Dataset Information

Behavioural and Psychiatric Phenotypes in Men and Boys with X-Linked Ichthyosis: Evidence from a Worldwide Online Survey.

ABSTRACT:

Background

X-linked ichthyosis (XLI) is a rare dermatological condition arising from deficiency for the enzyme steroid sulfatase (STS). Preliminary evidence in boys with XLI, and animal model studies, suggests that individuals lacking STS are at increased risk of developmental disorders and associated traits. However, the behavioural profile of children with XLI is poorly-characterised, and the behavioural profile of adults with XLI has not yet been documented at all.

Materials and methods

Using an online survey, advertised worldwide, we collected detailed self- or parent-reported information on behaviour in adult (n = 58) and younger (?18yrs, n = 24) males with XLI for comparison to data from their non-affected brothers, and age/gender-matched previously-published normative data. The survey comprised demographic and background information (including any prior clinical diagnoses) and validated questionnaires assaying phenotypes of particular interest (Adult ADHD Self-Report Scale v1.1, Barrett Impulsiveness Scale-11, adult and adolescent Autism Quotient, Kessler Psychological Distress Scales, and Disruptive Behaviour Disorder Rating Scale).

Results

Individuals with XLI generally exhibited normal sensory function. Boys with XLI were at increased risk of developmental disorder, whilst adults with the condition were at increased risk of both developmental and mood disorders. Both adult and younger XLI groups scored significantly more highly than male general population norms on measures of inattention, impulsivity, autism-related traits, psychological distress and disruptive behavioural traits.

Conclusions

These findings indicate that both adult and younger males with XLI exhibit personality profiles that are distinct from those of males within the general population, and suggest that individuals with XLI may be at heightened risk of psychopathology. The data are consistent with the notion that STS is important in neurodevelopment and ongoing brain function, and with previous work suggesting high rates of developmental disorders in boys with XLI. Our results suggest that individuals with XLI may require medical care from multidisciplinary teams, and should help to inform genetic counselling for the condition.

SUBMITTER: Chatterjee S

PROVIDER: S-EPMC5053497 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Behavioural and Psychiatric Phenotypes in Men and Boys with X-Linked Ichthyosis: Evidence from a Worldwide Online Survey.

Chatterjee Sohini S Humby Trevor T Davies William W

PloS one 20161006 10

<h4>Background</h4>X-linked ichthyosis (XLI) is a rare dermatological condition arising from deficiency for the enzyme steroid sulfatase (STS). Preliminary evidence in boys with XLI, and animal model studies, suggests that individuals lacking STS are at increased risk of developmental disorders and associated traits. However, the behavioural profile of children with XLI is poorly-characterised, and the behavioural profile of adults with XLI has not yet been documented at all.<h4>Materials and me ...[more]

PMID: 27711218

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Project description:X-linked ichthyosis (XLI) is a rare X-linked dermatological condition arising from deficiency for the enzyme steroid sulfatase (STS). STS is normally expressed in the brain, and males with XLI exhibit personality differences from males in the general population, and are at increased risk of developmental and mood disorders. As the STS gene escapes X-inactivation, female carriers of XLI-associated genetic mutations have reduced STS expression/activity relative to non-carrier females, and could manifest similar behavioural phenotypes to males with XLI. Additionally, as STS activity normally increases in female tissues towards late pregnancy and into the puerperium, carrier females could theoretically present with increased rates of postpartum psychopathology. Using a worldwide online survey comprising custom-designed demographic questionnaires and multiple validated psychological questionnaires, we collected detailed self-reported information on non-postpartum and postpartum behaviour in confirmed adult (>16yrs) female carriers of genetic mutations associated with XLI (n = 94) for statistical comparison to demographically-matched previously-published normative data from female controls (seven independent studies, 98?n?2562), adult males with XLI (n = 58), and to newly-obtained online survey data from a general population sample of mothers from the United Kingdom and United States of America (n = 263). The pattern of results in carrier females relative to controls was remarkably similar to that previously observed in males with XLI, with evidence for increased rates of developmental and mood disorders, and elevated levels of inattention, impulsivity, autism-related traits and general psychological distress. Carrier females exhibited a significantly elevated rate of postpartum mental health conditions (notably mild depression) relative to controls which could not be accounted for by social factors. Our data confirm the psychological profile associated with XLI-associated mutations, and suggest that female carriers may be at increased risk of psychopathology, including in the postpartum period. These findings are relevant to families affected by XLI, to clinicians involved in the care of these families, and to genetic counsellors.

