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Introduction: In this prospective cohort study over 40 years we investigated the effect of childhood attention-deficit/hyperactivity disorder (ADHD) and subthreshold ADHD on cognitive performance in adulthood., Methods: The cohort comprised individuals with mild perinatal risks. Childhood ADHD group (cADHD, n  = 39) was compared to a group with subthreshold childhood attention or hyperactivity symptoms (cAP; n  = 79), a group with similar perinatal risks but no ADHD symptoms ( n  = 255), and to controls without ADHD symptoms or perinatal risks ( n  = 69). The groups were assessed with multiple neuropsychological measures in domains of verbal reasoning, perceptual skills, memory, working memory, attention, executive functions, and speed. Group-level differences and frequencies of deficient functioning were analyzed., Results: Overall, the groups' performance differed in all cognitive domains at age 40. Verbal reasoning, perceptual skills, memory, and speed had the largest effect sizes (0.51-0.62). The cADHD group's performance was lower than the other groups' on 13 out of 21 measures. The cAP group performed poorer than controls on five measures. In the cADHD group, 23% had three or more deficient cognitive domains, compared to 4-6% in the other groups., Discussion: Childhood ADHD is associated with impaired cognitive functioning in adulthood on several cognitive domains whereas childhood subthreshold ADHD is linked to fewer cognitive deficits. Task complexity was linked to poorer performance within the ADHD group. Our results add to the scarce longitudinal evidence of cognitive outcomes related to childhood ADHD and subthreshold symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Schiavone, Virta, Leppämäki, Launes, Vanninen, Tuulio-Henriksson, Järvinen, Lehto and Hokkanen.)

Current knowledge of white matter changes in large-scale brain networks in adult attention-deficit/hyperactivity disorder (ADHD) is scarce. We collected diffusion-weighted magnetic resonance imaging data in 40 adults with ADHD and 36 neurotypical controls and used constrained spherical deconvolution-based tractography to reconstruct whole-brain structural connectivity networks. We used network-based statistic (NBS) and graph theoretical analysis to investigate differences in these networks between the ADHD and control groups, as well as associations between structural connectivity and ADHD symptoms assessed with the Adult ADHD Self-Report Scale or performance in the Conners Continuous Performance Test 2 (CPT-2). NBS revealed decreased connectivity in the ADHD group compared to the neurotypical controls in widespread unilateral networks, which included subcortical and corticocortical structures and encompassed dorsal and ventral attention networks and visual and somatomotor systems. Furthermore, hypoconnectivity in a predominantly left-frontal network was associated with higher amount of commission errors in CPT-2. Graph theoretical analysis did not reveal topological differences between the groups or associations between topological properties and ADHD symptoms or task performance. Our results suggest that abnormal structural wiring of the brain in adult ADHD is manifested as widespread intrahemispheric hypoconnectivity in networks previously associated with ADHD in functional neuroimaging studies., (© 2023 Massachusetts Institute of Technology.)

Background: Bipolar disorder (BD) is one of the leading causes of disability worldwide. However, the prevalence and predictors of long-term work disability among patients with type I and II BD have scarcely been studied. We investigated the clinical predictors of long-term work disability among patients with BD., Methods: The Jorvi Bipolar Study (JoBS) is a naturalistic prospective cohort study (n = 191) of adult psychiatric in- and out-patients with DSM-IV type I and II BD in three Finnish cities. Within JoBS we examined the prevalence and predictors of disability pension being granted during a six-year follow-up of the 152 patients in the labor force at baseline and collected information on granted pensions from national registers. We determined the predictors of disability pension using logistic regression models., Results: Over the 6 years, 44% of the patients belonging to the labor force at baseline were granted a disability pension. Older age; type I BD; comorbidity with generalized anxiety disorder, post-traumatic stress disorder or avoidant personality disorder; and duration of time with depressive or mixed symptoms predicted disability pensions. Including disability pensions granted before baseline increased their total prevalence to 55.5%. The observed predictors were similar., Conclusion: This regionally representative long-term prospective study found that about half of patients with type I or II bipolar disorder suffer from persistent work disability that leads to disability pension. In addition to the severity of the clinical course and type I bipolar disorder, the longitudinal accumulation of time depressed, psychiatric comorbidity, and older age predicted pensioning., (© 2022. The Author(s).)

Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with negative life outcomes and recent studies have linked it to increased mortality. These studies have examined nationwide registers or clinic-referred samples and mostly included participants up until the age of 30. No studies have investigated mortality associated with subthreshold levels of ADHD symptoms. Our aim was to analyze mortality in a perinatal risk cohort of 46-year-old adults with childhood ADHD (cADHD) and milder childhood attention problems (including hyperactivity and inattention; cAP) compared with a group with similar birth risks but no or low levels of childhood ADHD symptoms (Non-cAP). Causes of death obtained from a national register were examined., Methods: Mortality was analyzed with Cox proportional hazard models for all-cause mortality, cause-specific mortality (natural and unnatural causes), and age-specific mortality (under and over age 30). All models were adjusted with gender. The total n in the study was 839 (cADHD n = 115; cAP n = 216; Non-cAP n = 508)., Results: By the age of 46, 11 (9.6%) deaths occurred in the cADHD group, 7 (3.2%) in the cAP group, and 20 (3.9%) in the Non-cAP group. The cADHD group had the highest mortality risk (adjusted hazard ratio = 2.15; 95% CI 1.02, 4.54). Mortality was not elevated in the cAP group (adjusted hazard ratio = 0.72; 95% CI .30, 1.72). Mortality in the cADHD group was mainly attributed to unnatural causes of death (adjusted hazard ratio = 2.82; 95% CI 1.12, 7.12). The mortality risk in the cADHD group was sixfold before age 30 (adjusted hazard ratio = 6.20; 95% CI 1.78, 21.57)., Conclusions: Childhood ADHD was associated with a twofold risk of premature death by the age of 46 in this prospective longitudinal cohort study. Our results corroborate previous findings and the morbidity of ADHD. Subthreshold levels of childhood ADHD symptoms were not linked to increased mortality. Our results suggest that mortality risk is higher in young than middle adulthood. Future studies should examine mortality associated with ADHD in different ages in adulthood to identify those in greatest risk of premature death., (© 2022. The Author(s).)

