ADHD is a common behavioral syndrome with a heritability of 70–80%. Genome wide sequencing and association studies indicate that ADHD risk variants are distributed across a wide range of allele ...frequencies and relative risks. Several common single nucleotide variants (SNPs) have been identified that increase the risk of ADHD with a few percent. Many of the reported risk genes and copy number variants are shared with other neuropsychiatric disorders. Moreover, ADHD often coexists with common or rare somatic diseases, including rare Mendelian neurometabolic diseases that can affect normal brain development and function. Some genetic/metabolic syndromes masquerading as common ADHD may lead to irreversible brain damage if not properly identified and treated during early childhood. As ADHD is such a heterogeneous condition in terms of severity, clinical features and most probably also underlying biology, it is crucial to offer individualized treatments. Recent progress in ADHD genetics is reviewed, prospects of using this information for targeted pharmacotherapy are discussed and critical knowledge gaps are identified. It is suggested that genome guided therapies could be introduced gradually, starting with rare ADHD syndromes with highly penetrant risk genes. Routine diagnostic application of whole exome or whole genome sequencing combined with metabolomic screening, and brain imaging may be needed in cases with suspected neurometabolic disorders. Identification and treatment of ADHD patients with defined neurometabolic aberrations could be a first step toward genome guided personalized treatment of ADHD. Possibly, screening for relevant biomarkers may gradually be implemented to guide treatment choices in larger patient groups.
Objective: To systematically review, synthesize, and appraise available evidence, connecting adult ADHD with somatic disease. Method: Embase, Psychinfo, and Medline databases were searched for ...studies published from 1994 to 2015 addressing adult ADHD and somatic comorbidity. Somatic conditions were classified according to International Classification of Diseases (ICD-10) codes. Levels of evidence were graded as inconclusive, tentative, or well documented. Results: Most of the 126 studies included in the qualitative synthesis were small and of modest quality. Obesity, sleep disorders, and asthma were well-documented comorbidities in adult ADHD. Tentative evidence was found for an association between adult ADHD and migraine and celiac disease. In a large health registry study, cardiovascular disease was not associated with adult ADHD. Conclusion: There are few large systematic studies using standardized diagnostic criteria evaluating adult ADHD and somatic comorbidities. Significant associations are found between adult ADHD and several somatic diseases, and these are important to consider when assessing and treating either adult ADHD or the somatic diseases.
Attention-deficit/hyperactivity disorder (ADHD) is often comorbid with other psychiatric conditions in adults. Yet, less is known about its relationship with common metabolic disorders and how sex ...and ageing affect the overall comorbidity patterns of adult ADHD. We aimed to examine associations of adult ADHD with several common psychiatric and metabolic conditions. Through the linkage of multiple Swedish national registers, 5,551,807 adults aged 18 to 64 years and living in Sweden on December 31, 2013 were identified and assessed for clinical diagnoses of adult ADHD, substance use disorder (SUD), depression, bipolar disorder, anxiety, type 2 diabetes mellitus (T2DM), and hypertension. Logistic regression models and regression standardization method were employed to obtain estimates of prevalence, prevalence difference (PD), and prevalence ratio (PR). All comorbid conditions of interest were more prevalent in adults with ADHD (3.90% to 44.65%) than in those without (0.72% to 4.89%), with the estimated PRs being over nine for psychiatric conditions (p < 0.001) and around two for metabolic conditions (p < 0.001). Sex differences in the prevalence of comorbidities were observed among adults with ADHD. Effect modification by sex was detected on the additive scale and/or multiplicative scale for the associations of adult ADHD with all comorbidities. ADHD remained associated with all comorbidities in older adults aged 50 to 64 when all conditions were assessed from age 50 onwards. The comorbidity patterns of adult ADHD underscore the severity and clinical complexity of the disorder. Clinicians should remain vigilant for a wide range of psychiatric and metabolic problems in ADHD affected adults of all ages and both sexes.
Abstract Background The inclusion of biomarkers could improve diagnostic accuracy of attention-deficit/hyperactivity disorder (ADHD). One potential biomarker is the ADHD polygenic score (PGS), a ...measure of genetic liability for ADHD. This study aimed to investigate if the ADHD PGS can provide additional information alongside ADHD rating scales and examination of family history of ADHD to distinguish between ADHD cases and controls. Methods Polygenic scores were calculated for 576 adults with ADHD and 530 ethnically matched controls. ADHD PGS was used alongside scores from the Wender-Utah Rating Scale (WURS) and the Adult ADHD Self-Report Scale (ASRS) as predictors of ADHD diagnosis in a set of nested logistic regression models. These models were compared by likelihood ratio (LR) tests, Akaike information criterion corrected for small samples (AICc), and Lee R². These analyses were repeated with family history of ADHD as a covariate in all models. Results The ADHD PGS increased the variance explained of the ASRS by 0.58% points (pp) (R 2 ASRS = 61.11%, R 2 ASRS + PGS =61.69%), the WURS by 0.61pp (R 2 WURS = 77.33%, R 2 WURS + PGS = 77.94%), of ASRS and WURS together by 0.57pp (R 2 ASRS + WURS =80.84%, R 2 ASRS + WURS+PGS =81.40%), and of self-reported family history by 1.40pp (R 2 family = 28.06%, R 2 family + PGS =29.46%). These increases were statistically significant, as measured by LR tests and AICc. Conclusion We found that the ADHD PGS contributed additional information to common diagnostic aids. However, the increase in variance explained was small, suggesting that the ADHD PGS is currently not a clinically useful diagnostic aid. Future studies should examine the utility of ADHD PGS in ADHD prediction alongside non-genetic risk factors, and the diagnostic utility of the ADHD PGS should be evaluated as more genetic data is accumulated and computational tools are further refined.
