Cardiovascular risk in adults with Delayed Sleep Phase Syndrome (DSPS) and Attention-Deficit/Hyperactivity Disorder (ADHD).

TRIAL REGISTRATION: FASE, https://www.trialregister.nl/, #NTR3831.

Treatment of 95 post-Covid patients with SSRIs.

After Covid-19 infection, 12.5% develops post-Covid-syndrome (PCS). Symptoms indicate numerous affected organ systems. After a year, chronic fatigue, dysautonomia and neurological and neuropsychiatric complaints predominate. In this study, 95 PCS patients were treated with selective serotonin reuptake inhibitors (SSRIs). This study used an exploratory questionnaire and found that two-thirds of patients had a reasonably good to strong response on SSRIs, over a quarter of patients had moderate response, while 10% reported no response. Overall, patients experienced substantial improved well-being. Brainfog and sensory overload decreased most, followed by chronic fatigue and dysautonomia. Outcomes were measured with three different measures that correlated strongly with each other. The response to SSRIs in PCS conditions was explained by seven possible neurobiological mechanisms based on recent literature on PCS integrated with already existing knowledge. Important for understanding these mechanisms is the underlying biochemical interaction between various neurotransmitter systems and parts of the immune system, and their dysregulation in PCS. The main link appears to be with the metabolic kynurenine pathway (KP) which interacts extensively with the immune system. The KP uses the same precursor as serotonin: tryptophan. The KP is overactive in PCS which maintains inflammation and which causes a lack of tryptophan. Finally, potential avenues for future research to advance this line of clinical research are discussed.

Attention-Deficit/Hyperactivity Disorder and Delayed Sleep Phase Syndrome in Adults: A Randomized Clinical Trial on the Effects of Chronotherapy on Sleep.

Delayed sleep phase syndrome (DSPS) is the most common sleep disturbance in adults with attention-deficit/hyperactivity disorder (ADHD). We previously showed that chronotherapy with melatonin effectively advanced the dim-light melatonin onset (DLMO), a biomarker for the internal circadian rhythm, by 1.5 h and reduced ADHD symptoms by 14%. Melatonin combined with bright light therapy (BLT) advanced the DLMO by 2 h, but did not affect ADHD symptoms. This article explores whether sleep times advanced along with DLMO, leading to longer sleep duration and better sleep in general, which might explain the working mechanism behind the reduction in ADHD symptoms after treatment with melatonin. This article presents exploratory secondary analysis on objective and self-reported sleep characteristics from a three-armed double-blind randomized placebo-controlled clinical trial (RCT), which included 49 adults (18-55 years) with ADHD and DSPS. Participants were randomized to receive sleep education and 3 weeks of (1) 0.5 mg/day placebo, (2) 0.5 mg/day melatonin, or (3) 0.5 mg/day melatonin plus 30 min of bright light therapy (BLT) between 0700 and 0800 h. Sleep was assessed at baseline, directly after treatment, and 2 weeks after the end of treatment. Objective measures were obtained by actigraphy, self-reported measures by various sleep questionnaires and a sleep diary. Melatonin with or without BLT did not advance sleep times, improve sleep in general, or strengthen wake-activity rhythms. So even though the DLMO had advanced, sleep timing did not follow. Adding extensive behavioral coaching to chronotherapy is necessary for advancing sleep times along with DLMO and to further alleviate ADHD symptoms.

Review: Identification and Management of Circadian Rhythm Sleep Disorders as a Transdiagnostic Feature in Child and Adolescent Psychiatry.

