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Nikolaos Koutsouleris

Nikolaos Koutsouleris
Ludwig-Maximilians-University of Munich & King's College London

Prof. Dr. med.

About

290
Publications
43,567
Reads
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7,934
Citations
Introduction
My research aims at developing computational methods capable of extracting predictive information from neurobiological and behavioural data for an improved early recognition of psychiatric disorders. Based on prospective multi-modal studies of patients at risk poor disease outcomes, my team and I develop methods for an effective personalized management of high-risk persons, individualized stratification of risk for poor disease outcomes, and an improved understanding of the diagnostic boundaries between and within disease entities.
Additional affiliations
August 2011 - December 2011
University of Pennsylvania
Position
  • PostDoc Position
March 2004 - present
Ludwig-Maximilians-University of Munich
Position
  • Consultant
March 2004 - January 2017
Ludwig-Maximilians-University of Munich
Position
  • Managing Consultant, Coordinator of EU-FP7 project PRONIA ("Personalized Prognostic Tools for Early Psychosis Management")

Publications

Publications (290)
Preprint
Full-text available
Autism spectrum disorder (ASD) is associated with high structural heterogeneity in magnetic resonance imaging (MRI). This work uncovers three neuroanatomical dimensions of ASD ( N = 307) using machine learning methods and constructs their characteristic MRI signatures. The presence of these signatures, along with their clinical profiles and genetic...
Article
Schizotypy refers to a set of personality traits that bear resemblance, at subclinical level, to psychosis. Despite evidence of similarity at multiple levels of analysis, direct comparisons of schizotypy and clinical psychotic disorders are rare. Therefore, we used functional magnetic resonance imaging (fMRI) to examine the neural correlates and ta...
Article
Importance: Approaches are needed to stratify individuals in early psychosis stages beyond positive symptom severity to investigate specificity related to affective and normative variation and to validate solutions with premorbid, longitudinal, and genetic risk measures. Objective: To use machine learning techniques to cluster, compare, and comb...
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Objective: The prevalence and significance of schizophrenia-related phenotypes at the population level is debated in the literature. Here, the authors assessed whether two recently reported neuroanatomical signatures of schizophrenia-signature 1, with widespread reduction of gray matter volume, and signature 2, with increased striatal volume-could...
Article
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Objective Social dysfunction is a major feature of clinical-high-risk states for psychosis (CHR-P). Prior research has identified a neuroanatomical pattern associated with impaired social function outcome in CHR-P. The aim of the current study was to test whether social dysfunction in CHR-P is neurobiologically distinct or in a continuum with the l...
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Recent review articles provided an extensive collection of studies covering many aspects of format thought disorders (FTD) among their epidemiology and phenomenology, their neurobiological underpinnings, genetics as well as their transdiagnostic prevalence. However, less attention has been paid to the association of FTD with neurocognitive and func...
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Background Formal thought disorder (FTD) has been associated with more severe illness courses and functional deficits in patients with psychotic disorders. However, it remains unclear whether the presence of FTD characterises a specific subgroup of patients showing more prominent illness severity, neurocognitive and functional impairments. This stu...
Article
Progress in developing personalised care for mental disorders is supported by numerous proof-of-concept machine learning studies in the area of risk assessment, diagnostics and precision prescribing. Most of these studies primarily use clinical data, but models might benefit from additional neuroimaging, blood and genetic data to improve accuracy....
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Background Identifying neurobiologically based transdiagnostic categories of depression and psychosis may elucidate heterogeneity, and provide better candidates for predictive modelling. We aimed to identify clusters across patients with recent onset depression (ROD) and recent onset psychosis (ROP) based on structural neuroimaging data. We hypothe...
Preprint
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Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to structural covariance patterns across brain regions and individuals. We present a mega-analysis of structural covariance with magnetic resonance imaging of 50,699 healthy and diseased individuals (12 studies, 130 sites, and 12 countries)...
Article
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Continued cannabis use (CCu) is an important predictor for poor long-term outcomes in psychosis and clinically high-risk patients, but no generalizable model has hitherto been tested for its ability to predict CCu in these vulnerable patient groups. In the current study, we investigated how structured clinical and cognitive assessments and structur...
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The Federal Ministry of Education and Research (BMBF) issued a call for a new nationwide research network on mental disorders, the German Center of Mental Health (DZPG). The Munich/Augsburg consortium was selected to participate as one of six partner sites with its concept “Precision in Mental Health (PriMe): Understanding, predicting, and preventi...
Preprint
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Structural MRI studies in first-episode psychosis and the clinical high-risk state have consistently shown volumetric abnormalities. Aim of the present study was to introduce radiomics texture features in identification of psychosis. Radiomics texture features describe the interrelationship between voxel intensities across multiple spatial scales c...
