Gregor Berger

• MD
• Consultant at Psychiatrische Universitätsklinik PUK, Zürich, Switzerland

Introduction About half of all adolescents with major depressive disorder (MDD) have frequent suicidal thoughts and of those with suicidal ideations, about one-third attempt suicide. Identifying clinical characteristics associated with suicidal ideation and attempts is important for suicide prevention and clinical care. Methods Participants were f...

Dysregulation of inflammatory mediators and complement cascade proteins has been implicated in psychosis. In the current study, we aimed to investigate the relationship between complement cascade proteins and inflammatory cytokines in blood from people at clinical high risk (CHR) for psychosis and at first episode of psychosis (FEP). Baseline blood...

Background Almost 40% of individuals at ultra-high risk (UHR) for psychosis experience persistent attenuated psychotic symptoms (APS) yet it is unclear (1) whether they share overlapping clinical and functional outcomes compared to individuals who transition to psychosis, (2) when symptom and functioning trajectories begin to diverge between UHR in...

Background and Hypotheses In the past 2 decades, substantial effort has been put into research on therapeutic options for people at ultra-high risk (UHR) for developing a first episode of psychosis (FEP), focusing on omega-3 polyunsaturated fatty acids (PUFAs) in preventing transition to psychosis. Despite an initial positive finding, subsequent st...

Depression has been associated with subclinical hypothyroidism and altered hypothalamic-pituitary-thyroid axis functioning. Adequate iodine nutrition is essential for healthy thyroid functioning. We therefore determined associations of iodine and thyroid status with paediatric major depressive disorder (pMDD) among Swiss adolescents and explored wh...

Background: Pediatric major depressive disorder (MDD) represents a leading cause of disability worldwide in children and adolescents, while its underlying pathophysiology remains largely elusive. The endocannabinoid system (ECS) and the hypothalamus-pituitary-adrenal (HPA) axis are considered intertwined regulatory systems crucially implicated in t...

The concept of ultra-high risk for psychosis (UHR) has been at the forefront of psychiatric research for several decades, with the ultimate goal of preventing the onset of psychotic disorder in high-risk individuals. Orygen (Melbourne, Australia) has led a range of observational and intervention studies in this clinical population. These datasets h...

Introduction Depression is increasingly diagnosed in adolescence, necessitating specific prevention and treatment methods. However, there is a lack of animal models mimicking juvenile depression. This study explores a novel model using ultrasound (US) stress in juvenile mice. Methods We employed the US stress model in one-month-old C57/BL6 mice, e...

Aim Lithium, even at low doses, appears to offer neuroprotection against a wide variety of insults. In this controlled pilot, we examined the safety (i.e., side-effect profile) of lithium in a sample of young people identified at ultra-high risk (UHR) for psychosis. The secondary aim was to explore whether lithium provided a signal of clinical effi...

Adolescent major depressive disorder (MDD) is associated with altered resting-state connectivity between the default mode network (DMN) and the salience network (SN), which are involved in self-referential processing and detecting and filtering salient stimuli, respectively. Using spectral dynamical causal modelling, we investigated the effective c...

Purpose Depression is associated with low-grade systemic inflammation and impaired intestinal function, both of which may reduce dietary iron absorption. Low iron status has been associated with depression in adults and adolescents. In Swiss adolescents, we determined the associations between paediatric major depressive disorder (pMDD), inflammatio...

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accu...

Background: Observational studies suggest a link between n-3 polyunsaturated fatty acid (PUFA) intake, n-3 PUFA status, and depression in adults, but studies in adolescents are scarce. This study aimed to determine associations of n-3 PUFA status and intake with paediatric major depressive disorder (pMDD) in Swiss adolescents. Methods: We conduc...

Background Executive functions (EF) consolidate during adolescence and are impaired in various emerging psychiatric disorders, such as pediatric Major Depressive Disorder (pMDD) and Borderline Personality Disorder. Previous studies point to a marked heterogeneity of deficits in EF in pMDD. We examined the hypothesis that deficits in EF in adolescen...

Study objectives: We aimed to examine the association between self-rated and clinician-rated sleep disturbances and C-reactive protein (CRP), an objective marker of inflammation, in pediatric depression. Methods: Two hundred fifty-six children and adolescents (15.2 ± 1.6 y, 72.3% female) with moderate to severe symptoms of depression participate...

