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Fatigue, defined as a subjective lack of physical and/or mental energy, is a clinical symptom highly characterizing multiple sclerosis (MS). The present study utilized a novel approach to the study of fatigue, examining first person-mental imagery of the symptom. Eighteen right-handed patients with MS (14F, 4 M, mean age 45.8 ± 8.15 years) were evaluated and were compared to nineteen healthy controls (10F, 9 M, mean age 43.15 ± 8.34 years) Patients were all in relapsing remitting form and no patient had presented relapses in the 6 months prior to inclusion in the study. We evaluated their behavioral performance and fMRI activations. We used an fMRI paradigm used to trigger first person-mental imagery of fatigue, through short sentences describing the principal manifestations of fatigue. Participants were asked to imagine the corresponding sensations (Sensory Imagery, SI). As a control, they had to imagine the visual scenes (Visual Imagery, VI) described in short phrases. They made a vividness rating by pressing the corresponding button. Behaviorally, we found that patients' mean scores at the Multidimensional Fatigue Symptom Inventory for the general scale, physical scale, and mental scale were significantly higher than healthy controls (p = 0.05, p = 0.002, p = 0.006 respectively), but not for the emotional scale and for vigor scale (p = 0.207, n.s., p = 0.06, n.s.). In the imagery fMRI task, patients were significantly slower (mean reaction times and standard deviation: 2.24 s ± 0.33) than controls (mean reaction times and standard deviation: 1.918 s ± 0.455) for the SI task (Z=-2.058, p = 0.040), while no significant difference was found for the VI task. Regarding brain mapping, our main result is a group by task interaction. The SI task (vs. VI task) in healthy controls (relative to patients) increased activation in the left inferior parietal lobule. These preliminary results indicate that fatigue is related to dysfunctions in higher-order aspects of motor control, given the role of the posterior parietal lobe in motor planning and multisensory integration.
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BACKGROUND: Strategies of prevention for psychiatric disorders need a deep understanding of the aetiological factors involved in the psychopathological processes. Our twin study aims at disentangling the contributions of genes and environment to schizotypal and hypomanic dimensions, considering the role of stressful life events (LEs) and the quality of family relationships. METHODS: The Magical Ideation Scale (MIS) and Perceptual Aberration Scale (PAS) were used to assess positive schizotypy, while Hypomanic Personality Scale (HPS) and its sub-scales were used to investigate proneness to affective disorders. 268 twins (54.5 % female; aged 18.0 ± 6.68) were included. Participants filled out a questionnaire on LEs and their parents provided an evaluation of intra-family relationship (Relationship Quality Index, RQI). Classic univariate twin models for quantitative traits were fitted for scales, and the effects of covariates (LEs and RQI) were assessed. RESULTS: For MIS, HPS and its sub-scales, significant common and unique environmental effects were detected, with genetic factors affecting only HPS Social Vitality sub-scale. Unique environment was the only source of variance of PAS score. The number of recent LEs influenced MIS and PAS models, while RQI score affected MIS model. LIMITATIONS: The main limitation of the study is the small sample size, which reduces statistical power and may potentially lead to an underestimation of heritability. Additionally, the cross-sectional design limits the possibility to draw causal considerations. CONCLUSIONS: Findings provide preliminary evidence for a significant environmental role in modulating states of vulnerability. Moreover, the expression of positive schizotypy resulted influenced by recent stressors and intra-family relationships.
