Individualized differential diagnosis of schizophrenia and mood disorders using neuroanatomical biomarkers

MRI-based markers can distinguish patients with schizophrenia from healthy controls. Koutsouleris et al. now report a diagnostic signature that distinguishes major depression/bipolar disorder from schizophrenia in 80%/74% of cases. Classification accuracy generalizes to early phases of psychosis, and is moderated by disease stage, age of onset and accelerated brain agein

Individualized differential diagnosis of schizophrenia and mood disorders using neuroanatomical biomarkers

Magnetic resonance imaging-based markers of schizophrenia have been repeatedly shown to separate patients from healthy controls at the single-subject level, but it remains unclear whether these markers reliably distinguish schizophrenia from mood disorders across the life span and generalize to new patients as well as to early stages of these illnesses. The current study used structural MRI-based multivariate pattern classification to (i) identify and cross-validate a differential diagnostic signature separating patients with first-episode and recurrent stages of schizophrenia (n = 158) from patients with major depression (n = 104); and (ii) quantify the impact of major clinical variables, including disease stage, age of disease onset and accelerated brain ageing on the signature's classification performance. This diagnostic magnetic resonance imaging signature was then evaluated in an independent patient cohort from two different centres to test its generalizability to individuals with bipolar disorder (n = 35), first-episode psychosis (n = 23) and clinically defined at-risk mental states for psychosis (n = 89). Neuroanatomical diagnosis was correct in 80% and 72% of patients with major depression and schizophrenia, respectively, and involved a pattern of prefronto-temporo-limbic volume reductions and premotor, somatosensory and subcortical increments in schizophrenia versus major depression. Diagnostic performance was not influenced by the presence of depressive symptoms in schizophrenia or psychotic symptoms in major depression, but earlier disease onset and accelerated brain ageing promoted misclassification in major depression due to an increased neuroanatomical schizophrenia likeness of these patients. Furthermore, disease stage significantly moderated neuroanatomical diagnosis as recurrently-ill patients had higher misclassification rates (major depression: 23%; schizophrenia: 29%) than first-episode patients (major depression: 15%; schizophrenia: 12%). Finally, the trained biomarker assigned 74% of the bipolar patients to the major depression group, while 83% of the first-episode psychosis patients and 77% and 61% of the individuals with an ultra-high risk and low-risk state, respectively, were labelled with schizophrenia. Our findings suggest that neuroanatomical information may provide generalizable diagnostic tools distinguishing schizophrenia from mood disorders early in the course of psychosis. Disease course-related variables such as age of disease onset and disease stage as well alterations of structural brain maturation may strongly impact on the neuroanatomical separability of major depression and schizophrenia

Detecting the Psychosis Prodrome Across High-Risk Populations Using Neuroanatomical Biomarkers

To date, the MRI-based individualized prediction of psychosis has only been demonstrated in single-site studies. It remains unclear if MRI biomarkers generalize across different centers and MR scanners and represent accurate surrogates of the risk for developing this devastating illness. Therefore, we assessed whether a MRI-based prediction system identified patients with a later disease transition among 73 clinically defined high-risk persons recruited at two different early recognition centers. Prognostic performance was measured using cross-validation, independent test validation, and Kaplan-Meier survival analysis. Transition outcomes were correctly predicted in 80% of test cases (sensitivity: 76%, specificity: 85%, positive likelihood ratio: 5.1). Thus, given a 54-month transition risk of 45% across both centers, MRI-based predictors provided a 36%-increase of prognostic certainty. After stratifying individuals into low-, intermediate-, and high-risk groups using the predictor's decision score, the high- vs low-risk groups had median psychosis-free survival times of 5 vs 51 months and transition rates of 88% vs 8%. The predictor's decision function involved gray matter volume alterations in prefrontal, perisylvian, and subcortical structures. Our results support the existence of a cross-center neuroanatomical signature of emerging psychosis enabling individualized risk staging across different high-risk populations. Supplementary results revealed that (1) potentially confounding between-site differences were effectively mitigated using statistical correction methods, and (2) the detection of the prodromal signature considerably depended on the available sample sizes. These observations pave the way for future multicenter studies, which may ultimately facilitate the neurobiological refinement of risk criteria and personalized preventive therapies based on individualized risk profiling tool

