A unique strength of the development of the World Health Organization (WHO)’s ICD-11 classification of mental, behavioural and neurodevelopmental disorders has been the active input from multiple global stakeholders. Draft versions of the ICD-11 for Morbidity and Mortality Statistics (MMS), including brief definitions, have been available on the ICD-11 beta platform (https://icd.who.int/dev11/l-m/en) for public review and comment for the past several years1. Submissions were reviewed by the WHO for the development of both the MMS version of the ICD-11 and the version for clinical use by mental health specialists, the Clinical Descriptions and Diagnostic Guidelines (CDDG)1. Here, we summarize common themes of the submissions for the categories that generated the greatest response. All comments and proposals were reviewed for categories currently classified in the chapter on mental and behavioural disorders in ICD-10, although some of these have been reconceptualized and moved to new ICD-11 chapters on sleep-wake disorders and conditions related to sexual health2. Between January 1, 2012 and December 31, 2017, 402 comments and 162 proposals were submitted on mental, behavioural and neurodevelopmental disorders, sleep-wake disorders, and conditions related to sexual health. The largest number of submissions related to mental, behavioural and neurodevelopmental disorders focused on compulsive sexual behaviour disorder (N=47), complex post-traumatic stress disorder (N=26), bodily distress disorder (N=23), autism spectrum disorder (N=17), and gaming disorder (N=11). Submissions on conditions related to sexual health mainly addressed gender incongruence of adolescence and adulthood (N=151) and gender incongruence of childhood (N=39). Few submissions were related to sleep-wake disorders (N=18). We performed qualitative content analysis to identify the main themes of submissions related to categories on which there were at least 15 comments. Thus, 59% of all comments and 29% of all proposals were coded. Submissions were independently rated by two assessors. Multiple content codes could apply to each submission. Inter-rater reliability was calculated using Cohen's kappa; only codings with good inter-rater reliability (κ≥⃒0.6) are considered here (82.5%). Compulsive sexual behaviour disorder received the highest number of submissions of all mental disorders (N=47), but often from the same individuals (N=14). The introduction of this diagnostic category has been passionately debated3 and comments on the ICD-11 definition recapitulated ongoing polarization in the field. Submissions included antagonistic comments among commenters, such as accusations of a conflict of interest or incompetence (48%; κ=0.78) or claims that certain organizations or people would profit from inclusion or exclusion in ICD-11 (43%; κ=0.82). One group expressed support (20%; κ=0.66) and considered that there is sufficient evidence (20%; κ=0.76) for inclusion, whereas the other strongly opposed inclusion (28%; κ=0.69), stressing poor conceptualization (33%; κ=0.61), insufficient evidence (28%; κ=0.62), and detrimental outcomes (22%; κ=0.86). Both groups cited neuroscientific evidence (35%; κ=0.74) to support their arguments. Few commenters proposed actual changes to the definition (4%; κ=1). Instead, both sides discussed nosological questions such as conceptualization of the condition as impulsivity, compulsivity, behavioural addiction or expression of normal behavior (65%; κ=0.62). The WHO believes that the inclusion of this new category is important for a legitimate clinical population to receive services4. Concerns about overpathologizing are addressed in the CDDG, but this guidance does not appear in the brief definitions available to beta platform commenters. A number of submissions related to complex post-traumatic stress disorder supported its inclusion in ICD-11 (16%; κ=0.62), with none explicitly arguing against inclusion (κ=1). However, several submissions suggested changes to the definition (36%; κ=1), submitted critical comments (24%; κ=0.60) (e.g., concerning the conceptualization), or discussed the diagnostic label (20%; κ=1). Several comments (20%; κ=0.71) emphasized that recognition of this condition as a mental disorder would stimulate research and facilitate diagnosis and treatment. A majority of submissions regarding bodily distress disorder were critical, but were often made by the same individuals (N=8). Criticism mainly focused on conceptualization (48%; κ=0.64) and the disorder name (43%; κ=0.91). Use of a diagnostic term that is closely associated with the differently conceptualized bodily distress syndrome5 was seen as problematic. One criticism was that the definition relies too heavily on the subjective clinical decision that patients’ attention directed towards bodily symptoms is “excessive”. A number of comments (17%; κ=0.62) expressed concern that this would lead to patients being classified as mentally disordered and preclude them from receiving appropriate biologically-oriented care. Some contributors submitted proposals for changes to the definition (30%; κ=0.89). Others opposed inclusion of the disorder altogether (26%; κ=0.88), while no submission (κ=1) expressed support for inclusion. The WHO decided to retain bodily distress disorder as a diagnostic category6 and addressed concerns by requiring in the CDDG the presence of additional features, such as significant functional impairment. Submissions concerning conditions related to sexual health showed strong support for removal of sexual dysfunctions and gender diagnoses from the mental disorders chapter and creation of a separate chapter (35%; κ=0.88)7. Many submissions (25%; κ=0.97) used a template message provided by the World Association for Sexual Health. Several submissions argued that retaining gender incongruence in the disease classification would harm and stigmatize transgender people (14%; κ=0.80), proposed a different phrasing of the definition (18%; κ=0.71) or a different diagnostic label (23%; κ=0.62). The WHO changed the definitions in part based on the comments received7. Interestingly, a large group of submissions on the proposed ICD-11 definition for gender incongruence of childhood expressed opposition to current standards of care by explicitly objecting to social transition and gender-affirming treatment of minors (46%; κ=0.72), matters that, although important and controversial, have to do with treatment rather than with classification. The proposed definition was criticized or opposed in 31% of submissions (κ=0.62), with some using a template provided by the World Association for Sexual Health to urge a revision based on consultation from the community (15%; κ=0.93). Others opposed the diagnosis expressing fear of pathologizing childhood gender diversity (15%; κ=0.93) and claiming that it is unnecessary because there would be neither distress (11%; κ=0.80) nor need for gender-affirming health care (28%; κ=0.65) in children. Some also argued that a diagnosis is not necessary for research purposes, pointing out that research on homosexuality has flourished since its removal from the ICD (9%; κ=0.745). While acknowledging the controversies surrounding treatment, the WHO retained the category to help ensure access to appropriate clinical care while addressing stigma through its placement in the new chapter of conditions related to sexual health as well as through additional information in the CDDG7. In interpreting these comments, it is clear that many of the submissions have been made from an advocacy perspective, often focused on a particular category. It is appropriate for scientific experts to review their recommendations in the light of patient experience and feedback. The WHO has used the comments and proposals on the beta platform in combination with other sources of information, particularly developmental field studies8, 9, as a basis for making modifications in the MMS and CDDG.

