Movement initiation and preparation in subjects with schizophrenia - The amplitude of the readiness potential as a biological marker for negative symptom severity.

OBJECTIVE: Despite extensive research, the etiology of negative symptoms is not well understood. Preliminary findings are linking motor disturbances to negative symptom severity. We aimed to further the understanding to what extent motor movement preparation influences negative symptom severity. METHODS: In a cohort of 31 subjects with schizophrenia and 20 control subjects we recorded the readiness potential amplitude over Cz during spontaneous movements of the right and left thumb. We further assessed negative and positive symptom severity (scale for the assessment of negative and positive symptoms) as well as neurological soft signs (NSS). RESULTS: In subjects with schizophrenia the severity of negative symptoms was best predicted by the readiness potential amplitude and the NSS subdomain motor coordination. The correlation between deficits in motor coordination and negative symptom severity was partially mediated by the readiness potential amplitude in subjects with schizophrenia. CONCLUSIONS: Deficits in motor processing are linked to negative symptom severity in schizophrenia. The readiness potential may represent a biological marker of these basal deficits. In combination with the assessment of NSS, the readiness potential may be a marker of the course of negative symptom severity and help clarifying interdependencies between (pre)frontal networks for action initiation and coordination, as well as negative symptoms.

Psychosis Endophenotypes: A Gene-Set-Specific Polygenic Risk Score Analysis.

BACKGROUND AND HYPOTHESIS: Endophenotypes can help to bridge the gap between psychosis and its genetic predispositions, but their underlying mechanisms remain largely unknown. This study aims to identify biological mechanisms that are relevant to the endophenotypes for psychosis, by partitioning polygenic risk scores into specific gene sets and testing their associations with endophenotypes. STUDY DESIGN: We computed polygenic risk scores for schizophrenia and bipolar disorder restricted to brain-related gene sets retrieved from public databases and previous publications. Three hundred and seventy-eight gene-set-specific polygenic risk scores were generated for 4506 participants. Seven endophenotypes were also measured in the sample. Linear mixed-effects models were fitted to test associations between each endophenotype and each gene-set-specific polygenic risk score. STUDY RESULTS: After correction for multiple testing, we found that a reduced P300 amplitude was associated with a higher schizophrenia polygenic risk score of the forebrain regionalization gene set (mean difference per SD increase in the polygenic risk score: -1.15 µV; 95% CI: -1.70 to -0.59 µV; P = 6 × 10-5). The schizophrenia polygenic risk score of forebrain regionalization also explained more variance of the P300 amplitude (R2 = 0.032) than other polygenic risk scores, including the genome-wide polygenic risk scores. CONCLUSIONS: Our finding on reduced P300 amplitudes suggests that certain genetic variants alter early brain development thereby increasing schizophrenia risk years later. Gene-set-specific polygenic risk scores are a useful tool to elucidate biological mechanisms of psychosis and endophenotypes, offering leads for experimental validation in cellular and animal models.

Exercise elevates serum brain-derived neurotrophic factor in partially remitted depression.

Brain-derived neurotrophic factor (BDNF) is a pleiotropic cytokine implicated in the pathogenesis of major depressive disorder (MDD). In MDD, serum BDNF levels are attenuated. Healthy adults show BDNF elevation after exercise. To investigate activity-dependent BDNF elevation in MDD, thirty-seven participants with partially remitted MDD were allocated to either a bout of strenuous or light activity. Serum was collected before and after the intervention. BDNF was measured using a highly sensitive and specific enzyme-linked immunosorbent assay. Significant BDNF elevation in the strenuous activity group emerged. This study confirms exercise-dependent serum BDNF elevation in MDD. Preregistration: German Clinical Trials Register (DRKS0001515).

Feigning Adult ADHD on a Comprehensive Neuropsychological Test Battery: An Analogue Study.

