[What is adult ADHD after all?]

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset mental disorder, demonstrates genetical effects, and is characterized by attention deficit, hyperactivity, and impulsivity. While ADHD was previously only considered a childhood disorder, longitudinal studies over the past decades have proven that in a significant number of cases, the symptoms of the disorder can also be detected in adulthood, and therefore affects 2-4% of the adult population. In Hungary, adult ADHD programs started about 20 years ago and has been able to provide help to many adults living with ADHD. However, this form of care needs further development in many aspects and suffers from capacity deficits at the national level. On July 4-6, 2023 we organized a CME course on adult ADHD at the Department of Psychiatry and Psychotherapy Semmelweis University. The objective of this course was to deepen the knowledge of participants and alleviate care difficulties in the long term through the sharing of information and good practices. As part of this, a narrative review was written, which touches on the current issues of diagnosing and treating ADHD in adults.

Using informative prior based on expert opinion in Bayesian estimation of the transition probability matrix in Markov modelling-an example from the cost-effectiveness analysis of the treatment of patients with predominantly negative symptoms of schizophrenia with cariprazine.

BACKGROUND: When patient health state transition evidence is missing from clinical literature, analysts are inclined to make simple assumptions to complete the transition matrices within a health economic model. Our aim was to provide a solution for estimating transition matrices by the Bayesian statistical method within a health economic model when empirical evidence is lacking. METHODS: We used a previously published cost-effectiveness analysis of the use of cariprazine compared to that of risperidone in patients with predominantly negative symptoms of schizophrenia. We generated the treatment-specific state transition probability matrices in three different ways: (1) based only on the observed clinical trial data; (2) based on Bayesian estimation where prior transition probabilities came from experts' opinions; and (3) based on Bayesian estimation with vague prior transition probabilities (i.e., assigning equal prior probabilities to the missing transitions from one state to the others). For the second approach, we elicited Dirichlet prior distributions by three clinical experts. We compared the transition probability matrices and the incremental quality-adjusted life years (QALYs) across the three approaches. RESULTS: The estimates of the prior transition probabilities from the experts were feasible to obtain and showed considerable consistency with the clinical trial data. As expected, the estimated health benefit of the treatments was different when only the clinical trial data were considered (QALY difference 0.0260), its combination with the experts' beliefs were used in the economic model (QALY difference 0.0253), and when vague prior distributions were used (QALY difference 0.0243). CONCLUSIONS: Imputing zeros to missing transition probabilities in Markov models might be untenable from the clinical perspective and may result in inappropriate estimates. Bayesian statistics provides an appropriate framework for imputing missing values without making overly simple assumptions. Informative priors based on expert opinions might be more appropriate than vague priors.

General and domain-specific neurocognitive impairments in deficit and non-deficit schizophrenia.

Earlier studies suggested more severe overall cognitive impairments in deficit versus non-deficit schizophrenia; however, the specific contribution of different cognitive domains to this overall cognitive impairment remains unclear. The purpose of this study was to compare the two subtypes in general cognitive functioning as well as in individual cognitive domains using the composite score approach. One hundred and forty-three patients fulfilling the criteria for the deficit syndrome were compared with 123 patients diagnosed with non-deficit schizophrenia. Neurocognitive functioning was assessed by a neuropsychological test battery measuring the domains of sustained vigilance/attention, working memory, short-term memory, verbal memory, cognitive flexibility, and ideation fluency. Using the raw neuropsychological measures, we calculated a global index of cognitive impairment and domain-specific composite z-scores. Association between these composite scores and the deficit syndrome was examined by logistic regression analysis. After adjusting for relevant covariates including sex, age, education, smoking, and antipsychotic dose, results indicated a significant increase in the likelihood of deficit syndrome as a function of global (OR = 5.40; 95% CI 3.02-9.65) as well as domain-specific impairments (OR > 2 for all individual domains except for short-term memory). Cognitive flexibility was an independent predictor (OR = 2.92; 95% CI 1.47-5.80), whereas other cognitive domains demonstrated no unique contribution to the general cognitive impairment. Patients with deficit schizophrenia suffer from a more severe degree of neurocognitive impairment, which is qualitatively similar to the dysfunction seen in non-deficit schizophrenia. However, our results indicate that cognitive flexibility is specifically impaired in deficit versus non-deficit patients and may therefore represent a core feature of this subtype.

Use of generalized transfer function-derived central blood pressure for the calculation of baroreflex gain.