The variation between countries in treatments used for OCD needs further evaluation. Exposure and response prevention is not used as frequently as guidelines suggest and appears difficult to access in most countries. Updated treatment guidelines are recommended.

Young ultra-Orthodox women in Israel have been faced in recent years with a greater risk of developing disordered eating, as they are more exposed to Westernized norms of the thin-body ideal, self-realization, and personal choice. Most are treated by mainstream Israeli psychotherapists who likely have different value systems and different perspectives on the nature of the illness, aims of treatment, and recovery. Ultra-Orthodox psychotherapists may well experience a conflict between a need to be loyal to their patients and a concomitant need to honor the values of patients' families and the community from which they come. The current article presents a theoretical background and four case studies highlighting the complexities and controversies inherent in the treatment of these women. We conclude that both ultra-Orthodox and mainstream secular psychotherapists must be knowledgeable in regard to both Judaism and psychology, and be flexible, creative, and emphatic to all parties, to arrive at a compromised definition of recovery that can be accepted by the patient, her family, and her community.

Bill & Melinda Gates Foundation, National Health and Medical Research Centre (Australia).

Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.

The prevalence of ADHD in adolescents seeking bariatric surgery was very high. Diagnosed ADHD was not related to post-surgical weight loss, whereas baseline ADHD-related behaviour was associated with higher post-surgical weight loss.

Our findings indicate an association of plasma neopterin with risk of an inpatient hospital diagnosis of AF, which remains after adjustment for traditional risk factors as well as for CRP. This study highlights a role of cellular immune activation, in addition to inflammation, in AF pathogenesis.

HIV-associated neurocognitive impairments (HANI) are a spectrum of neurological disorders due to the effects of HIV-1 on the central nervous system (CNS). The HIV-1 subtypes; HIV-1 subtype B (HIV-1B) and HIV-1 subtype C (HIV-1C) are responsible for the highest prevalence of HANI and HIV infections respectively. The HIV transactivator of transcription (Tat) protein is a major contributor to the neuropathogenesis of HIV. The effects of the Tat protein on cells of the CNS is determined by the subtype-associated amino acid sequence variations. The extent to which the sequence variation between Tat-subtypes contribute to underlying mechanisms and neurological outcomes are not clear. In this review of the literature, we discuss how amino acid variations between HIV-1B Tat (TatB) and HIV-1C Tat (TatC) proteins contribute to the potential underlying neurobiological mechanisms of HANI. Tat-C is considered to be a more effective transactivator, whereas Tat-B may exert increased neurovirulence, including neuronal apoptosis, monocyte infiltration into the brain, (neuro)inflammation, oxidative stress and blood-brain barrier damage. These findings support the premise that Tat variants from different HIV-1 subtypes may direct neurovirulence and neurological outcomes in HANI.

Resilience is related to the behavioral health of vulnerable HIV-affected adolescents. Resilience-focused interventions hold promise for improving the behavioral health of adolescents living in high HIV prevalence settings.