Gender non-conformity in childhood and adolescence and mental health through to adulthood: a longitudinal cohort study, 1995-2018.

BACKGROUND: Few studies have examined associations between gender non-conformity (GNC) in childhood or adolescence and mental health outcomes later in life. This study examined associations between (1) GNC and mental health over multiple time points in childhood and adolescence, and (2) GNC in childhood and/or adolescence and mental health in adulthood. METHOD: Second generation participants from the Raine Study, a longitudinal cohort from Perth, Western Australia. Data were collected between 1995 and 2018, comprising seven waves: ages 5 (N = 2236), 8 (N = 2140), 10 (N = 2048), 14 (N = 1864), 17 (N = 1726), 22 (N = 1236) and 27 (N = 1190) years. History of GNC, v. absence of this history, was based on responses to item 110 from the Child Behaviour Checklist (CBCL)/Youth Self Report (YSR) ('wishes to be of opposite sex'). The CBCL/YSR were used to measure internalising and externalising symptoms. Items 18 ('deliberate self-harm [DSH] or attempts suicide') and 91 ('talks/thinks about killing self') were used as measures of suicidal ideation (SI) and DSH. For adults, Depression, Anxiety and Stress Subscales and Kessler Psychological Distress Scale assessed mental health. RESULTS: Child and adolescent GNC was associated with elevated internalising and externalising behaviours and increased odds of DSH. A history of GNC was also associated with vulnerability for severe psychological distress in adulthood in some symptom scales. CONCLUSION: GNC over the child and adolescent period is associated with significant emotional and behavioural difficulties, and psychological distress. A history of GNC in childhood and/or adolescence also predicts poorer mental health in adulthood on multiple symptom domains.

Functional connectivity of the vigilant-attention network in children and adolescents with attention-deficit/hyperactivity disorder.

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.

Hallucinations and inhibitory functioning in healthy young adults with high and low levels of hypomanic personality traits.

INTRODUCTION: Hallucinations in schizophrenia and hallucination proneness in healthy young adults are associated with a common cognitive mechanism, namely impaired inhibitory control. Hallucinatory-like experiences also seem related to hypomanic symptoms in non-clinical participants; however, the mechanisms involved are unknown. We sought to examine self-reported hallucinatory/anomalous perceptual experiences in students selected for high versus low levels of hypomanic personality traits, and whether hypomania is characterised by deficient inhibitory control. METHOD: Undergraduate students with either high (n = 26) or low (n = 28) scores on the Hypomanic Personality Scale-Revised (HPS-20) were compared on: (1) the Launay Slade Hallucination Scale-Revised (LSHS-R), a measure of hallucination proneness, (2) the Cardiff Anomalous Perceptions Scale (CAPS) and (3) the Inhibition of Currently Irrelevant Memories (ICIM) task, an index of intentional inhibition. RESULTS: The high HPS group had higher total scores, as well as higher frequency (on CAPS only), intrusiveness and distress (CAPS) scores compared to the low HPS group. They also produced significantly more false alarms on the second run of the ICIM task than the low hypomania traits group. CONCLUSIONS: Frequent, intrusive and distressing perceptual anomalies and proneness to hallucinations tend to occur in healthy individuals with hypomanic personality traits and may be associated with transient difficulties with inhibitory control. Inhibitory control may be a cognitive marker of vulnerability to hallucinations across diagnostic boundaries.

Atypical Antipsychotic Prescribing in Australian Children and Adolescents: A Survey of Medical Practitioners.

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.

The Perth Gender Picture (PGP): Young people's feedback about acceptability and usefulness of a new pictorial and narrative approach to gender identity assessment and exploration.

BACKGROUND: A number of psychological assessment tools have been developed to describe various dimensions of gender. Some of these tools are restricted to a binary gender concept and are inflexible in reflecting how a young person's gender may change and develop over time. Most are text questionnaires which require a good level of literacy. AIMS: This study aimed to evaluate a newly developed pictorial tool that facilitates a conversation about gender between a child or adolescent (aged 11-18) and their clinician, enabling a diverse understanding and expression of gender identity. METHODS: The Perth Gender Picture (PGP) was co-created between clinicians and young clients between 2016 and 2018. In 2018, the measure was evaluated through a pilot study at the Gender Diversity Service at Perth Children's Hospital in Western Australia. After use of the PGP during a clinical consultation, clients were invited to fill in a feedback questionnaire about their experience of its use. Clinicians participated in unstructured interviews to give their feedback. RESULTS: Most participants rated the PGP as easy to understand, acceptable and useful, and many stated that they found gender easier to describe with the picture rather than words. The results show positive uptake from clients, demonstrating feasible implementation with gender diverse young people. DISCUSSION: This evaluation positions the PGP as a useful tool to facilitate conversations about gender identity between gender diverse children and adolescents and their clinicians, in a nonjudgmental and playful manner. It is well-suited to young people who may have limited literacy or difficulty with complex language. The PGP has potential for use in other age groups and non-clinical contexts.

