Theta-burst rTMS in schizophrenia to ameliorate negative and cognitive symptoms: study protocol for a double-blind, sham-controlled, randomized clinical trial.

BACKGROUND: Treatment effects of conventional approaches with antipsychotics or psychosocial interventions are limited when it comes to reducing negative and cognitive symptoms in schizophrenia. While there is emerging clinical evidence that new, augmented protocols based on theta-burst stimulation can increase rTMS efficacy dramatically in depression, data on similar augmented therapies are limited in schizophrenia. The different patterns of network impairments in subjects may underlie that some but not all patients responded to given stimulation locations. METHODS: Therefore, we propose an augmented theta-burst stimulation protocol in schizophrenia by stimulating both locations connected to negative symptoms: (1) the left dorsolateral prefrontal cortex (DLPFC), and (2) the vermis of the cerebellum. Ninety subjects with schizophrenia presenting negative symptoms and aging between 18 and 55 years will be randomized to active and sham stimulation in a 1:1 ratio. The TBS parameters we adopted follow the standard TBS protocols, with 3-pulse 50-Hz bursts given every 200 ms (at 5 Hz) and an intensity of 100% active motor threshold. We plan to deliver 1800 stimuli to the left DLPFC and 1800 stimuli to the vermis daily in two 9.5-min blocks for 4 weeks. The primary endpoint is the change in negative symptom severity measured by the Positive and Negative Syndrome Scale (PANSS). Secondary efficacy endpoints are changes in cognitive flexibility, executive functioning, short-term memory, social cognition, and facial emotion recognition. The difference between study groups will be analyzed by a linear mixed model analysis with the difference relative to baseline in efficacy variables as the dependent variable and treatment group, visit, and treatment-by-visit interaction as independent variables. The safety outcome is the number of serious adverse events. DISCUSSION: This is a double-blind, sham-controlled, randomized medical device study to assess the efficacy and safety of an augmented theta-burst rTMS treatment in schizophrenia. We hypothesize that social cognition and negative symptoms of patients on active therapy will improve significantly compared to patients on sham treatment. TRIAL REGISTRATION: The study protocol is registered at "ClinicalTrials.gov" with the following ID: NCT05100888. All items from the World Health Organization Trial Registration Data Set are registered. Initial release: 10/19/2021.

Using Selective Enzymes to Measure Noncanonical DNA Building Blocks: dUTP, 5-Methyl-dCTP, and 5-Hydroxymethyl-dCTP.

Cells maintain a fine-tuned balance of deoxyribonucleoside 5'-triphosphates (dNTPs), a crucial factor in preserving genomic integrity. Any alterations in the nucleotide pool's composition or chemical modifications to nucleotides before their incorporation into DNA can lead to increased mutation frequency and DNA damage. In addition to the chemical modification of canonical dNTPs, the cellular de novo dNTP metabolism pathways also produce noncanonical dNTPs. To keep their levels low and prevent them from incorporating into the DNA, these noncanonical dNTPs are removed from the dNTP pool by sanitizing enzymes. In this study, we introduce innovative protocols for the high-throughput fluorescence-based quantification of dUTP, 5-methyl-dCTP, and 5-hydroxymethyl-dCTP. To distinguish between noncanonical dNTPs and their canonical counterparts, specific enzymes capable of hydrolyzing either the canonical or noncanonical dNTP analogs are employed. This approach provides a more precise understanding of the composition and noncanonical constituents of dNTP pools, facilitating a deeper comprehension of DNA metabolism and repair. It is also crucial for accurately interpreting mutational patterns generated through the next-generation sequencing of biological samples.

The complexity of theory of mind deficit in schizophrenia: A cross-sectional analysis of baseline data from a longitudinal schizophrenia study.

