Gregor Hasler

• Professor of Psychiatry, M.D.
• Chair at University of Fribourg

Rationale Psilocybin shows promise for treating neuropsychiatric disorders. However, insight into its acute effects on cognition is lacking. Given the significant role of executive functions in daily life and treatment efficacy, it is crucial to evaluate how psilocybin influences these cognitive domains. Objectives This meta-analysis aims to quant...

Background The Hallucinogen Rating Scale (HRS) has been widely used to measure the subjective effects of psychedelics and other psychoactive substances. Its advantages include a basis in phenomenological interviews and clinical studies, straightforward items, and broad coverage of psychedelic effects. Previous studies have attempted to resolve its...

Background Peripheral levels of brain-derived neurotrophic factor (BDNF) are often used as a biomarker for the rapid plasticity-promoting effects of ketamine, psychedelics, and other psychoplastogens in humans. However, studies analyzing peripheral BDNF after psychoplastogen exposure show mixed results. In this meta-analysis, we aimed to test wheth...

Objective: To identify the COVID-19 impact on well-being/mental health, coping strategies and risk factors in adolescent worldwide. Method: Anonymous online multi-national/language survey in the general population (representative/weighted non-representative samples, 14-17years), measuring change in well-being (WHO-5/range=0-100) and psychopathology...

Social cognitive deficits and social behavior impairments are common in major depressive disorder (MDD) and affect the quality of life and recovery of patients. This review summarizes the impact of standard and novel treatments on social functioning in MDD and highlights the potential of combining different approaches to enhance their effectiveness...

There is no multi-country/multi-language study testing a-priori multivariable associations between non-modifiable/modifiable factors and validated wellbeing/multidimensional mental health outcomes before/during the COVID-19 pandemic. Moreover, studies during COVID-19 pandemic generally do not report on representative/weighted non-probability sample...

Background Psychedelic-assisted therapy (PAT) is permitted in Switzerland under its limited medical use program. Data from patients in this program represent a unique opportunity to analyze the real-world practice of PAT. Aims This study compared the subjective effects of lysergic acid diethylamide (LSD) and psilocybin between patients undergoing...

Introduction: Studies of psychedelic-assisted therapy with LSD, psilocybin, MDMA, and related substances show clinical promise but inadequately assess side effects. Measuring side effects is challenging because they are not always easily differentiated from treatment effects or disease symptoms and show high heterogeneity, variable duration and imp...

Background Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of...

Though microdosing psychedelics has become increasingly popular, its long-term effects on cardiac health remain unknown. Microdosing most commonly involves ingesting sub-threshold doses of lysergic acid diethylamide (LSD), psilocybin, or other psychedelic drugs 2–4 times a week for at least several weeks, but potentially months or years. Concerning...

International studies measuring wellbeing/multidimensional mental health before/ during the COVID-19 pandemic, including representative samples for >2 years, identifying risk groups and coping strategies are lacking. COH-FIT is an online, international, anonymous survey measuring changes in well-being (WHO-5) and a composite psychopathology P-score...

Major depressive disorder (MDD) is one of the most common neuropsychiatric disorders, with symptoms including persistent sadness and loss of interest. MDD is associated with neurochemical alterations in GABA, glutamate, and glutamine levels but, to date, few studies have examined changes in glutathione (GSH) in MDD. This study investigated changes...

Background and Hypothesis Dysfunction of the dopamine system is the leading neurobiological hypothesis of schizophrenia. In this study, we tested this hypothesis in the context of aberrance salience theory of delusions using catecholamine depletion. We hypothesized that acute dopamine depletion improves both positive symptoms and salience attributi...

Eating disorders are serious illnesses showing high rates of mortality and comorbidity with other mental health problems. Psychedelic-assisted therapy has recently shown potential in the treatment of several common comorbidities of eating disorders, including mood disorders, post-traumatic stress disorder, and substance use disorders. The theorized...

This Viewpoint proposes methods for optimizing patient and therapist safety during psychedelic-assisted psychotherapy.