Objective: To compare psychiatric emergencies and self-harm at emergency departments (EDs) one year into the pandemic, to early pandemic and pre-pandemic, and to examine the changes in the characteristics of self-harm presentations. Method: This retrospective cohort study expanded on the Pandemic-Related Emergency Psychiatric Presentations (PREP-ki...

The high prevalence of mental health dysfunction in childhood and adolescence, together with the fact that many mental disorders in adulthood emerge and consolidate in this period, underlines the importance of effective and safe treatments. The present chapter on neuropsychopharmacotherapy summarizes and discusses the critical issues of efficacy, t...

Preliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were...

Suicide is the leading cause of death among Swiss adolescents. Often, a suicide attempt is the outcome of a "suicidal process" at the end of which death is perceived as the only means of escaping from intolerable psychic pain. A suicide attempt entails a high risk of repetition. AdoASSIP, a brief adjunctive therapy adapted for adolescents, which is...

Background: Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population. Aims: To investigate whether omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation improves cognitive fun...

Adolescence represents a critical developmental period where the prevalence of major depressive disorder (MDD) increases. Aberrant emotion processing is a core feature of adolescent MDD that has been associated with functional alterations within the prefrontal-amygdala circuitry. In this study, we tested cognitive and neural mechanisms of emotional...

The high prevalence of mental health dysfunction in childhood and adolescence, together with the fact that many mental disorders in adulthood emerge and consolidate in this period, underlines the importance of effective and safe treatments. The present chapter on neuropsychopharmacotherapy summarizes and discusses the critical issues of efficacy, t...

Background Functional outcomes are important measures in the overall clinical course of psychosis and individuals at clinical high-risk (CHR), however, prediction of functional outcome remains difficult based on clinical information alone. In the first part of this study, we evaluated whether a combination of biological and clinical variables could...

Background: Epidemiological evidence from population-based surveys suggest that the psychological well-being of adolescents has been severely affected by the COVID-19 pandemic itself, as well as by the safety measures implemented. The rationale of the study was to investigate the influence of the pandemic on psychiatric emergency service use, psyc...

Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class traject...

Objective This pilot study examines the feasibility and the effectiveness of add-on home treatment (HT) to family-based treatment (FBT) in adolescents with anorexia nervosa (AN). The HT intervention is delivered by specialised nurses and aims at supporting patients and parents to re-establish family meals in the home environment. Method We perform...

Background There is increasing evidence that dysregulation of polyunsaturated fatty acids (FAs) mediated membrane function plays a role in the pathophysiology of schizophrenia. Even though preclinical findings have supported the anti-inflammatory properties of omega-3 FAs on brain health, their biological roles as anti-inflammatory agents and their...

Causal interactions between specific psychiatric symptoms could contribute to the heterogenous clinical trajectories observed in early psychopathology. Current diagnostic approaches merge clinical manifestations that co-occur across subjects and could significantly hinder our understanding of clinical pathways connecting individual symptoms. Networ...

Objective This study examines the feasibility, acceptability, and preliminary effect sizes on outcome measures of home treatment (HT) as an add-on to family-based therapy (FBT) in adolescents with anorexia nervosa (AN). The HT intervention is delivered by specialized nurses and aims at supporting patients and parents to re-establish family meals in...

PurposeMigrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder.Methods Hazard ratios for the risk of trans...

Background Understanding the mechanisms in the brain’s incentive network that give rise to symptoms of major depressive disorder (MDD) during adolescence provides new perspectives to address MDD in early stages of development. This functional magnetic resonance imaging study determines whether instrumental vigor and brain responses to appetitive an...

Background: Understanding the mechanisms in the brain's incentive network that give rise to symptoms of major depressive disorder (MDD) during adolescence provides new perspectives to address MDD in early stages of development. This functional magnetic resonance imaging study determines whether instrumental vigor and brain responses to appetitive a...

Major depressive disorders (MDDs) are often associated with a deficiency in long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), as well as signs of low-grade inflammation. Epidemiological and dietary studies suggest that a high intake of fish, the major source of ω-3 PUFAs, is associated with lower rates of MDDs. Meta-analyses of randomized...

Objective: Severity ratings of psychopathology in minors are often based on a composite score of the parent's and child's reports. However, parent's and child's reports often differ substantially, resulting in the integration method affecting the final scores. Nevertheless, effects of integration algorithms are seldom assessed and poorly understood...