OBJECTIVE: Sleep disturbances are highly frequent features in a range of child and adolescent psychiatric conditions. However, it is commonly not clear if such sleep problems represent symptomatic features of, comorbidities of, or risk factors for these conditions. It is believed that underlying dysfunction in the daily biological (circadian) clock may play important roles in the etiology of many sleep disorders, and circadian rhythm changes are reported in a number of neuropsychiatric conditions. The aim of this review was to explore the key identifying features of circadian rhythm disorders (CRDs) in child and adolescent psychiatry and address how such disorders may be managed in the clinic. METHOD: A narrative review was conducted of the extant literature of CRDs in children and adolescents with psychiatric conditions. RESULTS: Key biological and social factors that contribute to CRDs in children and adolescents, and the cognitive and neurobehavioral consequences resulting from insufficient sleep were outlined. The roles of melatonin and other chronotherapeutic and behavioral interventions for the management of CRDs were also outlined. Further, the importance of careful investigation of circadian rhythm abnormalities in shaping the most effective treatment plan according to chronobiological principles was highlighted. CONCLUSION: CRDs are common in children and adolescents with psychiatric conditions and arise out of complex interactions between biological and social factors. Careful clinical attention to and management of CRDs in child and adolescent psychiatry have the potential for significant benefit not only in the domain of sleep but also in a range of cognitive, affective, and behavioral outcomes.

Effects of chronotherapy on circadian rhythm and ADHD symptoms in adults with attention-deficit/hyperactivity disorder and delayed sleep phase syndrome: a randomized clinical trial.

The majority of adults with Attention-Deficit/Hyperactivity Disorder (ADHD) have a delayed circadian rhythm that is a characteristic of Delayed Sleep Phase Syndrome (DSPS). Treatment of DSPS may improve both the circadian rhythm and ADHD symptoms. In this three-armed randomized clinical trial, 51 adults (18-55 y) with ADHD and DSPS received sleep education and 3 weeks of (1) 0.5 mg/d placebo, (2) 0.5 mg/d melatonin, or (3) 0.5 mg/d melatonin plus 30 minutes of 10,000 lux bright light therapy (BLT) between 07:00 and 08:00 h. Placebo/melatonin conditions were double-blind. Treatment took place in the participants' naturalistic home settings. Dim-light melatonin onset (DLMO) was measured in saliva as marker of internal circadian rhythm. Melatonin or placebo administration followed individual schedules, starting 3 hours before the individual DLMO and weekly advancing by 1 h. DLMO and ADHD Rating Scale score were assessed at baseline, directly after 3-week treatment, and two weeks after the end of treatment. Results show that at baseline 77% had a DLMO after 21:00 h with an average DLMO at 23:43 h ± 1h46. Directly after treatment, melatonin had advanced DLMO by 1h28 (p = .001), and melatonin plus BLT by 1h58 (p < .001). Placebo did not affect DLMO. ADHD symptoms reduced by 14% (p = .038) directly after melatonin treatment. Placebo and melatonin plus BLT did not impact ADHD symptoms. Two weeks after end of treatment, ADHD symptoms and DLMO had returned to baseline levels. It can be concluded that low doses of melatonin advanced the circadian rhythm and reduced self-reported ADHD symptoms. Given the large number of adult ADHD patients with concurrent DSPS, treating delayed sleep with melatonin is an important component of effective ADHD treatment.

Response and Side Effects Using Stimulant Medication in Older Adults With ADHD: An Observational Archive Study.

Objective: To examine the naturalistic response to and cardiovascular side effects of stimulant medication in older adults with ADHD. Methods: Electronic Health Record (EHR) data of adult patients with ADHD (≥55 years) at the specialized PsyQ outpatient clinic for adult ADHD (n = 113, 55-79 years) were collected. Response, cardiovascular status, side effects, and provided medical care before and after the first ADHD medication dose have been recorded. Results: A total of 65% of the patients reported positive response to the medication, and 42% of the patients quit their medication due to side effects or nonresponse. There was a small but significant decrease in weight and increase in heart rate before and after methylphenidate use. Conclusion: Our results indicate that the use of stimulants may be a relatively safe and effective treatment for older adults with ADHD, under the condition that the cardiovascular parameters are monitored before and during pharmacological treatment. Randomized controlled trials (RCTs) are needed to confirm these findings.

Reliability, Criterion and Concurrent Validity of the Farsi Translation of DIVA-5: A Semi-Structured Diagnostic Interview for Adults With ADHD.

