Sinan Guloksuz

Maastricht University | UM · Department of Psychiatry & Neuropsychology

Background and Hypothesis: Psychosis-related environmental risks are common in autism, with identified genetic connections to psychosis. Therefore, we hypothesized these risks may moderate the relationship between autistic traits (ATs) and psychotic experiences (PEs). Study Design: First-wave data from 792 twins and siblings in the TwinssCan Projec...

To assess the longitudinal associations of genomic and exposomic liabilities for schizophrenia, both independently and jointly, with distressing psychotic experiences (PEs) and their persistence in early adolescence. The Adolescent Brain and Cognitive Development Study data from children with European ancestry were used (n=5,122). The primary outco...

Background Previous studies assessing the hypothesis that the construct of ‘aberrant salience’ is associated with psychosis and psychotic symptoms showed conflicting results. For this reason, the association between measures to index aberrant salience and subclinical psychotic symptoms in a general population sample was analysed. In addition, genet...

Aims There is increasing concern over the mental distress of youth in recent years, which may impact mental healthcare utilisation. Here we aim to examine temporal patterns of mental healthcare expenditures in the Netherlands by age and sex in the period between 2015 and 2021. Methods Comprehensive data from health insurers in the Netherlands at t...

Background Mood disorders involve a complex interplay between multifaceted internal emotional states, and complex external inputs. Dynamical systems theory suggests that this interplay between aspects of moods and environmental stimuli may hence determine key psychopathological features of mood disorders, including the stability of mood states, the...

Brain cortical morphology, indexed by its surface area and thickness, is known to be highly heritable. Previous research has suggested a relationship of cortical morphology with several neuropsychiatric phenotypes. However, the multitude of potential confounders makes it difficult to establish causal relationships. Here, we employ Generalized Summa...

Background A previous study successfully identified 148 out of 23,098 exposures associated with any psychotic experiences (PE) in the UK Biobank using an exposome-wide association study (XWAS). Research has shown that the polygenic risk score for schizophrenia (PRS-SCZ) is associated with PE. However, the interaction of these exposures and PRS-SCZ...

Background and hypothesis Persistent distressing psychotic-like experiences (PLE) are associated with impaired functioning and future psychopathology. Prior research suggests that physical activities may be protective against psychopathology. However, it is unclear whether physical activities may interact with genetics in the development of psychos...

Dissecting exposome linked to mental health outcomes can help identify potentially modifiabletargets to improve mental well-being. However, the multiplicity of exposures and the complexityof mental health phenotypes pose a major challenge. Here we conducted hypothesis-freeexposome-wide analyses to identify factors associated with 7 psychiatric diag...

Importance Suicide is the third-leading cause of death among US adolescents. Environmental and lifestyle factors influence suicidal behavior and can inform risk classification, yet quantifying and incorporating them in risk assessment presents a significant challenge for reproducibility and clinical translation. Objective To quantify the aggregate...

Objectives: This survey assessed psychiatry residents'/early-career psychiatrists' attitudes towards the utility of therapeutic drug monitoring (TDM) of antipsychotics. Methods: A previously developed questionnaire on attitudes on TDM utility during antipsychotic treatment was cross-sectionally disseminated by national coordinators between 01/01...

Background The relationship between childhood trauma (CT) and psychotic symptoms in patients with schizophrenia (SCZ), and subthreshold psychotic experiences in non-clinical populations is well-established. However, little is known about the relationship between subtypes of trauma and specific symptoms in patients, their siblings, and controls. It...

INTRODUCTION: Late-onset Alzheimers disease (LOAD) has been associated with alterations in the morphology of multiple brain structures and it is likely that disease mechanisms differ between brain regions. Coupling genetic determinants of LOAD with measures of brain morphology could localize and identify primary causal neurobiological pathways. MET...

This Viewpoint discusses the potential of salutogenesis, or emphasis on health- and wellness-promoting practices, as a public health approach to mitigate increasing levels of mental illness and distress.

Background The current state of mental health care in the Netherlands faces challenges such as fragmentation, inequality, inaccessibility, and a narrow specialist focus on individual diagnosis and symptom reduction. Methods A review suggests that in order to address these challenges, an integrated public health approach to mental health care that...