Abstract
Introduction
Adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of suicidal spectrum behaviors (SSBs). However, there is limited knowledge ...about risk factors triggering SSBs in this group of people.
Objective
To explore published literature concerning factors that may increase the risk of SSBs in adults and adolescents with ADHD.
Methods
A systematic literature search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted on 22
nd
of February 2022 using the Ovid MEDLINE and Web of Science databases. Three categories of search terms were used: (1) self-harm, self-injury, self-mutilation, suicide, self-poisoning; (2) adults, adolescents; and (3) attention-deficit hyperactivity disorder/ADHD. Studies with data concerning mediating factors of SSBs in relation to a clinical diagnosis of ADHD in participants above 16 years of age were included.
Results
The literature search identified 604 articles, of which 40 were included in the final study selection. Factors found to increase the likelihood of SSBs included ADHD symptom severity and persistence, female gender, family history of ADHD, childhood and parental influences, and social functioning. Even when adjusting for psychiatric comorbidities, most studies showed that adults and adolescents with ADHD have an elevated risk of SSBs.
Conclusion
This systematic review has documented that several demographic and clinical features are associated with an increased risk of SSBs in adolescents and adults with ADHD. Notably, ADHD emerges as an independent risk factor for SSBs. This information ought to have clinical implications in terms of screening and suicide prevention strategies. Further longitudinal studies are needed to investigate the outcome of preventive strategies in individuals along the full spectrum of ADHD symptom severity.
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► 14-3-3 Proteins are abundant and have hundreds of binding partners in eukaryotic cells. ► Many of these target phosphoproteins are involved in metabolic control. ► 14-3-3 Binding ...can amplify and modulate the effects of phosphorylation events. ► 14-3-3 Targets include insulin, mTOR- and AMP dependent kinase signaling pathways. ► 14-3-3 Proteins can direct metabolic activities at different cellular locations.
Thirty years ago, it was discovered that 14-3-3 proteins could activate enzymes involved in amino acid metabolism. In the following decades, 14-3-3s have been shown to be involved in many different signaling pathways that modulate cellular and whole body energy and nutrient homeostasis. Large scale screening for cellular binding partners of 14-3-3 has identified numerous proteins that participate in regulation of metabolic pathways, although only a minority of these targets have yet been subject to detailed studies. Because of the wide distribution of potential 14-3-3 targets and the resurging interest in metabolic pathway control in diseases like cancer, diabetes, obesity and cardiovascular disease, we review the role of 14-3-3 proteins in the regulation of core and specialized cellular metabolic functions. We cite illustrative examples of 14-3-3 action through their direct modulation of individual enzymes and through regulation of master switches in cellular pathways, such as insulin signaling, mTOR- and AMP dependent kinase signaling pathways, as well as regulation of autophagy. We further illustrate the quantitative impact of 14-3-3 association on signal response at the target protein level and we discuss implications of recent findings showing 14-3-3 protein membrane binding of target proteins.
Attention-deficit hyperactivity disorder (ADHD) is one of the most frequent neurodevelopmental disorders in children and tends to persist into adulthood. Evidence from neuropsychological, ...neuroimaging, and electrophysiological studies indicates that alterations of error processing are core symptoms in children and adolescents with ADHD. To test whether adults with ADHD show persisting deficits and compensatory processes, we investigated performance monitoring during stimulus-evaluation and response-selection, with a focus on errors, as well as within-group correlations with symptom scores.
Fifty-five participants (27 ADHD and 28 controls) aged 19-55 years performed a modified flanker task during EEG recording with 64 electrodes, and the ADHD and control groups were compared on measures of behavioral task performance, event-related potentials of performance monitoring (N2, P3), and error processing (ERN, Pe). Adult ADHD Self-Report Scale (ASRS) was used to assess ADHD symptom load.
Adults with ADHD showed higher error rates in incompatible trials, and these error rates correlated positively with the ASRS scores. Also, we observed lower P3 amplitudes in incompatible trials, which were inversely correlated with symptom load in the ADHD group. Adults with ADHD also displayed reduced error-related ERN and Pe amplitudes. There were no significant differences in reaction time (RT) and RT variability between the two groups.