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Transtorno Bipolar , Acontecimentos que Mudam a Vida , Transtorno da Personalidade Esquizotípica , Humanos , Feminino , Masculino , Transtorno da Personalidade Esquizotípica/genética , Transtorno da Personalidade Esquizotípica/psicologia , Adulto , Adolescente , Adulto Jovem , Transtorno Bipolar/genética , Transtorno Bipolar/psicologia , Interação Gene-Ambiente , Inquéritos e Questionários , Relações Familiares , Família/psicologia , Gêmeos Dizigóticos/genética , Gêmeos Dizigóticos/psicologia , Escalas de Graduação PsiquiátricaRESUMO
Prenatal and perinatal complications represent well-known risk factors for the future development of psychiatric disorders. Such influence might become manifested during childhood and adolescence, as key periods for brain and behavioral changes. Internalizing and externalizing behaviors in adolescence have been associated with the risk of psychiatric onset later in life. Both brain morphology and behavior seem to be affected by obstetric complications, but a clear link among these three aspects is missing. Here, we aimed at analyzing the association between prenatal and perinatal complications, behavioral issues, and brain volumes in a group of children and adolescents. Eighty-two children and adolescents with emotional-behavioral problems underwent clinical and 3 T brain magnetic resonance imaging (MRI) assessments. The former included information on behavior, through the Child Behavior Checklist/6-18 (CBCL/6-18), and on the occurrence of obstetric complications. The relationships between clinical and gray matter volume (GMV) measures were investigated through multiple generalized linear models and mediation models. We found a mutual link between prenatal complications, GMV alterations in the frontal gyrus, and withdrawn problems. Specifically, complications during pregnancy were associated with higher CBCL/6-18 withdrawn scores and GMV reductions in the right superior frontal gyrus and anterior cingulate cortex. Finally, a mediation effect of these GMV measures on the association between prenatal complications and the withdrawn dimension was identified. Our findings suggest a key role of obstetric complications in affecting brain structure and behavior. For the first time, a mediator role of frontal GMV in the relationship between prenatal complications and internalizing symptoms was suggested. Once replicated on independent cohorts, this evidence will have relevant implications for planning preventive interventions.
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Cognitively impaired and spared patient subgroups were identified in psychosis and depression, and in clinical high-risk for psychosis (CHR). Studies suggest differences in underlying brain structural and functional characteristics. It is unclear whether cognitive subgroups are transdiagnostic phenomena in early stages of psychotic and affective disorder which can be validated on the neural level. Patients with recent-onset psychosis (ROP; N = 140; female = 54), recent-onset depression (ROD; N = 130; female = 73), CHR (N = 128; female = 61) and healthy controls (HC; N = 270; female = 165) were recruited through the multi-site study PRONIA. The transdiagnostic sample and individual study groups were clustered into subgroups based on their performance in eight cognitive domains and characterized by gray matter volume (sMRI) and resting-state functional connectivity (rsFC) using support vector machine (SVM) classification. We identified an impaired subgroup (NROP = 79, NROD = 30, NCHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 0.001). A spared subgroup (NROP = 61, NROD = 100, NCHR = 91) performed comparable to HC. Single-disease subgroups indicated that cognitive impairment is stronger pronounced in impaired ROP compared to impaired ROD and CHR. Subgroups in ROP and ROD showed specific symptom- and functioning-patterns. rsFC showed superior accuracy compared to sMRI in differentiating transdiagnostic subgroups from HC (BACimpaired = 58.5%; BACspared = 61.7%, both: p < 0.01). Cognitive findings were validated in the PRONIA replication sample (N = 409). Individual cognitive subgroups in ROP, ROD and CHR are more informative than transdiagnostic subgroups as they map onto individual cognitive impairment and specific functioning- and symptom-patterns which show limited overlap in sMRI and rsFC. CLINICAL TRIAL REGISTRY NAME: German Clinical Trials Register (DRKS). Clinical trial registry URL: https://www.drks.de/drks_web/ . Clinical trial registry number: DRKS00005042.
