[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.

Differential neurocognitive profiles in adult attention-deficit/hyperactivity disorder subtypes revealed by the Cambridge Neuropsychological Test Automated Battery.

Adult attention-deficit/hyperactivity disorder (aADHD) represents a heterogeneous entity incorporating different subgroups in terms of symptomatology, course, and neurocognition. Although neurocognitive dysfunction is generally associated with aADHD, its severity, association with self-reported symptoms, and differences between subtypes remain unclear. We investigated 61 outpatients (65.6% male, mean age 31.5 ± 9.5) diagnosed using DSM-5 criteria together with age-, sex-, and education-matched healthy controls (HC) (n = 58, 63.8% male, mean age 32.3 ± 9.6). Neurocognitive alterations were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and compared between groups using the generalized linear model (GLM) method. Multivariate effects were tested by principal component analysis combined with multivariate pattern analysis. Self-reported symptom severity was tested for correlations with neurocognitive performance. GLM analyses revealed nominally significant differences between the aADHD and HC groups in several domains, however, only the Rapid Visual Information Processing measures survived correction, indicating impaired sustained attention and response inhibition in the aADHD group. Comparison of the predominantly inattentive and the hyperactive-impulsive/combined subtypes yielded nominally significant differences with higher levels of dysfunction in the inattentive group. In the stepwise discriminant analysis aADHD and HC groups were best separated with 2 factors representing sustained attention and reaction time. We found only weak correlations between symptom severity and CANTAB factors. aADHD patients are neuropsychologically heterogeneous and subtypes show different neurocognitive profiles. Differences between the aADHD and HC groups were driven primarily by the inattentive subtype. Sustained attention and its factor derivative showed the most significant alterations in aADHD patients.

Genetics in the ADHD Clinic: How Can Genetic Testing Support the Current Clinical Practice?

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a childhood prevalence of 5%. In about two-thirds of the cases, ADHD symptoms persist into adulthood and often cause significant functional impairment. Based on the results of family and twin studies, the estimated heritability of ADHD approximates 80%, suggests a significant genetic component in the etiological background of the disorder; however, the potential genetic effects on disease risk, symptom severity, and persistence are unclear. This article provides a brief review of the genome-wide and candidate gene association studies with a focus on the clinical aspects, summarizing findings of ADHD disease risk, ADHD core symptoms as dimensional traits, and other traits frequently associated with ADHD, which may contribute to the susceptibility to other comorbid psychiatric disorders. Furthermore, neuropsychological impairment and measures from neuroimaging and electrophysiological paradigms, emerging as potential biomarkers, also provide a prominent target for molecular genetic studies, since they lie in the pathway from genes to behavior; therefore, they can contribute to the understanding of the underlying neurobiological mechanisms and the interindividual heterogeneity of clinical symptoms. Beyond the aforementioned aspects, throughout the review, we also give a brief summary of the genetic results, including polygenic risk scores that can potentially predict individual response to different treatment options and may offer a possibility for personalized treatment for the therapy of ADHD in the future.

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.

[Transdiagnostic study of impulsivity dimensions. Comparative analysis of impulsivity profiles in adult Attention Deficit Hyperactivity Disorder and Borderline Personality Disorder].