Deficits in socio-emotional reciprocity, in prosocial behavior and in developing social relationships are diagnostic criteria of autism spectrum disorder (ASD), usually assessed by self-report or observation. Simple social experiments developed by behavioral economists allow for quantification of ASD-related social behavior. In this study, we used...

Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome,...

Importance Major depressive disorder (MDD) is one of the most prevalent illnesses worldwide. Perturbations of the major inhibitory and excitatory neurotransmitters, γ-aminobutyric acid (GABA) and glutamate (Glu), respectively, as well as Glx (Glu or glutamine [Gln]) have been extensively reported in a multitude of brain areas of individuals with de...

The monoamine hypothesis has dominated research on the pathophysiology of mood disorders as well as the development of therapeutic drugs by over half a century. Nowadays a change of perspective is taking place. The glutamate system is increasingly implicated in the pathophysiology of mood disorders. The evidence spans from animal, post-mortem, imag...

Classic psychedelics, such as LSD, psilocybin, and the DMT-containing beverage ayahuasca, show some potential to treat depression, anxiety, and addiction. Importantly, clinical improvements can last for months or years after treatment. It has been theorized that these long-term improvements arise because psychedelics rapidly and lastingly stimulate...

Background: Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neu...

Toward the “helioscope” hypothesis of psychedelic therapy (ECNP Journal, Insights-invited authors only) Gregor Hasler, M.D. Stanislav Grof, the psychiatrist who pioneered psychedelics-assisted psychotherapy (PAP), considered psychedelics’ unpleasant acute effects part of the therapeutic process. He wrote: “Sedatives can do much harm in the course...

Patient-reported outcome (PRO) refers to measures that emphasize the subjective view of patients about their health-related conditions and behaviors. Typically, PROs include self-report questionnaires and clinical interviews. Defining PROs for borderline personality disorder (BPD) is particularly challenging given the disorder's high symptomatic he...

Rationale and Objectives Differences among psychedelic substances regarding their subjective experiences are clinically and scientifically interesting. Quantitative linguistic analysis is a powerful tool to examine such differences. This study compared five psychedelic substance report groups and a non-psychedelic report group on quantitative ling...

Background: Measures for the irregularity of the heartbeat, for example respiratory sinus arrhythmia, have been implicated as a measure for restorative functions of the vegetative nervous system. Methods: In the current observational study, we investigated 265 subjects, 70 of whom had a lifetime history of major depression, with a plethysmograph...

250/250 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 Outcome study on Health and Functioning during Infection...

Background Major depressive disorder (MDD) is a leading cause of disease burden and shows a marked sexual dimorphism. Previous studies reported changes in cerebral perfusion in MDD, an association between perfusion and dehydroepiandrosterone sulfate (DHEAS) levels, and large sex differences in perfusion. This study examines whether perfusion and DH...

Background Phenotypic heterogeneity is a major impediment to the elucidation of the neurobiology and genetics of bipolar disorder. Endophenotype could help in reducing heterogeneity by defining biological traits that are more direct expressions of gene effects. The aim of this review is to examine the recent literature on clinical, epidemiological,...

Background: Being the offspring of a parent with major depression disorder (MDD) is a strong predictor for developing MDD. Blunted striatal responses to reward were identified in individuals with MDD and in asymptomatic individuals with family history of depression (FHD). Stress is a major etiological factor for MDD and was also reported to reduce...

Background: Large-scale epidemiological studies demonstrate that house moves during adolescence lead to an increase in anxiety and stress-sensitivity that persists into adulthood. As such, it might be expected that moves during adolescence have strong negative and long-lasting effects on the brain. We hypothesized that moves during adolescence impa...

This review summarizes the evidence for the potential involvement of metabotropic glutamate receptor 5 (mGluR5) in the development of nicotine addiction. Nicotine is consumed worldwide and is highly addictive. Previous research has extensively investigated the role of dopamine in association with reward learning and addiction, which has provided st...

