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Author: Nikolaos Koutsouleris (45)


Jan
2018

Machine learning approaches for clinical psychology and psychiatry explicitly focus on learning statistical functions from multidimensional data sets to make generalizable predictions about individuals. The goal of this review is to provide an accessible understanding of why this approach is important for future practice because of its potential to augment decisions associated with the diagnosis, prognosis, and treatment of people suffering from mental illness using clinical and biological data. To this end, the limitations of current statistical paradigms in mental health research are critiqued, and an introduction is provided to the critical machine learning methods used in clinical studies.

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Dec
2017

Schizophrenia is associated with heterogeneous clinical symptoms and neuroanatomical alterations. In this work, we aim to disentangle the patterns of neuroanatomical alterations underlying a heterogeneous population of patients using a semi-supervised clustering method. We apply this strategy to a cohort of patients with schizophrenia of varying extends of disease duration, and we describe the neuroanatomical, demographic and clinical characteristics of the subtypes discovered.

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Nov
2017

Past work on relatively small, single-site studies using regional volumetry, and more recently machine learning methods, has shown that widespread structural brain abnormalities are prominent in schizophrenia. However, to be clinically useful, structural imaging biomarkers must integrate high-dimensional data and provide reproducible results across clinical populations and on an individual person basis. Using advanced multi-variate analysis tools and pooled data from case-control imaging studies conducted at 5 sites (941 adult participants, including 440 patients with schizophrenia), a neuroanatomical signature of patients with schizophrenia was found, and its robustness and reproducibility across sites, populations, and scanners, was established for single-patient classification.

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Aug
2017

The variability of responses to plasticity-inducing repetitive transcranial magnetic stimulation (rTMS) challenges its successful application in psychiatric care. No objective means currently exists to individually predict the patients' response to rTMS.
We used machine learning to develop and validate such tools using the pre-treatment structural Magnetic Resonance Images (sMRI) of 92 patients with schizophrenia enrolled in the multisite RESIS trial (http://clinicaltrials.

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Sep
2017

Multiple studies have examined functional and structural brain alteration in patients diagnosed with major depressive disorder (MDD). The introduction of multivariate statistical methods allows investigators to utilize data concerning these brain alterations to generate diagnostic models that accurately differentiate patients with MDD from healthy control subjects (HCs). However, there is substantial heterogeneity in the reported results, the methodological approaches, and the clinical characteristics of participants in these studies.

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Oct
2016

At present, no tools exist to estimate objectively the risk of poor treatment outcomes in patients with first-episode psychosis. Such tools could improve treatment by informing clinical decision-making before the commencement of treatment. We tested whether such a tool could be successfully built and validated using routinely available, patient-reportable information.

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Jul
2016

Findings from multiple lines of research provide evidence of aberrant functional brain connectivity in schizophrenia. By using graph-analytical measures, recent studies indicate that patients with schizophrenia exhibit changes in the organizational principles of whole-brain networks and that these changes relate to cognitive symptoms. However, there has not been a systematic investigation of functional brain network changes in schizophrenia to test the consistency of these changes across multiple studies.

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Jul
2016

Previous studies have shown that structural brain changes are among the best-studied candidate markers for schizophrenia (SZ) along with functional connectivity (FC) alterations of resting-state (RS) patterns. This study aimed to investigate effects of clinical and sociodemographic variables on the classification by applying multivariate pattern analysis (MVPA) to both gray matter (GM) volume and FC measures in patients with SZ and healthy controls (HC). RS and structural magnetic resonance imaging data (sMRI) from 74 HC and 71 SZ patients were obtained from a Mind Research Network COBRE dataset available via COINS (http://coins.

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Dec
1969

Most individuals at ultra-high risk (UHR) for psychosis do not transition to frank illness. Nevertheless, many have poor clinical outcomes and impaired psychosocial functioning. This study used voxel-based morphometry to investigate if baseline grey and white matter brain densities at identification as UHR were associated with functional outcome at medium- to long-term follow-up.

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Dec
1969

Schizophrenia is a group of severe psychiatric disorders with high heritability but only low odds ratios of risk genes. Despite progress in the identification of pathophysiological processes, valid biomarkers of the disease are still lacking.
This comprehensive review summarises recent efforts to identify genetic underpinnings, clinical and cognitive endophenotypes and symptom dimensions of schizophrenia and presents findings from neuroimaging studies with structural, functional and spectroscopy magnetic resonance imaging and positron emission tomography.