The development of treatments for attention impairments is hampered by limited knowledge about the malleability of underlying neural functions. We conducted the first randomized controlled trial to determine the modulations of brain activity associated with working memory (WM) training in adults with attention-deficit hyperactivity disorder (ADHD). At baseline, we assessed the aberrant functional brain activity in the n-back WM task by comparing 44 adults with ADHD with 18 healthy controls using fMRI. Participants with ADHD were then randomized to train on an adaptive dual n-back task or an active control task. We tested whether WM training elicits redistribution of brain activity as observed in healthy controls, and whether it might further restore aberrant activity related to ADHD. As expected, activity in areas of the default-mode (DMN), salience (SN), sensory-motor (SMN), frontoparietal (FPN), and subcortical (SCN) networks was decreased in participants with ADHD at pretest as compared with healthy controls, especially when the cognitive load was high. WM training modulated widespread FPN and SN areas, restoring some of the aberrant activity. Training effects were mainly observed as decreased brain activity during the trained task and increased activity during the untrained task, suggesting different neural mechanisms for trained and transfer tasks., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Two themes have puzzled the research on developmental and learning disorders for decades. First, some of the risk and protective factors behind developmental challenges are suggested to be shared and some are suggested to be specific for a given condition. Second, language-based learning difficulties like dyslexia are suggested to result from or correlate with non-linguistic aspects of information processing as well. In the current study, we investigated how adults with developmental dyslexia or ADHD as well as healthy controls cluster across various dimensions designed to tap the prominent non-linguistic theories of dyslexia. Participants were 18-55-year-old adults with dyslexia ( n = 36), ADHD ( n = 22), and controls ( n = 35). Non-linguistic theories investigated with experimental designs included temporal processing impairment, abnormal cerebellar functioning, procedural learning difficulties, as well as visual processing and attention deficits. Latent profile analysis (LPA) was used to investigate the emerging groups and patterns of results across these experimental designs. LPA suggested three groups: (1) a large group with average performance in the experimental designs, (2) participants predominantly from the clinical groups but with enhanced conditioning learning, and (3) participants predominantly from the dyslexia group with temporal processing as well as visual processing and attention deficits. Despite the presence of these distinct patterns, participants did not cluster very well based on their original status, nor did the LPA groups differ in their dyslexia or ADHD-related neuropsychological profiles. Remarkably, the LPA groups did differ in their intelligence. These results highlight the continuous and overlapping nature of the observed difficulties and support the multiple deficit model of developmental disorders, which suggests shared risk factors for developmental challenges. It also appears that some of the risk factors suggested by the prominent non-linguistic theories of dyslexia relate to the general level of functioning in tests of intelligence., (Copyright © 2020 Laasonen, Lahti-Nuuttila, Leppämäki, Tani, Wikgren, Harno, Oksanen-Hennah, Pothos, Cleeremans, Dye, Cousineau and Hokkanen.)

Individuals with attention-deficit/hyperactivity disorder (ADHD) have difficulties navigating dynamic everyday situations that contain multiple sensory inputs that need to either be attended to or ignored. As conventional experimental tasks lack this type of everyday complexity, we administered a film-based multi-talker condition with auditory distractors in the background. ADHD-related aberrant brain responses to this naturalistic stimulus were identified using intersubject correlations (ISCs) in functional magnetic resonance imaging (fMRI) data collected from 51 adults with ADHD and 29 healthy controls. A novel permutation-based approach introducing studentized statistics and subject-wise voxel-level null-distributions revealed that several areas in cerebral attention networks and sensory cortices were desynchronized in participants with ADHD (n = 20) relative to healthy controls (n = 20). Specifically, desynchronization of the posterior parietal cortex occurred when irrelevant speech or music was presented in the background, but not when irrelevant white noise was presented, or when there were no distractors. We also show regionally distinct ISC signatures for inattention and impulsivity. Finally, post-scan recall of the film contents was associated with stronger ISCs in the default-mode network for the ADHD and in the dorsal attention network for healthy controls. The present study shows that ISCs can further our understanding of how a complex environment influences brain states in ADHD., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

We investigated ADHD symptoms and life outcomes in adulthood and their association with childhood ADHD and subthreshold symptoms in a prospectively followed cohort with perinatal risks. We identified participants with childhood ADHD (cADHD, n = 37), subthreshold symptoms defined as attention problems (cAP, n = 64), and no ADHD or cAP (Non-cAP, n = 217). We compared the groups and a control group with no perinatal risks (n = 64) on self-reported ADHD symptoms, executive dysfunction, and life outcomes in adulthood. At age 40, 21.6% of the cADHD, 6.3% of the cAP, 6.0% of the Non-cAP group, and 1.6% of the controls reached a screener cutoff for possible ADHD. The cADHD group had lower educational level, more ADHD symptoms and executive dysfunction, and higher rates of drug use than the other groups. Childhood ADHD associated with perinatal risks persists into midlife whereas childhood subthreshold ADHD symptoms in this cohort were not associated with negative outcomes in adulthood., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