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Disfunção Cognitiva , Transtornos Psicóticos , Feminino , Humanos , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico , Função Executiva , Substância Cinzenta/diagnóstico por imagem , Transtornos Psicóticos/complicações , Transtornos Psicóticos/diagnóstico , Masculino , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Neurocognitive deficits are a core feature of psychosis and depression. Despite commonalities in cognitive alterations, it remains unclear if and how the cognitive deficits in patients at clinical high risk for psychosis (CHR) and those with recent-onset psychosis (ROP) are distinct from those seen in recent-onset depression (ROD). AIMS: This study was carried out within the European project 'Personalized Prognostic Tools for Early Psychosis Management', and aimed to characterise the cognitive profiles of patients with psychosis or depression. METHOD: We examined cognitive profiles for patients with ROP (n = 105), patients with ROD (n = 123), patients at CHR (n = 116) and healthy controls (n = 372) across seven sites in five European countries. Confirmatory factor analysis identified four cognitive factors independent of gender, education and site: speed of processing, attention and working memory, verbal learning and spatial learning. RESULTS: Patients with ROP performed worse than healthy controls in all four domains (P < 0.001), whereas performance of patients with ROD was not affected (P > 0.05). Patients at CHR performed worse than healthy controls in speed of processing (P = 0.001) and spatial learning (P = 0.003), but better than patients with ROP across all cognitive domains (all P ≤ 0.01). CHR and ROD groups did not significantly differ in any cognitive domain. These findings were independent of comorbid depressive symptoms, substance consumption and illness duration. CONCLUSIONS: These results show that neurocognitive abilities are affected in CHR and ROP, whereas ROD seems spared. Although our findings may support the notion that those at CHR have a specific vulnerability to psychosis, future studies investigating broader transdiagnostic risk cohorts in longitudinal designs are needed.
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Transtornos Cognitivos , Disfunção Cognitiva , Transtornos Psicóticos , Humanos , Depressão/epidemiologia , Testes Neuropsicológicos , Transtornos Psicóticos/psicologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologiaRESUMO
BACKGROUND: Studies investigating cognitive impairments in psychosis and depression have typically compared the average performance of the clinical group against healthy controls (HC), and do not report on the actual prevalence of cognitive impairments or strengths within these clinical groups. This information is essential so that clinical services can provide adequate resources to supporting cognitive functioning. Thus, we investigated this prevalence in individuals in the early course of psychosis or depression. METHODS: A comprehensive cognitive test battery comprising 12 tests was completed by 1286 individuals aged 15-41 (mean age 25.07, s.d. 5.88) from the PRONIA study at baseline: HC (N = 454), clinical high risk for psychosis (CHR; N = 270), recent-onset depression (ROD; N = 267), and recent-onset psychosis (ROP; N = 295). Z-scores were calculated to estimate the prevalence of moderate or severe deficits or strengths (>2 s.d. or 1-2 s.d. below or above HC, respectively) for each cognitive test. RESULTS: Impairment in at least two cognitive tests was as follows: ROP (88.3% moderately, 45.1% severely impaired), CHR (71.2% moderately, 22.4% severely impaired), ROD (61.6% moderately, 16.2% severely impaired). Across clinical groups, impairments were most prevalent in tests of working memory, processing speed, and verbal learning. Above average performance (>1 s.d.) in at least two tests was present for 40.5% ROD, 36.1% CHR, 16.1% ROP, and was >2 SDs in 1.8% ROD, 1.4% CHR, and 0% ROP. CONCLUSIONS: These findings suggest that interventions should be tailored to the individual, with working memory, processing speed, and verbal learning likely to be important transdiagnostic targets.
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Transtornos Cognitivos , Disfunção Cognitiva , Transtornos Psicóticos , Humanos , Adulto , Depressão/epidemiologia , Prevalência , Transtornos Psicóticos/psicologia , Disfunção Cognitiva/epidemiologia , Transtornos Cognitivos/psicologia , Testes NeuropsicológicosRESUMO
Theory of Mind (ToM) is involved in experiencing the mental states and/or emotions of others. A further distinction can be drawn between emotion and perception/sensation. We investigated the mechanisms engaged when participants' attention is driven toward specific states. Accordingly, 21 right-handed healthy individuals performed a modified ToM task in which they reflected about someone's emotion or someone's body sensation, while they were in a functional magnetic resonance imaging scanner. The analysis of brain activity evoked by this task suggests that the two conditions engage a widespread common network previously found involved in affective ToM (temporo-parietal junction (TPJ), parietal cortex, dorso-lateral prefrontal cortex (DLPFC), medial- prefrontal cortex (MPFC), Insula). Critically, the key brain result is that body sensation implicates selectively ventromedial prefrontal cortex (VMPFC). The current findings suggest that only paying attention to the other's body sensations modulates a self-related representation (VMPFC).