Objectives: This study evaluated the psychometrics of the Farsi translation of diagnostic interview for attention-deficit hyperactivity disorder (ADHD) in adults (DIVA-5) based on DSM-5 criteria. Methods: Referrals to a psychiatric outpatient clinic (N = 120, 61.7% males, mean age 34.35 ± 9.84 years) presenting for an adult ADHD (AADHD) diagnosis, were evaluated using the structured clinical interviews for DSM-5 (SCID-5 & SCID-5-PD) and the DIVA-5. The participants completed Conner's Adult ADHD Rating Scale-Self Report-Screening Version (CAARS-S-SV). Results: According to the SCID-5 and DIVA-5 diagnoses, 55% and 38% of the participants had ADHD, respectively. Diagnostic agreement was 81.66% between DIVA-5/SCID-5 diagnoses, 80% between SCID-5/CAARS-S-SV, and 71.66% between DIVA-5/CAARS-S-SV. Test-retest and inter-rater reliability results for the DIVA-5 were good to excellent. Conclusion: Findings support the validity and reliability of the Farsi translation of DIVA-5 among the Farsi-speaking adult outpatient population.

Prevalence of hormone-related mood disorder symptoms in women with ADHD.

This is the first study to assess the prevalence of symptoms of premenstrual dysphoric disorder (PMDD), episodes of postpartum depression symptoms (PPD) after first childbirth, and climacteric mood symptoms in Attention-Deficit/Hyperactivity Disorder (ADHD). 209 consecutive women (18-71 years) with ADHD completed the PMDD chapter of the Neuropsychiatric Interview Plus version 5.0.0 to assess PMDD, the Edinburgh Postnatal Depression Scale to assess PPD, and the Greene Climacteric Scale to assess climacteric symptoms. Comorbid psychiatric disorders, medication use, and chronobiological sleep characteristics were also assessed. The prevalence of PMDD and PPD were high in ADHD, compared to the general population. PMDD symptoms were associated with less use of contraceptives. Antidepressants were associated with more PMDD symptoms. The following GCS scores were significant increased: anxiety, depression, and sexual dysfunction, vasomotor and somatic complaints. No significant differences were found in sleep characteristics or current comorbidity between the groups with and without PPD or PMDD, or increased climacteric scores. The prevalences of PMDD, PPD and climacteric scores were high in women with ADHD. This is the first study in women with ADHD that suggests that female ADHD patients suffer from significant PMDD symptoms, experience PPD during the first child birth, and experience more severe climacteric symptoms.

Effects of prolonged methylphenidate treatment on amygdala reactivity and connectivity: a randomized controlled trial in stimulant treatment-naive, male participants with ADHD.

Background: Problems with emotional processing are widely reported in individuals with attention-deficit/hyperactivity disorder (ADHD). Although methylphenidate (MPH) effectively alleviates inattention and hyperactivity symptoms in ADHD, its effects on emotional processing and internalizing symptoms have remained elusive. While we previously found that acute MPH administration modulated neural mechanisms underlying emotional processing in an age-dependent manner, the effects of prolonged administration remained unknown. Objectives: Therefore, we investigated: (i) whether prolonged MPH treatment influences neural substrates (amygdala reactivity and connectivity) of emotional processing, and (ii) whether these effects are modulated by age. Methods: The "effects of Psychotropic drugs On Developing brain-MPH" ("ePOD-MPH") randomized controlled trial was a 16-week double-blind, placebo-controlled, multi-center trial with MPH in 50 boys (10-12 years of age) and 49 men (23-40 years of age), all stimulant treatment-naive and diagnosed with ADHD. Participants performed an emotional face-matching task during functional magnetic resonance imaging. We assessed their symptoms of ADHD and internalizing symptoms at baseline, during the trial (8 weeks), and 1 week after the trial end (17 weeks). Results and Conclusions: We did not find effects of prolonged MPH treatment on emotional processing, as measured by amygdala reactivity and connectivity and internalizing symptoms in this trial with stimulant treatment-naive participants. This differs from our findings on emotional processing following acute MPH administration and the effects of prolonged MPH treatment on the dopamine system, which were both modulated by age. Interestingly, prolonged MPH treatment did improve ADHD symptoms, although depressive and anxiety symptoms showed a medication-independent decrease. Furthermore, our data indicate that baseline internalizing symptoms may be used to predict MPH treatment effects on ADHD symptoms, particularly in (male) adults with ADHD.