Our findings show deviations of electrophysiological measures, suggesting reduced effortful engagement of attentional and error-monitoring processes in adults with ADHD. Associations between ADHD symptom scores, event-related potential amplitudes, and poorer task performance in the ADHD group further support this notion.
Higher vagally mediated heart rate variability (vmHRV), reflecting vagal activity as indexed by heart function and lower stress vulnerability, is associated with higher perceived social support. ...Seeking social support is an adaptive stress response, and evolutionary theories suggest that females use this strategy more than males. The current study investigated the hypothesis that higher vmHRV is related to higher perceived social support under conditions of higher, relative to lower, stress, and that this association is most prominent in females. A healthy student sample (n = 143; 82 males, 61 females; mean age 19.9) completed the short version of the Medical outcomes study social support survey (MOS) and the Perceived stress scale (PSS). Activity in the high frequency band of heart rate variability (HF-HRV), deducted from five-minute resting electrocardiogram (ECG) recordings, indexed vmHRV. A moderation analysis was conducted, with PSS and sex as moderators of the association between vmHRV and MOS. Statistical effects were adjusted for age, education, physical activity, body mass index (BMI), alcohol and drug use, ECG-derived respiration (EDR), and mean heart rate. Higher PSS scores moderated the association between vmHRV and MOS in females but not males. Lower PSS scores did not moderate the relation between vmHRV and MOS. This suggests that higher vmHRV is associated with higher perceived social support under conditions of higher stress in females but not males, consistent with evolution of different stress management strategies in the sexes. The results may have implications for individualized intervention strategies for increasing vmHRV and perceived social support.
Background:
Adults with attention deficit/hyperactivity disorder (ADHD) are predominantly treated with medication. However, there is also a need for effective, psychologically based interventions. As ...ADHD is strongly associated with reduced inhibitory control, cognitive remediation approaches should be efficient. Goal management training (GMT) aims at enhancing inhibitory control and has shown positive effects on inhibitory control in non-ADHD patient groups. The aim of the current study was to explore whether GMT would specifically enhance inhibitory control in adults with ADHD, and if such an enhancement would lead to secondary improvements in self-reported everyday functioning.
Methods:
Twenty-one participants with ADHD (mean age: 39.05 years SD 11.93) completed the intervention and assessments pre-, post- and 6 months after the intervention. Measures included neuropsychological tests and self-report questionnaires pertaining to cognitive- and executive functioning, emotion regulation, quality of life, and ADHD symptoms.
Results:
Compared to baseline, the participants showed enhanced inhibitory control on performance-based measures at post-assessment and 6-month follow-up. The participants also reported increased productivity and reduced cognitive difficulties in everyday life at both assessments post-treatment, as well as improvements in aspects of emotion regulation and a reduction in the severity of core ADHD-symptoms at 6-month follow-up.
Conclusion:
Our exploratory study showed that GMT seems to specifically improve one of the core executive dysfunctions in ADHD, namely inhibitory control, with a positive effect lasting at least 6 months post-treatment. The adults with ADHD also reported improved self-regulation in their everyday life after completing GMT, providing strong arguments for further investigations of GMT as a treatment option for this group of adults.
Clinical Trial Registration:
The study is registered under
ISRCTN.com
(ISRCTN91988877;
https://doi.org/10.1186/ISRCTN91988877
).
Objective
To validate the Adult ADHD Self‐Report Scale (ASRS) and the Wender Utah Rating Scale (WURS) in a well‐characterized sample of adult attention‐deficit/hyperactivity disorder (ADHD) patients ...and population controls.
Methods
Both the ASRS and the WURS were administered to clinically diagnosed adult ADHD patients (n = 646) and to population controls (n = 908). We performed principal component analyses (PCA) and calculated receiver operating curves (ROC) including area under the curve (AUC) for the full WURS and ASRS, as well as for the PCA generated factors and the ASRS short screener.
Results
We found an AUC of 0.956 (95% CI: 0.946–0.965) for the WURS, and 0.904 (95% CI: 0.888–0.921) for the ASRS. The ASRS short screener had an AUC of 0.903 (95%CI: 0.886–0.920). Combining the two full scales gave an AUC of 0.964 (95% CI: 0.955–0.973). We replicated the two‐factor structure of the ASRS and found a three‐factor model for the WURS.
Conclusion
The WURS and the ASRS both have high diagnostic accuracy. The short ASRS screener performed equally well as the full ASRS, whereas the WURS had the best discriminatory properties. The increased diagnostic accuracy may be due to the wider symptom range of the WURS and/or the retrospective childhood frame of symptoms.
To validate the adult ADHD Self‐Report Scale (ASRS) and the Wender Utah Rating Scale (WURS) in a well‐validated sample of adult attention‐deficit/hyperactivity disorder (ADHD) patients and population controls. Both the ASRS and the WURS was administered to clinically diagnosed adult ADHD patients (n = 646) and population controls (n = 908). The short ASRS screener performed equally well as the full ASRS, whereas the WURS had the best discriminatory properties.
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