A large number of trials have supported the functional significance of Theory of Mind (ToM) impairment in schizophrenia. However, the nature and the extent of the impairment are still unclear. Reviews on the topic suggest that, in many cases, studies use only one tool to assess the levels of difficulty in the field, limiting the validity of the measurement to one aspect of ToM. On the other hand, the divergence of the used assessment tools makes it hard to compare the result of these studies. Thus, we decided to use additional assessment tools to evaluate the extent of ToM in order to describe several aspects of the phenomenon. A hierarchical cluster analysis of variables was used on a sample of 68 participants with schizophrenia or schizoaffective disorder, to determine the similarity between variances of the assessed ToM subcomponents. Further cross-sectional correlational analysis was then performed to investigate the association between the identified clusters and other used measures (e.g.: neurocognition). The statistical analysis supported a five-cluster model. Identified clusters illustrate the difference between Hypo and HyperToM as well as the degree of ToM task complexity, allowing for a more accurate description of the nature of ToM deficit in schizophrenia.

Virtual reality-based theory of mind intervention in schizophrenia: Preliminary efficacy results.

BACKGROUND: In recent years, a growing body of literature has supported the core nature and functional significance of Theory of Mind (ToM) deficit in schizophrenia. These findings have made ToM impairment a promising treatment target. However, despite the encouraging results, its complexity makes it difficult to develop new interventions and even to understand the exact nature and scope of the deficit. Yet, further investigation has suggested that using modern technology and multilevel assessment may help solve the problem. METHODS: Virtual Reality-based Theory of Mind Intervention (VR-ToMIS) is a recently developed structured method using the combination of cognitive and behavioral therapeutic techniques and the advantages of Virtual Reality (VR) technology. A controlled study with a three-month follow-up was conducted with 42 patients (suffering from schizophrenia or schizo-affective disorder) randomly assigned to either an experimental (VR-ToMIS) or control group (passive-VR). Repeated two-way factorial analysis of covariance was used to evaluate the effects of VR-ToMIS on symptoms, neuro- and social cognition, pragmatic skills, and quality of life when the effect of IQ was controlled. RESULTS: Patients participating in VR-ToMIS showed significant improvements in all types of ToM tasks (except for hyper-ToM task, based on the results of Cartoon test, Faux pas test and and Baron-Cohen Minds in the Eyes Test) compared to the control group with moderate to large effect sizes. In the case of negative and cognitive symptoms, significant between-group differences were also supported. Improvement was moderated by IQ in the case of higher-order ToM, manner, and relevance implicatures. Results were proved to be sustainable three months after the treatment. CONCLUSION: Although the presented results are considered preliminary, they support the potential of the integration of modern technology and traditional methods for future interventions.

Case Report: Feasibility of a Novel Virtual Reality-Based Intervention for Patients With Schizophrenia.

Schizophrenia is a severe and disabling mental illness, associated with persistent difficulties in social functioning. While gaining and retaining a job or staying socially integrated can be very difficult for the patients, the treatment of poor functionality remains challenging with limited options in pharmacotherapy. To address the limitations of medical treatment, several interesting and innovative approaches have been introduced in the field of psychotherapy. Recent approaches incorporate modern technology as well, such as virtual reality. A potential therapeutic benefit of virtual reality is particularly significant when an interpersonal dimension of the problem needs to be addressed. One example is a Virtual Reality based Theory of Mind Intervention (VR-ToMIS), a novel method, which enables patients to practice complex social interactions without the burden of real-life consequences. Our paper presents a case report showing promising results of VR-ToMIS. Ms. Smith is a 50- year-old patient who has been suffering from schizophrenia for 20 years. Although in her case there was no problem with compliance throughout the years, she had severe problems regarding social functionality. With VR-ToMIS, she improved in ToM and communicative-pragmatic skills. The effects of the intervention went beyond the increased scores of the tests. Before the intervention there was a risk of the patient becoming unemployed as she was unable to follow the main principles of communicative exchange. Usually, her contribution was more informative than was required. After the intervention her communication became more balanced and she could retain her job. This case suggests that VR-ToMIS may be a promising tool for treating social disfunction in schizophrenia.

A novel virtual reality-based theory of mind intervention for outpatients with schizophrenia: A proof-of-concept pilot study.