Background: Schizophrenia is a highly heritable brain disorder with a typical symptom onset in early adulthood. The 2-hit hypothesis posits that schizophrenia results from differential early neurodevelopment, predisposing an individual, followed by a disruption of later brain maturational processes that trigger the onset of symptoms. Study design...

Engagement with a first episode-psychosis service (FES) reduces the risk of psychiatric hospitalization. However, the role of the duration of untreated psychosis (DUP) in impacting this outcome is disputed. This study aimed to examine whether DUP was an effect modifier of the post-FES reduction of risk of hospitalization, and to explore association...

Purpose To explore gender differences of the associations between childhood adversity (CA) subtypes and psychiatric symptoms in the general population. Methods Data of 791 participants were retrieved from a general population twin cohort. The Symptom Checklist-90 Revised (SCL-90) and the Childhood Trauma Questionnaire were used to assess overall p...

The present study examines whether neuroticism is predicted by genetic vulnerability, summarized as polygenic risk score for neuroticism (PRS N ), in interaction with bullying, parental bonding, and childhood adversity. Data were derived from a general population adolescent and young adult twin cohort. The final sample consisted of 202 monozygotic...

Background The trends of recreational use of cannabis and use of cannabis for medical indications (i.e. medical cannabis) have grown in recent years. Despite that, there is still limited scientific evidence to guide clinical decision-making and the strength of evidence for the medical use of cannabis is currently considered to be low. In contrast,...

In this interactive session, we will attempt to create a roadmap toward a research career in psychiatry, particularly in challenging settings. Participants will be able to share their experiences and ask questions. Through dialectical discourse, we will identify the essential skills and key competencies for a research career and how to develop them...

Introduction Prior evidence suggests that men and women might be differentially susceptible to distinct types of childhood adversity (CA), but research on gender-specific associations between CA subtypes and psychiatric symptoms is limited. Objectives To test the gender-specific associations of CA subtypes and psychiatric symptoms in the general p...

Introduction Exposome is all nongenetic exposures from the prenatal period to death. Exposome score for schizophrenia (ES-SCZ) is a cumulative measure of environmental liability for schizophrenia. Our previous studies showed that the ES-SCZ is associated with mental and physical health outcome. Objectives The aim of the study is to investigate the...

Introduction Neuroticism has societal, mental and physical health relevance, with an etiology involving genetic predisposition, psychological influence, and their interaction. Objectives To understand whether the association between polygenic risk score for neuroticism (PRS-N) and neuroticism is moderated by affective well-being. Methods Data wer...

Background and hypothesis: Although studies have identified social fragmentation as an important risk factor for schizophrenia and other psychotic disorders, it is unknown whether it may impact social functioning. This study investigates whether social fragmentation during childhood predicts maladaptation to school as well as social functioning du...

Background Previous studies assessing the hypothesis that the construct of ‘aberrant salience’ is associated with psychosis and psychotic symptoms showed conflicting results. For this reason, the association between measures to index aberrant salience and subclinical psychotic symptoms in a general population sample was analysed. In addition, genet...

An updated third edition of this award-winning book provides a comprehensive overview of the complex associations between cannabis and mental illness. Organised into easy to navigate sections, the book has been fully revised to feature eight entirely new chapters covering important novel aspects. Marijuana and Madness incorporates new research find...

Treatment-resistant symptoms occur in about a third of patients with schizophrenia and are associated with a substantial reduction in their quality of life. The development of new treatment options for clozapine-resistant schizophrenia constitutes a crucial, unmet need in psychiatry. Additionally, an overview of past and possible future research av...

Objective: To identify potential clinical utility of polygenic risk scores (PRS) and exposomic risk scores (ERS) for psychosis and suicide attempt in youth and assess the ethical implications of these tools. Study design: We conducted a narrative literature review of emerging findings on PRS and ERS scores for suicide and psychosis as well as a...

People with mental disorders, such as psychosis or autism spectrum disorder (ASD), often present impairments in social cognition (SC), which may cause significant difficulties in real-world functioning. SC deficits are seen also in unaffected relatives, indicating a genetic substratum. The present review evaluated the evidence on the association be...