The evaluation of performance validity is an essential part of any neuropsychological evaluation. Validity indicators embedded in routine neuropsychological tests offer a time-efficient option for sampling performance validity throughout the assessment while reducing vulnerability to coaching. By administering a comprehensive neuropsychological test battery to 57 adults with ADHD, 60 neurotypical controls, and 151 instructed simulators, we examined each test's utility in detecting noncredible performance. Cut-off scores were derived for all available outcome variables. Although all ensured at least 90% specificity in the ADHD Group, sensitivity differed significantly between tests, ranging from 0% to 64.9%. Tests of selective attention, vigilance, and inhibition were most useful in detecting the instructed simulation of adult ADHD, whereas figural fluency and task switching lacked sensitivity. Five or more test variables demonstrating results in the second to fourth percentile were rare among cases of genuine adult ADHD but identified approximately 58% of instructed simulators.

[Balance Evaluation Systems Test: German translation, cultural adaptation and preliminary results on psychometric properties]. / Balance Evaluation Systems Test: deutsche Übersetzung, kulturelle Anpassung und erste Ergebnisse zu Gütekriterien.

BACKGROUND: The Balance Evaluation Systems Test (BESTest) evaluates balance ability and identifies affected systems associated with balance deficits. OBJECTIVE: The primary objective was the translation and cultural adaptation of the BESTest into German. Secondary objective was the preliminary evaluation of psychometric properties of the BESTest. METHOD: In accordance with international guidelines, the BESTest was translated and adapted by a 7-step process. To test the psychometric properties, persons with subjective or objective balance deficits were included. Internal consistency was evaluated by means of Cronbach's alpha. The criterion validity was tested by measuring the correlation with the Berg Balance Scale (BBS). Construct validity was examined using the Activities-Specific Balance Confidence (ABC-D) scale and the known groups methods (fallers versus non-fallers). RESULTS: A total of 27 subjects were included in the testing of the psychometric properties. Cronbach's alpha was 0.95 for the total scale. The correlation of BESTest scores with those of the BBS revealed a Spearmen's ρ of 0.84 (p < 0.001) and 0.61 (p < 0.001) with those of the ABC­D scale. Fallers and non-fallers showed a trend towards different BESTest scores (p = 0.057). DISCUSSION: This paper provides a German translation of the BESTest authorized by the developer. Our preliminary results confirm reliability and validity.

Relevance of neurocognition in chronic pain syndrome: a systematic and methodical approach.

INTRODUCTION: Subjective and objective deficits in neurocognitive domains are well-documented in patients with chronic pain. However, neurocognitive deficits have not been investigated consistently. The main objective of this study was to conduct a comprehensive assessment of self-rated and objectively assessed cognitive differences between patients with chronic pain (CP) and healthy controls (HC). METHOD: The cognitive functioning of 40 CP and 41 HC was assessed using a standardized computer-based test battery, enabling a comparison of subjective and objective neurocognitive factors. To achieve this, the Vienna Test System (VTS) was utilized, incorporating standardized tests from the Cognitive Basic Assessment Battery (COGBAT) with the advantage of objectivity, reliability, validity, efficiency, utility, and standardization. This approach enables the evaluation of cognitive functioning across all pertinent domains. RESULTS: CP reported cognitive deficits in overall performance as well as specific functions, such as attention, memory, and executive functions. Across all neurocognitive domains, CP showed a poorer performance. Affected subdomains of attention were intensity and selectivity of attention. Lower performance was found also in concentration performance, obtaining and overview, visual orientation performance and reactive stress tolerance. Regarding memory, CP performed worse in figural episodic memory and recognition tasks. In addition, CP exhibited poorer performance in mental flexibility, working memory, planning ability, and inhibition as components of executive functioning, when compared to HC. CONCLUSIONS: CP expressed subjective cognitive deficits and demonstrated impaired neurocognitive performance.

Stability of Attention Performance of Adults with ADHD over Time: Evidence from Repeated Neuropsychological Assessments in One-Month Intervals.