Conventional antidepressants have several important limitations, including a lack of direct effects on negative self-schema, which is at the core of Beck’s cognitive theory of depression. Based on previous studies showing a positive effect of ketamine on negative cognition, we compared reductions in negative self-schema between responders and non-r...

Sustained anxiety is a key symptom of anxiety disorders and may be associated with neural activation in the right inferior parietal lobe (rIPL), particularly under unpredictable threat. This finding suggests a moderating role of the rIPL in sustained anxiety, which we tested in the current study. We applied cathodal or sham transcranial direct curr...

Background The brain's major inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the brain-derived neurotrophic factor (BDNF) play important roles in several stress-related disorders. Magnetic resonance spectroscopy (MRS) allows for non-invasive quantification of GABA concentration in the brain. We investigated the relationship between G...

Bulimia nervosa (BN) shares central features with substance-related and addictive disorders. The metabotropic glutamate receptor subtype 5 (mGlu5) plays an important role in addiction. Based on similarities between binge eating and substance-related and addictive disorders, we investigated mGlu5 in vivo in 15 female subjects with BN and 15 matched...

Introduction: Anhedonia, a core symptom of Major Depressive Disorder (MDD), manifests as a lack or loss of motivation as reflected by decreased reward responsiveness, at both behavioral and neural (i.e., striatum) levels. Exposure to stressful life events is another important risk factor for MDD. However, the mechanisms linking reward-deficit and...

Background: Extensive literature has investigated the role of serotonin (5-HT) in the control of central dopamine (DA) systems, and their dysfunction in pathological conditions. 5-HT stimulates local DA release in striatal regions via activation of various receptors including serotonin receptor-3 (5-HT3). Several studies have related polymorphisms...

Using positron emission tomography (PET), a profound alteration of the metabotropic glutamate receptor 5 (mGluR5) was found in human smoking addiction and abstinence. As human PET data either reflect the impact of chronic nicotine exposure or a pre-existing vulnerability to nicotine addiction, we designed a preclinical, longitudinal study to invest...

Introduction: Reward and stress are important determinants of motivated behaviors. Striatal regions play a crucial role in both motivation and hedonic processes. So far, little is known on how cognitive effort interacts with stress to modulate reward processes. This study examines how cognitive effort (load) interacts with an unpredictable acute s...

In major depression, remission rate in response to monoaminergic antidepressant is around 50%. The lack of strong synergies between classical antidepressants and psychotherapy may be due to the molecular effects of classical antidepressants. They modulate synapses but they do not substantially influence synaptogenesis. They also increase brain-deri...

There is growing evidence for GABA and glutamate–glutamine dysfunction in the pathogenesis of mood and anxiety disorders. It is important to study this pathology in the early phases of the illness in order to develop new approaches to secondary prevention. New magnetic resonance spectroscopy (MRS) measures allow determining glutamine, the principal...

Background The integration of findings from phenomenological, behavioral and neuroscience studies is a major challenge to improve understanding and interventions in mental health disorders. Here, we propose an innovative way to investigate the complexity of family risk of major depression disorder by combining neuroscience and Self-determination Th...

Anhedonia is a core symptom of major depression disorder (MDD), associated with dysfunc8onal reward processing. Striatal regions play a crucial role in reward processing, while exposure to stressful life events and increased stress sensitivity are major precipitants of MDD, both linked to anhedonic behaviors. Diminished cognitive resources reflecte...

The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner...

Glutamate signaling plays a major role in addiction. Preclinical research strongly suggests an implication of G-protein-coupled metabotropic glutamate receptor subtype 5 (mGluR5) in nicotine addiction and alcohol use disorder. In humans, smoking is related to a global reduction in mGluR5 availability. In the present study, we investigated mGluR5 in...

With advances in technology, artificial agents such as humanoid robots will soon become a part of our daily lives. For safe and intuitive collaboration, it is important to understand the goals behind their motor actions. In humans, this process is mediated by changes in activity in fronto-parietal brain areas. The extent to which these areas are ac...