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been described as positively associated with cognitive functioning. Current meta-analyses have identified eicosapentaenoic acid (EPA) as potentially more effective than docosahexaenoic acid (DHA). An especially vulnerable subgroup that might benefit from these beneficial effects are depressed you...

Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric neurodevelopmental disorders in children and adolescents. Although ADHD has been studied for nearly a century, the cause and pathophysiology of ADHD is yet largely unknown. However, findings from previous studies have resulted in the formation of a new hypothesis:...

Aim: The aim of this paper is to determine clinical factors related to hostility and disturbing and aggressive behaviour and to examine the effect of medication on these behaviours in FEP. Methods: Data from phase I and II of the OPTiMiSE trial are used. Outcome measures are the hostility item of the Positive and Negative Syndrome Scale (PANSS P...

Background: Neurocognitive impairments are core early features of psychosis and are observed in those at ultra-high risk (UHR) for psychosis. The aim of the present study was to explore whether neurocognition is associated with polyunsaturated fatty acids (PUFAs), as has been observed in other clinical populations. Method: Erythrocyte levels of...

The Zurich Specialist Clinic for Adolescent with Gender Dysphoria - Preliminary Follow-up Results The specialist clinic for children and adolescents with gender dysphoria (GD) of the Psychiatric University Hospital of Zurich shows an increasing number of referrals since its foundation in 2009. Since 2014 we started an observational study including...

The Zurich Specialist Clinic for Adolescent with Gender Dysphoria - Preliminary Follow-up Results The specialist clinic for children and adolescents with gender dysphoria (GD) of the Psychiatric University Hospital of Zurich shows an increasing number of referrals since its foundation in 2009. Since 2014 we started an observational study including...

Attention deficit hyperactivity disorder (ADHD) is among the most frequent disorders within child and adolescent psychiatry, with a prevalence of over 5%. Nosological systems, such as the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and the International Classification of Diseases, editions 10 and 11 (ICD-10/11) contin...

[This corrects the article DOI: 10.3389/fpsyt.2019.00393.].

Aim Several prediction models have been introduced to identify young people at greatest risk of transitioning to psychosis. To date, none has examined the possibility of developing a clinical prediction model of outcomes other than transition. The aims of this study were to examine the association between baseline clinical predictors and outcomes i...

Background Over the last two decades, several randomised controlled trials (RCTs) have indicated that preventive psychosocial, pharmacologic (Van der Gaag et al. 2013), and nutritional interventions (Amminger et al. 2010) are likely to be beneficial in people at ultra-high risk (UHR) of psychosis, in terms of delaying or preventing a transition to...

Background The prevalence of antibodies to Toxoplasma gondii, a ubiquitous parasitic protozoan causing the infectious disease toxoplasmosis, is increased in patients with psychotic disorders compared to the general population. We have previously shown that antibody titers for T.gondii correlate with the severity of positive symptoms in young people...

Background : Parents and their children often disagree on the existence and severity of psychopathological symptoms, especially in major depressive disorder (MDD). Discrepant estimations pose a problem for the validity of diagnoses and illness severity with major implications for treatment evaluation. Methods : 118 adolescents aged 13-18 years and...

The prevalence and predictive power of schizotypal and borderline personality disorders in ultra high risk for psychosis patients (n=293) was assessed. While the prevalence of borderline personality disorder was higher than in the general population but that this was not the case for schizopytal personality disorder. However, schizotypal personalit...

This study examined whether distress in relation to attenuated psychotic symptoms (DAPS) is associated with clinical outcomes in an ultra-high-risk (UHR) for psychosis sample. We also investigated whether DAPS is associated with cognitive style (attributional style and cognitive biases) and whether amount of psychosocial treatment provided is assoc...

Neurocognitive impairments are well established in both ultra-high risk (UHR) for psychosis and major depressive disorder (MDD). Despite this understanding, investigation of neurocognitive deficits in UHR individuals with MDD and its association with MDD within this population, has been scarce. Hence, this study aimed to examine any differences in...

Omega-3 fatty acids are vital for brain development. The aim of this meta-analysis was to broaden current knowledge of the effects of omega-3 supplementation on cognitive test performance in youths. Randomized controlled trials (RCTs) meeting selection criteria were identified through two independent literature searches on PubMed, Cochrane Library,...

There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the 'ultra high risk' (UHR) for psychosis approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of tra...

Background: Depressive disorders in childhood and adolescence are a major health problem and often follow a chronic course with severe consequences in later life. Depressive disorders cause the highest burden of disease in this age group across all medical conditions. Treatment adherence is usually very poor, and the use of antidepressant drugs is...

