Electrophysiological underpinnings of dysfunctional inhibitory control in adults with attention-deficit/hyperactivity disorder: evidence for reduced NoGo anteriorization.

Our aim was to delineate the electrophysiological basis of dysfunctional inhibitory control of adult ADHD via investigating the anteriorization of the P3 component of the event-related brain response associated with the NoGo task condition (i.e., NoGo anteriorization, NGA). NGA is a neurophysiological measure of brain topography for cognitive response control, which indexes an overall shift of the brain's electrical activity in anterior direction towards the prefrontal areas. While the NoGo P3 received considerable attention in the adult ADHD literature, the brain topography of this component, which reflects the inhibitory process, remains largely unaddressed. EEG recordings were obtained during a Go/NoGo task from 51 subjects (n = 26 adult patients with ADHD, n = 25 healthy controls) using a high-density, 128-channel BioSemi ActiveTwo recording system. ADHD patients had significantly lower P3 NGA response compared to controls. The decrease in NGA was related to impulsivity scores as measured by the Conners' Adult ADHD Rating Scale: patients with higher impulsivity scores had significantly lower NGA. Treatment with stimulant medication, as compared to the lack of such treatment, was associated with a correction of the lower NGA response in ADHD patients. The current study revealed a lower NGA in adult ADHD, a finding which is consistent with the inhibitory control and frontal lobe dysfunctions described in the disorder. Our finding of the inverse relationship between NGA and impulsivity suggests that clinically more severe impulsivity is linked to a more pronounced frontal dysfunction in adult ADHD subjects.

[Self-harming behavior and suicide attempts in autism spectrum disorder: A systematic overview].

Recent research indicates that the risk of suicide attempts in autism spectrum disorder is substantially higher than in the general population. Although a number of factors may play a role in suicide, in the present review we focused on the meta-analyses that examined self-injurious behavior and suicide attempts in autism due to the importance of these factors. Results to date suggest that the risk of self-harming behavior and suicide attempts in autism is approximately three-times higher than in the general population. Of concern, are findings that suggest that women with autism are 5-13 times more likely to complete suicide than women without autism. It is noteworthy that the high-functioning autistic group has a significantly higher risk of suicide than the low-functioning group. By contrast, the risk of death from somatic causes is higher in the low-functioning autistic group. The results of this systematic overview of the available meta-analyses may help health care professionals, decision-makers, affected persons and their relatives to recognize self-injurious behavior and suicide risk in time, thereby facilitating prevention.

Atypical resting-state gamma band trajectory in adult attention deficit/hyperactivity disorder.

Decreased gamma activity has been reported both in children and adults with attention deficit/hyperactivity disorder (ADHD). However, while ADHD is a lifelong neurodevelopmental disorder, our insight into the associations of spontaneous gamma band activity with age is limited, especially in adults. Therefore, we conducted an explorative study to investigate trajectories of resting gamma activity in adult ADHD patients (N = 42) versus matched healthy controls (N = 59). We investigated the relationship of resting gamma activity (30-48 Hz) with age in four right hemispheric electrode clusters where diminished gamma power in ADHD had previously been demonstrated by our group. We found significant non-linear association between resting gamma power and age in the lower frequency gamma1 range (30-39 Hz) in ADHD as compared to controls in all investigated locations. Resting gamma1 increased with age and was significantly lower in ADHD than in control subjects from early adulthood. We found no significant association between gamma activity and age in the gamma2 range (39-48 Hz). Alterations of gamma band activity might reflect altered cortical network functioning in adult ADHD relative to controls. Our results reveal that abnormal gamma power is present at all ages, highlighting the lifelong nature of ADHD. Nonetheless, longitudinal studies are needed to confirm our results.

Impaired early information processing in adult ADHD: a high-density ERP study.

