Settling a distracted globe: An overview of psychosocial and psychotherapeutic treatment of attention-deficit/hyperactivity disorder.

While the currently prevailing theory of ADHD postulates a neurobiological background and core deficits of behavioural inhibition and executive functioning as the basis of ADHD symptoms, our current conceptualisation also acknowledges the essential contributory role of psychosocial, ecological, and cognitive factors. Considering the multifactorial background of ADHD, its treatment equally needs to be multifactorial involving, besides pharmacotherapy, skill development and psychotherapy as well, especially if we postulate the increasing contribution of social factors in the background of the increasing burden of ADHD. Pharmacotherapies, including stimulants and non-stimulant ADHD medications applied as first-line treatments have a positive effect on core behavioural symptoms, however, they often do not sufficiently remediate several other symptoms and comorbid disorders, which are consequences of ADHD, especially considering that ADHD persists into adulthood and is present over the whole life span. Furthermore, pharmacological treatment is not sufficient to substitute for the skills needed to manage symptoms and adapt well to the environment. As part of a multimodal treatment approach, psychological therapies for ADHD target, besides core ADHD symptoms, other associated features including emotional dysregulation, personality development, neurocognitive dysfunction, depression, anxiety, and sleep problems. Insufficiently treated ADHD may contribute to psychological and personality developmental problems in children, as well as increased health costs and decreased productivity warranting multimodal treatment to address the areas not sufficiently targeted by ADHD-specific pharmacotherapy.

[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.

[A case of Turner syndrome associated with schizophrenia]. / Szkizofréniával társuló Turner-szindróma.

The authors present the case of a young woman with mosaic karyotype Turner's syndrome who was admitted to a partial hospitalization program due to comorbid schizophrenia. Psychiatric history of the patient included the diagnosis of mild mental retardation and an outpatient appointment due to depressive symptoms. Medical history included hormone replacement therapy due to primary ovarian insufficiency and autoimmune thyroiditis as well as a single case of physical polytrauma due to a road traffic accident years before her admission. On admission, the physical characteristics of Turner's syndrome, chronic phonemic hallucinations and paranoid delusion were found with secondary anger management and social adjustment problems. Brain imaging revealed global cerebral atrophy and a clinically not significant frontal meningioma. Neuropsychological tests confirmed the mild mental retardation and an imbalanced intelligence profile with better verbal than non-verbal functioning. Medication therapy was initiated with social skill training and outpatient follow-ups. Ten months after the initial admission, the antipsychotic monotherapy resulted in a good therapeutic response without a full remission of symptoms. We present our case in the context of a literature review. Orv Hetil. 2023; 164(19): 753-757.

Hg2+ and Cd2+ binding of a bioinspired hexapeptide with two cysteine units constructed as a minimalistic metal ion sensing fluorescent probe.

Hg2+ and Cd2+ complexation of a short hexapeptide, Ac-DCSSCY-NH2 (DY), was studied by pH-potentiometry, UV and NMR spectroscopy and fluorimetry in aqueous solutions and the Hg2+-binding ability of the ligand was also described in an immobilized form, where the peptides were anchored to a hydrophilic resin. Hg2+ was demonstrated to form a 1 : 1 complex with the ligand even at pH = 2.0 while Cd2+ coordination by the peptide takes place only above pH ∼ 3.5. Both metal ions form bis-ligand complexes by the coordination of four Cys-thiolates at ligand excess above pH ∼ 5.5 (Cd2+) and 7.0 (Hg2+). Fluorescence studies demonstrated a Hg2+ induced concentration-dependent quenching of the Tyr fluorescence until a 1 : 1 Hg2+ : DY ratio. The fluorescence emission intensity decreases linearly with the increasing Hg2+ concentration in a range of over two orders of magnitude. The fact that this occurs even in the presence of 1.0 eq. of Cd2+ per ligand reflects a complete displacement of the latter metal ion by Hg2+ from its peptide-bound form. The immobilized peptide was also shown to bind Hg2+ very efficiently even from samples at pH = 2.0. However, the existence of lower affinity binding sites was also demonstrated by binding of more than 1.0 eq. of Hg2+ per immobilized DY molecule under Hg2+-excess conditions. Experiments performed with a mixture of four metal ions, Hg2+, Cd2+, Zn2+ and Ni2+, indicate that this molecular probe may potentially be used in Hg2+-sensing systems under acidic conditions for the measurement of µM range concentrations.