BACKGROUND: Peripheral blood pressure measurement underestimates pressure changes during baroreflex testing, resulting in an overestimation of baroreflex gain. This error might be reduced by measuring central blood pressure; the invasive measurement, however, may represent ethical and practical problems. The solution may be the derivation of central blood pressure from the peripheral pulse using a generalized transfer function. METHODS: In the current study, we tested the agreement between catheter-measured and generalized transfer function derived central blood pressure measurements and corresponding baroreflex gains. ECG and blood pressure waveforms were monitored continuously during a phenylephrine-induced pressure rise in 22 subjects undergoing cardiac catheterization. Pressure was measured with a catheter positioned in the aorta and with applanation tonometry in the radial artery. Radial pressure waveforms were subject to a generalized transfer function built in the SphygmoCor device to derive central pressure waveforms. Radial tonometric signal was calibrated with catheter-measured (invasive) and sphygmomanometric (noninvasive) pressures. Baroreflex gains were calculated from the linear regressions between heart period and systolic pressure changes. RESULTS: When radial tonometric signal was calibrated invasively, there was no group difference between baroreflex gains calculated from SphygmoCor-derived and catheter-measured pressures (8.2 +/- 1.2 vs. 7.2 +/- 1.2 ms/mmHg, P = NS). When radial tonometric signal was calibrated noninvasively, however, baroreflex gains calculated from SphygmoCor-derived pressures overestimated those calculated from catheter-measured pressures. CONCLUSION: Using a generalized transfer function is an accurate method to derive central pressure changes for baroreflex gain calculation. The technique, however, requires invasive pressure measurements for calibration, leaving the problem of a fully noninvasive central pressure measurement unresolved.

Adaptation of baroreflex function to increased carotid artery stiffening in patients with transposition of great arteries.

We have shown previously that TGA (transposition of great arteries) is associated with increased carotid artery stiffness. It has been established that stiffening of the barosensory vessel wall results in reduced baroreceptor activation and impaired BRS (baroreflex sensitivity). In the present study we tested the hypothesis that the increased carotid artery stiffness in TGA patients was associated with reduced cardiovagal BRS. We studied 32 TGA patients aged 9-19 years, 12+/-3 years after surgical repair and 32 age-matched healthy control subjects. Carotid artery diastolic diameter and pulsatile distension was determined by echo wall tracking; carotid blood pressure was measured by tonometry. BRS was measured using spontaneous techniques [BRS(seq) and LF(gain) (low-frequency transfer function gain)] and by the phenylephrine method (BRS(phe)). Carotid artery distensibility was markedly reduced in patients as compared with controls (5.6+/-1.9 x 10(-3) compared with 8.7+/-2.7 x 10(-3)/mmHg P<0.05, as determined using an unpaired Student's t test), but BRS was not different in patients and controls (20.3+/-14.7 compared with 21.7+/-12.7 for BRS(seq); 13.1+/-9.2 compared with 10.6+/-4.5 for LF(gain); and 19.1+/-8.6 compared with 24.8+/-7.2 for BRS(phe) respectively). Carotid artery elastic function was markedly impaired in patients with TGA, but the increased stiffness of the barosensory vessel wall was not associated with reduced BRS. It appears that attenuation of baroreceptor stimulus due to arterial stiffening may be compensated by other, possibly neural, mechanisms when it exists as a congenital abnormality.

Transposition of great arteries is associated with increased carotid artery stiffness.

Transposition of great arteries is the consequence of abnormal aorticopulmonary septation. Animal embryonic data indicate that septation and elastogenesis are related events, but human and clinical data are not available. We tested the hypothesis that large artery elastic function was impaired in patients with transposition of great arteries. We studied 34 patients aged 9 to 19 years, 12+/-3 years after atrial switch operation; 14 patients aged 7 to 9 years, 8+/-1 years after arterial switch operation; and 108 healthy control subjects matched for age. Carotid artery diastolic diameter and pulsatile distension were determined by echo wall-tracking; carotid blood pressure was measured by tonometry. Systolic pressure was higher and diastolic pressure was lower in patients than in controls. Patients with atrial and arterial switch repair were compared with their respective controls by 2-factor ANOVA. For patients with atrial switch repair versus control, stiffness index beta was 4.9+/-1.5 versus 3.1+/-1.0 (P<0.001); for patients witch arterial switch versus control, stiffness index beta was 3.8+/-1.1 versus 2.1+/-0.6 (P<0.001). Similar differences were observed for carotid compliance, distensibility, and incremental elastic modulus as well. The interaction term was not significant for any of the elastic variables, indicating that carotid stiffening was a characteristic of the condition and not the consequence of different hemodynamics. Carotid artery is markedly stiffer in patients, suggesting that impaired elastogenesis may constitute part of the congenital abnormality. Since carotid artery stiffness has been established as an independent cardiovascular risk factor, this condition may have consequences in the clinical management of these patients.

Reduced baroreceptor sensitivity and elasticity of the carotid artery in a preeclamptic patient.