Gender-affirming hormones and surgery in transgender children and adolescents.

The Endocrine Society Clinical Practice Guidelines on the treatment of gender incongruent people recommend the use of gender-affirming cross-sex hormone (CSH) interventions in transgender children and adolescents who request this treatment, who have undergone psychiatric assessment, and have maintained a persistent transgender identity. The intervention can help to affirm gender identity by inducing masculine or feminine physical characteristics that are congruent with an individual's gender expression, while aiming to improve mental health and quality-of-life outcomes. Some transgender individuals might also wish to access gender-affirming surgeries during adolescence; however, research to inform best clinical practice for surgeons and other medical professionals is scarce. This Review explores the available published evidence on gender-affirming CSH and surgical interventions in transgender children and adolescents, amalgamating findings on mental health outcomes, cognitive and physical effects, side-effects, and safety variables. The small amount of available data suggest that when clearly indicated in accordance with international guidelines, gender-affirming CSHs and chest wall masculinisation in transgender males are associated with improvements in mental health and quality of life. Evidence regarding surgical vaginoplasty in transgender females younger than age 18 years remains extremely scarce and conclusions cannot yet be drawn regarding its risks and benefits in this age group. Further research on an international scale is urgently warranted to clarify long-term outcomes on psychological functioning and safety.

Acute Tryptophan Depletion Moja-De: A Method to Study Central Nervous Serotonin Function in Children and Adolescents.

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.

Mental Health Correlates of Autism Spectrum Disorder in Gender Diverse Young People: Evidence from a Specialised Child and Adolescent Gender Clinic in Australia.

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 predictor of Internalising behaviours (Anxious/Depressed, Withdrawn/Depressed, Somatic Complaints, Thought Problems subscales) on the Youth Self Report. Indicated ASD was also a significant predictor of scores on all subscales of the Paediatric Quality of Life Inventory. The current findings indicate that gender diverse children and adolescents with indicated ASD comprise an especially vulnerable group that are at marked risk of mental health difficulties, particularly internalising disorders, and poor quality of life outcomes. Services working with gender diverse young people should screen for ASD, and also provide pathways to appropriate care for the commonly associated mental health difficulties.

No detectable effects of acute tryptophan depletion on short-term immune system cytokine levels in healthy adults.

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.

The role of coping in the association between subclinical psychotic experiences and functioning: A within study replication in two independent adolescent samples.

An inverse association between psychosocial functioning and psychotic experiences is now established in both clinical and non-clinical populations, however the mechanisms which drive this are unclear. Adolescents with subclinical psychotic experiences (SPE) are more likely to use maladaptive coping strategies and less likely to use adaptive ones, and maladaptive coping has also been associated with poor functioning. A within study replication in two adolescent samples from the general populations of Melbourne, Australia (n = 723) and Birmingham, United Kingdom (n = 239), was conducted to determine whether the association between SPE and psychosocial functioning is mediated by coping style. SPE were associated with reduced general and family functioning and to a lesser extent with reduced peer functioning. Task-oriented (focusing on solving the problem) and emotion-oriented (negative emotional responses) coping were found to mediate the relationship between SPE and three types of functioning in both the Melbourne and the Birmingham samples. The within study replication consistently found that coping style mediates SPE and psychosocial functioning, despite significant differences in age, gender, functioning, use of coping styles, and level of SPE between the two samples. Longitudinal research is needed to fully understand any causal role coping may play in the relationship between SPE and poor functioning. The results have important public health and clinical implications, and suggest that techniques which increase levels of adaptive coping and reduce levels of maladaptive coping (in particular emotion-oriented styles) may help to break the cycle between SPE, functional decline, and eventual need for care.

Effects of Dietary Acute Tryptophan Depletion (ATD) on NPY Serum Levels in Healthy Adult Humans Whilst Controlling for Methionine Supply-A Pilot Study.

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.

Puberty suppression in transgender children and adolescents.

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 suspending puberty in this population, and propose key research priorities.