We explored the effects of daylight saving time clock changes on sleep duration in a large accelerometer dataset. Our sample included UK Biobank participants (n = 11,780; aged 43-78 years) with accelerometer data for one or more days during the 2 weeks surrounding the Spring and Autumn daylight saving time transitions from October 2013 and November 2015. Between-individual t-tests compared sleep duration on the Sunday (midnight to midnight) of the clock changes with the Sunday before and the Sunday after. We also compared sleep duration on all other days (Monday-Saturday) before and after the clock changes. In Spring, mean sleep duration was 65 min lower on the Sunday of the clock changes than the Sunday before (95% confidence interval -72 to -58 min), and 61 min lower than the Sunday after (95% confidence interval -69 to -53). In Autumn, the mean sleep duration on the Sunday of the clock changes was 33 min higher than the Sunday before (95% confidence interval 27-39 min), and 38 min higher than the Sunday after (95% confidence interval 32-43 min). There was some evidence of catch-up sleep after both transitions, with sleep duration a little higher on the Monday-Friday than before, although this was less pronounced in Autumn. Future research should use large datasets with longer periods of accelerometer wear to capture sleep duration before and after the transition in the same individuals, and examine other aspects of sleep such as circadian misalignment, sleep fragmentation or daytime napping., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background: Chronic nonspecific symptoms attributed to indoor nonindustrial work environments are common and may cause disability, but the medical nature of this disability is unclear. The aim was to medically characterize the disability manifested by chronic, recurrent symptoms and restrictions to work participation attributed to low-level indoor pollutants at workplace and whether the condition shares features with idiopathic environmental intolerance., Methods: We investigated 12 patients with indoor air-related work disability. The examinations included somatic, psychological, and psychiatric evaluations as well as investigations of the autonomic nervous system, cortisol measurements, lung function, and allergy tests. We evaluated well-being, health, disability, insomnia, pain, anxiety, depression, and burnout via questionnaires., Results: The mean symptom history was 10.5 years; for disabling symptoms, 2.7 years. Eleven patients reported reactions triggered mainly by indoor molds, one by fragrances only. Ten reported sensitivity to odorous chemicals, and three, electric devices. Nearly all had co-occurrent somatic and psychiatric diagnoses and signs of pain, insomnia, burnout, and/or elevated sympathetic responses. Avoiding certain environments had led to restrictions in several life areas. On self-assessment scales, disability showed higher severity and anxiety showed lower severity than in physician assessments., Conclusion: No medical cause was found to explain the disability. Findings support that the condition is a form of idiopathic environmental intolerance and belongs to functional somatic syndromes. Instead of endless avoidance, rehabilitation approaches of functional somatic syndromes are applicable.

