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.

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.

[Investigation of the acute effect of bilateral repetitive transcranial magnetic stimulation (rTMS) in therapy resistant major depression patients]. / Bilaterális repetitív transzkraniális mágneses stimuláció (rTMS) akut hatásának vizsgálata terápia rezisztens major depresszióban szenvedok körében.

INTRODUCTION: There is a 20-year history of rTMS treatment, however, is not available in Hungary in routine clinical practice for therapy resistant depression (TRD). In this study we analysed the change of symptom profile of a Hungarian cohort with TRD using bilateral rTMS treatment. METHODS: A cohort of 22 patients suffering from TRD was enrolled in the study. For assessment of the phenotypic profile the Beck Depression Inventory (BDI), The Beck Anxiety Inventory (BAI), The Montgomery-Asberg Depression Rating Scale (MADRS), the Snaith-Hamilton Pleasure Scale (SHAPS), the Insomnia Severity Index (ISI), and the Trail Making Test were applied. Differences of mean scores of scales were compared between the day 1 (before treatment) and the day 14 (after conclusion of treatment). Furthermore, we performed phenotypic comparisons between the gender subgroups. RESULTS: In the total sample significant reduction of symptom scores was found on the depression (pMADRS=0,022; pBDI=0,001) and the anxiety scales (pBAI=0,020) and in case of the TMT-A test (pTMT-A=0,019) at the end of the treatment. The mean scores of the SHAPS, the ISI and the TMT-B did not change up to the day 14. In the sex-specific analysis we found that in men only sleep disorder was improved (p=0,015), while in women both depression scores and TMT-A score decreased significantly (MADRSp=0,015; BDIp=0,005; TMT-Ap=0,036). There were no adverse events during the rTMS treatment. CONCLUSION: 2x5 sessions of bilateral rTMS treatment is an effective, safety applicable intervention in patients with TRD. Our results suggest that significant improvement of depressive, anxious and attention symptoms can be observed already after 10th session. Our findings highlighted that different symptoms evolve in women and men due to the acute effect of the rTMS treatment. Further follow-up study is required to evaluate the long-term effect of rTMS concerning the maintenance of symptom reduction and potential change of anhedonia and insomnia.

[The role of nutritional factors in the adjuvant treatment of major depressive disorder].

A growing body of data has accumulated in the past decades about the possible role of nutritional factors in influencing the initiation and course of mental disorders as well as in the treatment of these disorders. As a result of the aggregation of this data a new field emerged - "nutritional psychiatry". In our current review paper we discuss some of those natural agents that supposedly have antidepressive properties and, accordingly, may play a role in the stand-alone and/or adjuvant treatment of major depressive disorder.

[Four-year follow-up of a neurosyphilis case presenting psychiatric symptoms]. / Pszichiátriai tünetekkel jelentkezo neuroszifilisz négyéves utánkövetése.

The authors present a case of neurosyphilis associated with predominant psychiatric symptoms. The elderly man was admitted because of confused behavior, maniform state, lack of critical judgement and grandiose delusions. On admission, right central facial nerve paresis, hand tremor and parkinsonism were also found. Acute brain imaging and routine laboratory tests failed to identify a firm etiology of the confusional state. The psychiatric treatment resulted in complete recovery from delirium. Afterwards, maniform psychosis dominated the clinical picture for which antipsychotics were administered. Later, rapid cognitive deterioration and progression of motor symptoms were observed. MRI revealed cortical and hippocampal atrophy and white matter hyperintensities. Lumbar puncture found pleocytosis and elevated cerebrospinal fluid protein levels. Neurosyphilis had been confirmed by serologic tests. The cognitive symptoms improved and the psychiatric symptoms remitted under penicillin treatment. Four years after diagnosis, there is a gradual progression in the cognitive decline. Two additional hospitalizations were necessary due to the relapses of psychiatric symptoms. Orv Hetil. 2018; 159(6): 234-238.

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.

Theory of mind impairments in patients with deficit schizophrenia.

The deficit syndrome, a subgroup within schizophrenia, is characterized by enduring, idiopathic negative symptoms. Theory of mind (ToM), a domain of social cognition, is the ability of attributing mental states to ourselves and other people. ToM impairments have not been investigated earlier in deficit schizophrenia. The aim of the present study was to examine ToM differences between patients with deficit (SZ-D) and non-deficit schizophrenia (SZ-ND). Gender differences were also investigated, and based on the literature a better ToM performance was expected in female patients. The participants were 28 patients with SZ-ND, 30 patients with SZ-D, and 29 healthy control volunteers. The "Reading the Mind in the Eyes Test" was used to asses ToM deficits. Control subjects outperformed both patient groups, while there were no significant differences between the two schizophrenia subgroups. In female subjects, both controls and patients with SZ-ND performed significantly better than the SZ-D subgroup. In male subjects, controls performed significantly better than both patient groups. The "diminished emotional range" and the "curbing of interest" items of the Schedule for the Deficit Syndrome showed significant negative relationship with the ToM score. Our main finding is that female subjects with SZ-ND performed significantly better than female subjects with SZ-D.