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Córtex Pré-Frontal , Teoria da Mente , Humanos , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Encéfalo/fisiologia , Emoções/fisiologia , Teoria da Mente/fisiologia , Mapeamento Encefálico , Imageamento por Ressonância Magnética , SensaçãoRESUMO
Language production has often been described as impaired in psychiatric diseases such as in psychosis. Nevertheless, little is known about the characteristics of linguistic difficulties and their relation with other cognitive domains in patients with a first episode of psychosis (FEP), either affective or non-affective. To deepen our comprehension of linguistic profile in FEP, 133 patients with FEP (95 non-affective, FEP-NA; 38 affective, FEP-A) and 133 healthy controls (HC) were assessed with a narrative discourse task. Speech samples were systematically analyzed with a well-established multilevel procedure investigating both micro- (lexicon, morphology, syntax) and macro-linguistic (discourse coherence, pragmatics) levels of linguistic processing. Executive functioning and IQ were also evaluated. Both linguistic and neuropsychological measures were secondarily implemented with a machine learning approach in order to explore their predictive accuracy in classifying participants as FEP or HC. Compared to HC, FEP patients showed language production difficulty at both micro- and macro-linguistic levels. As for the former, FEP produced shorter and simpler sentences and fewer words per minute, along with a reduced number of lexical fillers, compared to HC. At the macro-linguistic level, FEP performance was impaired in local coherence, which was paired with a higher percentage of utterances with semantic errors. Linguistic measures were not correlated with any neuropsychological variables. No significant differences emerged between FEP-NA and FEP-A (p≥0.02, after Bonferroni correction). Machine learning analysis showed an accuracy of group prediction of 76.36% using language features only, with semantic variables being the most impactful. Such a percentage was enhanced when paired with clinical and neuropsychological variables. Results confirm the presence of language production deficits already at the first episode of the illness, being such impairment not related to other cognitive domains. The high accuracy obtained by the linguistic set of features in classifying groups support the use of machine learning methods in neuroscience investigations.
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Transtornos da Linguagem , Transtornos Psicóticos , Compreensão , Humanos , Idioma , Testes Neuropsicológicos , Transtornos Psicóticos/psicologiaRESUMO
OBJECTIVES: Cognitive deficits in Bipolar Disorder (BD) are significant enough to have an impact on daily functioning. Therefore, appropriate tools must be used to improve our understanding of the nature and severity of cognitive deficits in BD. In this study, we aimed to compare the cognitive profiles of patients with BD and healthy controls (HC) applying the Italian version of the Brief Assessment of Cognition in Affective Disorders (BAC-A). METHODS: This cross-sectional study included 127 patients with BD and 134 HC. The participants' cognitive profiles were evaluated using the Italian version of the BAC-A, which assesses verbal memory, working memory, motor speed, verbal fluency, attention & processing speed, executive functions, and two new measures of affective processing. The BAC-A raw scores were corrected using the normative data for the Italian population. In addition, we explored whether intelligence quotient (IQ) and specific clinical variables would predict the BAC-A affective, non-affective, and total composite scores of patients with BD and HC. RESULTS: HC performed better than patients with BD in all BAC-A subtests (all p < .001), except for subtests of the Affective Interference Test. (p ≥ .05). The effect sizes varied in magnitude and ranged between d = 0.02 and d = 1.27. In patients with BD, lower BAC-A composite scores were predicted by a higher number of hospitalizations. There was a significant association between IQ and BAC-A composite scores in both bipolar patients and HC. CONCLUSIONS: The Italian BAC-A is sensitive to the cognitive impairments of patients with BD in both affective and non-affective cognitive domains.