Schizophrenia is a severe and highly disabling mental illness. Although several pharmacological solutions are available to alleviate symptoms of schizophrenia, they do not seem to provide solution for accompanying social dysfunctions. To handle this unmet clinical need, many innovative interventions have been developed recently. Considering the promising results on this field and the development trend, characterized by the growing proportion of included interactive technology, our research team developed a novel virtual reality (VR)-based targeted theory of mind (ToM) intervention (VR-ToMIS) for stable outpatients with schizophrenia. VR-ToMIS is a nine-session long structured and individualized method that uses cognitive and behavioural therapeutic techniques in an immersive VR environment. Our study was a randomized, controlled pilot study. Twenty-one patients have been recruited and randomly allocated to either VR-ToMIS or passive VR condition. Patients assigned to passive VR condition could use the same VR software as the VR-ToMIS group, but without any interventions. Effects on psychiatric symptoms, neurocognitive and social cognitive functions, pragmatic language skills and quality of life were evaluated by using analysis of covariance. According to our results, VR-ToMIS was associated with improvements in negative symptoms, in one neurocognitive field (immediate memory), ToM and pragmatic language skills, but no significant change in quality of life scores was detected. Significant changes in VR-ToMIS group were associated with moderate to large therapeutic effects (ηp 2  = .24-.46, φ = .55-.67). On the background of the presented pilot results, VR-ToMIS is concluded to be feasible and tolerable.

Neuropsychiatric symptoms, quality of life and caregivers' burden in dementia.

The objective of this research is to identify the relationship between the neuropsychiatric symptoms (NPSs) of patients with major neurocognitive disorder (mNCD), their quality of life, illness intrusiveness and the caregiver's burden. We assessed 131 patients with mNCD. Examination methods included WHO well-being index short version, illness intrusiveness rating scale, Alzheimer's Disease Assessment Scale-Cog, Mini Mental State Examination and neuropsychiatric inventory. The results were analysed using standard statistical tests. In our sample, the prevalence of NPSs is 100%. A significant correlation (p < 0.0001) was observed with quality of life and illness intrusiveness. Additionally, a strong relationship was observed between NPSs and the caregiver's burden (r = 0.9). The result is significantly twice as much stronger in comparison to the relationship between NPS and cognitive symptoms (r = 0.4). This is the first study in Hungary to assess the impact of NPS on the burden of relatives and quality of life. NPS had twice stronger impact on caregivers' burden than cognitive decline. However, further studies are needed to assess the sub-syndromes in mNCD in relation to NPS.

Pathological and clinical comparison of Parkinson's disease dementia and dementia with Lewy bodies. / [A Parkinson-kórhoz társuló demencia és a Lewy-testes demencia patológiai és klinikai összehasonlítása].

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are two major neurodegenerative diseases sharing common clinical, pathophysiological and morphologic features. The pathological hallmark of both diseases is the presence of Lewy-bodies (LB). The main constituent of these inclusions is the pathologically aggregated α-synuclein protein. In DLB, LBs are predominantly located in the cortex, whereas in PDD, the subcortical regions are predominantly affected. Furthermore, in DLB, coexisting Alzheimer's disease (AD), pathology with ß-amyloid plaques and neurofibrillary tangles are more common. It is still debated whether DLB and PDD are two distinct entities or different phenotypes of the same disease. Clinical diagnosis is based on the temporal sequence of motor and cognitive symptoms. Dementia often precedes parkinsonism in DLB, while in PDD, cognitive decline generally appears after the onset of motor symptoms. Also, fluctuation of cognitive functions and neuroleptic sensitivity is more severe in DLB than PDD. The recent advancements of imaging techniques revealed that cortical damage, cholinergic deficit and concomitant AD pathology are more severe in DLB compared to PDD. The analysis of cerebrospinal fluid biomarkers shows higher oligomeric α-synuclein burden in PDD. Levodopa is less effective in DLB than in PDD and may increase the risk of psychosis. In this review, we comprehensively analyse the pathological, radiological and clinical features of DLB and PDD, highlighting the overlaps and differences. Orv Hetil. 2020; 161(18): 727-737.

Behavioural and Psychological Symptoms in Neurocognitive Disorders: Specific Patterns in Dementia Subtypes.