Baroreflex sensitivity, distensibility coefficient, and intima-media thickness (IMT) of the common carotid artery were determined in a preeclamptic patient during 1st and 3rd trimesters as well as after childbirth. From the beginning of her pregnancy, baroreflex sensitivity and distensibility coefficient of the carotid artery exhibited a parallel decline, whereas the IMT increased as compared with normotensive pregnancies. The values of all parameters examined returned to their initial levels after 14 weeks of delivery. These results suggest that augmented IMT and carotid stiffness coupled to baroreceptor dysfunction may have contributed to the perturbation of blood pressure control in our preeclamptic patient.

Cardiovagal autonomic function in sedentary and trained offspring of hypertensive parents.

In young normotensive subjects, parental hypertension is associated with stiffening of the carotid artery and reduction in cardiovagal outflow and baroreflex gain. In subjects without parental hypertension regular exercise training was found to attenuate age-related reduction in carotid compliance and baroreflex gain. The aim of the present study was to test the hypothesis that regular physical activity is associated with better parameters of carotid artery elasticity, increased cardiovagal outflow and higher baroreflex gain in normotensive offspring of hypertensive parents. We studied 98 healthy, sedentary or endurance exercise trained subjects (49 men, 18-27 years of age) with or without family history of hypertension (FH(+) and FH(-), respectively) in a cross-sectional design. In the sedentary group spontaneous baroreflex indices (sequence method and spectral techniques) were lower in FH(+) subjects than in their FH(-) peers, while in trained subjects these indices were not different between FH(+) and FH(-). Furthermore, in the FH(+) group trained subjects had higher baroreflex indices than their sedentary peers, while in the FH(-) group no significant differences were found. Carotid compliance and distensibility coefficient (echo-tracking ultrasound and applanation tonometry) were not different in FH(-) sedentary and trained subjects, but were higher in FH(+) trained subjects as compared to their sedentary peers. Significant but modest relationships were found between spontaneous baroreflex indices and carotid artery elastic parameters across all subjects. Our present data indicate that in subjects with parental hypertension aerobic exercise training is associated with higher levels of cardiovagal outflow and baroreflex gain, which finding, however, is not explained by greater elasticity of the carotid artery.

Opposite changes in carotid versus aortic stiffness during healthy human pregnancy.

Systemic arterial compliance has been known to increase during healthy pregnancy, whereas, recently, the carotid artery has been reported to stiffen. To clarify this controversy, we simultaneously measured aortic PWV (pulse wave velocity) and carotid artery elastic parameters in a cohort of pregnant women. Twelve normotensive pregnant women were studied longitudinally during the three trimesters of pregnancy (T1, T2 and T3 respectively) and 12 weeks PP (postpartum). Carotid artery diastolic diameter and pulsatile distension was measured by an echo-wall tracking method and carotid pulse pressure by applanation tonometry. Carotid strain, compliance, distensibility coefficient, stiffness index beta, Einc (incremental elastic modulus) and augmentation index were calculated. Aortic PWV was determined to estimate aortic distensibility. All carotid artery elastic parameters indicated significant stiffening from T1 to T3 (1.8+/-0.2 versus 2.9+/-0.3 mmHg for Einc), which was reversed after delivery (2.3+/-0.2 mmHg). Aortic PWV decreased during pregnancy (6.2+/-0.2 versus 5.4+/-0.2 m/s) and increased in the PP period (6.7+/-0.2 m/s). No correlation was found between changes in carotid artery elastic parameters and changes in aortic PWV either from T1 to T3 or from T3 to PP. The carotid artery exhibits regionally specific stiffening during pregnancy, which appears to represent a qualitatively different change in arterial elastic behaviour.

Carotid artery elasticity and baroreflex sensitivity in patients with glaucoma.

PURPOSE: To investigate non-invasively the elasticity of common carotid artery and the arterial baroreflex function in patients with chronic open-angle glaucoma. PATIENTS AND METHODS: Data were obtained from patients with chronic open-angle glaucoma (n = 16) [primary open angle- and juvenile open-angle glaucoma] and from age- and sex-matched healthy control subjects (n = 18). End diastolic diameter and pulsatile distension of the common carotid artery were measured with a high-precision, automated ultrasound wall-tracking system (WTS). Spontaneous fluctuation in cardiac interval and systolic pressure were used to determine baroreflex sensitivity. RESULTS: There was no difference in heart rate and pulse pressure between patients with glaucoma and the control subjects. In the glaucoma patients both distensibility coefficient of common carotid artery and baroreflex sensitivity were reduced (two-way factorial ANOVA; P < 0.002). Stiffness (characterizing the rigidity of vessel wall) was higher in the glaucoma patients than in the controls (P = 0.002). CONCLUSIONS: Our results suggest that in patients with chronic open-angle glaucoma the arterial rigidity is significantly increased and therefore the baroreflex function is significantly decreased. These findings may have relevance in the understanding of the autonomic dysfunction and vascular dysregulation in glaucoma.