BACKGROUND: Children with attention-deficit/hyperactivity disorder (ADHD) often demonstrate sensory processing difficulties in the form of altered sensory modulation, which may contribute to their symptomatology. Our objective was to investigate the neurophysiological correlates of sensory processing deficits and the electrophysiological characteristics of early information processing in adult ADHD, measured by the P1 event-related potential (ERP). METHODS: We obtained ERPs during a Go/NoGo task from 26 adult patients with ADHD and 25 matched controls using a high-density 128-channel BioSemi ActiveTwo recording system. RESULTS: ADHD patients had a significantly reduced P1 component at occipital and inferotemporal scalp areas compared to controls. The reduction was associated with inattention and hyperactivity symptom severity, as measured by the Conners' Adult ADHD Rating Scale. ADHD patients with higher inattention scores had significantly smaller P1 amplitudes at posterior scalp sites, while higher hyperactivity scores were associated with higher P1 amplitudes. CONCLUSIONS: Deficits in early sensory processing, as measured by the P1 ERP component, are present in adult ADHD patients and are associated with symptom severity. These findings are suggestive of bottom-up cognitive deficits in ADHD driven by impairments in early visual processing, and provide evidence that sensory processing problems are present at the neurophysiological level in this population.

Alterations in resting-state gamma activity in patients with schizophrenia: a high-density EEG study.

Alterations of EEG gamma activity in schizophrenia have been reported during sensory and cognitive tasks, but it remains unclear whether changes are present in resting state. Our aim was to examine whether changes occur in resting state, and to delineate those brain regions where gamma activity is altered. Furthermore, we wanted to identify the associations between changes in gamma activity and psychopathological characteristics. We studied gamma activity (30-48 Hz) in 60 patients with schizophrenia and 76 healthy controls. EEGs were acquired in resting state with closed eyes using a high-density, 256-channel EEG-system. The two groups were compared in absolute power measures in the gamma frequency range. Compared to controls, in patients with schizophrenia the absolute power was significantly elevated (false discovery rate corrected p < 0.05). The alterations clustered into fronto-central and posterior brain regions, and were positively associated with the severity of psychopathology, measured by the PANSS. Changes in gamma activity can lead to disturbed coordination of large-scale brain networks. Thus, the increased gamma activity in certain brain regions that we found may result in disturbances in temporal coordination of task-free/resting-state networks in schizophrenia. Positive association of increased gamma power with psychopathology suggests that altered gamma activity provides a contribution to symptom presentation.

Suicidal ideation in adult ADHD: Gender difference with a specific psychopathological profile.

OBJECTIVE: To investigate suicidal ideation (SI) in patients with adult ADHD (aADHD), and its association with gender and psychopathology. METHODS: Case-control study with 206 participants (patients = 103/healthy controls = 103; matched on gender, age, and education). SI was assessed by the Beck-I Depression-Inventory. The Conners' Adult ADHD Rating Scale (CAARS) was used to characterize the ADHD symptom-domains. RESULTS: Compared to controls, the likelihood of SI was significantly higher in females with ADHD (odds ratio[OR] = 25.0 (95%CI:2.98-200.0); the difference was not significant in males (OR = 2.09 (95%CI:0.75-5.81). In females, "Problems with Self-Concept" scores on the CAARS showed the closest association with SI (OR = 5.60,95%CI:2.34-13.41]), while in males it was "Impulsivity" scores (OR = 3.01,95%CI:1.50-6.06). CONCLUSION: Our findings extend previously described transdiagnostic associations of specific psychopathological risk factors to aADHD, including problems with self-concept and impulsivity, which are robustly associated with suicidality across diagnostic boundaries. In addition, they indicate that these associations exhibit pronounced gender-specificity in aADHD.

Neural Correlates of Error Monitoring in Adult Attention Deficit Hyperactivity Disorder After Failed Inhibition in an Emotional Go/No-Go Task.

The authors' aim was to investigate the modulation of event-related potentials (ERPs) by the affective content of stimuli in adult attention deficit hyperactivity disorder (ADHD) patients during error monitoring. By obtaining ERPs from 26 adult ADHD patients and 14 healthy controls in an emotional go/no-go task, the authors investigated two error-related ERP components, the error-related negativity (ERN) and error positivity (Pe). In ADHD patients, the ERN amplitude decreased for negative stimuli after failed response inhibition ("no-go response") and Pe amplitude decreased for neutral stimuli compared with the controls. These findings suggest that ADHD patients differ from controls both in the early and in the later stages of error processing.