The Ultra-High Risk (UHR) for psychosis group is known to be heterogeneous with diverse outcomes. This study aimed to: 1. Identify subclasses of UHR individuals based on trajectories of symptomatic and functional change over time, 2. Identify predictors of these trajectories. A sample of 304 UHR individuals participating in the Neurapro trial were...

Abstract: Background: NEURAPRO was a multicenter, double-blind, randomised, placebo-controlled trial RCT of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) ('fish oil') therapy provided for 6 months in individuals at ultra-high risk (UHR) for psychotic disorders, followed by an additional 6-month follow-up period. The study was conducted...

Omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) are necessary for optimum mental health, with recent studies showing low n-3 LCPUFA in people at ultra-high risk (UHR) of developing psychosis. Furthermore, people at UHR of psychosis had increased erythrocyte sphingomyelin (SM) and reduced phosphatidylethanolamine (PE) concentrations as w...

In adults, anxious depression has been identified as a more severe form of major depressive disorder (MDD), associated with higher depression severity, more suicidal ideation and worse treatment outcome. Research in pediatric depression, however, has been sparse. 126 children and adolescents aged 8–18 years with a primary diagnosis of MDD were cate...

Background: NEURAPRO was a multicenter, placebo-controlled trial of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) (fish oil) in 304 individuals at ultra-high risk for psychotic disorders. The study failed to show benefits of n-3 PUFAs over placebo. Although the randomized controlled trial design is placed at the top of the evidence hi...

Population-based data suggest that high intake of omega-3 (n-3) polyunsaturated fatty acids (PUFA) may be beneficial in a variety of health conditions. It is likely that mainly those patients with preexisting n-3 deficiency are those that benefit most from n-3 fatty acid supplementation. Therefore, for targeted interventions, a fast and reliable sc...

Despite over a century of intensive research, no single biological marker has successfully translated into daily clinical practice. A key challenge in psychiatric research is that traditional diagnostic categories represent phenomenological constructs that do not necessarily circumscribe a biological homogenous entity, but encompass a whole range o...

Background: Elevated homocysteine is observed in schizophrenia and associated with illness severity. The aim of this study was to determine whether vitamins B12, B6, and folic acid lower homocysteine and improve symptomatology and neurocognition in first-episode psychosis. Whether baseline homocysteine, genetic variation, sex, and diagnosis intera...

People classified as ultra-high risk (UHR) of developing psychosis have reduced cellular membrane omega-3 and omega-6 polyunsaturated fatty acids (PUFA). We aimed to compare omega-3 index, fatty acids and molecular phospholipid species from erythrocytes of people with UHR (n = 285) with age-matched healthy controls (n = 120) assessed by mass spectr...

Background Deficiencies in membrane polyunsaturated fatty acids (PUFA) such as omega-3 (n-3) fatty acids are thought to contribute to the pathophysiological processes underlying psychotic disorders. Emerging evidence suggests that the levels of PUFA are related to clinical symptoms but significant heterogeneity exists between studies. Here, we inve...

This study reports a medium-term follow-up of a randomised, double-blind, placebo-controlled trial of omega-3 polyunsaturated fatty acids (PUFA) in ultra-high risk for psychosis (UHR) patients. Primary outcomes of interest were transition to psychosis and symptomatic and functional outcome. A secondary aim was to investigate clinical predictors of...

Background: Neurocognitive impairments experienced by individuals at ultra-high risk (UHR) for psychosis are potential predictors of outcome within this population, however there is inconsistency regarding the specific neurocognitive domains implicated. This study aimed to examine whether baseline neurocognition predicted transition to psychosis,...

BACKGROUND No established treatment algorithm exists for patients with schizophrenia. Whether switching antipsychotics or early use of clozapine improves outcome in (first-episode) schizophrenia is unknown. METHODS This three-phase study was done in 27 centres, consisting of general hospitals and psychiatric specialty clinics, in 14 European countr...

In the last decade, there is an increasing application of induced pluripotent stem cells (iPSCs) for disease modelling. The iPSC technology enables the study of patient-specific neuronal cell lines in vitro to evaluate dysfunction at the cellular level and identify the responsible genetic factors. This approach might be particularly valuable for fi...