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.

[Neurobiological correlates of cognitive flexibility in ADHD - A systematic review of the literature]. / A kognitív rugalmasság neurobiológiai korrelátumainak vizsgálata ADHD-ban lrodalmi áttekintés.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed childhood psychiatric disorders, which persists to adulthood in 30-50% of the cases. Previous studies have shown that cognitive flexibility, which means to switch between two different rules, that can be tested with task switching paradigms, is affected. Although poor performance in cognitive flexibility tests has been demostrated, the neurobiological background is only partly known. OBJECTIVE: The aim of our review was to examine the neurobiological background of impairment of cognitive flexibility in ADHD, with a specific focus on functional MRI (fMRI) and electrophysiological (electroencephalography, EEG) studies. METHODS: We searched MEDLINE, PubMed, and PsychInfo using the following keywords: 'ADHD', 'cognitive flexibility', 'set shifting', 'task switching', 'EEG', 'fMRI'. RESULTS: Compared to healthy controls, ADHD patients showed reduced activation in regions of the prefrontal and parietal lobe and in the basal ganglia. However in two studies, increased activation was also observed in specific regions of temporal lobe and in anterior cingulate cortex. Magnetoencephalographic results indicated that instead of an increased activity in medio-temporal lobe, ADHD patients showed an enhanced activation in the superior temporal gyrus and in the left inferior parietal lobe. CONCLUSIONS: Based on our review, patients with ADHD, as compared to healthy controls, showed reduced activation in brain regions associated with cognitive flexibility. Based on the differences in the spatial and temporal patterns of activation in the temporal lobe we conclude that ADHD patient engage different brain regions to resolve the conflicts caused by task switching. However, further studies are required to corroborate this conclusion.

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.

How do different diagnostic criteria, age and gender affect the prevalence of attention deficit hyperactivity disorder in adults? An epidemiological study in a Hungarian community sample.

The goal of the study was twofold: (1) to investigate the effect of different diagnostic criteria on prevalence estimates of adult attention deficit hyperactivity disorder (ADHD), and (2) to provide prevalence estimates of adult ADHD for the first time in a Hungarian sample. Subjects between 18 and 60 years were included in the screening phase of the study (N = 3,529), conducted in 17 GP practices in Budapest. Adult self-report scale 6-item version was used for screening. Out of 279 positively screened subjects 161 subjects participated in a clinical interview and filled out a self-report questionnaire to confirm the diagnosis. Beside DSM-IV diagnostic criteria, we applied four alternative diagnostic criteria: 'No-onset' (DSM-IV criteria without the specific requirement for onset); full/Sx (DSM-IV "symptoms only" criteria); and reduced/Sx (DSM-IV "symptoms only" criteria with a reduced threshold for symptom count). Crude prevalence estimates adjusted for the specificity and sensitivity data of the screener were 1.35% in the 'DSM-IV' group, 1.64% in the 'No-onset' group, 3.65% in the 'Sx/full' group and 4.16% in the 'Sx/reduced' group. Logistic regression analysis showed that ADHD was significantly more prevalent with younger age and male gender [chi(2) = 14.46; P = 0.0007]. Prevalence estimates corrected for the 'not-interviewed' subsample and adjusted for specificity and sensitivity data of the screener was 2.3% in males, 0.91% in females; 2.02% in the < or =40 years age group and 0.70% in the >40 years age group, based on DSM-IV diagnostic criteria. Prevalence rates found in this study are somewhat lower, but still are in line with those reported in the literature.

Pharmacotherapy of adult attention deficit hyperactivity disorder (ADHD): a meta-analysis.