Background: Patients with bipolar disorder (BD) differ in their relative predominance of types of episodes, yielding predominant polarity, which has important treatment implications. However, few prospective studies of predominant polarity exist., Methods: In the Jorvi Bipolar Study (JoBS), a regionally representative cohort of 191 BD I and BD II in- and outpatients was followed for five years using life-chart methodology. Differences between depressive (DP), manic (MP), and no predominant polarity (NP) groups were examined regarding time ill, incidence of suicide attempts, and comorbidity., Results: At baseline, 16% of patients had MP, 36% DP, and 48% NP. During the follow-up the MP group spent significantly more time euthymic, less time in major depressive episodes, and more time in manic states than the DP and NP groups. The MP group had significantly lower incidence of suicide attempts than the DP and NP group, lower prevalence of comorbid anxiety disorders but more psychotic symptoms lifetime and more often (hypo)manic first phase of the illness than the DP group. Classification of predominant polarity was influenced by the timeframe used., Limitations: The retrospective counting of former phases is vulnerable to recall bias. Assignment of dominant polarity may necessitate a sufficient number of illness phases., Conclusions: Predominant polarity has predictive value in predicting group differences in course of illness, but individual patients' classification may change over time. Patients with manic polarity may represent a more distinct subgroup than the two others regarding illness course, suicide attempts, and psychiatric comorbidity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness. Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated. Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated? Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD., (Copyright © 2018 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Defining homogeneous subgroups of bipolar disorder (BD) is a major goal in personalized psychiatry and research. According to the neurodevelopmental theory, age at onset may be a key variable. As potential trait markers of neurodevelopment, cognitive and functional impairment should be greater in the early form of the disease, particularly type 1 BD (BD I). The age at onset was assessed in a multicenter, observational sample of 4190 outpatients with BD. We used a battery of neuropsychological tests to assess six domains of cognition. Functioning was measured using the Functioning Assessment Short Test (FAST). We studied the potential moderation of the type of BD on the associations between the age at onset and cognitive and functioning in a subsample of 2072 euthymic participants, controlling for potential clinical and socio-demographic covariates. Multivariable analyses showed cognition to not be impaired in individuals with early (21-30 years) and very early-life (before 14 years) onset of BD. Functioning was equivalent between individuals with early and midlife-onset of BD II and NOS but better for individuals with early onset of BD I. In contrast, functioning was not worse in individuals with very early-onset BD I but worse in those with very early-onset BD II and NOS. Early-life onset BDs were not characterized by poorer cognition and functioning. Our results do not support the neurodevelopmental view that a worse cognitive prognosis characterizes early-life onset BD. This study suggests that functional remediation may be prioritized for individuals with midlife-onset BD I and very early life onset BD 2 and NOS., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Modern environments are full of information, and place high demands on the attention control mechanisms that allow the selection of information from one (focused attention) or multiple (divided attention) sources, react to changes in a given situation (stimulus-driven attention), and allocate effort according to demands (task-positive and task-negative activity). We aimed to reveal how attention deficit hyperactivity disorder (ADHD) affects the brain functions associated with these attention control processes in constantly demanding tasks. Sixteen adults with ADHD and 17 controls performed adaptive visual and auditory discrimination tasks during functional magnetic resonance imaging (fMRI). Overlapping brain activity in frontoparietal saliency and default-mode networks, as well as in the somato-motor, cerebellar, and striatal areas were observed in all participants. In the ADHD participants, we observed exclusive activity enhancement in the brain areas typically considered to be primarily involved in other attention control functions: During auditory-focused attention, we observed higher activation in the sensory cortical areas of irrelevant modality and the default-mode network (DMN). DMN activity also increased during divided attention in the ADHD group, in turn decreasing during a simple button-press task. Adding irrelevant stimulation resulted in enhanced activity in the salience network. Finally, the irrelevant distractors that capture attention in a stimulus-driven manner activated dorsal attention networks and the cerebellum. Our findings suggest that attention control deficits involve the activation of irrelevant sensory modality, problems in regulating the level of attention on demand, and may encumber top-down processing in cases of irrelevant information., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Incidence of obsessive-compulsive disorder (OCD) has been suspected to increase but nationwide epidemiological studies are limited. This study aims to examine sex-specific incidence time trends and characterize psychiatric and neurodevelopmental comorbidities and sociodemographic risk factors of OCD in specialist healthcare in Finland., Methods: A nationwide register-based study using data from four Finnish registers identified 3372 OCD cases and 13,372 matched controls (1:4). Cumulative incidence in subjects born between 1987 and 2001 was estimated at ages of 10, 15, 20 and 23 years. Conditional logistic regression was used to examine the sociodemographic factors., Results: The cumulative incidence of OCD was 0.4% by age 23. Incidence by age 15 among three cohorts increased from 12.4 to 23.7 /10000 live born males and 8.5 to 28.0 /10000 live born females. 73% of the sample had a comorbid condition. Males were significantly more comorbid with psychotic and developmental disorders; females were more comorbid with depressive and anxiety disorders (p <0.001). Higher maternal SES was associated with an increased risk of OCD (OR 1.4; 95% CI 1.1-1.6)., Conclusions: These findings suggest that incidence of treated OCD in specialist healthcare has increased. The reason may be increased awareness and rate of referrals but a true increase cannot be ruled out. Further research on risk factors of OCD is warranted.

Objectives: Few long-term studies on bipolar disorder (BD) have investigated the incidence and risk factors of suicide attempts (SAs) specifically related to illness phases. We examined the incidence of SAs during different phases of BD in a long-term prospective cohort of bipolar I (BD-I) and bipolar II (BD-II) patients, and risk factors specifically for SAs during major depressive episodes (MDEs)., Methods: In the Jorvi Bipolar Study (JoBS), 191 BD-I and BD-II patients were followed using life-chart methodology. Prospective information on SAs of 177 patients (92.7%) during different illness phases was available up to 5 years. The incidence of SAs and their predictors were investigated using logistic and Poisson regression models. Analyses of risk factors for SAs occurring during MDEs were conducted using two-level random-intercept logistic regression models., Results: During the 5 years of follow-up, 90 SAs per 718 patient-years occurred. The incidence was highest, over 120-fold higher than in euthymia, during mixed states (765/1000 person-years; 95% confidence interval [CI] 461-1269 person-years), and also very high in MDEs, almost 60-fold higher than in euthymia (354/1000 person-years; 95% CI 277-451 person-years). For risk of SAs during MDEs, the duration of MDEs, severity of depression, and cluster C personality disorders were significant predictors., Conclusions: We confirmed in this long-term study that the highest incidences of SAs occur in mixed and major depressive illness phases. The variations in incidence rates between euthymia and illness phases were remarkably large, suggesting that the question "when" rather than "who" may be more relevant for suicide risk in BD. However, risk during MDEs is likely also influenced by personality factors., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Responses to atomoxetine vary for individual patients with attention-deficit/hyperactivity disorder (ADHD). However, we do not know whether any factors can be used to reliably predict how individuals with ADHD will respond to treatment., Objective: Our objective was to evaluate background variables that facilitate early identification of those adults with ADHD who are likely to respond to treatment with atomoxetine., Methods: We pooled data for atomoxetine-treated adults with ADHD from 12 clinical trials for a short-term (10-week) analysis, and from 11 clinical trials for a long-term (24-week) analysis. Patients not meeting a response definition [≥30 % reduction in Conners' Adult ADHD Rating Scales-Investigator Rated: Screening Version (CAARS-Inv:SV) total score and Clinical Global Impressions of ADHD Severity Scale (CGI-S) score ≤3 at endpoint], or who discontinued, were defined as non-responders. Another definition of response (≥30 % reduction in CAARS-Inv:SV total score at endpoint) was also used in these analyses; only the results with the former definition are shown in this abstract, as the same conclusions were gained with both definitions. A treatment-specified subgroup detection tool (a resampling-based ensemble tree method) was used to identify predictors of response., Results: Of 1945 adults in the long-term analysis, 548 (28.2 %) were responders to atomoxetine at week 24; 65.2 % of 1397 non-responders had discontinued. Of 4524 adults in the short-term analysis, 1490 (32.9 %) were responders at week 10; 33.2 % of 1006 non-responders had discontinued. No analyzed baseline parameters (age, sex, prior stimulant use, ADHD subtype, CAARS-Inv:SV, CGI-S) were statistically significant predictors of response. Reductions in CAARS-Inv:SV total, CAARS-Inv:SV subscores, and CGI-S at week 4 in the short-term analysis, and at weeks 4 or 10 in the long-term analysis, were statistically significant predictors of response, i.e., patients with versus without these reductions early in treatment were more likely to be clinical responders at later time points. Sensitivity ranged from 28.6 to 85.9 %, and specificity ranged from 23.8 to 86.7 %. Predictors with higher sensitivity had lower specificity, and vice versa., Conclusions: Reductions in CAARS-Inv:SV and CGI-S scores at weeks 4 and 10 are statistically significant predictors of response to atomoxetine at later time points in adults with ADHD. However, the predictors identified by these analyses are not reliable enough for use in clinical practice. The only currently available method to judge whether individuals with ADHD will respond to atomoxetine is to start treatment and assess the response over an extended period, sometimes longer than 10 weeks.