BACKGROUND: Preventing or delaying the onset of psychosis requires identification of those at risk for developing psychosis. For predictive purposes, the prodrome, a constellation of symptoms which may occur before the onset of psychosis, has been increasingly recognized as having utility. However, it is unclear what proportion of patients are expe...

The current study was conducted to provide a general guidance for model specifications in polygenic risk score (PRS) analyses of the UK Biobank, such as adjusting for covariates (i.e. age, sex, recruitment centers, and genetic batch) and the number of principal components (PCs) that need to be included. To cover behavioral, physical and mental heal...

It is unknown how smoking behavior polygenic scores (PRS) relate to psychosis and psychotic symptoms. To elucidate this, genotype and phenotype data were collected from patients with schizophrenia, their unaffected siblings, and healthy controls in a six-year follow-up prospective cohort study. Associations between smoking behaviors, PRS and schizo...

Background: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected...

Introduction Sleep quality is closely linked with mental health. Two factors that influence sleep are coping style and locus of control, yet these have not been investigated in daily life. In this study, we examined associations between coping styles and sleep quality in daily life and the potential mediating effect of daily locus of control in a s...

Importance Predictors consistently associated with psychosis liability and course of illness in schizophrenia (SCZ) spectrum disorders (SSD), including the need for clozapine treatment, are lacking. Longitudinally ascertained medication use may empower studies examining associations between polygenic risk scores (PRSs) and pharmacotherapy choices....

Importance: Predictors consistently associated with psychosis liability and course of illness in schizophrenia (SCZ) spectrum disorders (SSD), including the need for clozapine treatment, are lacking. Longitudinally ascertained medication use may empower studies examining associations between polygenic risk scores (PRSs) and pharmacotherapy choices....

Exposures to perinatal, familial, social, and physical environmental stimuli can have substantial effects on human development. We aimed to generate a single measure that capture’s the complex network structure of the environment (i.e., exposome) using multi-level data (participant’s report, parent report and geocoded measures) of environmental exp...

Age is the main risk factor of neurodegenerative diseases, but environmental exposure and lifestyle are important candidates for understanding their etiology. Accumulating evidence suggests that “exposome”, described as the totality of human environmental exposures from conception onwards, represents major modifiable risk factors for most neurodege...

Schizophrenia is frequently accompanied with social cognitive disturbances. Cannabis represents one established environmental factor associated with the onset and progression of schizophrenia. The present cross-sectional study aimed to investigate the association of facial emotion recognition (FER) performance with cannabis use in 2039 patients wit...

Electroconvulsive therapy (ECT) appears to be the most effective treatment for severe depression. However, its mechanisms of action are incompletely understood. Evidence suggests ECT enhances neuroplasticity and neurogenesis. While studies on ECT-induced neuroplasticity focused on brain-derived neurotrophic factor (BDNF), other factors of the BDNF/...

Reduced positive future thinking has been associated with suicidal ideation and behavior in adults, and appears to be exacerbated by negative affect. Yet, this has received little attention in youth. Prior research has also focused on longer-term future thinking, e.g., months and years, and relied on lab-based assessments. Using the experience samp...

Background Empirical evidence suggests that people use cannabis to ameliorate anxiety and depressive symptoms, yet cannabis also acutely worsens psychosis and affective symptoms. However, the temporal relationship between cannabis use, anxiety and depressive symptoms and psychotic experiences (PE) in longitudinal studies is unclear. This may be inf...

Introduction Previously, environmental vulnerability for schizophrenia assessed through exposome score for schizophrenia (ES-SCZ) was associated with the risk for psychosis development. Objectives The current study aims to investigate the longitudinal association between ES-SCZ and symptom severity in individuals with first episode psychosis (FEP)...

Introduction Social cognition refers to a complex set of mental abilities that support the construction of adequate social competence and adaptation. Impairments in social cognition can be found in several psychiatric disorders, particularly in psychoses. Polygenic Risk Scores (PRSs) represent single metrics of molecular genetic risk and are a pred...

1) Background: Our aims in this study were (i) to compare effort allocation capacity measured between patients with recent-onset schizophrenia (SCZ) and healthy controls (HCs), (ii) within the SCZ, to investigate the association of effort allocation capacity with negative symptoms (NS), and (iii) to compare this association with the type of NS scal...