Multiple Sclerosis: Improved Detection of Active Cerebral Lesions With 3-Dimensional T1 Black-Blood Magnetic Resonance Imaging Compared With Conventional 3-Dimensional T1 GRE Imaging

Objectives: The aim of this study was to assess the diagnostic accuracy of a modified high-resolution whole-brain three-dimensional T1-weighted black-blood sequence (T1-weighted modified volumetric isotropic turbo spin echo acquisition [T1-mVISTA]) in comparison to a standard three-dimensional T1-weighted magnetization-prepared rapid gradient echo (MP-RAGE) sequence for detection of contrast-enhancing cerebral lesions in patients with relapsing-remitting multiple sclerosis (MS).& para;& para;Materials and Methods: After institutional review board approval and informed consent, 22 patients (8 men;aged 31.0 +/- 9.2 years) with relapsing-remitting MS were included in this monocentric prospective cohort study.& para;& para;Contrast-enhanced T1-mVISTA and MP-RAGE, both with 0.8 mm(3) resolution, were performed in all patients. In a substudy of 12 patients, T1-mVISTA was compared with a T1-mVISTA with 1.0 mm(3) resolution (T1-mVISTA_1.0). Reference lesions were 2-defined by an experienced neuroradiologist using all available sequences and served as the criterion standard. T1-mVISTA, T1-mVISTA_1.0, and MP-RAGE sequences were read in random order 4 weeks apart. Image quality, visual contrast enhancement, contrast-to-noise-ratio (CNR), diagnostic confidence, and lesion size were assessed and compared by Wilcoxon and Mann-Whitney U tests.& para;& para;Results: Eleven of 22 patients displayed contrast-enhancing lesions. Visual contrast enhancement, CNR, and diagnostic confidence of contrast-enhancing MS lesions were significantly increased in T1-mVISTA compared with MP-RAGE (P < 0.001). Significantly more contrast-enhancing lesions were detected with T1-mVISTA than with MP-RAGE (71 vs 39, respectively;P < 0.001). With MP-RAGE, 25.6% of lesions were missed in the initial reading, whereas only 4.2% of lesions were missed with T1-mVISTA. Increase of the voxel volume from 0.8 mm to 1.0 mm isotropic in T1-mVISTA_1.0 did not affect the detect-ability of lesions, whereas scan time was decreased from 4:43 to 1:55 minutes.& para;& para;Conclusions: Three-dimensional T1-mVISTA improves the detection rates of contrast-enhancing cerebral MS lesions compared with conventional 3D MP-RAGE sequences by increasing CNR of lesions and might, therefore, be useful in patient management

Variation within the Huntington's Disease Gene Influences Normal Brain Structure

Genetics of the variability of normal and diseased brain structure largely remains to be elucidated. Expansions of certain trinucleotide repeats cause neurodegenerative disorders of which Huntington's disease constitutes the most common example. Here, we test the hypothesis that variation within the IT15 gene on chromosome 4, whose expansion causes Huntington's disease, influences normal human brain structure. In 278 normal subjects, we determined CAG repeat length within the IT15 gene on chromosome 4 and analyzed high-resolution T1-weighted magnetic resonance images by the use of voxel-based morphometry. We found an increase of GM with increasing long CAG repeat and its interaction with age within the pallidum, which is involved in Huntington's disease. Our study demonstrates that a certain trinucleotide repeat influences normal brain structure in humans. This result may have important implications for the understanding of both the healthy and diseased brain

Percepción socio-emocional autoevaluada y sus correlativos neuropsicológicos y cardiacos al ver un film que muestra el sufrimiento de otras personas