INTRODUCTION: High levels of impulsivity represent a core feature of various psychiatric conditions, such as Attention Deficit Hyperactivity Disorder (ADHD), Borderline Personality Disorder (BPD), Impulse Control and Conduct Disorders, Bulimia Nervosa, Substance Use Disorders, and other maladaptive behaviors, like non-suicidal self-harm and suicidal behavior. The overall aim of our research is to carry out a trans-diagnostic study of impulsivity as a common behavioral risk factor, taking into consideration the different dimensions of impulsivity (motor, attentional, non-planning). The project investigates inhibitory neurocognitive deficits, electrophysiological correlates, childhood adversities and genetic vulnerability factors in the background of impulsivity. METHODS: In this report, we describe the results of our pilot study which aims to compare impulsivity profiles, personality traits, and levels of aggression in patients with adult ADHD (aADHD) and BPD primary diagnoses, and healthy control subjects, based on self report questionnaires (Barratt Impulivity Scale, Cloninger Temperament and Character Inventory). We have also carried out analyses on the role of childhood adverse events in the background of impulsivity. Because of the predominance of female participants in the BPD group, we restrict our analyses to only female subjects (N=111 out of 152 patients overall). RESULTS: Comparing the three groups significant differences were observed in each impulsivity domain: higher levels of attentional and motor impulsivity were present in aADHD, while non-planning impulsivity was more characteristic to BPD (p<0.001). Using the Cloninger Temperament and Character Inventory aADHD patients reached significant higher levels on six subscales (novelty seeking, harm avoidance, reward dependency, perseverance, selfdirection, cooperation) than BPD patients (p<001). Childhood emotional neglect results in higher levels of impulsivity in adulthood (R=0.54, p<0.001) regardless of diagnosis. CONCLUSION: Impulsivity, as a diagnostic criterion of different psychiatric disorders is a heterogenous construct. Different characteristics of impulsivity are pronounced with respect to the condition it is part of. Studying impulsivity can improve our understanding of the etiology of different psychiatric conditions, which can result in more specific and effective therapeutic interventions.

[New directions in psychiatric genetics: Genome-wide association studies, polygenic risk score and cross-disorder analysis].

The field of psychiatric genetics investigates the genetic background of psychiatric disorders. In a broader sense, this discipline aims to understand the molecular pathways underlying psychopathology, therefore, it is also referred to as molecular psychiatry. The most important question of this field was originally the following: What type of inheritance is responsible for the overrepresentation of psychiatric disorders in certain families, and which variants of the human genome account for the heritability of these disorders? Moreover, can we get closer to understanding the biological mechanisms of psychiatric disorders by studying and identifying such genetic variants? Technological development during the past decades has enabled us to collect, analyze and compare genetic data from large sample sets of patients and healthy control individuals. Genome-wide association studies (GWAS) have identified common variants that convey increased risk of small effect for the development of different psychiatric disorders. Furthermore, we are now able to compose polygenic risk scores (PRS) from these disease-causing variants and quantify the overall genetic risk of individuals. The implementation of this method supports the polygenic nature of psychiatric disorders. Finally, cross-disorder analyses have the potential to compare the genetic background of different psychiatric disorders and to determine overlapping and distinct marker sets between disorders. These new research methods are described in our review paper through the examples of schizophrenia and attention deficit-hyperactivity disorder (ADHD). Psychiatric genetics has not yet entered the everyday clinical practice in psychiatry, however, it informs us about the biological underpinnings and genetic architecture of psychiatric disorders.

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.

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.

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.

Post-Error Slowing in Patients With ADHD: A Meta-Analysis.

OBJECTIVE: Post-error slowing (PES) is a cognitive mechanism for adaptive responses to reduce the probability of error in subsequent trials after error. To date, no meta-analytic summary of individual studies has been conducted to assess whether ADHD patients differ from controls in PES. METHOD: We identified 15 relevant publications, reporting 26 pairs of comparisons (ADHD, n = 1,053; healthy control, n = 614). Random-effect meta-analysis was used to determine the statistical effect size (ES) for PES. RESULTS: PES was diminished in the ADHD group as compared with controls, with an ES in the medium range (Cohen's d = 0.42). Significant group difference was observed in relation to the inter-stimulus interval (ISI): While healthy participants slowed down after an error during long (3,500 ms) compared with short ISIs (1,500 ms), ADHD participants sustained or even increased their speed. CONCLUSION: The pronounced group difference suggests that PES may be considered as a behavioral indicator for differentiating ADHD patients from healthy participants.

[Gamma oscillation synchronization in schizophrenia--literature review]. / Gamma oszcilláció szinkronizáció szkizofréniában. Irodalmi összefoglaló.