Low Functional network integrity in cognitively unimpaired and MCI subjects with depressive symptoms: results from a multi-center fMRI study.

Evidence suggests that depressive symptomatology is a consequence of network dysfunction rather than lesion pathology. We studied whole-brain functional connectivity using a Minimum Spanning Tree as a graph-theoretical approach. Furthermore, we examined functional connectivity in the Default Mode Network, the Frontolimbic Network (FLN), the Salience Network, and the Cognitive Control Network. All 183 elderly subjects underwent a comprehensive neuropsychological evaluation and a 3 Tesla brain MRI scan. To assess the potential presence of depressive symptoms, the 13-item version of the Beck Depression Inventory (BDI) or the Geriatric Depression Scale (GDS) was utilized. Participants were assigned into three groups based on their cognitive status: amnestic mild cognitive impairment (MCI), non-amnestic MCI, and healthy controls. Regarding affective symptoms, subjects were categorized into depressed and non-depressed groups. An increased mean eccentricity and network diameter were found in patients with depressive symptoms relative to non-depressed ones, and both measures showed correlations with depressive symptom severity. In patients with depressive symptoms, a functional hypoconnectivity was detected between the Anterior Cingulate Cortex (ACC) and the right amygdala in the FLN, which impairment correlated with depressive symptom severity. While no structural difference was found in subjects with depressive symptoms, the volume of the hippocampus and the thickness of the precuneus and the entorhinal cortex were decreased in subjects with MCI, especially in amnestic MCI. The increase in eccentricity and diameter indicates a more path-like functional network configuration that may lead to an impaired functional integration in depression, a possible cause of depressive symptomatology in the elderly.

Virtual affinity fingerprints for target fishing: a new application of Drug Profile Matching.

We recently introduced Drug Profile Matching (DPM), a novel virtual affinity fingerprinting bioactivity prediction method. DPM is based on the docking profiles of ca. 1200 FDA-approved small-molecule drugs against a set of nontarget proteins and creates bioactivity predictions based on this pattern. The effectiveness of this approach was previously demonstrated for therapeutic effect prediction of drug molecules. In the current work, we investigated the applicability of DPM for target fishing, i.e. for the prediction of biological targets for compounds. Predictions were made for 77 targets, and their accuracy was measured by Receiver Operating Characteristic (ROC) analysis. Robustness was tested by a rigorous 10-fold cross-validation procedure. This procedure identified targets (N = 45) with high reliability based on DPM performance. These 45 categories were used in a subsequent study which aimed at predicting the off-target profiles of currently approved FDA drugs. In this data set, 79% of the known drug-target interactions were correctly predicted by DPM, and additionally 1074 new drug-target interactions were suggested. We focused our further investigation on the suggested interactions of antipsychotic molecules and confirmed several interactions by a review of the literature.

[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.

Drug effect prediction by polypharmacology-based interaction profiling.

Most drugs exert their effects via multitarget interactions, as hypothesized by polypharmacology. While these multitarget interactions are responsible for the clinical effect profiles of drugs, current methods have failed to uncover the complex relationships between them. Here, we introduce an approach which is able to relate complex drug-protein interaction profiles with effect profiles. Structural data and registered effect profiles of all small-molecule drugs were collected, and interactions to a series of nontarget protein binding sites of each drug were calculated. Statistical analyses confirmed a close relationship between the studied 177 major effect categories and interaction profiles of ca. 1200 FDA-approved small-molecule drugs. On the basis of this relationship, the effect profiles of drugs were revealed in their entirety, and hitherto uncovered effects could be predicted in a systematic manner. Our results show that the prediction power is independent of the composition of the protein set used for interaction profile generation.

Distractor filtering and its electrophysiological correlates in schizophrenia.

OBJECTIVE: Patients with schizophrenia are characterized by compromised working memory (WM) performance and increased distractibility. Theta synchronization (especially over the frontal midline areas) is related to cognitive control and executive processes during WM encoding and retention. Alpha event-related desynchronization (ERD) is associated with information processing and attention. METHODS: Participants (35 patients and 39 matched controls) performed a modified Sternberg WM task, containing salient and non-salient distractor items in the retention period. A high-density 128 channel EEG was recorded during the task. Theta (4-7 Hz) and fast alpha (10-13 Hz) event-related spectral perturbation (ERSP) were analyzed during the retention and encoding period. RESULTS: Patients with schizophrenia showed worse WM performance and increased attentional distractibility in terms of lower hit rates and increased distractor-related commission errors compared to healthy controls. Theta synchronization was modulated by condition (learning vs. distractor) in both groups but it was modulated by salience only in controls. Furthermore, salience of distractors modulated less the fast alpha ERD in patients. CONCLUSIONS: Our results suggest that patients with schizophrenia process salient and non-salient distracting information less efficiently and show weaker cognitive control compared to controls. SIGNIFICANCE: These differences may partly account for diminished WM performance and increased distractibility in schizophrenia.