Alterations in resting-state gamma-activity is adults with autism spectrum disorder: A High-Density EEG study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a wide range of symptoms that include deficits in social cognition and difficulties with social interactions. Neural oscillations in the EEG gamma band have been proposed as an important candidate neurobiological marker of higher order cognitive processes and social interactions. We investigated resting-state gamma-activity of patients with ASD (n=23) in order to delineate alterations as compared to typically developing (TD) subjects (n=24). EEG absolute power was examined in the gamma (30-100Hz) frequency band. We found significantly reduced spectral power across the entire gamma range in the ASD group. The decrease was most pronounced over the inferior-frontal and temporo-parietal junction areas. We also found a significant decrease in gamma-activity over the dorsolateral prefrontal cortex, especially in the left side. Since these brain areas have been associated with social functioning, the reduced gamma-activity in ASD may represent a cortical dysfunction that could underlie a diminished capacity to interpret socially important information, thereby interfering with social functioning. The alterations we found may lend support for an improved diagnosis. Furthermore, they can lead to focused therapies, by targeting the dysfunctional brain activity to improve social cognitive and interaction abilities that are compromised in ASD.

[Teenage and adult pregnancy: different correlations between socio-economic status and smoking]. / A dohányzás és az anyagi helyzet összefüggése serdülokori és felnottkori terhesség esetén.

INTRODUCTION: Smoking occurs frequently during pregnancy, thereby putting mother and child at health risks. Low socio-economic status is a risk factor for smoking. AIM: To investigate the relationship between smoking and low income in teenage and adult pregnancy, which is an important measure of poor socioeconomic status. METHOD: The authors used subject-level data from the US NSDUH database, which contains information on pregnancies and smoking. RESULTS: Teenage pregnancy is associated with higher, whereas adult pregnancy with lower prevalence of smoking, compared to the age-matched female population. The association between income and smoking is age-dependent. Among adults there is an inverse relationship (high income -- low-risk of smoking), while in teenage pregnancy smoking increases with income. CONCLUSIONS: To investigate in teenage and adult pregnancy the relationship between smoking and low income, which is an important measure of poor socio-economic status. Higher socioeconomic status may be associated with risky behaviour, thereby increasing both the risk of smoking and early pregnancy.

[Psychiatric disorders are associated with high mortality rates: somatic comorbidity and mortality in autism spectrum disorder and schizophrenia]. / A pszichiátriai betegségekre jelentos korai halálozási arányszámok jellemzok: szomatikus komorbiditás és mortalitás autizmusspektrum-zavarban és szkizofréniában.

A significant proportion of the high mortality associated with psychiatric illness is due to premature death in comorbidity with somatic illness, and to a lesser extent suicide and accidents. In our literature review, we demonstrate that the risk of mortality for individuals diagnosed with autism spectrum disorder and schizophrenia is more than twice of that of controls. With respect to schizophrenia diagnosis, national data from Hungary are available, and consistent with the international data show an increased risk of mortality. In Hungary, the mortality risk of persons with a diagnosis of schizophrenia is about 2.4 times higher than that of controls matched by age, sex and postcode. In particular, the risk of dying from schizophrenia is increased among young people (7-10 times) and we highlight that although the risk of death in schizophrenia is higher for men than for women, the risk of dying from schizophrenia for women diagnosed with schizophrenia is higher than for men compared to the female control group (relative risk). Considering the high prevalence of psychiatric disorders, an important prerequisite for improving the national mortality rates recorded for somatic illnesses is the early diagnosis and treatment of psychiatric illnesses comorbid with somatic illnesses. The data presented here can help to support the reforms needed in medical education and training and in the organization of health care to reduce mortality. Orv Hetil. 2023; 164(33): 1287-1293.

Placebo Response in Trials of Negative Symptoms in Schizophrenia: A Critical Reassessment of the Evidence.