Validity of the Korean Version of DIVA-5: A Semi-Structured Diagnostic Interview for Adult ADHD.

BACKGROUND: This study was to assess the validity of the Korean version of the semi-structured Diagnostic Interview for Adult ADHD, third edition (DIVA-5). The secondary aim was to compare sociodemographic and psychiatric comorbidities in adult patients with and without a diagnosis of ADHD. METHODS: A total of 279 participants were recruited from nine psychiatric outpatient clinics in Korea. All participants were administered the Mini-International Neuropsychiatric Interview (MINI) Plus v.5.0.0, the Adult ADHD Self-Report Scale v1.1 (ASRS-v1.1) Symptom Checklist, and DIVA-5. Diagnosis concordance between two board-certified psychiatrists and DIVA-5 were analysed. RESULTS: The DIVA-5 showed a diagnostic accuracy of 92%, a sensitivity of 91.30%, and a specificity of 93.62%. Significant clinical and demographic differences between ADHD and control groups were found. CONCLUSION: The Korean version of DIVA-5 is a reliable tool for assessing and diagnosing ADHD in adult Korean populations.

Delayed sleep-onset and biological age: late sleep-onset is associated with shorter telomere length.

STUDY OBJECTIVES: We evaluated the relationship between leukocyte telomere length (LTL) and sleep duration, insomnia symptoms, and circadian rhythm, to test whether sleep and chronobiological dysregulations are associated with cellular aging. METHODS: Data from the Netherlands Study of Depression and Anxiety (N = 2,936) were used at two waves 6 years apart, to measure LTL. Telomeres shorten during the life span and are important biomarkers for cellular aging. LTL was assessed by qualitative polymerase chain reaction and converted into base pair number. Sleep parameters were: sleep duration and insomnia symptoms from the Insomnia Rating Scale. Circadian rhythm variables were: indication of Delayed Sleep Phase Syndrome (DSPS), mid-sleep corrected for sleep debt on free days (MSFsc), sleep-onset time, and self-reported chronotype, from the Munich Chronotype Questionnaire. Generalized estimating equations analyzed the associations between LTL, sleep, and chronobiological factors, adjusted for baseline age, sex, North European ancestry, and additionally for current smoking, depression severity, obesity, and childhood trauma. RESULTS: Indicators of delayed circadian rhythm showed a strong and consistent effect on LTL, after adjustment for sociodemographic and health indicators. Late MSFsc (B = -49.9, p = .004), late sleep-onset time (B = -32.4, p = .001), indication of DSPS (B = -73.8, p = .036), and moderately late chronotype in adulthood (B = -71.6, p = .003) were associated with significantly shorter LTL across both waves; whereas sleep duration and insomnia symptoms were not. Extremely early chronotype showed significantly less LTL shortening than intermediate chronotype (B = 161.40, p = .037). No predictors showed accelerated LTL attrition over 6 years. CONCLUSIONS: Individuals with delayed circadian rhythm have significantly shorter LTL, but not faster LTL attrition rates.

Objective assessment of attention-deficit/hyperactivity disorder in older adults compared with controls using the QbTest.

OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) persists into old age, with prevalence rates of 2.8% to 3.3% in adults over 60 years of age. Most diagnostic assessment tools are not validated for older adults. The Quantified behavioral Test (QbTest) is an objective assessment for the core symptoms of ADHD and is validated for children and younger adults. We investigated whether the QbTest can be used to differentiate between older adults with ADHD and healthy controls. METHODS: Older adults aged 55 to 79 years with (n = 97) or without (n = 112) ADHD were assessed with the QbTest. They also rated their ADHD symptom severity. QbTest raw scores were compared between groups. Factor scores were computed using factor loadings from a confirmatory factor analysis (CFA). Multilevel regressions were used to determine effects of background characteristics and comorbidity. Logistic regressions were performed to determine whether the QbTest differentiated between patients with ADHD and healthy controls. RESULTS: The factor structure of the CFA was comparable with that of younger age groups. Older age was associated with higher Inattention score. Parameters comprising the factors Hyperactivity and Inattention, but not Impulsivity, were shown to contribute significantly in differentiating between the groups. The QbTest had a correct classification rate of 70%, which was increased to 91% when combining QbTest scores and self-reports of ADHD symptom severity. CONCLUSIONS: The QbTest is feasible for older adults, and the factors Hyperactivity and Inattention are valid parameters for the diagnostic assessment of ADHD in older adults, when used in addition to self-reports.