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Transtorno Bipolar , Humanos , Transtorno Bipolar/complicações , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Estudos Transversais , Cognição , Testes Neuropsicológicos , Transtornos do Humor/diagnóstico , Transtornos do Humor/psicologia , Memória de Curto Prazo , ItáliaRESUMO
BACKGROUND: Identifying neurobiologically based transdiagnostic categories of depression and psychosis may elucidate heterogeneity and provide better candidates for predictive modeling. We aimed to identify clusters across patients with recent-onset depression (ROD) and recent-onset psychosis (ROP) based on structural neuroimaging data. We hypothesized that these transdiagnostic clusters would identify patients with poor outcome and allow more accurate prediction of symptomatic remission than traditional diagnostic structures. METHODS: HYDRA (Heterogeneity through Discriminant Analysis) was trained on whole-brain volumetric measures from 577 participants from the discovery sample of the multisite PRONIA study to identify neurobiologically driven clusters, which were then externally validated in the PRONIA replication sample (n = 404) and three datasets of chronic samples (Centre for Biomedical Research Excellence, n = 146; Mind Clinical Imaging Consortium, n = 202; Munich, n = 470). RESULTS: The optimal clustering solution was two transdiagnostic clusters (cluster 1: n = 153, 67 ROP, 86 ROD; cluster 2: n = 149, 88 ROP, 61 ROD; adjusted Rand index = 0.618). The two clusters contained both patients with ROP and patients with ROD. One cluster had widespread gray matter volume deficits and more positive, negative, and functional deficits (impaired cluster), and one cluster revealed a more preserved neuroanatomical signature and more core depressive symptomatology (preserved cluster). The clustering solution was internally and externally validated and assessed for clinical utility in predicting 9-month symptomatic remission, outperforming traditional diagnostic structures. CONCLUSIONS: We identified two transdiagnostic neuroanatomically informed clusters that are clinically and biologically distinct, challenging current diagnostic boundaries in recent-onset mental health disorders. These results may aid understanding of the etiology of poor outcome patients transdiagnostically and improve development of stratified treatments.
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Depressão , Transtornos Psicóticos , Substância Cinzenta/diagnóstico por imagem , Humanos , Neuroimagem , Fenótipo , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/psicologiaRESUMO
Mental imagery is part of people's own internal processing and plays an important role in everyday life, cognition and pathology. The neural network supporting mental imagery is bottom-up modulated by the imagery content. Here, we examined the complex associations of gender and age with the neural mechanisms underlying emotion imagery. We assessed the brain circuits involved in emotion mental imagery (vs. action imagery), controlled by a letter detection task on the same stimuli, chosen to ensure attention to the stimuli and to discourage imagery, in 91 men and women aged 14-65 years using fMRI. In women, compared with men, emotion imagery significantly increased activation within the right putamen, which is involved in emotional processing. Increasing age, significantly decreased mental imagery-related activation in the left insula and cingulate cortex, areas involved in awareness of ones' internal states, and it significantly decreased emotion verbs-related activation in the left putamen, which is part of the limbic system. This finding suggests a top-down mechanism by which gender and age, in interaction with bottom-up effect of type of stimulus, or directly, can modulate the brain mechanisms underlying mental imagery.
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Mapeamento Encefálico , Emoções , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Emoções/fisiologia , Feminino , Humanos , Imagens, Psicoterapia , Imageamento por Ressonância Magnética , MasculinoRESUMO
Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted ß for Total BIS score: 5.35, p < 0.001). No significant interaction effect was evident between disease status (HC vs. BD) and SNP status for any polymorphism. Considering the whole sample, BDNF Met/Met homozygosis was associated with lower BIS scores across all three factors (adjusted ß for Total BIS score: −10.2, p < 0.001). A significant 5-HTTLPR x gender interaction was found for the SS genotype, associated with higher BIS scores in females only (adjusted ß for Total BIS score: 12.0, p = 0.001). Finally, COMT polymorphism status was not significantly associated with BIS scores. In conclusion, BD diagnosis did not influence the effect on impulsivity scores for any of the three SNPs considered. Only one SNPthe BDNF rs6265 Met/Met homozygosiswas independently associated with lower impulsivity scores. The 5-HTTLPR SS genotype was associated with higher impulsivity scores in females only. Further studies adopting genome-wide screening in larger samples are needed to define the genetic basis of impulsivity in BD.