Article
Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/re...
Article
Background Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to...
Article
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 f...
Article
Children and adolescents could benefit from the use of predictive tools that facilitate personalized diagnoses, prognoses, and treatment selection. Such tools have not yet been deployed using traditional statistical methods, potentially due to the limitations of the paradigm and the need to leverage large amounts of digital data. This review will s...
Preprint
Full-text available
The prevalence and significance of schizophrenia-related phenotypes at the population-level are debated in the literature. Here we assess whether two recently reported neuroanatomical signatures of schizophrenia, signature 1 with widespread reduction of gray matter volume and signature 2 with increased striatal volume, could be replicated in an ind...
Article
Full-text available
Cognitive gains following cognitive training interventions are associated with improved functioning in people with schizophrenia (SCZ). However, considerable inter-individual variability is observed. Here, we evaluate the sensitivity of brain structural features to predict functional response to auditory-based cognitive training (ABCT) at a single-...
Article
Aggression can have a hedonistic aspect in predisposed individuals labeled as appetitive aggression. The present study investigates the neurobiological correlates of this appetitive type of aggression in non-clinical samples from community. Applying functional magnet resonance imaging (fMRI), we tested whether 20 martial artists compared to 26 cont...
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Disease heterogeneity is a significant obstacle to understanding pathological processes and delivering precision diagnostics and treatment. Clustering methods have gained popularity for stratifying patients into subpopulations (i.e., subtypes) of brain diseases using imaging data. However, unsupervised clustering approaches are often confounded by...
Article
Personalised prediction of functional outcomes is a promising approach for targeted early intervention in psychiatry. However, generalisability and resource efficiency of such prognostic models represent challenges. In the PRONIA study (German Clinical Trials Register: DRKS00005042), we demonstrate excellent generalisability of prognostic models in...
Article
Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (C...
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Full-text available
Individuals with Autism Spectrum Disorder (ASD) are thought to under-rely on prior knowledge in perceptual decision-making. This study examined whether this applies to decisions of attention allocation, of relevance for ‘predictive-coding’ accounts of ASD. In a visual search task, a salient but task-irrelevant distractor appeared with higher probab...
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Background: Psychiatric disorders have been historically classified using symptom information alone. Recently, there has been a dramatic increase in research interest not only in identifying the mechanisms underlying defined pathologies but also in redefining their etiology. This is particularly relevant for the field of personalized medicine, whic...
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Background: Validated clinical prediction models of short-term remission in psychosis are lacking. Our aim was to develop a clinical prediction model aimed at predicting 4-6-week remission following a first episode of psychosis. Method: Baseline clinical data from the Athens First Episode Research Study was used to develop a Support Vector Machi...
Article
Adult gyrification provides a window into coordinated early neurodevelopment when disruptions predispose individuals to psychiatric illness. We hypothesized that the echoes of such disruptions should be observed within structural gyrification networks in early psychiatric illness that would demonstrate associations with developmentally relevant var...
Article
Background In the medical imaging domain, deep learning-based methods have yet to see widespread clinical adoption, in part due to limited generalization performance across different imaging devices and acquisition protocols. The deviation between estimated brain age and biological age is an established biomarker of brain health and such models may...
Preprint
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Multitask learning allows the simultaneous learning of multiple 'communicating' algorithms. It is increasingly adopted for biomedical applications, such as the modeling of disease progression. As data protection regulations limit data sharing for such analyses, an implementation of multitask learning on geographically distributed data sources would...
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Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristi...
Article
Full-text available
Reliably diagnosing autism spectrum disorders (ASD) in adulthood poses a challenge to clinicians due to the absence of specific diagnostic markers. This study investigated the potential of interpersonal synchrony (IPS), which has been found to be reduced in ASD, to augment the diagnostic process. IPS was objectively assessed in videos of diagnostic...
Article
Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID�19 pandemic are needed. Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/r...
Article
Background Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, an...
Article
Background Transition to psychosis is among the most adverse outcomes of the clinical high-risk (CHR) syndromes encompassing ultra-high-risk (UHR) and basic symptoms states. Clinical risk calculators may facilitate an early and individualized interception of psychosis, but their real-world implementation requires thorough validation across diverse...
Article
Full-text available
Schizotypal personality traits show similarity with schizophrenia at various levels of analysis. It is generally agreed that schizotypal personality is multidimensional; however, it is still debated whether impulsive nonconformity should be incorporated into theories and measurement of schizotypy. In addition, relatively little is known about the n...