Using electroencephalographic (EEG) and cardiac measures, the study examined relevant mechanisms that may explain individual differences in self-rated emotion perception (i.e., the propensity of perceiving the emotional states of other persons in everyday life). Healthy women (n = 122) were confronted with film scenes showing the suffering of other people. Functional coupling between prefrontal and posterior cortices, measured by EEG coherences, more strongly decreased in individuals higher on emotion perception. This finding suggests that the propensity to loosen prefrontal inhibitory control on posterior cortical areas involved in basic processes of emotion perception is associated with higher susceptibility to social-emotional information and, therefore, with higher scores on self-rated emotion perception. In addition, higher self-rated perception of other persons' emotions was related to more pronounced cardiac responses to the observation of horrifying events occurring to people in the film which indicate enhanced attention and heightened perceptual processing.Usando medidas electroencefalográficas (EEG) y cardiacas, el estudio examinó los mecanismos pertinentes que puedan explicar las diferencias individuales en la percepción de la emoción autoevaluada (es decir, la tendencia de percibir los estados emocionales de otras personas en la vida cotidiana). Las mujeres sanas (n = 122) fueron confrontadas con escenas de películas que muestran el sufrimiento de otras personas. El acoplamiento funcional entre la corteza prefrontal y posterior, medido por coherencias EEG, disminuyó más fuertemente en las personas con mayor percepción de la emoción. Este hallazgo sugiere que la propensión a relajar el control inhibitorio prefrontal en las áreas corticales posteriores implicados en los procesos básicos de la percepción de la emoción se asocia con una mayor susceptibilidad a la información socio-emocional y por tanto, con las puntuaciones más altas en la percepción de la emoción autoevaluada. Además, una mayor percepción autoevaluada de las emociones de otras personas estuvo relacionada con las respuestas cardíacas más explícitas a la observación de los terribles acontecimientos que ocurren a la gente en la película, lo cual indica una mayor atención e intensificación del procesamiento perceptual

State-dependent changes of prefrontal–posterior coupling in the context of affective processing: Susceptibility to humor

The aim of the present study was to examine whether interindividual differences in the coupling or decoupling of prefrontal and posterior cortices during the exposure to social–emotional information may predict an individual's positive emotional responsiveness. Susceptibility to humor was assessed in a behavioral paradigm several weeks after the EEG recordings. State-dependent changes of prefrontal–posterior EEG beta coherence were recorded during stimulation with other people's auditory expressions of cheerfulness and sadness. Greater decreases of coherence during the stimulation with positive affect expressions prospectively predicted greater positive emotional responsiveness, indicated by higher amusement ratings in response to cartoons and higher scores in a questionnaire measure of exhilarability. Greater increases of coherence during the stimulation with negative affect expressions did not predict perceived funniness but were related to shorter response latencies to the amusement ratings. The results further support the notion that a more loose prefrontal–posterior coupling may be related to loosening of control of the prefrontal cortex over incoming emotional information and, thus, to a propensity to deeper emotional involvement and a greater impact of perceptual input, whereas increased prefrontal–posterior coupling may be related to strong control and the propensity to protect oneself from becoming emotionally affected

Influences of COMT and 5-HTTLPR polymorphisms on cognitive flexibility in healthy women: inhibition of prepotent responses and memory updating.

Understanding genetic factors that affect monoamine neurotransmitters flux in prefrontal cortex may help to further specify the complex neurobiological processes that underlie cognitive function and dysfunction in health and illness. The current study examined the associations between the polymorphisms of dopaminergic (COMT Met158Val) and serotoninergic (5-HTTLPR) genes and the sequential pattern of responses in a motor random generation task providing well-established indexes for executive functioning in a large sample of 255 healthy women. Participants homozygous for the Met allele of the COMT polymorphism showed impaired inhibition of prepotent responses, whereas individuals homozygous for the s-allele of the 5-HTTLPR showed a restricted ability to update information in working memory. Taken together the results indicate differentiated influences of dopaminergic and serotonergic genes on important and definite executive sub-processes related to cognitive flexibility