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Transtorno Bipolar , Transtorno Bipolar/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Catecol O-Metiltransferase/genética , Feminino , Humanos , Comportamento Impulsivo , Polimorfismo de Nucleotídeo Único/genética , Proteínas da Membrana Plasmática de Transporte de SerotoninaRESUMO
OBJECTIVE: Psychotic disorders are frequently associated with decline in functioning and cognitive difficulties are observed in subjects at clinical high risk (CHR) for psychosis. In this work, we applied automatic approaches to neurocognitive and functioning measures, with the aim of investigating the link between global, social and occupational functioning, and cognition. METHODS: 102 CHR subjects and 110 patients with recent onset depression (ROD) were recruited. Global assessment of functioning (GAF) related to symptoms (GAF-S) and disability (GAF-D). and global functioning social (GF-S) and role (GF-R), at baseline and of the previous month and year, and a set of neurocognitive measures, were used for classification and regression. RESULTS: Neurocognitive measures related to GF-R at baseline (r = 0.20, p = 0.004), GF-S at present (r = 0.14, p = 0.042) and of the past year (r = 0.19, p = 0.005), for GAF-F of the past month (r = 0.24, p < 0.001) and GAF-D of the past year (r = 0.28, p = 0.002). Classification reached values of balanced accuracy of 61% for GF-R and GAF-D. CONCLUSION: We found that neurocognition was related to psychosocial functioning. More specifically, a deficit in executive functions was associated to poor social and occupational functioning.
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Transtornos Cognitivos , Transtornos Psicóticos , Humanos , Escalas de Graduação Psiquiátrica , Depressão , Testes Neuropsicológicos , Transtornos Psicóticos/diagnóstico , Transtornos Cognitivos/psicologiaRESUMO
BACKGROUND: Borderline Personality Disorder (BPD) is characterized by mood dysregulation, impulsivity, identity disturbances, and a higher risk for suicide. Currently, the diagnosis is solely based on clinical observation of overt symptoms, and this can delay the detection of the disease and the timely start of appropriate treatment. Several candidate clinical tools have been studied to better characterize BPD, including event-related potentials (ERP). This review aimed at summarizing the results of the available ERP studies on BPD to clarify the possible application of this technique in the early diagnosis of BPD. METHODS: A bibliographic search on PubMed and PsycInfo was performed in order to identify studies comprising individuals with BPD diagnosis and a control group that evaluated the ERP elicited by auditory stimuli. RESULTS: Ten studies that explored various ERP components associated with auditory stimuli in BPD were included. Overall, the results showed that positive ERP (P50, P100, and P300) amplitude and latencies as well as loudness dependance were altered in BPD patients compared to controls, possibly reflecting deficits involving attention, mainly at its early stage, and executive functions. LIMITATIONS: The reviewed studies used different ERP approaches and non-homogeneous BPD diagnostic criteria. CONCLUSIONS: Auditory ERP appear to be a promising tool for the assessment of BPD patients, especially for early diagnosis and evaluation of cognitive symptoms.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno da Personalidade Borderline , Transtorno da Personalidade Borderline/diagnóstico , Eletroencefalografia , Potenciais Evocados , Humanos , Comportamento ImpulsivoRESUMO
This study aims to investigate the genetic and neural determinants of attention and hyperactivity problems. Using a proof-of-concept imaging genetics mediation design, we explore the relationship between the glutamatergic GRIN2B gene variants and inattention/hyperactivity with neuroanatomical measures as intermediates. Fifty-eight children and adolescents were evaluated for behavioral problems at three time points over approximately 7 years. The final assessment included blood drawing for genetic analyses and 3T magnetic resonance imaging. Attention/hyperactivity problems based on the Child Behavior Checklist/6-18, six GRIN2B polymorphisms and regional cortical thickness, and surface area and volume were estimated. Using general linear model (GLM) and mediation analyses, we tested whether GRIN2B exerted an influence on stable inattention/hyperactivity over development, and to what extent this effect was mediated by brain morphology. GLM results enlightened the relation between GRIN2B rs5796555-/A, volume in the left cingulate isthmus and inferior parietal cortices and inattention/hyperactivity. The mediation results showed that rs5796555-/A effect on inattention/hyperactivity was partially mediated by volume in the left isthmus of the cingulate cortex, suggesting a key role of this region in translating glutamatergic GRIN2B variations to attention/hyperactivity problems. This evidence can have important implications in the management of neurodevelopmental and psychiatric disorders.