BACKGROUND: Summarizing evidence from clinical trials of patients with schizophrenia with predominant or prominent negative symptoms (NS), a prior meta-analysis reported a large placebo effect in negative symptoms (Cohen's d = 2.909). Assuming that such an effect was clinically not plausible, we performed a critical re-assessment and an update of the previous results with newly available data from add-on and monotherapy studies. STUDY DESIGN: Random-effect meta/regression analysis of trials that focused on predominant or prominent NS; and adopted a double-blind, randomized, placebo-controlled design. The final pooled meta-analytic database, based on the available add-on and monotherapy studies combined, included 24 publications containing data on a total of 25 studies (21 add-on, 4 monotherapy). STUDY RESULTS: The pooled overall estimate for the placebo effect from the primary analysis for all included studies had a medium effect size, with a Cohen's d value of 0.6444 (SE = 0.091). The estimates were similar in the add-on and monotherapy studies. Meta-regression indicated that the high placebo response was significantly associated with clinical trial characteristics, including the high ratio of patients assigned to active vs. placebo treatment and short trial duration. CONCLUSIONS: These results represent a major downward correction for a current effect size estimate of the placebo response in the negative symptoms of schizophrenia. Our findings also pinpoint certain clinical trial characteristics, which may serve as important predictors of the placebo response. The knowledge of these factors can have important implications for drug development and trial design for new drugs for negative symptoms of schizophrenia.

Attention deficit hyperactivity disorder: Last in, first out - delayed brain maturation with an accelerated decline?

While early neurodevelopmental processes during the emergence of ADHD in childhood received considerable attention, the neurobiological mechanisms that underlie the changes in ADHD in adulthood remain largely unaddressed. We wanted to delineate neurodevelopmental changes in adult ADHD using an electrophysiological measure, the fronto-central NoGo P3 event-related potential (ERP), which is an important neurophysiological index of brain functioning in ADHD, and biomarker for response inhibition and aging. ERPs were obtained from 45 ADHD and 41 healthy subjects using a 128-channel BioSemi recording-system, applying emotionally-valenced and neutral stimuli in a response inhibition task. Our results indicated that ADHD subjects manifested delayed developmental P3-trajectory in young-adulthood as compared to controls; they also showed P3 reduction across all emotional valences, and the reduction was most pronounced at younger ages. The differences in P3 diminished by mid-adulthood, and started to increase again at more advanced ages. Thus, similar to structural-MRI indices, developmental brain differences in the fronto-central NoGo P3 in ADHD largely normalize in young-adulthood. However, a reduction of P3 occurs again starting from mid-adulthood. As the fronto-central NoGo P3 reflects the functioning of the frontal areas (which show delayed maturation in ADHD), our findings are consistent with the ''last in, first out'' hypothesis, which refers to a mirroring pattern of brain development and aging, and posits that brain regions that develop relatively late degenerate relatively early with age. Thus, ADHD may not only be associated with delayed neurodevelopment, but also with a premature age-related deterioration, at least in some measures of electrophysiological functioning.

Decreased resting gamma activity in adult attention deficit/hyperactivity disorder.

Objectives: To delineate task-free gamma activity in adult ADHD and healthy control subjects based on high-density EEG recordings. Relationship of gamma activity with symptom severity was also examined, since gamma activity is considered to be an index of network functions in the brain that underlie higher-order cognitive processes.Methods: Spontaneous EEG was recorded in adult ADHD subjects (N = 42; 25 methylphenidate-naïve and 17 on methylphenidate treatment) and controls (N = 59) with eyes open. EEG absolute power gamma was investigated in the gamma1 (30.25-39 Hz) and gamma2 (39.25-48 Hz) frequency bands.Results: Gamma1 and gamma2 activity was diminished in ADHD compared with healthy control subjects. The difference between ADHD and controls was the most pronounced in the right centroparietal region for both gamma1 and gamma2. Inverse associations were found between gamma1 and gamma2 activity and ADHD symptoms in centroparietal scalp regions.Conclusions: Gamma activity is reduced in adult ADHD, and the reduction has a predominantly right centroparietal distribution. Our findings are consistent with childhood ADHD literature with respect to diminished posterior gamma activity in patients, which may reflect altered dorsal attention network functions. Gamma abnormalities might provide a link between neurophysiological functioning and neuropsychological deficiencies, thereby offering an opportunity to investigate the neurobiological mechanisms that underlie the clinical symptoms of ADHD.