The role of the circadian system in the etiology and pathophysiology of ADHD: time to redefine ADHD?

Attention-deficit/hyperactivity disorder (ADHD) is highly associated with the delayed sleep phase disorder, a circadian rhythm sleep-wake disorder, which is prevalent in 73-78% of children and adults with ADHD. Besides the delayed sleep phase disorder, various other sleep disorders accompany ADHD, both in children and in adults. ADHD is either the cause or the consequence of sleep disturbances, or they may have a shared etiological and genetic background. In this review, we present an overview of the current knowledge on the relationship between the circadian rhythm, sleep disorders, and ADHD. We also discuss the various pathways explaining the connection between ADHD symptoms and delayed sleep, ranging from genetics, behavioral aspects, daylight exposure, to the functioning of the eye. The treatment options discussed are focused on improvement of sleep quality, quantity, and phase-resetting, by means of improving sleep hygiene, chronotherapy, treatment of specific sleep disorders, and by strengthening certain neuronal networks involved in sleep, e.g., by sensorimotor rhythm neurofeedback. Ultimately, the main question is addressed: whether ADHD needs to be redefined. We propose a novel view on ADHD, where a part of the ADHD symptoms are the result of chronic sleep disorders, with most evidence for the delayed circadian rhythm as the underlying mechanism. This substantial subgroup should receive treatment of the sleep disorder in addition to ADHD symptom treatment.

Criteria and Concurrent Validity of DIVA 2.0: A Semi-Structured Diagnostic Interview for Adult ADHD.

Objective: The aim of this study was to assess for the first time the criterion validity of the semi-structured Diagnostic Interview for ADHD in adults (DIVA 2.0), and its concurrent validity in comparison with the Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID) and other ADHD severity scales, following the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria. Method: A transversal study was performed on 40 out-patients with ADHD to check the criteria and concurrent validity of the DIVA 2.0 compared with the CAADID. Results: The DIVA 2.0 interview showed a diagnostic accuracy of 100% when compared with the diagnoses obtained with the CAADID interview. The concurrent validity demonstrated good correlations with three self-reported rating scales: the Wender Utah Rating Scale (WURS; r = .544, p < .0001), the ADHD-Rating Scale (r = .720, p < .0001), and Sheehan's Dysfunction Inventory (r = .674, p < .0001). Conclusion: The DIVA 2.0 is a reliable tool for assessing and diagnosing Adult ADHD and is the only one that offers free online access for clinical and research purposes.

Seasonal Variations in the Severity of ADHD Symptoms in the Dutch General Population.

OBJECTIVE: This is the first study to examine self-reported seasonal differences in the severity of ADHD symptoms in adults from the general population. METHOD: Data were analyzed from N = 5,303 respondents participating in the second wave of the Netherlands Mental Health Survey and Incidence Study-2, a population-based study on mental health. ADHD symptoms were assessed using the Adult ADHD Self-Report Scale Screener. As indicators of the severity of ADHD symptoms, the total ADHD symptom score and inattention and hyperactivity subscale scores were examined. RESULTS: Compared with participants who were assessed in autumn, total ADHD and inattention subscale scores were significantly higher among participants who were assessed in spring or summer; the hyperactivity subscale score was significantly higher in spring. CONCLUSION: We found seasonal variations in the severity of ADHD symptoms, which was highest in those assessed in spring and summer. Researchers should be aware of this in the diagnostic process.

Distribution of ADHD symptoms, and associated comorbidity, exposure to risk factors and disability: Results from a general population study.