Our objective was to conduct a meta-analysis of therapeutic efficacy of pharmacological treatment of adult ADHD based on data from controlled clinical trials. We used the search engines PubMed and Medline to identify relevant clinical trials. Short-term studies with double-blind parallel-group design were selected for the analysis. Altogether, we identified 11 trials that met the criteria, and investigated a total of 1991 subjects, 694 and 1297 of whom were treated with placebo or active medication, respectively. In order to pool efficacy data from studies with different characteristics, including different number of participants, different trial duration and measures of efficacy, the statistical effect sizes for each study had to be calculated. Our findings showed that the pooled effect size across all treatments was in the medium-to-high range (Cohen's d=0.65, p<0.0001 vs. placebo), and the effect size for stimulants (Cohen's d=0.67, p<0.0001 vs. placebo) was somewhat higher than for non-stimulant medications (Cohen's d=0.59, p<0.0001 vs. placebo). The current database of controlled trials for adult ADHD is relatively small, and does not include data for many of the potentially important agents. In addition, effect-size estimates for different classes of medications (i.e. stimulant and non-stimulant medications) were based on separate studies; head-to-head comparisons of various agents are severely lacking. Nonetheless, results of this meta-analysis across all ADHD medications in adult subjects demonstrated statistically significant and clinically robust improvement in symptom severity compared to placebo treatment.

Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis.

BACKGROUND: In spite of the growing literature about adult attention-deficit hyperactivity disorder (ADHD), relatively little is known about the prevalence and correlates of this disorder. AIMS: To estimate the prevalence of adult ADHD and to identify its demographic correlates using meta-regression analysis. METHOD: We used the MEDLINE, PsycLit and EMBASE databases as well as hand-searching to find relevant publications. RESULTS: The pooled prevalence of adult ADHD was 2.5% (95% CI 2.1-3.1). Gender and mean age, interacting with each other, were significantly related to prevalence of ADHD. Meta-regression analysis indicated that the proportion of participants with ADHD decreased with age when men and women were equally represented in the sample. CONCLUSIONS: Prevalence of ADHD in adults declines with age in the general population. We think, however, that the unclear validity of DSM-IV diagnostic criteria for this condition can lead to reduced prevalence rates by underestimation of the prevalence of adult ADHD.

[The relationship between cognition and functional outcome in schizophrenia]. / A szkizofréniában tapasztalható kognitív deficit osszefüggése a mindennapi funkcióképességgel.

Schizophrenia is associated with poor functional outcome, which has been shown to be associated with cognitive impairment, a core feature of the illness. The aim of the present study is to provide an overview of measurements of cognitive deficit and everyday functioning in schizophrenia. The authors demonstrate that cognitive impairment is a predictor of subsequent functional outcome measures by reviewing the relevant cross-sectional and longitudinal studies. Furthermore, models proposing intermediate variables that may provide a link between cognition and functional outcome are discussed. Such mediator variables are social cognition and functional capacity. Future avenues of research on cognition and functional outcome in schizophrenia are outlined, as there is considerable interest in finding treatments to improve cognition in schizophrenia. Improvements in cognitive deficits are expected to lead to benefits in the everyday functioning of the patients.

[Neuropsychological impairments in adult attention deficit hyperactivity disorder: a literature review]. / A felnottkori figyelemhiányos/hiperaktivitás-zavarban tapasztalható neuropszichológial deficit: irodalmi áttekintés.

INTRODUCTION: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most frequently diagnosed childhood psychiatric disorders. Based on various empirical estimates, symptoms of ADHD persist into adulthood in about 30-50% of the childhood cases. METHOD: The objective of the present investigation was to conduct a systematic review of neuropsychological studies to characterize executive and attentional performance in subjects with adult ADHD and to examine whether these neuropsychological tools are useful to diagnose the disorder. 29 relevant publications were identified from 1993 to 2007 via a comprehensive research in Medline and Pubmed databases. RESULTS: The neuropsychological characteristics of adults with ADHD are comparable to those described in the pediatric population. Results indicate that in ADHD the frontal lobe neurocognitive functions, such as attention, planning, behaviour inhibition and problem solving, are the ones primarily impaired in the disorder. DISCUSSION: A better understanding of the nature and extent of the impairment of the cognitive functions involved in the disorder would offer opportunities for the development of disease-specific cognitive therapies and psychopharmacological therapies for patients with ADHD. Furthermore, a finer specification of the neurocognitive profile in adult ADHD might be of great importance as a sensitive marker for the efficacy of pharmaceutical agents.