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Oct
2016

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that has shown promising results in various neuropsychiatric disorders in adults. This review addresses the therapeutic use of tDCS in children and adolescents including safety, ethical, and legal considerations. There are several studies addressing the dosage of tDCS in children and adolescents by computational modeling of electric fields in the pediatric brain.

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Jan
2017

The aim of this review is to assess the potential for neuroimaging measures to facilitate prediction of the onset of psychosis. Research in this field has mainly involved people at 'ultra-high risk' (UHR) of psychosis, who have a very high risk of developing a psychotic disorder within a few years of presentation to mental health services. The review details the key findings and developments in this area to date and examines the methodological and logistical challenges associated with making predictions in an individual subject in a clinical setting.

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Dec
1969

The psychosis high-risk state is accompanied by alterations in functional brain activity during working memory processing. We used binary automatic pattern-classification to discriminate between the at-risk mental state (ARMS), first episode psychosis (FEP) and healthy controls (HCs) based on n-back WM-induced brain activity. Linear support vector machines and leave-one-out-cross-validation were applied to fMRI data of matched ARMS, FEP and HC (19 subjects/group).

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Jul
2015

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).

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Dec
1969

To date, research into the biomarker-aided early recognition of psychosis has focused on predicting the transition likelihood of clinically defined individuals with different at-risk mental states (ARMS) based on structural (and functional) brain changes. However, it is currently unknown whether neuroimaging patterns could be identified to facilitate the individualized prediction of symptomatic and functional recovery. Therefore, we investigated whether cortical surface alterations analyzed by means of multivariate pattern recognition methods could enable the single-subject identification of functional outcomes in twenty-seven ARMS individuals.

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May
2015

Previous evidence indicates that structural brain alterations are already present in the early phases of psychosis. In this study we aim to investigate the relationships among the different diagnoses in the spectrum of non-affective psychosis. A hundred-and-one first-episode psychosis patients (FEP) and 69 healthy volunteers, matched for age, gender, handedness and educational level were analyzed by structural MRI and high-dimensional voxel-based morphometry as implemented in SPM8 software.

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Jun
2015

Multivariate pattern recognition approaches have recently facilitated the search for reliable neuroimaging-based biomarkers in psychiatric disorders such as schizophrenia. By taking into account the multivariate nature of brain functional and structural changes as well as their distributed localization across the whole brain, they overcome drawbacks of traditional univariate approaches. To evaluate the overall reliability of neuroimaging-based biomarkers, we conducted a comprehensive literature search to identify all studies that used multivariate pattern recognition to identify patterns of brain alterations that differentiate patients with schizophrenia from healthy controls.

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Jan
2015

Schizophrenia is a multifaceted mental disorder characterized by cognitive, perceptual, and affective symptom dimensions. This heterogeneity at the phenomenological level may be subserved by complex and heterogeneous patterns of structural abnormalities. Thus, delineating such patterns may improve the insight into the variability of disease and facilitate future magnetic resonance imaging-based diagnosis.

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Mar
2015

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.

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Dec
1969

Schizotypy refers to a set of temporally stable traits that are observed in the general population and that resemble the signs and symptoms of schizophrenia. Here, we review evidence from studies on genetics, cognition, perception, motor and oculomotor control, brain structure, brain function, and psychopharmacology in schizotypy. We specifically focused on identifying areas of overlap between schizotypy and schizophrenia.

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Sep
2014

Structural brain abnormalities are central to schizophrenia (SZ), but it remains unknown whether they are linked to dysmaturational processes crossing diagnostic boundaries, aggravating across disease stages, and driving the neurodiagnostic signature of the illness. Therefore, we investigated whether patients with SZ (N = 141), major depression (MD; N = 104), borderline personality disorder (BPD; N = 57), and individuals in at-risk mental states for psychosis (ARMS; N = 89) deviated from the trajectory of normal brain maturation. This deviation was measured as difference between chronological and the neuroanatomical age (brain age gap estimation [BrainAGE]).

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Dec
1969

Alzheimer's disease (AD), the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI)-based biomarker that predicts the individual progression of mild cognitive impairment (MCI) to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject.

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Aug
2013

Measurement of the upper cervical cord area (UCCA) from brain MRI may be an effective way to quantify spinal cord involvement in neurological disorders such as multiple sclerosis. However, knowledge on the determinants of UCCA in healthy controls (HCs) is limited.
In two cohorts of 133 and 285 HCs, we studied the influence of different demographic, body-related, and brain-related parameters on UCCA by simple and partial correlation analyses as well as by voxel-based morphometry (VBM) across both cerebral gray matter (GM) and white matter (WM).

