Faculty Bibliography

OBJECTIVE:To evaluate zonulin and occludin levels, potentially associated with immunological pathways in the gut-brain axis, in children with attention-deficit/hyperactivity disorder (ADHD). METHOD/METHODS:We examined the association between serum levels of zonulin and occluding, and behavioral/emotional problems in children with ADHD. 40 medication-naïve children meeting Diagnostic and statistical (DSM-5) criteria for ADHD (11 females; mean (SD) age 9.4 (1.6) years) and 39 healthy comparisons (12 females; mean (SD) age 9.3 (1.9) years) were studied. Serum zonulin and occludin levels were measured by (ELISA). RESULTS:We found higher mean (SD) serum zonulin levels [37.1 (28.2) vs 8.1 (4.5) ng/mL; P<0.001) and occludin levels [2.4 (1.6) vs 0.6 (0.4) ng/mL; P<0.001] in the ADHD group compared to control group. Serum zonulin levels had a positive correlation with weight (r=0.452; P=0.003) and BMI (r=0.401; P=0.01) among children with ADHD. Serum zonulin and occludin levels also had a positive correlation with Conners parent rating scale scores (r=0.58; P<0.001), and Strengths and difficulties questionnaire scores (r=0.49; P<0.001). Multiple linear regression analysis revealed that age, sex, weight, conduct problems and oppositional sub-scores were significant predictors of increased serum zonulin levels. CONCLUSION/CONCLUSIONS:These data confirm an association between ADHD, and serum zonulin and occludin levels. Pathophysiological and clinical significance of these findings needs to be elucidated.

The COVID-19 pandemic led ADHD services to modify the clinical practice to reduce in-person contact as much as possible to minimise viral spread. This had far-reaching effects on day-to-day clinical practice as remote assessments were widely adopted. Despite the attenuation of the acute threat from COVID, many clinical services are retaining some remote practices. The lack of clear evidence-based guidance about the most appropriate way to conduct remote assessments meant that these changes were typically implemented in a localised, ad hoc, and un-coordinated way. Here, the European ADHD Guidelines Group (EAGG) discusses the strengths and weaknesses of remote assessment methods of children and adolescents with ADHD in a narrative review based on available data and expert opinions to highlight key recommendations for future studies and clinical practice. We conclude that going forward, despite remote working in clinical services functioning adequately during the pandemic, all required components of ADHD assessment should still be completed following national/international guidelines; however, the process may need adaptation. Social restrictions, including changes in education provision, can either mask or exacerbate features associated with ADHD and therefore assessment should carefully chart symptom profile and impairment prior to, as well as during an ongoing pandemic. While remote assessments are valuable in allowing clinical services to continue despite restrictions and may have benefits for routine care in the post-pandemic world, particular attention must be paid to those who may be at high risk but not be able to use/access remote technologies and prioritize these groups for conventional face-to-face assessments.

We conducted a systematic review and a meta-analysis to quantitatively summarize evidence on the association between attention-deficit/hyperactivity disorder (ADHD) and type 2 diabetes (T2D). Moreover, a register-based sibling study was conducted to simultaneously control for confounding factors. A systematic search identified four eligible observational studies (N = 5738,287). The meta-analysis showed that individuals with ADHD have a more than doubled risk of T2D when considering adjusted estimates (OR=2.29 [1.48-3.55], d=0.46). Results from the register-based Swedish data showed a significant association between ADHD and T2D (HR=2.35 [2.14-2.58]), with substance use disorder, depression, and anxiety being the main drivers of the association, and cardiovascular and familiar risk playing a smaller role. While results from the meta-analysis provide evidence for an increased risk of T2D in individuals with ADHD, the register-based analyses show that the association between ADHD and T2D is largely explained by psychiatric comorbidities. Pending further evidence of causal association, our findings suggest that early identification and treatment of ADHD comorbidities might greatly reduce the risk of developing T2D in individuals with ADHD.