BACKGROUND: Behavioural and psychological symptoms in dementia (BPSD) form an important sub-syndrome of dementia. We assessed the frequency and severity of BPSD in a random sample of Hungarian treatment-naïve dementia patients. Furthermore, we examined the relationship between cognitive symptoms and BPSD and the pattern of BPSD in specific types of dementias. METHODS: Patients (n=131) were classified into 3 groups: Alzheimer's (AD), vascular (VD), and mixed (MD) dementia. The Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Neuropsychiatric Inventory (NPI) neuropsychological tests were employed. RESULTS: Mean age and MMSE score did not differ significantly among groups. BPSD was frequent (100% prevalence, NPI mean total Frequency score: 14.58, SD=7.55); abnormal motor behaviour showed the highest frequency. Hallucinations and delusions were related to the aetiology of dementia and were independent of the level of cognitive deterioration, whereas irritability, sleep-wake cycle dysfunctions, and eating-appetite change were associated with cognitive deterioration and were independent from aetiology. Both aberrant motor behaviour and disinhibition were significantly associated with aetiology and cognitive deterioration. CONCLUSIONS: BPSD symptoms are significant constituents of dementia syndromes, affecting quality of life and substantially contributing to the caregiver's burden. Specific symptom patterns can be identified in different types of dementia.

Interventions for the treatment of theory of mind deficits in schizophrenia: Systematic literature review.

Theory of Mind (ToM) plays a central role in regulating social interactions and its impairment is consistently reported in schizophrenia. Regarding schizophrenia, ToM is usually discussed as a sub-domain of social cognition. Since social cognitive deficits have drawn the attention of researchers, a variety of novel treatment techniques and approaches targeting social cognitive deficits have been developed. Encouraging results have repeatedly been reported on the modifiability of social cognitive impairment through these techniques. However, emotional perception seems to be over-represented in these approaches at the expense of other areas, such as ToM. This article presents a systematic review on the social cognitive interventions of the last 10 years, which focused on the remediation of ToM or used techniques primarily focusing on one or more social cognitive domains other than ToM, but with hypothetical effects on it. The aim of our systematic review was to compare these intervention techniques in order to see how effective they are in the remediation of ToM, and to find the best techniques to ameliorate ToM deficits in schizophrenia. According to our findings targeted ToM intervention produced more improvement in ToM tasks, while data regarding non-ToM interventions showed contradictory results with limited effects on ToM.

[Clinical and neuropathological characteristics of dementia with Lewy bodies]. / A Lewy-testes demencia klinikai és neuropatológiai jellemzoi.

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia. The accurate diagnosis is often possible only by neuropathological examination. The morphologic hallmarks are the presence of α-synuclein-rich Lewy bodies and Lewy neurites, identical to those seen in Parkinson's disease (PD) and Parkinson's disease dementia (PDD). Neurotransmitter deficits, synaptic and ubiquitin-proteasome system (UPS) dysfunction play major role in the pathomechanism. Characteristic symptoms are cognitive fluctuation, parkinsonism and visual hallucinations. Due to the often atypical clinical presentation novel imaging techniques and biomarkers could help the early diagnosis. Although curative treatment is not available, therapies can improve quality of life. Clinicopathological studies are important in exploring pathomechanisms, ensuring accurate diagnosis and identifying therapeutic targets. Orv Hetil. 2017; 158(17): 643-652.

Regional grey matter structure differences between transsexuals and healthy controls--a voxel based morphometry study.

Gender identity disorder (GID) refers to transsexual individuals who feel that their assigned biological gender is incongruent with their gender identity and this cannot be explained by any physical intersex condition. There is growing scientific interest in the last decades in studying the neuroanatomy and brain functions of transsexual individuals to better understand both the neuroanatomical features of transsexualism and the background of gender identity. So far, results are inconclusive but in general, transsexualism has been associated with a distinct neuroanatomical pattern. Studies mainly focused on male to female (MTF) transsexuals and there is scarcity of data acquired on female to male (FTM) transsexuals. Thus, our aim was to analyze structural MRI data with voxel based morphometry (VBM) obtained from both FTM and MTF transsexuals (n = 17) and compare them to the data of 18 age matched healthy control subjects (both males and females). We found differences in the regional grey matter (GM) structure of transsexual compared with control subjects, independent from their biological gender, in the cerebellum, the left angular gyrus and in the left inferior parietal lobule. Additionally, our findings showed that in several brain areas, regarding their GM volume, transsexual subjects did not differ significantly from controls sharing their gender identity but were different from those sharing their biological gender (areas in the left and right precentral gyri, the left postcentral gyrus, the left posterior cingulate, precuneus and calcarinus, the right cuneus, the right fusiform, lingual, middle and inferior occipital, and inferior temporal gyri). These results support the notion that structural brain differences exist between transsexual and healthy control subjects and that majority of these structural differences are dependent on the biological gender.