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Sep
2013

The at-risk mental state for psychosis (ARMS) and the first episode of psychosis have been associated with structural brain abnormalities that could aid in the individualized early recognition of psychosis. However, it is unknown whether the development of these brain alterations predates the clinical deterioration of at-risk individuals, or alternatively, whether it parallels the transition to psychosis at the single-subject level.
We evaluated the performance of an magnetic resonance imaging (MRI)-based classification system in classifying disease stages from at-risk individuals with subsequent transition to psychosis (ARMS-T) and patients with first-episode psychosis (FE).

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Sep
2012

Neuropsychological deficits are a core feature of established psychosis and have been previously linked to fronto-temporo-limbic brain alterations. Both neurocognitive and neuroanatomical abnormalities characterize clinical at-risk mental states (ARMS) for psychosis. However, structure-cognition relationships in the ARMS have not been directly explored using multivariate neuroimaging techniques.

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Dec
1969

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.

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Jun
2012

Fully automated classification algorithms have been successfully applied to diagnose a wide range of neurological and psychiatric diseases. They are sufficiently robust to handle data from different scanners for many applications and in specific cases outperform radiologists. This article provides an overview of current applications taking structural imaging in Alzheimer's disease and schizophrenia as well as functional imaging to diagnose depression as examples.

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Nov
2012

Reliable prognostic biomarkers are needed for the early recognition of psychosis. Recently, multivariate machine learning methods have demonstrated the feasibility to predict illness onset in clinically defined at-risk individuals using structural magnetic resonance imaging (MRI) data. However, it remains unclear whether these findings could be replicated in independent populations.

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Oct
2012

Schizophrenia is associated with replicable grey matter volume reductions in fronto-temporo-limbic and subcortical regions. Psychometric schizotypy refers to a set of behavioural traits and cognitions thought to represent the subclinical manifestation of schizophrenia in the general population. While there is evidence of a continuum between schizophrenia and schizotypy at phenotypic, genetic and cognitive levels, no previous study has observed grey matter volume reductions associated with increased psychometric schizotypy levels in healthy individuals.

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Nov
2012

Neuropsychological deficits predate overt psychosis and overlap with the impairments in the established disease. However, to date, no single neurocognitive measure has shown sufficient power for a prognostic test. Thus, it remains to be determined whether multivariate neurocognitive pattern classification could facilitate the diagnostic identification of different at-risk mental states (ARMS) for psychosis and the individualized prediction of illness transition.

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May
2011

People experiencing possible prodromal symptoms of psychosis have a very high risk of developing the disorder, but it is not possible to predict, on the basis of their presenting clinical features, which individuals will subsequently become psychotic. Recent neuroimaging studies suggest that there are volumetric differences between individuals at ultra-high risk (UHR) for psychosis who later develop psychotic disorder and those who do not. However, the samples examined to date have been small, and the findings have been inconsistent.

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Jan
2011

Attention deficit hyperactivity disorder (ADHD) is a psychiatric disease that affects children and persists in 50% of cases into adulthood. Magnetic Resonance Imaging (MRI) studies in children suggest that ADHD is associated with structural abnormalities in the brain. However, very little research has been carried out on adult ADHD.

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Apr
2011

Antidepressants with different mechanisms of action might have different effects on brain functions. The aim of the study was therefore to investigate effects of 2 antidepressants on brain activation and to identify predictors for therapy response.
Twenty-four untreated patients with major depressive disorder (according to Structured Clinical Interview for DSM-IV) were enrolled in a prospective, randomized, 4-week trial with mirtazapine and venlafaxine.

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Nov
2010

The at-risk mental state for psychosis (ARMS) has been associated with abnormal structural brain dynamics underlying disease transition or non-transition. To date, it is unknown whether these dynamic brain changes can be predicted at the single-subject level prior to disease transition using MRI-based machine-learning techniques.
First, deformation-based morphometry and partial-least-squares (PLS) was used to investigate patterns of volumetric changes over time in 25 ARMS individuals versus 28 healthy controls (HC) (1) irrespective of the clinical outcome and (2) according to illness transition or non-transition.

