Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory proteome.

The association between Attention Deficit Hyperactivity Disorder (ADHD) and low-grade inflammation has been explored in children but rarely in adults. Inflammation is characteristic of some, but not all, patients with ADHD and might be influenced by ADHD medication but also lifestyle factors including nutrition, smoking, and stress. It is also still unclear if any specific symptoms are related to inflammation. Therefore, we assessed 96 inflammatory proteins in a deeply phenotyped cohort of 126 adult ADHD participants with a stable medication status using OLINK technology. A data-based, unsupervised hierarchical clustering method could identify two distinct biotypes within the 126 ADHD participants based on their inflammatory profile: a higher inflammatory potential (HIP) and a lower inflammatory protein potential (LIP) group. Biological processes that differed strongest between groups were related to the NF-κB pathway, chemokine signaling, IL-17 signaling, metabolic alterations, and chemokine attraction. A comparison of sample characteristics revealed that the HIP group was more likely to have higher levels of chronic stress (p < 0.001), a higher clinical global impression scale score (p = 0.030), and a higher risk for suicide (p = 0.032). Medication status did not influence protein levels significantly (p ≥ 0.074), but psychotropic co-medication (p ≤ 0.009) did. In conclusion, our data suggest the presence of two distinct biotypes in adults with ADHD. Higher levels of inflammatory proteins in ADHD are linked to higher levels of chronic perceived stress in a linear fashion. Further research on inflammation in adults with ADHD should take stress levels into account.

Stress and coping strategies of families of pediatric solid organ transplant recipients in times of pandemic.

Objective: Pediatric solid organ transplantation (SOT) is a chronic condition that impacts the whole family system. The objective of this study is to evaluate psychopathology, family stress, and coping strategies in families of SOT recipients compared to families of healthy children and adolescents. Moreover, it analyzes if the stress related to the COVID-19 pandemic has had an additional impact on these families. Methods: The sample was recruited between May and July 2021, during the fourth and fifth wave of the pandemic in Spain. It consisted of 102 families, 51 with a pediatric recipient who had undergone a SOT (liver, kidney, heart, or lung) and 51 healthy controls, matched by child age and gender. A primary caregiver from each family answered an online sociodemographic questionnaire and different tests to evaluate family stress, depression, anxiety, coping strategies, and effects of the pandemic on the family. Results: Caregivers were mostly mothers (89.2%). Families of SOT recipients showed greater anxiety (U = 863.5, p = 0.003) and more total stress, stress related to childcare (t = -2.043; p = 0.045), and parent-child interaction stress (U = 355.5, p = 0.015). SOT families used more avoidance strategies, specifically denial (U = 889.5; p = 0.010) and abandonment of coping efforts (U = 1,013; p = 0.047), more religious strategies (U = 792.5; p = 0.031), and fewer social support coping strategies (t = 2.098; p = 0.038). No differences were found between groups in terms of exposure, impact, and distress more than 1 year after the start of the pandemic. Conclusion: SOT families showed clinical levels of anxiety, more parent-child interaction stress, more difficulties in taking care of their child, more avoidance and religious strategies, and less use of social support strategies, even 4 years after transplantation. The pandemic did not have an additional differential effect on SOT families. Caregivers of SOT patients can benefit from psychological interventions focused on parents' mental health, parent-child connectedness, skill building, and social support aid groups, with attention to multiculturalism and promoting a better balance between caregivers. There is a need for family interventions that are maintained over time. Strategies that offer this support to families through digital resources can facilitate adjustment to chronic illness, especially in pandemic times.

Impact of COVID-19 on Families of Pediatric Solid Organ Transplant Recipients.

OBJECTIVE: The COVID-19 pandemic and lockdown measures have had a clear psychological impact on families, and specifically those with children with chronic illnesses have reported greater overloads and exhaustion. The objective of this study was to evaluate the exposure, impact and experience of the pandemic on families of pediatric solid organ transplant (SOT) recipients compared to families of healthy children and adolescents. METHODS: We recruited 96 families, 48 with a pediatric SOT recipient and 48 healthy controls, matched by child age and gender. A primary caregiver from each family responded to an online sociodemographic questionnaire and the COVID-19 Exposure and Family Impact Survey (CEFIS), which explores the exposure, impact and experience of the pandemic and lockdown on families. RESULTS: Exposure to the pandemic was greater in families of healthy children and adolescents. The impact was mostly negative in both groups: caregivers reported increased anxiety (76%) and mood disturbances (71.9%) and hindered quality of sleep (64.6%) and health habits (58.3%). On the positive side, family relationships improved. Qualitatively, the SOT group positively perceived isolation and established hygienic measures as protective and destigmatizing, although they reported fear of virus transmission to their child. CONCLUSIONS: The psychological impact of the pandemic has been similar in both groups, although families of transplant recipients have protected themselves more, probably because they are used to prevention measures and they see contagion as a graver risk. Additionally, SOT recipients' families presented some idiosyncratic elements, especially a decrease in their perception of stigma associated with the medical condition.