Article
Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, m...
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Age plays a crucial role in the performance of schizophrenia vs. controls (SZ-HC) neuroimaging-based machine learning (ML) models as the accuracy of identifying first-episode psychosis from controls is poor compared to chronic patients. Resolving whether this finding reflects longitudinal progression in a disorder-specific brain pattern or a system...
Article
Full-text available
Negative symptoms occur frequently in individuals at clinical high risk (CHR) for psychosis and contribute to functional impairments. The aim of this study was to predict negative symptom severity in CHR after 9 months. Predictive models either included baseline negative symptoms measured with the Structured Interview for Psychosis-Risk Syndromes (...
Article
Non-segmented MRI brain images are used for the identification of new Magnetic Resonance Imaging (MRI) biomarkers able to differentiate between schizophrenic patients (SCZ), major depressive patients (MD) and healthy controls (HC). Brain texture measures such as entropy and contrast, capturing the neighboring variation of MRI voxel intensities, wer...
Preprint
Full-text available
Background: Studying the phenotypic and genetic characteristics of age and polarity at onset (AAO, PAO) in bipolar disorder (BD) can provide new insights into disease pathology and facilitate the development of screening tools. Aims: To examine the genetic architecture of AAO and PAO and their association with BD disease characteristics. Methods: G...
Article
Introduction Different electrophysiological indices have been investigated to identify diagnostic and prognostic markers of schizophrenia (SCZ). However, these indices have limited use in clinical practice, since both specificity and association with illness outcome remain unclear. In recent years, machine learning techniques, through the combinati...
Article
Introduction Despite innovative treatments, the impairment in real-life functioning in subjects with schizophrenia (SCZ) remains an unmet need in the care of these patients. Recently, real-life functioning in SCZ was associated with abnormalities in different electrophysiological indices. It is still not clear whether this relationship is mediated...
Article
Full-text available
Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hit...
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Full-text available
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...
Article
Current hypotheses on the therapeutic action of non-invasive brain stimulation (NIBS) in psychiatric disorders build on the abundant data from neuroimaging studies. This makes NIBS a very promising tool for developing personalized interventions within a precision medicine framework. NIBS methods fundamentally vary in their neurophysiological proper...
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Diagnostic heterogeneity within and across psychotic and affective disorders challenges accurate treatment selection, particularly in the early stages. Delineation of shared and distinct illness features at the phenotypic and brain levels may inform the development of more precise differential diagnostic tools. We aimed to identify prototypes of de...
Article
A multitude of prediction models for a first psychotic episode in individuals at clinical high-risk (CHR) for psychosis have been proposed, but only rarely validated. We identified transition models based on clinical and neuropsychological data through a registered systematic literature search and evaluated their external validity in 173 CHRs from...
Article
Full-text available
Background Assessment of risks of illnesses has been an important part of medicine for decades. We now have hundreds of ‘risk calculators’ for illnesses, including brain disorders, and these calculators are continually improving as more diverse measures are collected on larger samples. Methods We first replicated an existing psychosis risk calcula...
Article
Full-text available
Recent life events have been implicated in the onset and progression of psychosis. However, psychological processes that account for the association are yet to be fully understood. Using a network approach, we aimed to identify pathways linking recent life events and symptoms observed in psychosis. Based on previous literature, we hypothesized that...
Article
Neuregulin-1 (NRG1) represents an important factor for multiple processes including neurodevelopment, brain functioning or cognitive functions. Evidence from animal research suggests an effect of NRG1 on the excitation-inhibition (E/I) balance in cortical circuits. However, direct evidence for the importance of NRG1 in E/I balance in humans is stil...
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Full-text available
Aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei are among the most consistent large-scale brain imaging findings in schizophrenia. A pathophysiological link between these two alterations is suggested by theoretical models based on striatal...
Article
Importance Diverse models have been developed to predict psychosis in patients with clinical high-risk (CHR) states. Whether prediction can be improved by efficiently combining clinical and biological models and by broadening the risk spectrum to young patients with depressive syndromes remains unclear. Objectives To evaluate whether psychosis tra...
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Full-text available
In community studies, both attenuated psychotic symptoms (APS) and basic symptoms (BS) were more frequent but less clinically relevant in children and adolescents compared to adults. In doing so, they displayed differential age thresholds that were around age 16 for APS, around age 18 for perceptive BS, and within the early twenties for cognitive B...
Article
Full-text available
Background: Greater impairments in early sensory processing predict response to auditory computerized cognitive training (CCT) in patients with recent-onset psychosis (ROP). Little is known about neuroimaging predictors of response to social CCT, an experimental treatment that was recently shown to induce cognitive improvements in patients with psy...