[Formulation strategies of intraoral dosage forms]. / Intraorális gyógyszerformák fejlesztési lehetoségei.

The active pharmaceutical ingredient can be administered by several different routes. Although the oral route (per os) has been one of the most convenient and widely accepted delivery system for most drugs, it has number of disadvantages like the very low pH of the stomach, the high enzymatic activity, and extensive first-pass metabolism. Difficulty in swallowing (dysphagia) is common among all age groups, especially in "problematic" subpopulations like children and the elderly. Several novel intraoral dosage forms (IODs) have recently become available to modulate the physicochemical and pharmacokinetic characteristics of drugs, while improving patient compliance. The present article summarizes and categorizes their formulation possibilities.

[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 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.

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.

Are weight gain and metabolic side effects of atypical antipsychotics dose dependent? A literature review.

BACKGROUND: Numerous publications have provided evidence for clinically important metabolic adverse effects of antipsychotics, but there is no systematic evaluation as to whether weight gain and other metabolic changes are dose dependent. OBJECTIVE: This review of the available literature aimed to explore a possible relationship between dosage of second-generation antipsychotics (SGAs) and the degree of metabolic side effects. DATA SOURCES: A literature review was conducted in 3 steps: (1) Articles published between 1975 and 2004 were identified on the basis of the bibliography of an extensive review of the metabolic effects of SGAs. (2) Articles published between 2004 and 2008 were identified by a PubMed search with the keywords weight gain, metabolic, glucose, insulin, and lipid AND dose combined with amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, and ziprasidone. (3) A hand search was conducted based on the bibliography of the identified articles. STUDY SELECTION AND DATA EXTRACTION: All studies that provided information on metabolic side-effects in different dose ranges were selected. Data extraction was carried out independently by 2 observers. DATA SYNTHESIS: Preliminary evidence suggests a dose-response relationship between clozapine and olanzapine serum concentrations and metabolic outcomes, although the association between administered daily dose and metabolic outcomes is not clear. Data are controversial with regard to risperidone, and no study has as yet assessed risperidone serum concentrations in association with metabolic outcomes. For the other SGAs, there was little evidence to suggest a dose-response relationship, although, in these agents also, no assessment of serum concentrations was conducted. CONCLUSIONS: The finding that metabolic complications may be associated with clozapine and olanzapine plasma concentrations provides further evidence for a causal contribution to the metabolic disturbances observed with these agents. Further well-designed, prospective studies investigating a possible association between SGA serum concentrations and metabolic outcomes are needed.

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 relation between neurocognitive dysfunction and impaired insight in patients with schizophrenia.

OBJECTIVES: The present study aimed to (i) evaluate the association between insight and measures of executive functions and working memory in a sample of 132 patients with schizophrenia and (ii) to explore to what proportion neurocognitive dysfunction contributed to the variance in insight after controlling for symptomatology. METHODS: Subjects were evaluated with a standardized neurocognitive test battery and a semi-structured interview, the Psychosis Evaluation tool for Common use by Caregivers (PECC). PECC, apart from evaluating symptoms and side-effects, measures insight on a 4-point scale by two of its dimensions: awareness of having a mental illness (AMI) and awareness of having symptoms attributed to a mental illness (ASAMI). Executive functioning was measured by the Wisconsin Card Sort Test (WCST) and the Trail Making B (TMB). Working memory was measured by the Letter Number Sequencing (LNS) test from the Wechsler Adult Intelligence Scale (WAIS). RESULTS: Only one significant association was found after correction for multiple testing, between WCST categories completed and AMI (r=-0.29, p=0.0006). WCST categories completed explained only 7.9% of the variance in AMI, while symptomatology explained 20% of variance in AMI and 16.5% of variance in ASAMI. CONCLUSIONS: The current results show a significant but subtle association with the WCST, which is in agreement with earlier literature. No other associations between cognitive functioning and insight were found. In general, these findings seem to suggest that factors other than cognition have a greater impact on insight in patients with schizophrenia.