Neuropsychological assessments of attention are valuable sources of information in the clinical evaluation of adults with attention-deficit/hyperactivity disorder (ADHD). However, it is unclear whether the attention performance of adults with ADHD is stable or fluctuates over time, which is of great importance in the interpretation of clinical assessments. This study aimed to explore the stability of attention performance of adults with ADHD in repeated assessments at one-month intervals. Twenty-one adults diagnosed with ADHD took part in this study by completing selective attention and vigilance tests three times, each one month apart. Test scores of participants were compared with and interpreted based on test norms. A considerable proportion of 'below average' performance scores were observed in most of the variables of selective attention and vigilance in all three assessments. Further, selective attention and vigilance performance scores did not differ significantly between the three repeated assessments. Finally, the majority of participants received consistent test score interpretations across the three repeated assessments. This study confirms previous research and highlights abnormal selective attention and vigilance performance in adults with ADHD. Further, this study preliminarily demonstrates relatively stable attention performance across repeated assessments, which has the potential to support clinical assessment, treatment planning, and evaluation.

Basic and complex cognitive functions in Adult ADHD.

BACKGROUND: Many clinical studies reported deficits in basic and complex cognitive functions in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the extent in which deficits in basic functions (i.e., processing speed and distractibility) contribute to complex cognitive impairments (i.e., working memory, planning, cognitive flexibility, memory functions) in adults with ADHD is not well-studied. So far, literature show only one study, revealing that basic functions explain 27-74% of executive dysfunctions. Yet, the authors reported that findings could be affected by the selection of neuropsychological tests. The goal of the present research is to replicate such a finding using a different sample and a different set of neuropsychological tests. METHODS: Forty-eight adult patients with ADHD were compared with 48 healthy controls in basic cognitive functions, namely processing speed and distractibility and more complex cognitive functions, namely selective attention, cognitive flexibility, planning, working memory, verbal fluency, and verbal memory. Basic and complex cognitive functions were assessed using the Vigilance and Sustained Attention, Selective Attention, N-Back, Tower of London, Trail Making Test, Word Fluency, and Verbal Learning and Memory. RESULTS AND CONCLUSION: Logistic regression analyses showed that impairments in complex cognitive functions explained 25% of the variance in ADHD diagnosis. The explained variance dropped from 25% to 9% after considering basic functions of processing speed and distractibility. This 64% reduction highlights the importance of basic functions for impairments in complex functions in patients with ADHD.

Early and middle latency auditory event-related potentials do not explain differences in neuropsychological performance between schizophrenia spectrum patients and matched healthy controls.

Abnormalities of early and middle latency auditory event-related potentials (ERPs) are widespread in schizophrenia and have been suggested to be associated with cognitive deficits in schizophrenia patients. In this cross-sectional study with schizophrenia patients (n=30) and psychiatrically healthy counterparts (n=31) (matched for age, sex, education), we investigated whether auditory information processing (measured via amplitudes and gating of the auditory ERPs P50, N100 and P200) correlates with neuropsychological performance across cognitive domains. The groups differed significantly in amplitudes and gating of N100 and P200 potentials as well as in neuropsychological performance, but not in P50 amplitude and gating. Neither amplitudes nor gating of auditory ERPs correlated with neuropsychological performance. Neuropsychological intergroup differences could not be explained by abnormalities in auditory information processing. Although pronounced impairments exist on the levels of both auditory information processing and cognitive performance in schizophrenia, these abnormalities are not directly associated with each other.

Acute effects of a single dose of 2 mA of anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex on executive functions in patients with schizophrenia-A randomized controlled trial.

