adult populations, it was only recently that modifications were made to enable the use of ATD in child and adolescent populations. Additionally, the Moja-De modification of the ATD challenge methodology has demonstrated benefits over other ATD techniques used previously. The aim of this protocol paper is to describe the ATD Moja-De methodology in detail, its benefits, as well as studies that have been conducted to validate the procedure in child and adolescent samples. The ATD Moja-De protocol provides a potential methodology for investigating the role of central nervous 5-HT via manipulation of brain tryptophan availability in human psychopathology from a developmental viewpoint.

12.
Trials ; 19(1): 434, 2018 Aug 10.
Article in English | MEDLINE | ID: mdl-30097056

ABSTRACT

BACKGROUND: 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. METHODS: 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 subjected to acute tryptophan depletion (ATD) and the balanced control condition on two separate study days within a first study phase (Phase A), and the order in which these conditions (ATD/balanced control condition) occur will be random. This phase will be followed by Phase B, where participants will receive open label pharmacological treatment as usual with the SSRI fluoxetine and followed-up over a 12-week period. DISCUSSION: ATD is a neurodietary method typically used to investigate the impact of lowered brain 5-HT synthesis on mood and behaviour. The major hypothesis of this study is that ATD will be negatively associated with mood and cognitive functioning, therefore reflecting individual serotonergic sensitivity and related depressive symptoms. Additionally, we expect the aforementioned effects of ATD administration on mood to predict clinical improvement with regard to overall depressive symptomatology 12 weeks into SSRI treatment. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616001561471 . Registered on 11 November 2016.


Subject(s)
Adolescent Behavior/drug effects , Affect/drug effects , Amino Acids/administration & dosage , Antidepressive Agents, Second-Generation/therapeutic use , Brain/drug effects , Child Behavior/drug effects , Depressive Disorder, Major/diet therapy , Dietary Supplements , Fluoxetine/therapeutic use , Selective Serotonin Reuptake Inhibitors/therapeutic use , Serotonin/metabolism , Tryptophan/deficiency , Adolescent , Age Factors , Amino Acids/adverse effects , Antidepressive Agents, Second-Generation/adverse effects , Brain/metabolism , Child , Combined Modality Therapy , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/metabolism , Depressive Disorder, Major/psychology , Dietary Supplements/adverse effects , Double-Blind Method , Female , Fluoxetine/adverse effects , Humans , Male , Randomized Controlled Trials as Topic , Selective Serotonin Reuptake Inhibitors/adverse effects , Time Factors , Treatment Outcome , Western Australia
13.
J Phys Chem A ; 122(33): 6799-6808, 2018 Aug 23.
Article in English | MEDLINE | ID: mdl-30044096

ABSTRACT

Kinetics and mechanistic pathways for atmospheric oxidation of HFE-7500 ( n-C3F7CF(OCH2CH3)CF(CF3)2) initiated by Cl atom and NO3 radical have been studied using density functional theory. Oxidative degradation pathways facilitated by H-abstraction from the -OCH2 or -CH3 groups in HFE-7500 have been considered. It has been shown that H-abstraction from the α-site (-OCH2) is favored over other reaction pathways. The rate constants were computed employing transition-state theory and canonical variation transition-state theory incorporating small curvature tunnelling correction, over the temperature range of 250-450 K at atmospheric pressure. Calculated rate constants at 298 K and 1 atm compare well with earlier experiments. Temperature dependence of the rate constants and branching ratios for these pathways contributing to overall reaction are described. It has been shown that the rate constants over the studied temperature range was found to fit well to the modified Arrhenius equation (in cm3 molecule-1 s-1) kCl = 1.10 × 10-14  T0.04 exp(-69.87 ± 1.41/T) and kNO3 = 7.66 × 10-26 T3.30 exp(596.40 ± 1.22/T). Standard enthalpies of formation for the reactant (C3F7CF(OCH2CH3)CF(CF3)2) and the products [C3F7CF(OC•HCH3)CF(CF3)2 and C3F7CF(OCH2C•H2)CF(CF3)2] during H-abstraction are derived using the isodesmic approach. Atmospheric implications of the titled molecule are presented.