ADHD: a hidden comorbidity in adult psychiatric patients.

Adult attention-deficit/hyperactivity disorder (aADHD) has recently been better recognized and treated in many European countries. In spite of this development, aADHD still features as a "hidden" comorbidity, often not diagnosed even in patients under psychiatric treatment for other psychiatric disorders. The aim of this study was to establish the prevalence rates of unrecognized aADHD in academic centers providing regular psychiatric services in the Czech Republic and Hungary. In a population of psychiatric in-and outpatients, Adult ADHD Self-Report Scale was administered. All positively and about half of the negatively screened subjects were clinically interviewed and the DSM diagnosis of ADHD was determined based on the symptom list and Conners' Adult ADHD Rating Scale. The estimated point prevalence rate of unrecognized comorbid aADHD among psychiatric in-and out patients was 6.99% (95% lower CI: 5.11, 95% upper CI 8.86) according to the DSM-IV-TR criteria and 9.27% (95% lower CI: 7.13, 95% upper CI 11.40) according to the DSM-5 criteria. Current suicide risk was significantly associated with the presence of undiagnosed aADHD; however, life time suicide attempts, depression, dysthymia, alcohol and substance dependence, anxiety and stress related disorders were not. Further educational efforts are needed to improve the recognition and treatment of aADHD in adults.

Electrophysiological indices of aberrant error-processing in adults with ADHD: a new region of interest.

Deficits in error-processing are postulated in core symptoms of ADHD. Our goal was to investigate the neurophysiological basis of abnormal error-processing and adaptive adjustments in ADHD, and examine whether error-related alterations extend beyond traditional Regions of Interest (ROIs), particularly to those involved in adaptive adjustments, such as the Salience Network system. We obtained event-related potentials (ERPs) during a Go/NoGo task from 22 adult-ADHD patients and 29 matched healthy controls using a high-density 256-electrode array. Error-related ERPs with error-negativity (ERN) and error-positivity (Pe) served as probes of error-processing. In ADHD patients both ERN and Pe were significantly reduced, and the reduction was associated with core psychopathological symptoms. The ERP-attenuation was prominent not only at traditional ROI-electrodes but across many other brain areas, with a distinctive subset of group-differences and symptom-correlations manifested at temporo-parietal sites, with right-lateralization. Source-localization uncovered two neural-sources for the error-related ERPs: one in the cingulate cortex near midline, which was present in both groups; and one in the right insular cortex, which was present only in the control group. The neural patterns of impairments may be the result of coexisting deficits in the dorsal midline error-processing brain network involved in "error-processing proper" and the right-lateralized temporo-parietal salience network involved in the evaluation of significance of the error-signals. Our source-localization findings potentially identify a missing link between the previously reported structural change, i.e., reduced insular volume, and the well-established behavioral deficits in ADHD.

Altered response-preparation in patients with adult ADHD: A high-density ERP study.

Aberrations in early-developing bottom-up processes, such as stimulus-driven response preparation, are thought to play a critical role in the onset of ADHD, and in its persistence over time. Electrophysiology offers a unique tool to gain insight into response preparation, since response preparation has been associated with distinctive ERP changes, including negative potential-shifts which occur predominantly over frontal brain areas. We examined response-preceding negative potential shifts (RPNS) as a probe of response-preparation in adult ADHD patients by obtaining high-density event-related potentials from 33 ADHD and 29 matched healthy subjects during a Go/Nogo task using a 128-channel BioSemi recording-system. Compared to controls, ADHD patients showed enhancement of the RPNS in fronto-central brain regions in the Go condition during correct responses. This change was associated with poor performance in the Stroop incongruency-task: the greater the enhancement, the higher the proportion of errors. Moreover, the ERP-enhancement showed association with the severity of ADHD-symptoms; and with heightened response-variability. Thus, ADHD patients demonstrate neurophysiological alterations in response-preparation and response-preceding brain activity, suggestive of excessive activation of prefrontal neural circuits. Given the correlation with neuropsychological and psychopathological measures, these changes may constitute a pathway for core symptoms of ADHD, including premature and impaired response-preparation and motor-hyperactivity.