Abnormal wiring of the structural connectome in adults with ADHD.

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.

Long-term work disability due to type I and II bipolar disorder: findings of a six-year prospective study.

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.

Mortality in individuals with childhood ADHD or subthreshold symptoms - a prospective perinatal risk cohort study over 40 years.

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.

Project DyAdd: Non-linguistic Theories of Dyslexia Predict Intelligence.

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.

Working memory training restores aberrant brain activity in adult attention-deficit hyperactivity disorder.

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.

ADHD desynchronizes brain activity during watching a distracted multi-talker conversation.

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.

ADHD and subthreshold symptoms in childhood and life outcomes at 40 years in a prospective birth-risk cohort.

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.

Clinical Characteristics of Disability in Patients with Indoor Air-Related Environmental Intolerance.

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.

Predominant polarity in bipolar I and II disorders: A five-year follow-up study.

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.

Out of focus - Brain attention control deficits in adult ADHD.

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.

Incidence and predictors of suicide attempts in bipolar I and II disorders: A 5-year follow-up study.

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.

Register-based study of the incidence, comorbidities and demographics of obsessive-compulsive disorder in specialist healthcare.

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.

Post Hoc Analysis of Potential Predictors of Response to Atomoxetine for the Treatment of Adults with Attention-Deficit/Hyperactivity Disorder using an Integrated Database.

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.

Reorganization of functionally connected brain subnetworks in high-functioning autism.

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.

Abnormal wiring of the connectome in adults with high-functioning autism spectrum disorder.

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.

Predictors of long-term work disability among patients with type I and II bipolar disorder: a prospective 18-month follow-up study.

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.

[Tourette's syndrome--diverse group of patients, individual need for treatment]. / Touretten oireyhtymä--monimuotoinen sairaus, yksilöllinen hoidon tarve.

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.

Constrained spherical deconvolution-based tractography and tract-based spatial statistics show abnormal microstructural organization in Asperger syndrome.

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.

Five-year outcome of bipolar I and II disorders: findings of the Jorvi Bipolar Study.

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.