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Nov
2010

Deficits in executive functioning have been described as a core feature of schizophrenia and have been linked to patterns of fronto-temporo-limbic brain alterations. To date, such structure-cognition relationships have not been explored in a clinically defined at-risk mental state (ARMS) for psychosis using whole-brain neuroimaging techniques. Therefore, we used voxel-based morphometry in 40 ARMS and 30 matched healthy control (HC) individuals to investigate whether gray and white matter volumes (1) correlated with the performance in the Trail-Making Test B (TMT-B), an established measure of executive functioning, and (2) were volumetrically linked to the ventromedial prefrontal cortex (VMPFC), found to be associated with TMT-B in the ARMS during the first analysis step.

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Sep
2010

Major depressive disorder is associated with both structural and functional alterations in the emotion regulation network of the central nervous system. The relation between structural and functional changes is largely unknown. Therefore, we sought to determine the relation between structural differences and functional alterations during the recognition of emotional facial expressions.

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May
2010

The underlying neurobiology of major depression (MD) is likely to represent an interaction between genetic susceptibility and environmental factors such as stress. We investigated, in a multimodal high-resolution magnetic resonance imaging (MRI) genetic study, whether reduced hippocampal volumes and other brain alterations are associated with the tri-allelic polymorphism of the serotonin transporter and childhood stress in patients with MD and healthy subjects. Patients with MD and healthy participants were investigated using high-resolution MRI and genotyping for serotonin transporter polymorphism in the promoter region of the serotonin transporter gene (SLC6A4, 5-HTTLPR).

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Oct
2010

Early emotional stress is associated with a life-long burden of risk for later depression and stressful life events contribute to the development of depressive episodes. In this study we investigated whether childhood stress is associated with structural brain alterations in patients with major depression (MD). Forty-three patients with MD and 44 age as well as gender matched healthy control subjects were investigated using high-resolution magnetic resonance imaging (MRI).

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Sep
2009

Structural brain abnormalities have been described in individuals with an at-risk mental state for psychosis. However, the neuroanatomical underpinnings of the early and late at-risk mental state relative to clinical outcome remain unclear.
To investigate grey matter volume abnormalities in participants in a putatively early or late at-risk mental state relative to their prospective clinical outcome.

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Jul
2009

Identification of individuals at high risk of developing psychosis has relied on prodromal symptomatology. Recently, machine learning algorithms have been successfully used for magnetic resonance imaging-based diagnostic classification of neuropsychiatric patient populations.
To determine whether multivariate neuroanatomical pattern classification facilitates identification of individuals in different at-risk mental states (ARMS) of psychosis and enables the prediction of disease transition at the individual level.

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Mar
2010

Several studies have demonstrated that structural brain change is detectable in the hippocampus in both patients, with schizophrenia and major depression. Only few studies, however, compared both clinical disease entities directly and no larger study has tried to take different disease stages into account. The objectives of this study are to investigate whether hippocampal volumes are reduced in patients with schizophrenia and those with major depression with the same duration of illness compared to healthy controls and to assess further changes at different disease stages.

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Oct
2008

Results of experimental studies suggest that neuroplastic changes may occur during depressive episodes. These effects have not been confirmed in patients with depression, to our knowledge.
To examine changes in the brains of patients with major depression vs those of healthy control subjects.

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Feb
2008

Structural neuroimaging has substantially advanced the neurobiological research of schizophrenia by describing a range of focal brain alterations as possible neuroanatomical underpinnings of the disease. Despite this progress, a considerable heterogeneity of structural findings persists that may reflect the phenomenological diversity of schizophrenia. It is unclear whether the range of possible clinical disease manifestations relates to a core structural brain deficit or to distinct structural correlates.

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Dec
1969

Affective facial processing is an important component of interpersonal relationships, which is altered in patients with major depression. The study was designed to examine differences in functional brain activity between patients with major depression and healthy controls using functional magnetic resonance imaging (fMRI). Twelve patients with major depression and 12 age-, gender- and handedness-matched healthy controls were studied using fMRI.

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Nov
2007

The anterior cingulate cortex (ACC) is part of the rostral limbic system and is involved in cognitive and affective processes that have been reported to be disturbed in schizophrenia. Despite the evidence for ACC abnormalities in schizophrenia indicated by functional imaging studies, structural magnetic resonance imaging (MRI) studies of this region of interest (ROI) have been relatively few and the results inconsistent. The aim of the present study was to examine the hypothesis that different subregions of the ACC are differentially affected by the disease process of schizophrenia, a circumstance that might contribute to contradictory results of earlier structural ACC studies.

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