Project description:Background: According to epidemiological data, over 450 million people worldwide suffer from mental disorders, presenting one of the major challenges of modern medicine. In their everyday lives, patients, in addition to fighting the disease itself, often struggle with stigmatization. This phenomenon negatively affects both the diagnostic and therapeutic processes, as well as the patients' everyday functioning. This study aimed to assess stigma attitudes toward psychiatry and psychiatric patients among undergraduate medical students. Methods: This study used a Computer-Assisted Web Interview (CAWI), which included the standardized items from the Mental Illness: Clinicians' Attitudes (MICA-2) scale to evaluate stigma. The study was disseminated via the internet to students from medical universities from 65 countries worldwide. Participation was voluntary and anonymous. The study involved 1,216 students from these 65 countries. Most of the sample were women, and most were medical faculty students and students living in cities with more than 500,000 residents. Taking into consideration Gross Domestic Product (GDP) per capita and Human Development Index (HDI) variables, it can be seen that there was a prevalence of medical students from highly developed countries. Results: For the whole sample, the mean MICA-2 score was 40.5 points. Women and medical and nursing students showed more positive attitudes toward psychiatric patients. Students from countries with the highest economic development levels also achieved statistically lower MICA-2 scores. Lower score means a more positive attitude. Conclusion: Stigma toward both psychiatry and psychiatric patients is common among undergraduate medical students. Female students and respondents with a history of mental disorders in countries with high HDI and GDP per capita indices show more favorable attitudes than other medical students. There is a need to further our understanding of the problem of stigmatization, both among the general population and among medical personnel, and to implement and maintain appropriate measures to reduce stigma toward psychiatry.

Project description:BACKGROUND:X-linked ichthyosis (XLI) is an uncommon dermatological condition resulting from a deficiency of the enzyme steroid sulfatase (STS), often caused by X-linked deletions spanning STS. Some medical comorbidities have been identified in XLI cases, but small samples of relatively young patients has limited this. STS is highly expressed in subcortical brain structures, and males with XLI and female deletion carriers appear at increased risk of developmental/mood disorders and associated traits; the neurocognitive basis of these findings has not been examined. METHODS:Using the UK Biobank resource, comprising participants aged 40-69?years recruited from the general UK population, we compared multiple medical/neurobehavioural phenotypes in males (n=86) and females (n=312) carrying genetic deletions spanning STS (0.8-2.5?Mb) (cases) to male (n=190?577) and female (n=227?862) non-carrier controls. RESULTS:We identified an elevated rate of atrial fibrillation/flutter in male deletion carriers (10.5% vs 2.7% in male controls, Benjamini-Hochberg corrected p=0.009), and increased rates of mental distress (p=0.003), irritability (p<0.001) and depressive-anxiety traits (p<0.05) in male deletion carriers relative to male controls completing the Mental Health Questionnaire. While academic attainment was unaffected, male and female deletion carriers exhibited impaired performance on the Fluid Intelligence Test (Cohen's d?0.05, corrected p<0.1). Neuroanatomical analysis in female deletion carriers indicated reduced right putamen and left nucleus accumbens volumes (Cohen's d?0.26, corrected p<0.1). CONCLUSION:Adult males with XLI disease-causing deletions are apparently at increased risk of cardiac arrhythmias and self-reported mood problems; altered basal ganglia structure may underlie altered function and XLI-associated psychiatric/behavioural phenotypes. These results provide information for genetic counselling of deletion-carrying individuals and reinforce the need for multidisciplinary medical care.