Introduction: Stress and reward are two important determinants of motivated behavior (Haber & Knutson, 2009; Ossewaarde et al., 2011). Experimentally induced acute stress affects reward-related neural responses to monetary reward, especially in the dorsal striatum (Porcelli et al., 2012). Striatal regions play a crucial role in reward processing (H...

The integration of reward magnitudes and effort costs is required for an effective behavioral guidance. This reward-effort integration was reported to be dependent on dopaminergic neurotransmission. As bulimia nervosa has been associated with a dysregulated dopamine system and catecholamine depletion led to reward processing deficits in remitted bu...

Einleitung: Die Beteiligung des Dopamin-Systems (DA) bei der Schmerzverarbeitung und bei Belohnungsprozessen wurde beschrieben. Das Fibromyalgie-Syndrom (FMS), welches durch Schmerzen in verschiedenen Körperarealen charakterisiert ist, kann mit depressiven Episoden assoziiert sein. Ein gestörter DA-Stoffwechsel und verminderte Reaktionen auf Belohn...

Rewards are important determinants of motivational behavior. In concert with the striatum, the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and precuneus are involved in reward processing (1–5). Recently, neuroimaging studies reported the effect of stress inductions on reduced brain activations in areas implicated in reward processi...

Background Deep brain stimulation (DBS) for refractory psychiatric disorders shows promising effects on symptom-reduction, however, little is known regarding the effects of DBS on social outcome. Methods A PubMed search based on original studies of DBS for psychiatric disorders [treatment resistant depression (TRD), Gilles de la Tourette's syndrom...

Objectives: Major Depressive Disorder (MDD) is one of the most common mental disorders worldwide and an important global burden in term of personal, familial, social, professional and economic impact. The World Health Organization (WHO) has defined the promotion of research investigating vulnerability to MDD as a priority. First grade relatives of...

Received: May 10, 2016 Accepted: January 08, 2017 Published online: May 11, 2017 Issue release date: May 2017

Bulimia nervosa has been associated with a dysregulated catecholamine system. Nevertheless, the influence of this dysregulation on bulimic symptoms, on neural activity, and on the course of the illness is not clear yet. An instructive paradigm for directly investigating the relationship between catecholaminergic functioning and bulimia nervosa has...

Introduction: To determine if mavoglurant (modified release) as an augmentation therapy to selective serotonin reuptake inhibitors (SSRIs) could have beneficial effects reducing Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score in patients with obsessive-compulsive disorder (OCD) resistant to SSRI treatment. Methods: This was a multicen...

Besides of conventional clinical and preclinical research and the mutual translation thereof, 'Computational Psychiatry' has emerged as an innovative novel research strategy in recent years. Its goal is to establish a scientific framework to integrate multidimensional molecular, cellular and systemic as well as psychological and social factors usin...

Zusammenfassung. Ein zentraler Aspekt vieler psychischer Erkrankungen ist die Storung eines oder mehrerer Entscheidungsfindungsprozesse in sozialen Interaktionen. Die neuartige Kombination aus okonomischer Spieltheorie und Neurowissenschaft ermoglicht es, aufgrund der Spieltheorie Abweichungen im Sozialverhalten psychischer Patienten „komputational...

Despite effective pharmacological and psychotherapeutic treatment options for depression, about one third of patients affected by depression prove resistant to therapy. The injection of botulinum toxin A (BTA) into the glabellar muscles of the forehead constitutes a new approach to treating depression. Such treatment exhibits relatively significant...

The metabotropic glutamate receptor 5 (mGluR5) is a promising drug target for the treatment of schizophrenia. In this study, we compared mGluR5 distribution volume ration (DVR) in subjects with schizophrenia and healthy controls. Given our previous findings, we matched samples for gender, age, and smoking status. Binding to mGluR5 was determined us...

Received: July 31, 2016 Accepted: July 31, 2016 Published online: October 15, 2016 Issue release date: October 2016

There is growing evidence that fear-learning abnormalities are involved in the development of posttraumatic stress disorder (PTSD) and chronic pain. More than 50% of PTSD patients suffer from chronic pain. This study aimed to examine the role of fear-learning deficits in the link between pain perception and PTSD. We included 19 subjects with PTSD a...