OBJECTIVE: Cognitive impairments are a frequent and difficult to treat symptom in patients with schizophrenia and the strongest predictor for a successful reintegration in occupational and everyday life. Recent research suggests transcranial direct current stimulation (tDCS) to enhance cognition in this patient group. However, the question regarding its acute effectiveness on executive functions remains largely unanswered. Here, we examined in a randomized, double blind, sham-controlled repeated-measures design the impact of tDCS on performance in several executive functions in patients with schizophrenia, schizoaffective disorder or acute transient psychotic disorder. METHODS: Patients (N = 48) were tested twice using standardized, well-constructed and clinically validated neuropsychological tests assessing verbal working memory, response inhibition, mental flexibility and problem solving. In session 1 they solely underwent the neuropsychological assessment, whereas in session 2 they additionally received 2 mA of anodal tDCS stimulation over the left dorsolateral prefrontal cortex (DLPFC), cathode right supraorbital ridge, or sham stimulation for 20 minutes. RESULTS: Patients of both groups were not able to correctly discriminate the type of stimulation received confirming the success of the blinding procedure. However, analyzing the whole sample the change in performance from session 1 to session 2 was the same in the verum as in the sham condition (all p >.5). Moreover, a subsequent exploratory analysis showed that performance in the response inhibition task was worse for patients that engaged in the task within 20 minutes after the end of the verum stimulation. CONCLUSION: Hence, 2 mA of anodal tDCS applied over the left DLPFC did not acutely enhance executive functions in patients with schizophrenia or related disorders but impaired performance in the response inhibition task shortly after. Future studies should continue to seek for effective stimulation configurations for this patient group. CLINICAL TRIAL REGISTRATION: The study is registered in the "Deutsches Register Klinischer Studien DRKS", German Clinical Trial Register and has been allocated the following number: DRKS00022126.

Metacognition, psychopathology and daily functioning in adult ADHD.

OBJECTIVE: Previous research indicated that adults with ADHD may have deficits in metacognition, yet the evidence base is scarce. This study aims to explore the existence and nature of metacognitive deficits in adults with ADHD, how psychopathology (such as inattention and depression) may affect metacognition and whether metacognition may impact daily functioning in adults with ADHD. METHOD: Forty-six adult patients with ADHD and 46 controls completed questionnaires for metacognition, psychopathology and daily functioning (subjective assessment; self- and informant report). Participants performed two attention tests in a neuropsychological assessment. After test completion, participants were asked to evaluate their performance with the help of a visual aid and this self-evaluation of test performance was compared with their actual test performance (objective assessment). RESULTS: Patients with ADHD reported large deficits in knowledge of cognition and medium deficits in regulation of cognition compared to controls. Self-evaluation of cognitive test performance revealed no significant deficits. Regression analyses revealed that psychopathology may explain a part of the variation in metacognition. Further regressions indicated that metacognition may account for a significant and meaningful proportion of variance in daily functioning, both self-rated and informant-rated. CONCLUSIONS: Current findings of compromised metacognitive functioning of adults with ADHD suggest that clinicians may not want to rely on patients' self-reports in the clinical assessment. Inattention predicted impairments in metacognition, pointing toward the importance of attention for awareness and metacognition. Finally, we recommend that metacognition is addressed in the treatment trajectory of patients with ADHD, given that aspects of metacognition were directly linked to impairments in daily functioning as rated by participants and their relatives.

Subjective cognitive and neurocognitive functions over the course of CBT.

The aim of the study was to investigate changes in both subjectively and objectively measured cognitive functions as well as their discrepancy in outpatients with major depression disorder in the course of cognitive-behavioural therapy (CBT). A neuropsychological test battery with cognitive tests measuring the domains of attention, memory, and executive functions as well as a questionnaire for the self-assessment of cognitive functions (FLei) in these domains were administered to depressed outpatients (n = 46) at the beginning of CBT, post-treatment after on average 40 sessions, as well as six months after the end of treatment. We found that subjectively as well as objectively measured cognitive functions did not change. The discrepancy between subjective and objective cognitive functions found at the beginning of therapy was no longer significant at post-treatment and six months later. The results indicate, that self-perceived and neuropsychologically measured cognitive impairments show stability despite improved depression. Specific interventions such as cognitive remediation therapy should be additionally applied to depressed patients who suffer from cognitive deficits.