BACKGROUND:Several studies have shown associations between maternal interpersonal violence-related posttraumatic stress disorder (PTSD), child mental health problems, and impaired socioemotional development. However, the existing literature lacks evidence linking constellations of risk factors such as maternal interpersonal-violence-related PTSD, psychopathology, and interactive behavior with toddlers and outcome measures at school-age. METHODS:This study involved a prospective, longitudinal investigation of 62 mothers and examined the relationship between maternal variables measured when children were in early childhood (mean age 27 months), and child outcomes when children were school-age (age mean = 83.2 months) while retaining a focus on the context of maternal PTSD. To identify and weigh associated dimensions comparatively, we employed sparse canonical correlation analysis (sCCA) aimed at associating dimensions of a dataset of 20 maternal variables in early childhood with that of more than 20 child outcome variables (i.e., child psychopathology, life-events, and socioemotional skills) at school-age. RESULTS:Phase 1 variables with the highest weights were those of maternal psychopathology: PTSD, depressive and dissociative symptoms, and self-report of parental stress. The highest weighted Phase 2 child outcome measures were those of child psychopathology: PTSD, anxiety, and depressive symptoms as well as peer bullying and victimization. CONCLUSIONS:sCCA revealed that trauma-related concepts in mothers were significantly and reliably associated with child psychopathology and other indicators of risk for intergenerational transmission of violence and victimization. The results highlight the dimensional and multifaceted nature-both for mothers as well as children-of the intergenerational transmission of violence and associated psychopathology.

Previous studies have linked peer bullying to nonsuicidal self-injury (NSSI). However, the evidence is largely limited to population-based groups. This study examined whether there is a relationship between NSSI and being a victim of peer bullying among adolescents in a clinical sample and how this may be influenced by types of bullying. The sample consisted of 96 outpatients with NSSI and 107 healthy adolescents. The Inventory of Statements About Self-Injury, Peer Bullying Scale, and Rosenberg Self-Esteem Scale were applied. Whereas the scores of each bullying type of adolescents with NSSI were significantly higher, their self-esteem scores were significantly lower. Each victimization score of bullying had a negative correlation with NSSI-onset age and self-esteem scores and a positive correlation with self-injury scores. This study demonstrated that being a victim of any type of bullying is strongly associated with self-injury. It would be advisable to screen adolescents with self-injury for exposure to bullying, and vice versa.

Identifying substance use disorders (SUDs) early and accurately improves case formulation and treatment. Previous studies have investigated validity and reliability of the Child and Adolescent Symptom Inventory (CASI) for anxiety, mood, and behavior problems. The present study's aim was to test if the embedded CASI Substance Use (SU) subscale can discriminate adolescents and young adults (AYA) with and without a SUD diagnosis accurately enough to justify clinical application within an evidence-based assessment framework. N = 479 outpatient AYA (age 14-21) and their caregivers completed K-SADS-PLW semistructured diagnostic interviews; caregivers completed the CASI and adolescents completed a parallel version, the Youth (self-report) Inventory (YI). K-SADS-PLW indicated that 33 youth met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for SUDs. Receiver Operating Characteristic (ROC) analyses found that both CASI and YI Substance Use subscale scores significantly identified K-SADS-diagnosed SUDs in AYA: Caregiver area under curve (AUC) = .91, p < .0005; YI(AUC) = .90, p < .0005. There was no significant difference in diagnostic accuracy between informants. Both subscales showed diagnostic and clinical utility in identifying AYA SUDs in outpatient mental health settings. Findings suggest that the CASI-4R subscale could be a helpful screening instrument for AYA SUDs. A case vignette illustrates the clinical application of study findings. Future research should examine rapport as a moderator of reporting accuracy, and replicate use of these measures under varying clinical scenarios. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

OBJECTIVE:Symptoms of attention-deficit/hyperactivity disorder (ADHD) and sleep disturbances frequently co-occur, and can result in significant functional impairments that worsen quality of life. Despite a growing number of studies focusing on the association between sleep disturbances and ADHD symptoms over the last 20 years, the directionality of this association from childhood to early adulthood remains unclear. METHOD:A sample of French parents (n = 1,055) were followed-up over a 9-year period. At children mean ages of 9, 13, and 18 years, parents were interviewed about their children's ADHD symptoms and sleep disturbances. Random-intercept cross-lagged panel models assessed the directionality of the association from childhood to early adulthood. RESULTS:Parent-reported sleep disturbances at a mean age of 13 years predicted increased ADHD symptoms 5 years later. Additional analyses suggested that this effect might be limited to inattentive symptoms, and that ADHD symptoms at a mean age of 9 predicted increased sleep disturbances 4 years later. CONCLUSION:The present study provides evidence of a directional longitudinal association between parent-reported sleep disturbances and ADHD symptoms from adolescence to early adulthood. Our results highlight the importance of identifying sleep disturbances and ADHD symptoms for the design of preventive interventions. Future studies investigating this association in children with a clinical diagnosis of ADHD have the potential to provide important information for clinical practice.