14.
Nutrients ; 10(5)2018 May 11.
Article in English | MEDLINE | ID: mdl-29751614

ABSTRACT

Central nervous serotonin (5-HT) can influence behaviour and neuropsychiatric disorders. Evidence from animal models suggest that lowered levels of neuropeptide Y (NPY) may have similar effects, although it is currently unknown whether decreased central nervous 5-HT impact NPY concentrations. Given that the production of NPY is dependent on the essential amino acid methionine (MET), it is imperative to account for the presence of MET in such investigations. Hence, this study sought to examine the effects of acute tryptophan depletion (ATD; a dietary procedure that temporarily lowers central nervous 5-HT synthesis) on serum concentrations of NPY, whilst using the potential renal acid load indicator (PRAL) to control for levels of MET. In a double-blind repeated measures design, 24 adult humans randomly received an AA-load lacking in TRP (ATD) on one occasion, and a balanced control mixture with TRP (BAL) on a second occasion, both with a PRAL of nearly 47.3 mEq of MET. Blood samples were obtained at 90, 180, and 240 min after each of the AA challenges. ATD, and therefore, diminished substrate availability for brain 5-HT synthesis did not lead to significant changes in serum NPY concentrations over time, compared to BAL, under an acute acidotic stimulus.


Subject(s)
Neuropeptide Y/blood , Tryptophan/administration & dosage , Tryptophan/blood , Adult , Body Mass Index , Brain/drug effects , Brain/metabolism , Diet , Double-Blind Method , Female , Humans , Male , Methionine , Pilot Projects , Serotonin/metabolism , Young Adult
15.
World J Urol ; 36(4): 537-541, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29427003

ABSTRACT

PURPOSE: For the last 20 years, the predominant robot used in laparoscopic surgery has been Da Vinci by Intuitive Surgical. This monopoly situation has led to rising costs and relatively slow innovation. This article aims to discuss the two new robotic devices for laparoscopic surgery which have received regulatory approval for human use in different parts of the world. MATERIALS: A short description of the Senhance Surgical Robotic System and the REVO-I Robot Platform and their pros and cons compared to the Da Vinci system is presented. A discussion about the differences between the three robotic systems now in the market is presented, as well as a short review of the present state of robotic assistance in surgery and where we are headed.


Subject(s)
Laparoscopy/methods , Robotic Surgical Procedures , Robotics , Urologic Surgical Procedures , Device Approval , Economic Competition , Humans , Robotic Surgical Procedures/economics , Robotic Surgical Procedures/instrumentation , Urologic Surgical Procedures/instrumentation , Urologic Surgical Procedures/methods
16.
Trials ; 18(1): 617, 2017 Dec 22.
Article in English | MEDLINE | ID: mdl-29273063

ABSTRACT

BACKGROUND: 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 mood over and above the benefits from SSRI administration alone, and, (3) investigate whether the effect seen following N2O administration can be used as a predictor of SSRI treatment response. METHODS/DESIGN: In this study, we will use a single-blind, randomised, placebo-controlled design. Patients aged between 12 and 17 years with major depressive disorder will be recruited. This study will consist of two phases: phase A and phase B. During phase A, participants will be randomised to receive either inhaled N2O or placebo (air) for 1 h. In phase B, participants will receive open-label pharmacological treatment with the SSRI fluoxetine and will be followed over a 12-week period. Participants will undertake mood assessments at 2 and 24 h after N2O or placebo administration (phase A) and weekly during the 12-week follow up in phase B. DISCUSSION: We expect an antidepressant effect from a single dose of inhaled N2O compared with placebo at 24 h after administration. Additionally, we expect that subjects treated with N2O will also show greater improvements than the placebo group after 6 and 12 weeks into fluoxetine treatment because of potential additive antidepressant effects. Such findings would be of clinical importance because currently children and adolescents often do not experience any symptom alleviation for several weeks following the initiation of SSRIs. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12616001568404 . Registered on 14 November 2016.


Subject(s)
Depressive Disorder, Major/drug therapy , Fluoxetine/administration & dosage , Nitrous Oxide/administration & dosage , Selective Serotonin Reuptake Inhibitors/administration & dosage , Adolescent , Child , Data Interpretation, Statistical , Depressive Disorder, Major/psychology , Drug Therapy, Combination , Humans , Randomized Controlled Trials as Topic , Single-Blind Method
17.
Neuropsychiatr Dis Treat ; 13: 2621-2630, 2017.
Article in English | MEDLINE | ID: mdl-29089768

ABSTRACT

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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 in serum Zn concentrations. Of note, remitted patients had a significantly higher body weight when compared to the other two groups. Overall, there were no significant differences in dietary preferences with regard to Zn containing foods between the groups. CONCLUSION: The present study provides preliminary evidence that the underlying factors for changes in Zn serum concentrations in young patients with BN do not vary with regard to the stage of illness (acute versus remitted BN). Further prospective research is needed in order to disentangle the possible interplay between serum Zn status and bulimic eating behaviors.