The aim of this study was to examine whether ADHD is a dimensional trait in the adult general population. We studied whether an increased number of ADHD symptoms was associated with higher comorbidity, exposure to risk factors (childhood abuse and parental psychopathology), and disability. We ascertained whether even low numbers of ADHD symptoms were associated with an increased burden of disease. Data were used from the second wave of the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2, N = 5303). NEMESIS-2 is a nationally representative face-to-face survey on mental health of the Dutch general population. ADHD symptoms, mental comorbidity, and disability were assessed using the Adult ADHD Self-Report Scale Screener, the Composite International Diagnostic Interview version 3.0, and the Medical Outcomes Study Short Form Health Survey, respectively. Dose-response relationships were found between the number of ADHD symptoms and Axis I and II mental disorders; exposure to risk factors; and mental and physical disability. Our study supports the notion that ADHD is a dimensional trait in the adult general population. Even low numbers of symptoms were associated with an increased burden of disease, and therefore these should be identified and treated.

The Association Between Insomnia and Sleep Duration in Adults With Attention-Deficit Hyperactivity Disorder: Results From a General Population Study.

STUDY OBJECTIVES: Insomnia and short or long sleep duration are important comorbid conditions in adults with attention-deficit hyperactivity disorder (ADHD), but reports of the association vary. In a general population study, we evaluated the relationship between ADHD symptom severity, insomnia symptoms, and sleep duration in adults. METHODS: Data were from the third wave of the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2; n = 4,618). ADHD symptom severity and symptom dimensions (hyperactivity and inattention) were assessed using the Adult ADHD Self-Report Scale screener. Self-reported insomnia symptoms (Insomnia Rating Scale; IRS) were defined as clinically relevant if IRS ≥ 9. Self-reported short sleep duration was defined as ≤ 6 hours, and long sleep duration as ≥ 10 hours. RESULTS: Within the group with clinically relevant ADHD symptoms, 43% reported significant insomnia symptoms (odds ratio [OR] = 2.66, 95% confidence interval [CI] 1.74-4.07); 41% short sleep duration (relative risk ratio [RRR] = 1.94, 95% CI 1.31-2.85) and 6% long sleep (RRR = 5.87, 95% CI 1.97-17.45). Increased inattention symptoms were associated with IRS ≥ 9, short and long sleep duration in fully adjusted models (OR = 1.10, 95% CI 1.06-1.14; RRR = 1.06, 95% CI 1.02-1.09; RRR = 1.16, 95% CI 1.05-1.28, respectively). Increased hyperactivity symptoms were associated with IRS ≥ 9 (OR = 1.17, 95% CI 1.11-1.23) and short sleep duration (RRR = 1.12, 95% CI 1.05-1.19). CONCLUSIONS: Both clinically significant ADHD symptoms and inattention and hyperactivity symptom dimensions were consistently associated with insomnia symptoms and altered sleep duration. These associations confirm that sleep disturbances should be assessed and given appropriate clinical attention in adults with ADHD.

The Association Between Metabolic Syndrome, Obesity-Related Outcomes, and ADHD in Adults With Comorbid Affective Disorders.

OBJECTIVE: ADHD may predispose to obesity, a metabolic syndrome component. Affective disorders are also associated with MetSyn and ADHD. This study examined whether ADHD confers any added risk of MetSyn and obesity-related associations in a large sample with varying stages of affective disorders. METHOD: Participants included 2,303 adults from the Netherlands Study of Depression and Anxiety. Three groups were compared (controls, those with depressive/anxiety disorders without ADHD; and those with depressive/anxiety disorders and ADHD) for presence of MetSyn risk factors, body mass index, and waist-hip ratio. ADHD symptoms were identified by using a T-score > 65 (Conners Adult ADHD Rating Scale). RESULTS: Multivariable analyses were additionally adjusted for sociodemographic, lifestyle, health factors, and affective disorders. Analyses showed no significant association between MetSyn, obesity-related variables, and comorbid ADHD. High Inattention and Hyperactivity/Impulsivity symptoms were not associated with MetSyn. CONCLUSION: This study did not confirm that MetSyn and obesity-related parameters are increased in comorbid ADHD.