Previous functional connectivity studies have found both hypo- and hyper-connectivity in brains of individuals having autism spectrum disorder (ASD). Here we studied abnormalities in functional brain subnetworks in high-functioning individuals with ASD during free viewing of a movie containing social cues and interactions. Twenty-six subjects (13 with ASD) watched a 68-min movie during functional magnetic resonance imaging. For each subject, we computed Pearson's correlation between haemodynamic time-courses of each pair of 6-mm isotropic voxels. From the whole-brain functional networks, we derived individual and group-level subnetworks using graph theory. Scaled inclusivity was then calculated between all subject pairs to estimate intersubject similarity of connectivity structure of each subnetwork. Additional 54 individuals (27 with ASD) from the ABIDE resting-state database were included to test the reproducibility of the results. Between-group differences were observed in the composition of default-mode and ventro-temporal-limbic (VTL) subnetworks. The VTL subnetwork included amygdala, striatum, thalamus, parahippocampal, fusiform, and inferior temporal gyri. Further, VTL subnetwork similarity between subject pairs correlated significantly with similarity of symptom gravity measured with autism quotient. This correlation was observed also within the controls, and in the reproducibility dataset with ADI-R and ADOS scores. Our results highlight how the reorganization of functional subnetworks in individuals with ASD clarifies the mixture of hypo- and hyper-connectivity findings. Importantly, only the functional organization of the VTL subnetwork emerges as a marker of inter-individual similarities that co-vary with behavioral measures across all participants. These findings suggest a pivotal role of ventro-temporal and limbic systems in autism., (© 2015 Wiley Periodicals, Inc.)

Background: Recent brain imaging findings suggest that there are widely distributed abnormalities affecting the brain connectivity in individuals with autism spectrum disorder (ASD). Using graph theoretical analysis, it is possible to investigate both global and local properties of brain's wiring diagram, i.e., the connectome., Methods: We acquired diffusion-weighted magnetic resonance imaging data from 14 adult males with high-functioning ASD and 19 age-, gender-, and IQ-matched controls. As with diffusion tensor imaging-based tractography, it is not possible to detect complex (e.g., crossing) fiber configurations, present in 60-90 % of white matter voxels; we performed constrained spherical deconvolution-based whole brain tractography. Unweighted and weighted structural brain networks were then reconstructed from these tractography data and analyzed with graph theoretical measures., Results: In subjects with ASD, global efficiency was significantly decreased both in the unweighted and the weighted networks, normalized characteristic path length was significantly increased in the unweighted networks, and strength was significantly decreased in the weighted networks. In the local analyses, betweenness centrality of the right caudate was significantly increased in the weighted networks, and the strength of the right superior temporal pole was significantly decreased in the unweighted networks in subjects with ASD., Conclusions: Our findings provide new insights into understanding ASD by showing that the integration of structural brain networks is decreased and that there are abnormalities in the connectivity of the right caudate and right superior temporal pole in subjects with ASD.

Objectives: Bipolar disorder (BD) is one of the leading causes of disability worldwide. However, vocational ability and predictors of long-term work disability have rarely been studied among patients with BD. We investigated clinical predictors of work disability among patients with BD in psychiatric care., Methods: The Jorvi Bipolar Study (JoBS) is a naturalistic prospective cohort study (N = 191) representing adult (18-59 years) psychiatric inpatients and outpatients with DSM-IV bipolar I disorder (BD-I) and bipolar II disorder (BD-II) in three Finnish cities. Within the JoBS, we investigated the prevalence of disability pensions at baseline, and predictors for being granted a disability pension during an 18-month follow-up of the 151 patients in the labor force at baseline. Cox models were used to determine predictors for onset of disability pension., Results: At baseline, 21% (40/191) of the patients already had a disability pension. During the follow-up, a further 38 patients (25% of the 151 followed) were granted a new disability pension. The predictors included older age, male gender, depressive index episode, higher number of psychiatric hospitalizations, generalized anxiety disorder, avoidant personality disorder, and depressive burden during follow-up. However, the predictors differed depending on bipolar subtype, age, and gender., Conclusions: BD-I and BD-II are associated with a major risk of long-term work disability, the proportion of patients with a disability pension rising to 41% in the medium-term follow-up of the Finnish cohort investigated in the present study. Severe clinical course, depression, comorbidities, age, and gender are likely to be the main predictors but predictors may vary depending on the subgroup., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The project Adult Dyslexia and Attention Deficit Disorder in Finland (Project DyAdd) compares adults (n = 119, 18-55 years) with dyslexia, attention-deficit/hyperactivity disorder (ADHD), dyslexia together with ADHD (comorbid), and healthy controls with neuropsychological, psychophysical, and biological methods. The focus of this article is on the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III). The clinical groups performed well compared to the norms, and they did not differ from each other. However, compared to the controls, all of them were slightly poorer in their Full IQ, and of the factors, processing speed was relatively difficult for all of them. In addition to the group comparisons, a cluster analysis based on subtest scores was conducted over the clinical groups. It did not suggest a solution that would differentiate between the clinical groups. Instead, four clusters emerged: above average, average, poor perceptual organization, and poor working memory. Thus, differentiating between these clinical groups with the WAIS-III was not possible. However, all of them shared a relative difficulty in processing speed, and group-independent clusters with perceptual or memory difficulties emerged. [ABSTRACT FROM AUTHOR]