INTRODUCTION: Gamma oscillation - as a basic operating mode of cortical networks - has received considerable interest in the the current EEG literature. Research in the field of gamma synchronization in schizophrenia has become the focus of psychiatry research in the past two decades, obtaining significant attention from the beginning, since the idea that a deficit in synchronization, especially in gamma oscillation synchronization might play a principal role in certain schizophrenia symptoms has emerged. METHODS: In our review we aim to provide a brief description of the theoretical background, as well as an overview of differences in gamma oscillation synchronization observed in patients with schizophrenia compared to healthy controls. In order to identify relevant articles, we used PubMed and Medline search engines. For the current paper we reviewed articles published between 1999-2009, which reported results of clinical studies. RESULTS: Consistent evidence for gamma synchronization deficit in both visual and acoustic modalities has been found in patients with schizophrenia as compared to healthy controls from most of the available studies, but the methodological heterogeneity observable in the field make the generalization of findings difficult. CONCLUSIONS: The alteration observed in gamma oscillations and synchrony in patients with schizophrenia might play an important role in the pathophysiology of the disease. The potential relevance of the topic with regard to clinical practice underlines the need for more research.

[Event-related EEG potentials associated with error detection in psychiatric disorder: literature review]. / Hibázáshoz kötött eseményfüggô EEG potenciálok a pszichiátriai betegségekben. Irodalmi áttekintés.

INTRODUCTION: Error-related bioelectric signals constitute a special subgroup of event-related potentials. Researchers have identified two evoked potential components to be closely related to error processing, namely error-related negativity (ERN) and error-positivity (Pe), and they linked these to specific cognitive functions. In our article first we give a brief description of these components, then based on the available literature, we review differences in error-related evoked potentials observed in patients across psychiatric disorders. METHODS: The PubMed and Medline search engines were used in order to identify all relevant articles, published between 2000 and 2009. For the purpose of the current paper we reviewed publications summarizing results of clinical trials. RESULTS: Patients suffering from schizophrenia, anorexia nervosa or borderline personality disorder exhibited a decrease in the amplitude of error-negativity when compared with healthy controls, while in cases of depression and anxiety an increase in the amplitude has been observed. Some of the articles suggest specific personality variables, such as impulsivity, perfectionism, negative emotions or sensitivity to punishment to underlie these electrophysiological differences. CONCLUSION: Research in the field of error-related electric activity has come to the focus of psychiatry research only recently, thus the amount of available data is significantly limited. However, since this is a relatively new field of research, the results available at present are noteworthy and promising for future electrophysiological investigations in psychiatric disorders.

[Event-related potentials associated with error detection in adult ADHD--literature review]. / Eseményfüggô agyi potenciál eltérések felnôttkori ADHD-ban. Irodalmi áttekintés.

INTRODUCTION: According to a recent assessment the prevalence of adult attention-deficit/hyperactivity disorder (ADHD) was 1.5% in the Hungarian adult population (1), which is in line with previous results indicating that ADHD is a disorder of high prevalence. The core symptoms, including the attention deficit, the hyperactivity and impulsivity are all characteristics that have a significant impact on cognitive functions. Our review focuses on event-related potentials of patients suffering from adult ADHD. With information gained from electrophysiological measurement, our goal is to give an overview of the process leading to a functional impairment based on the available literature. METHOD: PubMed and Medline search engines were used in order to identify all relevant articles, published between 1993 and 2010. For the purpose of the current paper we reviewed publications summarizing results of clinical studies. RESULTS: With regard to evoked potentials reflecting early sensorial information processing a significant difference between ADHD and control subjects was detected in the auditory N2 and P2, and visual N2 components. The P300 component, which is independent of modality, was significantly lower in ADHD patients compared to the control group. Similar results were reported with regard to error related negativity (ERN). CONCLUSION: Since electrophysiological research investigating event-related evoked potientials in adults suffering from ADHD have come to the focus of scientific interest only recently, the amount of literature available is relatively limited. Considering that all three core symptoms of the disorder have a significant impact on both information processing and on concomitant cognitive functions, patients with ADHD should be divided into subgroups based on their neuropsychologically measured dominant symptoms.