Sleep disturbances in autism spectrum disorder without intellectual impairment: relationship with executive function and psychiatric symptoms.

The autism spectrum disorder (ASD) is a neurodevelopmental condition, frequently accompanied by medical and psychiatric pathology. One of the most commonly found problems associated with ASD is sleep disturbances, which are estimated to affect approximately 80% of the people with ASD, not only during childhood but also in the adolescence and adult stages. Nevertheless, the relationship of these sleep difficulties with autism severity, as well as other associated impairments such as executive functioning and psychiatric disorders (eg, depression), has not yet been widely studied. The main objective of the present study was to explore the relationship between sleep disturbances, subjective measures of executive function, and psychiatric pathology in the ASD population. To reach that goal, a group of 89 participants with ASD (44 children/adolescents and 45 adults) was recruited and evaluated with self-reported measures of executive function performance and psychiatric pathology tests. Multivariate analysis showed a significant association between sleep disturbances and psychiatric symptoms in both ASD groups, with greater sleep disturbances predicting more severe psychiatric pathology. No significant association was found with executive function in any group. Limitations included a small sample size and lack of objective measures. Sleep problems seem to be associated with the severity of psychiatric pathology throughout the lifespan, increasing the chance of developing psychiatric symptoms when they were present. Improving sleep quality in ASD at all ages may result in preventing and/or decreasing psychiatric pathology in this population.

COVID-19 pandemic effects in people with Autism Spectrum Disorder and their caregivers: Evaluation of social distancing and lockdown impact on mental health and general status.

Among the difficulties associated with Autism Spectrum Disorder (ASD) are those related to adaptation to changes and new situations, as well as anxious-depressive symptoms frequently related to excessive environmental requirements. The main objective of this research is to study the psychological impact of the lockdown due to the social emergency situation (COVID-19) in children/adolescents and adults diagnosed with ASD. Participants were 37 caregivers of children/adolescents with ASD, also 35 ASD adults and 32 informants. Evaluation was conducted through a web survey system and included standardized clinical questionnaires (CBCL and SCL-90-R), which were compared with results before lockdown start, and a brief self-reported survey addressing the subjective perception of changes in daily functioning areas. The results revealed a reduction of psychopathological symptoms in both age groups, but only reaching statistical significance in the adult group, except for Somatization, Anxiety, and Obsessive-Compulsive domains. ASD severity Level 2 showed greater improvement after lockdown onset in the children/adolescent group when compared to ASD Level 1 participants. Younger adults (18-25 yoa) reported greater improvement than older adults (=>25 yoa). Survey results indicate an improvement of feeding quality and a reduction in the number of social initiations during the lockdown. Adult ASD participants perceived a decrease in stress levels after the lockdown onset, whereas caregivers reported higher stress levels at the same point in both age groups. Limitations included the small number of participants and a heterogeneous evaluation window between measures. Pyschopathological status after two months of social distancing and lockdown seems to improve in ASD young adult population.

Treating impulsivity with probiotics in adults (PROBIA): study protocol of a multicenter, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Impulsivity and compulsivity are related to emotional and social maladjustment and often underlie psychiatric disorders. Recently, alterations in microbiota composition have been shown to have implications for brain development and social behavior via the microbiota-gut-brain axis. However, the exact mechanisms are not fully identified. Recent evidence suggests the modulatory effect of synbiotics on gut microbiota and the contribution of these agents in ameliorating symptoms of many psychiatric diseases. To date, no randomized controlled trial has been performed to establish the feasibility and efficacy of this intervention targeting the reduction of impulsivity and compulsivity. We hypothesize that supplementation with synbiotics may be an effective treatment in adults with high levels of impulsivity and/or compulsivity. METHODS/DESIGN: This is a prospective, multicenter, double-blind, randomized controlled trial with two arms: treatment with a synbiotic formula versus placebo treatment. The primary outcome is the response rate at the end of the placebo-controlled phase (response defined as a Clinical Global Impression-Improvement Scale score of 1 or 2 = very much improved or much improved, plus a reduction in the Affective Reactivity Index total score of at least 30% compared with baseline). A total of 180 participants with highly impulsive behavior and a diagnosis of attention deficit/hyperactivity disorder (ADHD) and/or borderline personality disorder, aged 18-65 years old, will be screened at three study centers. Secondary outcome measures, including changes in general psychopathology, ADHD symptoms, neurocognitive function, somatic parameters, physical activity, nutritional intake, and health-related quality of life, will be explored at assessments before, during, and at the end of the intervention. The effect of the intervention on genetics, microbiota, and several blood biomarkers will also be assessed. Gastrointestinal symptoms and somatic complaints will additionally be explored at 1-week follow-up. DISCUSSION: This is the first randomized controlled trial to determine the effects of supplementation with synbiotics on reducing impulsive and compulsive behavior. This clinical trial can contribute to explaining the mechanisms involved in the crosstalk between the intestinal microbiome and the brain. If effects can be established by reducing impulsive and compulsive behavior, new cost-effective treatments might become available to these patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03495375. Registered on 26 February 2018.