Project description:Background and Objectives There are no therapies for preventing cerebral demyelination in X-linked adrenoleukodystrophy (ALD). Higher plasma vitamin D levels have been linked to lower risk of inflammatory brain lesions. We assessed the safety and pharmacokinetics of oral vitamin D dosing regimens in boys and young men with ALD. Methods In this open-label, multicenter, phase 1 study, we recruited boys and young men with ALD without brain lesions to a 12-month study of daily oral vitamin D3 supplementation. Our primary outcome was attainment of plasma 25-hydroxyvitamin D levels in target range (40–80 ng/mL) at 6 and 12 months. Secondary outcomes included safety and glutathione levels in the brain, measured with magnetic resonance spectroscopy, and blood, measured via mass spectrometry. Participants were initially assigned to a fixed dosing regimen starting at 2,000 IU daily, regardless of weight. After a midstudy safety assessment, we modified the dosing regimen, so all subsequent participants were assigned to a weight-stratified dosing regimen starting as low as 1,000 IU daily. Results Between October 2016 and June 2019, we enrolled 21 participants (n = 12, fixed-dose regimen; n = 9, weight-stratified regimen) with a median age of 6.7 years (range: 1.9–22 years) and median weight of 20 kg (range: 11.7–85.5 kg). The number of participants achieving target vitamin D levels was similar in both groups at 6 months (fixed dose: 92%; weight stratified: 78%) and 12 months (fixed dose: 67%; weight stratified: 67%). Among the 12 participants in the fixed-dose regimen, half had asymptomatic elevations in either urine calcium:creatinine or plasma 25-hydroxyvitamin D; no laboratory deviations occurred with the weight-stratified regimen. Glutathione levels in the brain, but not the blood, increased significantly between baseline and 12 months. Discussion Our vitamin D dosing regimens were well tolerated and achieved target 25-hydroxyvitamin D levels in most participants. Brain glutathione levels warrant further study as a biomarker for vitamin D and ALD. Classification of Evidence This study provides Class IV evidence that fixed or weight-stratified vitamin D supplementation achieved target levels of 25-hydroxyvitamin D in boys and young men with X-ALD without brain lesions.

Project description:BackgroundHigh rates of adverse mood/neurodevelopmental traits are seen in multiple dermatological conditions, and can significantly affect patient quality of life. Understanding the sex-specific nature, magnitude, impact and basis of such traits in lesser-studied conditions like ichthyosis, is important for developing effective interventions.AimTo quantify and compare relevant psychological traits in men with X-linked ichthyosis (XLI, n = 54) or in XLI carrier women (n = 83) and in patients with ichthyosis vulgaris (IV, men n = 23, women n = 59) or psoriasis (men n = 30, women n = 122), and to identify factors self-reported to contribute most towards depressive, anxious and irritable phenotypes.MethodsParticipants recruited via relevant charities or social media completed an online survey of established questionnaires. Data were analysed by sex and skin condition, and compared with general population data.ResultsCompared with the general population, there was a higher rate of lifetime prevalence of mood disorder diagnoses across all groups and of neurodevelopmental disorder diagnoses in the XLI groups. The groups exhibited similarly significant elevations in recent mood symptoms (Cohen d statistic 0.95-1.28, P < 0.001) and neurodevelopmental traits (d = 0.31-0.91, P < 0.05) compared with general population controls, and self-reported moderate effects on quality of life and stigmatization. There were strong positive associations between neurodevelopmental traits and recent mood symptoms (r > 0.47, P < 0.01), and between feelings of stigmatization and quality of life, particularly in men. Numerous factors were identified as contributing significantly to mood symptoms in a condition or sex-specific, or condition or sex-independent, manner.ConclusionWe found that individuals with XLI, IV or psoriasis show higher levels of mood disorder diagnoses and symptoms than matched general population controls, and that the prevalence and severity of these is similar across conditions. We also identified a number of factors potentially conferring either general or condition-specific risk of adverse mood symptoms in the three skin conditions, which could be targeted clinically and/or through education programmes. In clinical practice, recognizing mood/neurodevelopmental problems in ichthyosis and psoriasis, and addressing the predisposing factors identified by this study should benefit the mental health of affected individuals.

Dataset Information

Behavioural and Psychiatric Phenotypes in Men and Boys with X-Linked Ichthyosis: Evidence from a Worldwide Online Survey.

Background

Materials and methods

Results

Conclusions

Publications

Behavioural and Psychiatric Phenotypes in Men and Boys with X-Linked Ichthyosis: Evidence from a Worldwide Online Survey.

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