Objectives: The long-term outcome of bipolar disorder (BD) has been extensively investigated. However, previous studies may be biased towards hospitalized patients with bipolar I disorder (BD-I), and generalizability to the current treatment era remains uncertain. In this naturalistic study, we followed a secondary-care cohort of patients with BD., Methods: In the Jorvi Bipolar Study, 191 patients with BD-I and bipolar II disorder (BD-II) were followed using a life-chart method. Interviews were conducted at six months, 18 months, and five years. Time to full remission, time to first recurrence, total time ill, their predictors, and BD-I versus BD-II differences were investigated among the 151 patients remaining in follow-up., Results: Nearly all subjects recovered from the index episode, but almost all (90%) had a recurrence, and most had multiple recurrences. The patients spent about one-third of their time in illness episodes and 15% of their time with subthreshold symptoms; half of the time they were euthymic. After controlling for confounders, no difference in time spent in depressive states between patients with BD-I and BD-II persisted. Among patients with a depressive index phase, cluster C personality disorders [hazard ratio (HR) = 0.452, p = 0.040] and higher 17-item Hamilton Depression Scale score (HR = 0.951, p = 0.022) predicted longer time to remission, whereas lifetime psychotic symptoms (HR = 2.162, p = 0.016) predicted shorter time to first recurrence., Conclusions: Among patients with BD, chronicity as uninterrupted persistence of illness was rare, but multiple recurrences were the norm. Patients with BD spent only half of their time euthymic. Patients with BD-I and BD-II may differ little in proneness to depressive states. Severity of depression, cluster C personality disorders, and psychotic symptoms predicted outcome., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The aim of this study was to investigate potential differences in neural structure in individuals with Asperger syndrome (AS), high-functioning individuals with autism spectrum disorder (ASD). The main symptoms of AS are severe impairments in social interactions and restricted or repetitive patterns of behaviors, interests or activities., Methods: Diffusion weighted magnetic resonance imaging data were acquired for 14 adult males with AS and 19 age, sex and IQ-matched controls. Voxelwise group differences in fractional anisotropy (FA) were studied with tract-based spatial statistics (TBSS). Based on the results of TBSS, a tract-level comparison was performed with constrained spherical deconvolution (CSD)-based tractography, which is able to detect complex (for example, crossing) fiber configurations. In addition, to investigate the relationship between the microstructural changes and the severity of symptoms, we looked for correlations between FA and the Autism Spectrum Quotient (AQ), Empathy Quotient and Systemizing Quotient., Results: TBSS revealed widely distributed local increases in FA bilaterally in individuals with AS, most prominent in the temporal part of the superior longitudinal fasciculus, corticospinal tract, splenium of corpus callosum, anterior thalamic radiation, inferior fronto-occipital fasciculus (IFO), posterior thalamic radiation, uncinate fasciculus and inferior longitudinal fasciculus (ILF). CSD-based tractography also showed increases in the FA in multiple tracts. However, only the difference in the left ILF was significant after a Bonferroni correction. These results were not explained by the complexity of microstructural organization, measured using the planar diffusion coefficient. In addition, we found a correlation between AQ and FA in the right IFO in the whole group., Conclusions: Our results suggest that there are local and tract-level abnormalities in white matter (WM) microstructure in our homogenous and carefully characterized group of adults with AS, most prominent in the left ILF.

Tourette's syndrome is a neuropsychiatric syndrome having its onset in childhood and presenting tics as the characteristic feature. In spite of clear diagnostic criteria the syndrome often remains unrecognized. Recognition and treatment of comorbidities are essential. Drug treatment and cognitive therapy may be used, if tics cause functional or social handicap. In very difficult situations, deep brain stimulation may be considered for adult patients. While the natural course of the syndrome is usually favorable, 10 to 20% of the patients continue to have disturbing symptoms in adulthood.