Maturation of cardiovagal autonomic function from childhood to young adult age.

BACKGROUND: Cardiovagal autonomic control declines with age in adult subjects, which is related in part to increasing stiffness of the barosensory vessel wall. It is not known, however, whether autonomic function changes with age in children. METHODS AND RESULTS: We studied 137 healthy subjects divided into 4 age groups: group 1, 7 to 14 years; group 2, 11 to 14 years; group 3, 15 to 18 years; and group 4, 19 to 22 years. Brachial artery pressure was measured by sphygmomanometry and continuous radial artery pressure and carotid artery pulse pressure (DeltaP) by applanation tonometry. The R-R interval was derived from the ECG. Autonomic function was assessed by spontaneous sequence and frequency-domain indices, which indicate the extent of coupling between fluctuations in heart rate and systolic pressure. Carotid artery diastolic diameter (DD) and pulsatile distension (DeltaD) were measured by echo wall tracking; carotid compliance coefficient (CC) was defined as DeltaD/DeltaP and distensibility coefficient as 2DeltaD/DD . DeltaP. From group 1 to group 3, spontaneous indices increased significantly (18.1+/-1.7 versus 33.3+/-4.0; 14.4+/-1.1 versus 25.5+/-22; 12.9+/-1.1 versus 20.8+/-2.0; and 6.4+/-0.6 versus 16.2+/-1.4 ms/mm Hg [mean+/-SEM] for Seq+, Seq-, LFalpha, and LF(gain), respectively), with no significant changes afterward. CC and DC were inversely proportional to age (r=-0.49 and -0.62, respectively, P<0.001). The efficiency of neural integrative mechanisms, estimated as the ratio of spontaneous indices and CC, more than doubled from group 1 to group 3. Spontaneous indices were linearly related to measures of cardiac vagal activity. CONCLUSIONS: The increase in spontaneous indices from early childhood to adolescence, despite gradual stiffening of the carotid artery, may indicate improved cardiovagal autonomic function, which is most likely a result of maturation of neural mechanisms, attaining peak level at adolescence.

Effect of vitamin E on carotid artery elasticity and baroreflex gain in young, healthy adults.

In this study we tested the hypothesis that dietary vitamin E supplementation can improve carotid artery elasticity and cardio-vagal baroreflex gain in young, healthy individuals. A total of 20 subjects were studied in a double-blind, placebo-controlled, randomized study. Subjects in the active treatment group received 700 IU/day vitamin E for 1 month. Each subject was studied three times: before, during and 1 month after treatment. Plasma vitamin E levels were determined using high-performance liquid chromatography. Carotid artery diameter was measured by ultrasound and radial artery pressure by tonometry. Baroreflex function was assessed by time and frequency domain spontaneous indices. Plasma vitamin E levels increased by 123%, which was associated with a 20% increase in carotid artery compliance and a 30-60% increase in baroreflex indices. All these changes regressed 1 month after cessation of vitamin E supplementation. Significant correlations were observed across conditions (control, treatment and recovery), among plasma vitamin E concentrations, carotid artery compliance and distensibility values and two of the baroreflex gain indices in the treatment group. Our results demonstrate that vitamin E supplementation can increase carotid artery compliance and baroreflex gain in young, apparently healthy adults.

Carotid artery stiffening does not explain baroreflex impairment in pre-eclampsia.

Stiffening of the barosensory vessel wall in hypertension has been suggested to play a role in the associated baroreflex impairment. The carotid distensibility-BRS (baroreflex sensitivity) relationship, however, has not been studied in pre-eclampsia, a condition where hypertension is spontaneously reversible. Twelve normotensive pregnant women and 12 patients with pre-eclampsia matched for maternal age and week of gestation were studied in the third trimester and 3 months postpartum. Carotid artery diastolic diameter and pulsatile distension was measured by echo-wall tracking and carotid pulse pressure by applanation tonometry, and the carotid distensibility coefficient was calculated. Spontaneous BRS was determined by the sequence and spectral methods from 10 min continuous recording of ECG and finger arterial blood pressure. In the third trimester, carotid distensibility was lower in patients with pre-eclampsia than in normotensive pregnant women (2.47+/-0.17 compared with 4.08+/-0.16 x 10(-3)/mmHg); postpartum, it increased moderately in patients, but remained below normotensive values (3.25+/-0.12 compared with 4.25+/-0.19 x 10(-3)/mmHg). In the third trimester, both patients and healthy pregnant women had equally low BRS values; postpartum, the various BRS indices increased markedly (by 60-190%) and to the same level in both groups. No correlation was found between changes in carotid artery distensibility and those in BRS from the third trimester to postpartum period in patients and healthy pregnant women. The lack of association between changes in carotid distensibility and BRS suggest that stiffening of the carotid artery in pre-eclampsia is not responsible for baroreflex dysfunction.