Non-credible symptom report in the clinical evaluation of adult ADHD: development and initial validation of a new validity index embedded in the Conners' adult ADHD rating scales.

As attention-deficit/hyperactivity disorder (ADHD) is a feasible target for individuals aiming to procure stimulant medication or accommodations, there is a high clinical need for accurate assessment of adult ADHD. Proven falsifiability of commonly used diagnostic instruments is therefore of concern. The present study aimed to develop a new, ADHD-specific infrequency index to aid the detection of non-credible self-report. Disorder-specific adaptations of four detection strategies were embedded into the Conners' Adult ADHD Rating Scales (CAARS) and tested for infrequency among credible neurotypical controls (n = 1001) and credible adults with ADHD (n = 100). The new index' ability to detect instructed simulators (n = 242) and non-credible adults with ADHD (n = 22) was subsequently examined using ROC analyses. Applying a conservative cut-off score, the new index identified 30% of participants instructed to simulate ADHD while retaining a specificity of 98%. Items assessing supposed symptoms of ADHD proved most useful in distinguishing genuine patients with ADHD from simulators, whereas inquiries into unusual symptom combinations produced a small effect. The CAARS Infrequency Index (CII) outperformed the new infrequency index in terms of sensitivity (46%), but not overall classification accuracy as determined in ROC analyses. Neither the new infrequency index nor the CII detected non-credible adults diagnosed with ADHD with adequate accuracy. In contrast, both infrequency indices showed high classification accuracy when used to detect symptom over-report. Findings support the new indices' utility as an adjunct measure in uncovering feigned ADHD, while underscoring the need to differentiate general over-reporting from specific forms of feigning.

[Cognitive impairments in patients with depression]. / Kognitive Störungen bei Patienten mit Depression.

Cognitive impairments are frequent in patients suffering from major depressive disorders. They are among the first symptoms, often persist independently of improvement even after remission of the affective symptoms and are an important predictor of psychosocial functioning. In the clinical practice it is mandatory to ask about subjective complaints of the patient as well as to assess the cognitive abilities with the help of a standardized neuropsychological test battery. Cognitive remediation, selective serotonin reuptake inhibitors (SSRI) and vortioxetine as well as repetitive transcranial magnetic stimulation have proven their effectiveness as treatment options.

Visual N80 latency as a marker of neuropsychological performance in schizophrenia: Evidence for bottom-up cognitive models.

OBJECTIVE: Cognitive deficits and visual impairment in the magnocellular (M) pathway, have been independently reported in schizophrenia. The current study examined the association between neuropsychological (NPS) performance and visual evoked potentials (VEPs: N80/P1 to M- and P(parvocellular)-biased visual stimuli) in schizophrenia and healthy controls. METHODS: NPS performance and VEPs were measured in n = 44 patients and n = 34 matched controls. Standardized NPS-scores were combined into Domains and a PCA (Principal Component Analysis) generated Composite. Group differences were assessed via (M)ANOVAs, association between NPS and VEP parameters via PCA, Pearson's coefficient and bootstrapping. Logistic regression was employed to assess classification power. RESULTS: Patients showed general cognitive impairment, whereas group differences for VEP-parameters were non-significant. In patients, N80 latency across conditions loaded onto one factor with cognitive composite, showed significant negative correlations of medium effect sizes with NPS performance for M/P mixed stimuli and classified low and high performance with 70% accuracy. CONCLUSION: The study provides no evidence for early visual pathway impairment but suggests a heightened association between early visual processing and cognitive performance in schizophrenia. SIGNIFICANCE: Our results lend support to bottom-up models of cognitive function in schizophrenia and implicate visual N80 latency as a potential biomarker of cognitive deficits in schizophrenia.