Are patients with schizophrenia rational maximizers? Evidence from an ultimatum game study.

Schizophrenia is associated with impaired social cognition and community functioning. Social decision-making strategies of healthy controls and patients with schizophrenia were compared by using the ultimatum game (UG). In this game two players have to split a sum of money. The proposer offers a portion to the responder, who decides to either accept or reject the offer. Rejection results in no income to either of the parties. Unfair proposals are frequently rejected by nonclinical individuals, a phenomenon described as altruistic punishment. Patients and controls participated in a series of UG interactions as responders in a computerized test setting. We also tested the effect of the proposer's facial expression on decision-making. Our results indicate that patients with schizophrenia accepted unfair offers at a significantly higher rate than did healthy controls. In contrast, at fair proposals, the acceptance rate was lower in patients compared with controls. At higher offers, the proposer's facial expression (positive/negative) significantly influenced the acceptance rate (positive facial expression increased the likelihood of acceptance) in the control group. This effect was not observed in the patient group. These results suggest that schizophrenia patients are impaired in socioeconomic interactions requiring emotion recognition and decision-making, which may result in unstable behavioral strategies.

Peripheral endocannabinoid serum level in association with repetitive transcranial magnetic stimulation (rTMS) treatment in patients with major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an effective and well tolerable biological intervention in major depressive disorder (MDD) contributing to rapid symptom improvement. Molecular mechanisms underpinning the therapeutic effects of rTMS have still not been clarified. Recently published animal data implicated relevant associations with changes in endocannabinoid (eCB) brain levels during rTMS treatment, human studies, however, have not been published. In our study we assessed the detailed phenotypic spectrum of MDD and serum 2-arachidnoylglycerol (2-AG) and anandamide (AEA) levels in 18 patients with treatment-resistant depression before, immediately following, and two weeks after completion of a 10-day rTMS treatment. We found significant associations between serum 2-AG level changes from pretreatment to 2 weeks after treatment and symptom reduction. The greater the increase of 2-AG levels, the greater the improvement of depressive (p = 0.031), anxious (p = 0.007) and anhedonia symptoms (p = 0.047). Here we report for the first time a significant association of human circulating eCB and antidepressant effect of rTMS. Our data may indicate that direct stimulation of targeted brain areas can rapidly alleviate depressive complaints via activation of the eCB system.

[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.

[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.

Salient distractors open the door of perception: alpha desynchronization marks sensory gating in a working memory task.

Focusing attention on relevant information while ignoring distracting stimuli is essential to the efficacy of working memory. Alpha- and theta-band oscillations have been linked to the inhibition of anticipated and attentionally avoidable distractors. However, the neurophysiological background of the rejection of task-irrelevant stimuli appearing in the focus of attention is not fully understood. We aimed to examine whether theta and alpha-band oscillations serve as an indicator of successful distractor rejection. Twenty-four students were enrolled in the study. 64-channel EEG was recorded during a modified Sternberg working memory task where weak and strong (salient) distractors were presented during the retention period. Event-related spectral perturbation in the alpha frequency band was significantly modulated by the saliency of the distracting stimuli, while theta oscillation was modulated by the need for cognitive control. Moreover, stronger alpha desynchronization to strong relative to weak distracting stimuli significantly increased the probability of mistakenly identifying the presented distractor as a member of the memory sequence. Therefore, our results suggest that alpha activity reflects the vulnerability of attention to distracting salient stimuli.

Natural health products, dietary minerals and over-the-counter medications as add-on therapies to antidepressants in the treatment of major depressive disorder: a review.

Given the moderate efficacy of the currently available antidepressants (ADs) in the treatment of major depressive disorder (MDD), the identification of agents that are both able to enhance the effectiveness of ADs and have a good safety profile is a reasonable task for current psychopharmacology. In addition to the well-known drugs (second-generation antipsychotics, levothyroxine, dopaminergic agents, etc.) for augmentation, investigations suggest that several nutraceuticals and over-the-counter (OTC) drugs may be effective and safe as adjunct therapeutic agents to conventional ADs. To identify such active ingredients we first performed a systematic literature search using PubMed and then conducted both backward and forward citation searches. For the PubMed search, we used the following combinations of keywords: 1) "adjunctive" + "therapy" + "antidepressant"; 2) "add-on" + "therapy" + "antidepressant"; 3) "supplementation" + "therapy" + "antidepressant". As a result of those efforts, we found more than 20 agents (e.g. S-Adenosyl-L-Methionine; folate; ω-3 fatty acids; curcumin; N-acetylcysteine; saffron; 5-hydroxytryptophan; NSAIDs) that are supposedly effective in the augmentation of standard AD treatment. We discussed the possible mechanisms of the antidepressant actions of those agents, as well as the preclinical and clinical evidence for their efficacy as stand-alone and adjunct treatments for MDD.

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.