Empirical evidence indicates a significant bidirectional association between mental disorders and physical diseases, but the prospective impact of men-tal disorders on clinical outcomes of physical diseases has not been comprehensively outlined. In this PRISMA- and COSMOS-E-compliant umbrella review, we searched PubMed, PsycINFO, Embase, and Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, up to March 15, 2022, to identify systematic reviews with meta-analysis that examined the prospective association between any mental disorder and clinical outcomes of physical diseases. Primary outcomes were disease-specific mortality and all-cause mortality. Secondary outcomes were disease-specific incidence, functioning and/or disability, symptom severity, quality of life, recurrence or progression, major cardiac events, and treatment-related outcomes. Additional inclusion criteria were further applied to primary studies. Random effect models were employed, along with I² statistic, 95% prediction intervals, small-study effects test, excess significance bias test, and risk of bias (ROBIS) assessment. Associations were classified into five credibility classes of evidence (I to IV and non-significant) according to established criteria, complemented by sensitivity and subgroup analyses to examine the robustness of the main analysis. Statistical analysis was performed using a new package for conducting umbrella reviews (https://metaumbrella.org). Population attributable fraction (PAF) and generalized impact fraction (GIF) were then calculated for class I-III associations. Forty-seven systematic reviews with meta-analysis, encompassing 251 non-overlapping primary studies and reporting 74 associations, were included (68% were at low risk of bias at the ROBIS assessment). Altogether, 43 primary outcomes (disease-specific mortality: n=17; all-cause mortality: n=26) and 31 secondary outcomes were investigated. Although 72% of associations were statistically significant (p<0.05), only two showed convincing (class I) evidence: that between depressive disorders and all-cause mortality in patients with heart failure (hazard ratio, HR=1.44, 95% CI: 1.26-1.65), and that between schizophrenia and cardiovascular mortality in patients with cardiovascular diseases (risk ratio, RR=1.54, 95% CI: 1.36-1.75). Six associations showed highly suggestive (class II) evidence: those between depressive disorders and all-cause mortality in patients with diabetes mellitus (HR=2.84, 95% CI: 2.00-4.03) and with kidney failure (HR=1.41, 95% CI: 1.31-1.51); that between depressive disorders and major cardiac events in patients with myocardial infarction (odds ratio, OR=1.52, 95% CI: 1.36-1.70); that between depressive disorders and dementia in patients with diabetes mellitus (HR=2.11, 95% CI: 1.77-2.52); that between alcohol use disorder and decompensated liver cirrhosis in patients with hepatitis C (RR=3.15, 95% CI: 2.87-3.46); and that between schizophrenia and cancer mortality in patients with cancer (standardized mean ratio, SMR=1.74, 95% CI: 1.41-2.15). Sensitivity/subgroup analyses confirmed these results. The largest PAFs were 30.56% (95% CI: 27.67-33.49) for alcohol use disorder and decompensated liver cirrhosis in patients with hepatitis C, 26.81% (95% CI: 16.61-37.67) for depressive disorders and all-cause mortality in patients with diabetes mellitus, 13.68% (95% CI: 9.87-17.58) for depressive disorders and major cardiac events in patients with myocardial infarction, 11.99% (95% CI: 8.29-15.84) for schizophrenia and cardiovascular mortality in patients with cardiovascular diseases, and 11.59% (95% CI: 9.09-14.14) for depressive disorders and all-cause mortality in patients with kidney failure. The GIFs confirmed the preventive capacity of these associations. This umbrella review demonstrates that mental disorders increase the risk of a poor clinical outcome in several physical diseases. Prevention targeting mental disorders - particularly alcohol use disorders, depressive disorders, and schizophrenia - can reduce the incidence of adverse clinical outcomes in people with physical diseases. These findings can inform clinical practice and trans-speciality preventive approaches cutting across psychiatric and somatic medicine.

Neuroleptic malignant syndrome (NMS) is a life-threatening condition classically associated with the use of antipsychotic medications. NMS commonly presents with initial mental status changes, followed by muscle rigidity, fever, and eventual dysautonomia. Cocaine intoxication can present with symptoms that are very similar to those found in NMS, making differentiating the two disorders challenging. We present the case of a 28-year-old female with a history of cocaine use disorder who presented with acute cocaine intoxication. She had severe agitation associated with her intoxication, requiring the use of antipsychotic medications. Subsequently, she developed atypical NMS from abrupt dopamine withdrawal after receiving the antipsychotics. Although overlapping dopamine pathways between cocaine use and NMS could deter one from this practice and guidelines recommend against it, antipsychotics are routinely used in the emergency setting for cocaine-associated agitation. This case highlights the need for a more standardized treatment protocol, provides an explanation of why treating cocaine intoxication with antipsychotics is inappropriate, and suggests that chronic cocaine users may be more prone to NMS in this scenario. Furthermore, this is a unique case because it describes atypical NMS in the context of cocaine intoxication, chronic cocaine use, and administration of antipsychotics to an antipsychotic-naïve patient.