Longitudinal Changes of Cognitive Deficits and Treatment Outcome of Cognitive Behavioral Therapy for Major Depression.

ABSTRACT: The current study examined neuropsychological changes over the course of cognitive behavioral therapy (CBT) in outpatients with major depressive disorder and the influence of cognitive deficits as predictors of clinical outcome in depression. A neuropsychological test battery was carried out on depressed outpatients (N = 54) at the beginning and at the end of CBT. Small improvements were found in divided attention, figural memory, and processing speed from pre- to posttreatment. Cognitive deficits in executive functions before treatment predicted the clinical outcome at the end of CBT. The present study reveals that attention and memory deficits are most likely to improve over the course of treatment, whereas executive functions remain stable in the long term. Depressed patients with worse executive functions at the beginning of treatment seem to benefit more from long-term CBT therapy.

Right parietotemporal activity predicts sense of agency under uncertain delays of sensory outcomes.

Sense of agency is the experience of control over one's own action and its consequent outcomes. The perceived time between a motor action and its consequent sensory outcomes (e.g., a flash of light) is shorter for a voluntary than involuntary action, a phenomenon known as intentional binding, which has been used extensively as an implicit measure of sense of agency. We developed a novel task in which participants had to respond whether a flash appeared immediately or with a delay relative to their voluntary action. We found that under high, but not low, uncertainty about the perceived time between voluntary finger movement and a subsequent flash of light, a prediction signal was generated in the right inferior parietal lobule prior to motor action. This prediction signal was linked to the emergence of a sudden insight solution (colloquially referred to as "Aha!" moment) in the right superior temporal gyrus prior to response. Single-trial event-related potential analysis revealed a reliable correlation between amplitudes of premotor and preresponse activities. The results suggest the existence of a predictive mechanism under high uncertainty about the timing of the sensory consequences of a voluntary motor action. The results are in line with the optimal cue integration theory of sense of agency, which states that both predictive and postdictive agency cues are crucial for the formation of sense of agency and the weight of each type of cue (predictive or postdictive) depends on their availability and reliability.NEW & NOTEWORTHY According to the optimal cue integration theory, the formation of sense of agency relies on both predictive and postdictive agency cues and how they are weighted based on their availability and reliability. Using a novel paradigm, we show for the first time a possible existence of a prediction signal prior to voluntary movement, which appears when postdictive agency cues (i.e., the judgment of the time between voluntary movement and a subsequent flash) are not reliable.

ADHD at the workplace: ADHD symptoms, diagnostic status, and work-related functioning.

Adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) commonly experience impairments in multiple domains of daily living. Work has a central role in daily life and is susceptible to ADHD due to its cognitive demands. The present study seeks to examine the nature of work-related problems and impairments of adults with ADHD, and explores the association to ADHD symptoms and neuropsychological test performance. A community sample of 1231 individuals took part in this study and completed a set of questionnaires assessing ADHD symptoms and work-related problems. Furthermore, a clinical sample of 134 adults diagnosed with ADHD were recruited from an ADHD outpatient clinic, who completed the same set of questionnaires. A subsample of 51 patients with ADHD additionally performed a neuropsychological assessment using tests of attention and executive functions. Work-related problems were found both in individuals of the community sample with symptoms of ADHD and individuals diagnosed with ADHD. Individuals with ADHD reported work related problems particularly in not meeting their own standards and perceived potential, yet it less commonly manifests in negative performance evaluations at work or job loss. ADHD symptoms, in particular symptoms of inattention, were found to be strongly associated with work-related problems, whereas neuropsychological test performance was no meaningful predictor of functioning at work. This study emphasizes the susceptibility of individuals' functioning at work to ADHD symptoms and impairments associated with ADHD. ADHD related difficulties at work should be considered in the clinical evaluation and targeted screening at the work place to provide support when indicated.