Background: No established treatment algorithm exists for patients with schizophrenia. Whether switching antipsychotics or early use of clozapine improves outcome in (first-episode) schizophrenia is unknown. Methods: This three-phase study was done in 27 centres, consisting of general hospitals and psychiatric specialty clinics, in 14 European c...

Considerable research has been conducted seeking risk factors and constructing prediction models for transition to psychosis in individuals at ultra-high risk (UHR). Nearly all such research has only employed baseline predictors, i.e. data collected at the baseline time point, even though longitudinal data on relevant measures such as psychopatholo...

Background Ever since the establishment of strategies for identifying people at ultra-high risk (UHR) of developing psychosis about twenty years ago, much research has been conducted in seeking risk factors and in developing prediction models for predicting which UHR individuals will actually make a transition to psychosis. The goal is to provide s...

Background Adherence to a medication is generally defined as the extent to which patients take medications as prescribed by their health care providers. Poor adherence to study medication is not uncommon posing a major challenge to treatment trails. However, poor adherence may not be randomly distributed but rather be associated with demographic or...

Background Converging evidence suggests that people at ultra-high risk (UHR) for psychosis have depleted levels of several fatty acids (FAs), and that changes in omega-3 (n-3) FA levels may indicate a higher risk for transition to psychosis. However, limited information is available on how FA deficiencies relate to psychopathology in individuals wi...

Background Neurocognitive impairments are a core feature of psychosis and major depressive disorder (MDD) and are associated with poorer functioning outcomes in these illnesses. Individuals at ultra-high risk (UHR) for psychosis have been shown to experience mild but significant cognitive impairments relative to healthy controls. Evidence suggests...

Background The NEURAPRO multicentre randomised controlled trial (RCT) of long-chain polyunsaturated omega-3 fatty acids (ω-3 PUFAs) (‘fish oil’) in combination with high-quality psychosocial intervention (cognitive behavioural case management [CBCM]) vs. placebo in combination with CBCM in young people at ultrahigh risk (UHR) of psychosis showed th...

Background: Traditionally, research in the ultra-high risk (UHR) for psychosis population has focused on the treatment of existing symptomatology and prevention of transition to psychosis. Recently, there has been an increase in focus on outcomes in individuals who do not transition to psychosis. However, there is a lack of standardised definition...

Attention-deficit hyperactivity disorder (ADHD) is one of the highest prevalent psychiatric disorders and has a major lifetime impact [1]. Despite tremendous research efforts, the exact causative mechanisms of this neurodevelopmental disorder still have to be elucidated. One major challenge is the difficulty to reflect the complexity and simultaneo...

Background: Cognitive-behavioural therapy (CBT) is the first-choice treatment in clients with ultra-high risk (UHR) for psychosis. However, CBT is an umbrella term for a plethora of different strategies, and little is known about the association between the intensity and content of CBT and the severity of symptomatic outcome. Methods: A sample o...

Objective: Ventricular enlargement is common in established schizophrenia; however, data from ultra high-risk for psychosis and first-episode psychosis studies are inconclusive. This study aims to investigate ventricular volumes at different stages of psychosis. Methods: Ventricular volumes were measured using a semi-automated and highly reliabl...

Background: The NEURAPRO-E trial is a randomized controlled multicenter trial of long-chain omega-3 polyunsaturated fatty acids in 304 young people at clinical risk of psychosis. The trial failed to replicate the earlier single-center trial in 81 participants (the Vienna omega-3 study). This analysis aims to investigate if antidepressant (AD) use d...

Background: A number of interventions have been trialed in the ultra-high risk for psychosis population with the aim of preventing onset of psychotic disorder and improving outcomes. Among the most promising has been dietary supplementation with long-chain omega-3 polyunsaturated acids (PUFA), which in a single-center study involving 81 participant...

Importance: A promising treatment to prevent onset and improve outcomes in patients at ultrahigh risk for psychosis is dietary supplementation with long-chain ω-3 polyunsaturated fatty acids (PUFAs). Objective: To determine whether treatment with ω-3 PUFAs in combination with a high-quality psychosocial intervention (cognitive behavioral case ma...

Paola Bozzatello et al. [1] have done a comprehensive qualitative review of the potential use of long-chain polyunsaturated fatty acids in the prevention and treatment of mental disorders.[...].

Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble...

Background: Most studies provide evidence that the skin flush response to nicotinic acid (niacin) stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR) phase of psychotic disorders. Methods: We compared visual ratings of niacin sensitivity between adolescents at UHR for psyc...