Schizophrenia is a highly heritable brain disorder with a typical symptom onset in early adulthood. The two-hit hypothesis posits that schizophrenia results from deviant early neurodevelopment, predisposing an individual, followed by a disruption of later brain maturational processes that trigger the onset of symptoms. Here, we investigate how the...

Purpose The health correlates of polygenic risk (PRS-SCZ) and exposome (ES-SCZ) scores for schizophrenia may vary depending on age and sex. We aimed to examine age- and sex-specific associations of PRS-SCZ and ES-SCZ with self-reported health in the general population. Methods Participants were from the population-based Netherlands Mental Health S...

Over the last years, the decreased costs and enhanced accessibility to large genome-wide associstion studies datasets have laid the foundations for the development of polygenic risk scores (PRSs). A PRS is calculated on the weighted sum of single nucleotide polymorphisms and measures the individual genetic predisposition to develop a certain phenot...

Importance: Although hypothesis-driven research has identified several factors associated with psychosis, this one-exposure-to-one-outcome approach fails to embrace the multiplicity of exposures. Systematic approaches, similar to agnostic genome-wide analyses, are needed to identify genuine signals. Objective: To systematically investigate nonge...

Duration of untreated psychosis (DUP), the period between psychosis onset and entry into care, is a time of great vulnerability. Longer DUP predicts poorer outcomes, and delayed treatment access can limit the effectiveness of coordinated specialty care (CSC) services. This column details one component of a broader early detection campaign, a qualit...

Background The exposome comprises all non-genetic factors an individual is exposed to across their lifespan. Research suggests that exposomic vulnerability for schizophrenia is not only associated with psychosis but also general psychopathology to a degree. Here, we investigated to what degree exposome factors are associated with psychosis and gene...

Various environmental exposures have been associated with psychosis spectrum disorder. However, the role of gender in this association has received little attention. Therefore, we conducted a systematic review to evaluate gender-related differences and identified 47 research articles investigating the associations of psychosis with childhood advers...

Challenges associated with operationalising services for the at-risk mental state for psychosis solely in that same diagnostic silo are increasingly well recognised—namely, the differential risk for psychosis being a function of sampling enrichment strategies, declining transition rates to psychosis, questions regarding the validity of transition a...

Prenatal period, early childhood and adolescence are considered sensitive periods for brain and behavior development, when environmental exposures may have long lasting effects on mental health. Psychosis spectrum disorder (PSD) is developmental disorder that often manifests with non-specific clinical presentations long before a “full-blown” PSD is...

Background: Adolescence is a period of both great social change, and of vulnerability to psychiatric distress. However, little is known about the associations between early psychopathology and social interactions at the fundamental level of daily life. To better understand the social correlates of subclinical psychopathology in adolescence, we ass...

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are exp...

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are exp...

Reduced positive future thinking has been associated with suicidal ideation and behaviour in adults, and appears to be exacerbated by negative affect. Yet, this has received little attention in youth. Prior research has also focussed on longer-term future thinking, e.g. months and years, and relied on lab-based assessments. Using the experience sam...

Parents are known to provide a lasting basis for their children's social development. Understanding parent-driven socialization is particularly relevant in adolescence, as an increasing social independence is developed. However, the relationship between key parenting styles of care and control and the microlevel expression of daily-life social inte...

Objective: Youth suicide rates in the United States have been increasing in recent years, especially in Black Americans, the reasons for which are unclear. Environmental adversity is key in youth suicidality; hence there is a need to study stressors that have a disproportionate impact on Black youths. We aimed to disentangle the unique contributio...

This study aims to disentangle the contribution of genetic liability, educational attainment (EA), and their overlap and interaction in lifetime smoking. We conducted genome-wide association studies (GWASs) in UK Biobank (N = 394,718) to (i) capture variants for lifetime smoking, (ii) variants for EA, and (iii) variants that contribute to lifetime...

Objective Duration of Untreated Psychosis (DUP) remains unacceptably long and limits effectiveness of care. To determine whether an early detection campaign (‘Mindmap’) can reduce DUP in a US community setting. Methods In this non-randomized controlled trial, Mindmap targeted the catchment of one specialty first-episode service or FES (STEP, Great...