18.
J Phys Chem A ; 121(3): 595-607, 2017 Jan 26.
Article in English | MEDLINE | ID: mdl-28026954

ABSTRACT

HFO-1345fz (CF3CF2CH═CH2 or 3,3,4,4,4-pentafluoro-1-butene) belongs to a class of hydrofluoro-olefins and represents a new generation of potential foam expansion agents. Its atmospheric impact and environmental acceptability can be estimated from the studies of kinetics and mechanism of its oxidative degradation. The molecular insights accompanying the reaction pathways in terms of the characterization of intermediates or products and radiative properties should prove useful for large-scale industrial applications. Systematic mechanistic gas-phase kinetics investigations on the reactivity of HFO-1345fz with the •OH facilitating a variety of degradation routes have been carried out employing the M06-2x-based density functional theory. Structure and energetics of different reaction pathways such as hydrogen abstraction, •OH addition, isomerization-dissociation, or interaction with atmospheric O2 have been analyzed. The formation of gaseous products from the interaction of HFO-1345fz with •OH in the absence and presence of NOx atmospheric conditions has been reported. Calculated branching ratios have shown that the addition channel dominates such oxidative degradation, whereas the abstraction channel contributes negligibly to the global rate constant and addition of •OH to the terminal carbon is favored over the nonterminal one. The rate constants for all reaction channels were computed by conventional transition state theory (TST) and canonical variation transition state theory (CVT) including small curvature tunneling (SCT) over the temperature range of 200-1000 K at atmospheric pressure. The CVT calculated rate constant for the reaction at 298 K was shown to be 1.17 × 10-12 cm3 molecule-1 s-1, which compares well with the 1.24 × 10-12 cm3 molecule-1 s-1 as obtained from TST and is in excellent agreement with the experiments reported earlier. The atmospheric lifetime, radiative efficiency, and global warming potential (GWP) have also been obtained.

19.
Int J Bipolar Disord ; 4(1): 23, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27837521

ABSTRACT

BACKGROUND: Despite growing consensus on nosology and epidemiology of bipolar disorder (BD) in minors, differences remain. We contribute to this discussion by measuring long-term trends in the inpatient discharge rates of BD in minors. METHODS: Nationwide German inpatient discharge diagnoses of BD and other related psychiatric disorders were mapped between 2008 and 2013 using registry data from the German Federal Health Monitoring System. This was compared with previously published data, 2000-2007, to assess long-term trends in diagnosis of BD at discharge. Long-term trends (2000-2013) were also computed. RESULTS: Discharge diagnosis of BD increased by 18% (2.02-2.46 per 100,000) in minors. There was a significant increase of 24.1% in adolescents 15-19 years old (6.56-8.14 per 100,000). BD, at discharge, as a proportion of all psychiatric disorders, increased from 0.26% in 2008 to 0.27% in 2013. When analysing long-term trends (2000-2013), the rates for BD increased significantly as did trends for all mental disorders, except for psychotic disorders, which fell by almost 14%. Between 2000 and 2013, the rate for depression in minors increased by 730%. LIMITATIONS: The dataset consisted of cross-sectional administrative data points with diagnoses based on clinical criteria. CONCLUSIONS: The rate of BD as a discharge diagnosis in German minors has increased significantly, consistently exceeding the general trend for a rise in rates for mental disorders. Overall, the rate of discharge diagnosis of BD from inpatient units in Germany remains a small proportion of all psychiatric diagnoses.

20.
J Mol Model ; 19(11): 4815-22, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24022782

ABSTRACT

The present work deals with the theoretical investigation on the Cl initiated H-atom abstraction reaction of sevoflurane, (CF3)2CHOCH2F. A dual-level procedure has been adopted for studying the kinetics of the reaction. Geometrical optimization and frequency calculation were performed at DFT(BHandHLYP)/6-311G(d,p) while single-point energy calculation was made at CCSD(T)/6-311G(d,p) level of theory. The intrinsic reaction coordinate (IRC) calculation has also been performed to confirm the smooth transition from the reactant to product through the respective transition state. The rate constants were calculated using conventional transition state theory (TST). It has been found that 99 % of the reaction proceeded via the H-atom abstraction from the ­CH2F end of the sevoflurane. The rate constant of the dominant path is found to be 1.13 × 10⁻¹³ cm³ molecule⁻¹ s⁻¹. This is in excellent agreement with the reported experimental rate constant of 1.10 × 10⁻¹³ cm³ molecule⁻¹ s⁻¹ obtained by relative rate method using FTIR/Smog chamber and LP/LIF techniques.

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