[Detailed review of epidemiologic studies on adult Attention Deficit/Hyperactivity Disorder (ADHD)]. / A felnôttkori Figyelemhiányos/Hiperaktivitási Zavar (Attention Deficit/Hyperactivity Disorder--ADHD) epidemiológiai vizsgálatainak részletes áttekintése.

INTRODUCTION: Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most frequently diagnosed psychiatric disorders of childhood. It occurs approximately in 3-9% of school age children. Despite the fact that it also occurs in adults, ADHD represents a barely known and rarely recognized disorder in practice. The objective of this article is to provide a detailed review of epidemiological research into ADHD in adults. METHODS: Our research group conducted a systematic review of the epidemiologic literature on adult ADHD based on the Medline and Psychlit databases and papers that have been published during the past 10 years (search was conducted on the following key words: "adult", "adhd", "prevalence" "epidemiology". RESULTS: Findings from follow-up studies indicate that the persistence of symptoms of ADHD in adulthood is in the range of 4-66%. Of the population studies that are presented, one estimated the cumulative incidence between 5 and 19 years of age; the lower and upper limits of the estimates were 7.5% and 16%, respectively. Four population studies were concerned with prevalence in the general population; thus, providing the most reliable estimates for adult ADHD. These studies indicated that, depending on the diagnostic criteria employed, the prevalence of ADHD ranged between 1 and 4.7%. CONCLUSION: In view of the above epidemiological data and of the fact that most studies dealing with adult ADHD have indicated a close link between the symptoms of ADHD and severe difficulties in social adaptation (including the ability to work, functional problems related to criminal behaviour, and psychiatric comorbidity), research into adult ADHD in Hungary, improvement of its diagnosis and recognition, and its adequate treatment is of prime importance from the perspective of clinical practice.

[Pharmacotherapy of adult Attention Deficit/Hyperactivity Disorder (ADHD): a systematic review]. / A felnottkori figyelemhiányos/hiperaktivitás zavar (ADHD) gyógyszeres kezelésének hatékonysága: irodalmi áttekintés.

INTRODUCTION: Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent psychiatric disorders of childhood, which persists into adulthood in 10-60% of the cases. A growing body of data suggests that pharmacotherapy of the disorder is efficacious but a comprehensive summary of available evidence from clinical trials is lacking. The aim of the article was to provide a systematic review of therapeutic efficacy observed in the pharmacological treatment of ADHD based on data from controlled clinical trials. METHODS: We used the search engines PubMed and Medline to identify relevant clinical trials. Studies with short term, double-blind and parallel design were selected for the review. RESULTS: Altogether, 11 trials were included in the review. Our systematic review indicated that adult ADHD is treated with the same medications as the childhood form of the disorder, including psychostimulants as the first line of treatment, antidepressants as the second line, and more recently atomoxetine as well. In view of the fact that only relatively few investigations were available within the individual drug classes, no statistically significant differences could be demonstrated among the classes; thus, our data with regard to effect size should only be considered as descriptive. Most of the investigations focused on psychostimulants, which produced a strong effect size vs. placebo. With regard to atomoxetine, only a few studies were found, in which, however, a large number of subjects were enrolled, representing the largest studies in the literature. The effect size of atomoxetine in these studies was in the medium range. This result is noteworthy since the average age of the subjects in these studies was the highest among the selected studies (more than 40 years, in contrast to less than 40 years in all other studies); this (considering the chronicity of the illness) is viewed as a predictor of poor therapeutic response. Among antidepressants, most clinical trials tested bupropion; based on these trials, this compound is expected to produce an effect size in the medium range. CONCLUSIONS: Pharmacologic agents affecting the dopamine and norepinephrine system have been found to be effective in reducing the symptoms of adult ADHD. In half of the trials, the tested drug was a psychostimulant. The effect sizes of the studies with amphetamine, methylphenidate and dexmethylphenidate were in the high effect size range, and owing to the small number of investigations, we could not discriminate between these drugs. Based on the data available from the literature, non-stimulant medications are indicated when substance dependence or abuse is in the history, or when the side effects of psychostimulants are not tolerated by the patient.