Background: Transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex (DLPFC) is a promising technique for enhancing working memory (WM) performance in healthy and psychiatric populations. However, limited information is available about the effectiveness of transcranial random noise stimulation (tRNS) applied to the left DLPFC on WM. This study investigated the effectiveness of tRNS on WM compared with that of tDCS, which has established functional evidence. Methods: This randomized, double-blind, sham-controlled trial enrolled 120 healthy right-handed adults who were randomly allocated to four stimulation groups: tRNS + direct current (DC) offset, tRNS, tDCS, or sham. Each stimulus was placed over the left DLPFC and had a current intensity of 2 mA applied for 20 min during the dual n-back task. The dual n-back task was repeated thrice: pre-stimulation, during stimulation, and post-stimulation. The d-prime scores, and response times were calculated as the main outcome measures. A linear mixed model was created to identify the main effects and interactions between the groups and times, with the group and time as fixed effects, and baseline performance and the subject as a covariate and random effect, respectively. The relationships between the benefit of each stimulus and baseline WM performance were also examined. Results: For the d-prime score during stimulation, the tRNS group significantly performed better than the sham group at online assessment (β = 0.310, p = 0.001). In the relationships between the benefit of each stimulus and baseline WM performance, the tRNS group had significantly larger negative line slopes than the sham group for the d-prime score (β = −0.233, p = 0.038). Conclusions: tRNS applied to the left DLPFC significantly improved WM performance and generated greater benefits for healthy individuals with lower WM performance. These findings highlight the potential utility of tRNS for enhancing WM performance in individuals with lower WM performance and contribute evidence for clinical application to patients with cognitive decline. Trial Registration: This study was registered in the University Hospital Medical Information Network Clinical Trial Registry in Japan (UMIN000047365) on April 1, 2022; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054021. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to objectively assess signs of hyperactivity in adults suspected of having ADHD, addressing potential sex bias in diagnosis. Methods: About 13,179 (49% female) adults with an average age of 33 years with ADHD and 1,910 (41% female) adults with an average age of 36 years without ADHD were included. Motor activity was measured using the Quantified Behavioral Test, analyzing "provoked," and "basal" activity. Sex by group differences were analyzed using analysis of variance. Results: Results showed significant ADHD effects on the basal and provoked activity measures, while sex effects were only notable for provoked activity. Males, irrespective of diagnosis, exhibited higher provoked activity than females, while both sexes with ADHD displayed approximately twice the basal activity and about three times the provoked activity compared to their respective sex controls. Conclusion: These findings suggest that females with ADHD suffer equally from hyperactivity compared to males, challenging the notion of a sex-dependent presentation of hyperactivity. This may lead to more accurate and timely diagnoses, reducing ADHD-related burdens and comorbidities in females. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to establish which specific cognitive abilities are phenotypically related to reading skill in adolescence and determine whether this phenotypic correlation is explained by polygenetic overlap. Method: In an Australian population sample of twins and non-twin siblings of European ancestry (734 ≤ N ≤ 1542 [50.7% < F < 66%], mean age = 16.7, range = 11–28 years) from the Brisbane Adolescent Twin Study, mixed-effects models were used to test the association between a dyslexia polygenic score (based on genome-wide association results from a study of 51,800 dyslexics versus >1 million controls) and quantitative cognitive measures. The variance in the cognitive measure explained by the polygenic score was compared to that explained by a reading difficulties phenotype (scores that were lower than 1.5 SD below the mean reading skill) to derive the proportion of the association due to genetic influences. Results: The strongest phenotypic correlations were between poor reading and verbal tests (${R^2}$ R 2 up to 6.2%); visuo-spatial working memory was the only measure that did not show association with poor reading. Dyslexia polygenic scores could completely explain the phenotypic covariance between poor reading and most working memory tasks and were most predictive of performance on a test of arithmetic (${R^2} = 2.9\% $ R 2 = 2.9 %). Conclusion: Shared genetic pathways are thus highlighted for the commonly found association between reading and mathematics abilities, and for the verbal short-term/working memory deficits often observed in dyslexia. [ABSTRACT FROM AUTHOR]

Neurostimulation/neurorecording are tools to study, diagnose, and treat neurological/psychiatric conditions. Both techniques depend on volume conduction between scalp and excitable brain tissue. Here, we examine how neurostimulation with transcranial magnetic stimulation (TMS) is affected by hydration status, a physiological variable that can influence the volume of fluid spaces/cells, excitability, and cellular/global brain functioning. Normal healthy adult participants (32, 9 males) had common motor TMS measures taken in a repeated-measures design from dehydrated (12-h overnight fast/thirst) and rehydrated (identical dehydration protocol followed by rehydration with 1 L water in 1 h) testing days. The target region was left primary motor cortex hand area. Response at the target muscle was recorded with electromyography. Urinalysis confirmed hydration status. Motor hotspot shifted in half of participants. Motor threshold decreased in rehydration, indicating increased excitability. Even after redosing/relocalizing TMS to the new threshold/hotspot, rehydration still showed evidence of increased excitability: recruitment curve measures generally shifted upward and the glutamate-dependent paired-pulse protocol, short intracortical facilitation (SICF), was increased. Short intracortical inhibition (SICI), long intracortical inhibition (LICI), long intracortical facilitation (LICF), and cortical silent period (CSP) were relatively unaffected. The hydration perturbations were mild/subclinical based on the magnitude/speed and urinalysis. Motor TMS measures showed evidence of expected physiological changes of osmotic challenges. Rehydration showed signs of macroscopic and microscopic volume changes including decreased scalp-cortex distance (brain closer to stimulator) and astrocyte swelling-induced glutamate release. Hydration may be a source of variability affecting any techniques dependent on brain volumes/volume conduction. These concepts are important for researchers/clinicians using such techniques or dealing with the wide variety of disease processes involving water balance. NEW & NOTEWORTHY: Hydration status can affect brain volumes and excitability, which should affect techniques dependent on electrical volume conduction, including neurostimulation/recording. We test the previously unknown effects of hydration on neurostimulation with TMS and briefly review relevant physiology of hydration. Rehydration showed lower motor threshold, shifted motor hotspot, and generally larger responses even after compensating for threshold/hotspot changes. This is important for clinical and research applications of neurostimulation/neurorecording and the many clinical disorders related to water balance. [ABSTRACT FROM AUTHOR]