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Transtorno do Deficit de Atenção com Hiperatividade/genética , Encéfalo/patologia , Receptores de N-Metil-D-Aspartato/genética , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Encéfalo/diagnóstico por imagem , Criança , Comportamento Infantil , Estudos de Coortes , Feminino , Frequência do Gene , Genótipo , Humanos , Modelos Lineares , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Projetos PilotoRESUMO
OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental condition with a heterogeneous phenotype. The role of biomarkers in ASD diagnosis has been highlighted; cortical thickness has proved to be involved in the etiopathogenesis of ASD core symptoms. We apply support vector machine, a supervised machine learning method, in order to identify specific cortical thickness alterations in ASD subjects. METHODS: A sample of 76 subjects (9.5 ± 3.4 years old) has been selected, 40 diagnosed with ASD and 36 typically developed subjects. All children underwent a magnetic resonance imaging (MRI) examination; T1-MPRAGE sequences were analyzed to extract features for the characterization and parcellation of regions of interests (ROI); average cortical thickness (CT) has been measured for each ROI. For the classification process, the extracted features were used as input for a classifier to identify ASD subjects through a "learning by example" procedure; the features with best performance was then selected by "greedy forward-feature selection." Finally, this model underwent a leave-one-out cross-validation approach. RESULTS: From the training set of 68 ROIs, five ROIs reached accuracies of over 70%. After this phase, we used a recursive feature selection process in order to identify the eight features with the best accuracy (84.2%). CT resulted higher in ASD compared to controls in all the ROIs identified at the end of the process. CONCLUSION: We found increased CT in various brain regions in ASD subjects, confirming their role in the pathogenesis of this condition. Considering the brain development curve during ages, these changes in CT may normalize during development. Further validation on a larger sample is required.
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Transtorno do Espectro Autista , Máquina de Vetores de Suporte , Transtorno do Espectro Autista/diagnóstico por imagem , Encéfalo , Mapeamento Encefálico , Criança , Humanos , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Psychopathological symptoms during euthymia in Bipolar Disorder (BD) affect quality of life and predispose to the occurrence of new acute episodes, however only few studies investigated potential risk-factors. This study aims to explore the association between childhood trauma (CT), lifetime stressful events (SLEs) and psychopathological symptoms in BD patients during euthymia and controls (HC). METHODS: A total of 261 participants (93 euthymic patients with BD, 168 HC) were enrolled. Generalized linear models and multiple logistic models were used to assess the association among the Symptom Check List-90-R (SCL-90-R), the Infancy Trauma Interview, the Paykel Life Events Scale. RESULTS: The rate of participants reporting CT was higher in BD (n=47; 53%) than HC (n=43; 30%) (p=0.001). The experience of neglect was strongly related to BD (OR 6.5; p=0.003). CT was associated to higher scores on the SCL-90-R subscales (all the subscales except Phobia). No effects of the interaction between CT and diagnosis were found on SCL-90-R. Finally, there was a main effect of CT on lifetime SLEs (p<.001), that was not associated with diagnosis (p=0.833), nor with the interaction between CT and diagnosis (p=0.624). LIMITATIONS: The cross-sectional design does not allow causal inferences; the exclusion of subjects reporting medical or psychiatric comorbidity limits generalizability. CONCLUSIONS: CT was associated both to psychopathological symptoms during euthymia and the lifetime SLEs, thus it may represent a vulnerability factor influencing the course of BD. Overall, these data contribute to overcome the limited evidences documenting the influence of environmental factors on euthymic phase in BD.
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Transtorno Bipolar , Transtorno Bipolar/epidemiologia , Estudos Transversais , Transtorno Ciclotímico , Voluntários Saudáveis , Humanos , Qualidade de VidaRESUMO
In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (Nspared = 40, Nimpaired = 13). Impaired patients showed significantly increased negative symptomatology (pfdr = 0.003), reduced cognitive performance (pfdr < 0.001) and general functioning (pfdr < 0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in both discovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balanced accuracy = 60.1%, p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.