Depression is associated with social risk factors, social impairments and poor social functioning. This paper gives an overview of these social aspects using the NIMH Research and Domain Criteria ‘Systems for Social Processes’ as a framework. In particular, it describes the bio-psycho-social interplay regarding impaired affiliation and attachment (...

Introduction: Rewards are important determinants of motivational behavior. Striatal regions have been found to play a crucial role in reward processing. Recently, studies investigated whether stress affected the reactivity to reward, and showed that experimentally induced acute stress altered reward-related neural responses to monetary reward, espe...

Inconsistent social behavior is a core psychopathological feature of borderline personality disorder. The goal of the present study was to examine inconsistency in social decision-making using simple economic social experiments. We investigated the decisions of 17 female patients with BPD, 24 patients with major depressive disorder (MDD), and 36 he...

Background: Price's social competition hypothesis interprets the depressive state as an unconscious, involuntary losing strategy, which enables individuals to yield and accept defeat in competitive situations. Aims: We investigated whether patients who suffer from major depressive disorder (MDD) would avoid competition more often than either pat...

Background: Abundant evidence at the anatomical, electrophysiological, and molecular level implicates metabotropic glutamate receptors subtype 5 (mGluR5) in addiction. Consistently, the effects of a wide range of doses of different mGluR5 negative allosteric modulators (NAMs) have been tested in various animal models of addiction. Here, these studi...

Schizophrenia is a complex disorder, characterized by the interplay between genetic and environmental factors. Human endogenous retroviruses (HERVs), genetic elements that originated from infections by exogenous retroviruses millions of years ago, comprise ~8% of the human genome. Here, we provide a comprehensive review of accumulating evidence, de...

Dopamine D2/D3 receptor availability at rest and its association with individual pain perception was investigated using the [(11)C] raclopride PET-method in 24 female Fibromyalgia (FMS) participants with (FMS+, N=11) and without (FMS-, N=13) comorbid depression and in 17 healthy women. Thermal pain thresholds (TPT) and pain responses were assessed...

Background The objective of this article is to give an overview of the advantages and disadvantages of the use of depot antipsychotics in the treatment of schizophrenia. The focus is on efficacy, tolerability, relapse prevention, patient compliance and satisfaction compared to oral administration forms. Material and methods A literature search was...

In the present review, we deliver an overview of the involvement of metabotropic glutamate receptor 5 (mGluR5) activity and density in pathological anxiety, mood disorders and addiction. Specifically, we will describe mGluR5 studies in humans that employed Positron Emission Tomography (PET) and combined the findings with preclinical animal research...

Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catecholaminergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increas...

Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catecholaminergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increas...

Nicotine addiction is a major public health problem and is associated with primary glutamatergic dysfunction. We recently showed marked global reductions in metabotropic glutamate receptor type 5 (mGluR5) binding in smokers and recent ex-smokers (average abstinence duration of 25 weeks). The goal of this study was to examine the role of mGluR5 down...

In bipolar disorders, there are unclear diagnostic boundaries with unipolar depression and schizophrenia, inconsistency of treatment guidelines, relatively long trial-and-error phases of treatment optimization, and increasing use of complex combination therapies lacking empirical evidence. These suggest that the current definition of bipolar disord...

Introduction: This report from the World Psychiatric Association Section on Pharmacopsychiatry examines the possible relationship of antiepileptic drugs with suicide-related clinical features and behaviors in patients with epilepsy. Materials and methods: A systematic review of the MEDLINE search returned 1039 papers, of which only 8 were consid...

Background: A relationship between bulimia nervosa (BN) and reward-related behavior is supported by several lines of evidence. The dopaminergic dysfunctions in the processing of reward-related stimuli have been shown to be modulated by the neurotrophin brain derived neurotrophic factor (BDNF) and the hormone leptin. Methods: Using a randomized, dou...