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Background: Young people and adults with ADHD are at risk of a range of physical health problems. There is limited guidance on how to approach health problems in ADHD, and especially around 16-25 year olds who will be transitioning from paediatric to adult care. The aim of this scoping review was to identify psychosocial interventions that target physical health in young people and adults with ADHD. Methods: We constructed searches in MEDLINE, PsycInfo, EMBASE of adolescents, young people and adults. Inclusion criteria were; studies of psychosocial interventions examining a component of physical health, applicable to people aged 16-25, with clinical or research diagnoses of ADHD. Data were extracted using a data extraction tool and tabulated, including study intervention framing/aims, population, intervention, and relevant outcomes (including specific statistics where relevant). Results: Our search identified 22 unique papers covering, psychosocial interventions targeting at least one of sleep (n=7), smoking (n=3), substance/alcohol use (n=4), physical health/exercise (n=6) and general health (n=3). Studies examined psychotherapy/behaviour interventions (n=12), psychoeducation (n=4), digital (n=2) and social interventions (n=4). There was significant heterogeneity in intervention framing, outcome measures and population. Conclusion: Further work on the impact of targeted physical health interventions, with explicit reference to a conceptual framework of poor health in ADHD is required. Furthermore, future work standardising reporting of physical health outcomes in ADHD is crucial for the development of an evidence base in this field. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) and obsessive–compulsive disorder (OCD) typically have distinct diagnostic criteria and treatment approaches. SCZ is characterized by delusions, hallucinations, disorganized speech, and cognitive impairments, while OCD involves persistent, intrusive thoughts (obsessions) and repetitive behaviors (compulsions). The co-occurrence of these disorders increases clinical complexity and poses significant challenges for diagnosis and treatment. Epidemiological studies indicate a significant overlap, with prevalence rates of comorbid OCD in SCZ patients ranging from 12% to 25%, which is higher than in the general population. Etiological hypotheses suggest shared genetic, neurobiological, and environmental factors, with genetic studies identifying common loci and pathways, such as glutamatergic and dopaminergic systems. Neuroimaging studies reveal both overlapping and distinct neural abnormalities, indicating shared and unique neurobiological substrates. Environmental factors, like early life stressors and urbanicity, also contribute to the comorbidity. The overlapping clinical features of both disorders complicate diagnosis. Treatment approaches include combining SSRIs with antipsychotics and cognitive behavioral therapy (CBT). The complexity of SCZ and OCD comorbidity underscores the need for a dimensional, spectrum-based perspective on psychiatric disorders, alongside traditional categorical approaches, to improve diagnosis and treatment outcomes. [ABSTRACT FROM AUTHOR]

Stimulants, including methylphenidate and amphetamines, are the first-line pharmacological treatment of ADHD in adults. However, in patients who do not respond or poorly tolerate stimulants, non-stimulant medications are usually recommended. The authors provide a narrative review of the literature on non-stimulant treatments for adult ADHD, including controlled and observational clinical studies conducted on adult samples. Atomoxetine has been extensively studied and showed significant efficacy in treating adult ADHD. Issues related to dosing, treatment duration, safety, and use in the case of psychiatric comorbidity are summarized. Among other compounds indicated for ADHD in adults, antidepressants sharing at least a noradrenergic or dopaminergic component, including tricyclic compounds, bupropion, and viloxazine, have shown demonstratable efficacy. Evidence is also available for antihypertensives, particularly guanfacine, as well as memantine, metadoxine, and mood stabilizers, while negative findings have emerged for galantamine, antipsychotics, and cannabinoids. While according to clinical guidelines, atomoxetine may serve as the only second-line option in adults with ADHD, several other nonstimulant compounds may be effectively used in order to personalize treatment based on comorbid conditions and ADHD features. Nevertheless, further research is needed to identify and test more personalized treatment strategies for adults with ADHD. [ABSTRACT FROM AUTHOR]

In this study of the project DyAdd, implicit learning was investigated through two paradigms in adults (18-55 years) with dyslexia (n = 36) or with attention deficit/hyperactivity disorder (ADHD, n = 22) and in controls (n = 35). In the serial reaction time (SRT) task, there were no group differences in learning. However, those with ADHD exhibited faster RTs compared to other groups. In the artificial grammar learning (AGL) task, the groups did not differ from each other in their learning (i.e., grammaticality accuracy or similarity choices). Further, all three groups were sensitive to fragment overlap between learning and test-phase items (i.e., similarity choices were above chance). Grammaticality performance of control participants was above chance, but that of participants with dyslexia and participants with ADHD failed to differ from chance, indicating impaired grammaticality learning in these groups. While the main indices of AGL performance, grammaticality accuracy and similarity choices did not correlate with the neuropsychological variables that reflected dyslexia-related (phonological processing, reading, spelling, arithmetic) or ADHD-related characteristics (executive functions, attention), or intelligence, the explicit knowledge for the AGL grammar (i.e., ability to freely generate grammatical strings) correlated positively with the variables of phonological processing and reading. Further, SRT reaction times correlated positively with full scale intelligence quotient (FIQ). We conclude that, in AGL, learning difficulties of the underlying rule structure (as measured by grammaticality) are associated with dyslexia and ADHD. However, learning in AGL is not related to the defining neuropsychological features of dyslexia or ADHD. Instead, the resulting explicit knowledge relates to characteristics of dyslexia.