Helge Frieling

Hannover Medical School | MHH · Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie

Introduction Precision medicine in psychiatry is still in its infancy. To establish patient-tailored treatment, adequate indicators predicting treatment response are required. Electroconvulsive therapy (ECT) is considered one of the most effective options for pharmacoresistant major depressive disorder (MDD), yet remission rates were reported to be...

The significance of neurological soft signs (NSS) in major depressive disorder (MDD) remains unclear and the stability of NSS in relation to antidepressant treatment has never been investigated. We hypothesized that NSS are relatively stable trait markers of MDD. We thus predicted that patients show more NSS than healthy controls, irrespective of i...

Objective: To investigate the frequency and characteristics of adverse drug reactions (ADRs) that occurred on the gerontopsychiatric ward of Hannover Medical School over a 6-year period. Design: Retrospective monocentric cohort study. Results: Six hundred thirty-four patient cases (mean age 76.6 ± 7.1 years; 67.2% female) were analysed. In tot...

Alcohol abuse accounts for 3.3 million deaths annually, rendering it a global health issue. Recently, fibroblast growth factor 2 (FGF-2) and its target, fibroblast growth factor receptor 1 (FGFR1), were discovered to positively regulate alcohol-drinking behaviors in mice. We tested whether alcohol intake and withdrawal alter DNA methylation of Fgf-...

Aims: The dopamine receptor D2 (DRD2) is substantially involved in several forms of addiction. In addition to genetic polymorphisms, epigenetic mechanisms have emerged as an important means of regulation. Previously, DRD2 hypo- and hyper-methylation have been observed in alcohol use disorder (AUD). Blood samples are commonly used as a surrogate ma...

Background: This study sought to investigate the frequency and characteristics of duplicate prescriptions (DPs) in elderly psychiatric inpatients using a novel categorisation of DPs that differentiates between appropriate duplicate prescriptions (ADPs) and potentially inappropriate duplicate prescriptions (PIDPs). Methods: The study was conducte...

Objective: Geriatric patients account for a significant proportion of the collective treated by psychiatric consultation service in hospitals. In the Emergency Department (ED), psychotropic drugs are frequently recommended, notwithstanding their extensive side-effect profiles. This study sought to investigate medication safety of geriatric patient...

Background BDNF exon IV promoter methylation is a potential biomarker for treatment response to antidepressants in MDD. We have previously shown CpG-87 methylation as a successful biomarker for the prediction of non-response to monoaminergic antidepressants like the SSRI Fluoxetine or the SNRI Venlafaxine. This study aimed to dissect the biological...

Schizophrenia is highly heritable and aggregating in families, but genetics alone does not exclusively explain the pathogenesis. Many risk factors, including childhood trauma, viral infections, migration, and the use of cannabis, are associated with schizophrenia. Adolescence seems to be the critical period where symptoms of the disease manifest. T...

Background Different functional somatic syndromes (FSS), fibromyalgia (FMS) and other unexplained painful conditions share many common clinical traits and are characterized by troubling and functionally disabling somatic symptoms. Chronic pain is most frequently reported and at the center of patients’ level of disease burden. The construct of multi...

Major depressive disorder (MDD) and bipolar disorder (BD) are psychiatric disorders with a high morbidity and mortality. Both disease entities share in common that there are statistically relatively low response and remission rates after a first monotherapeutic medication trial (regarding the treatment of depressive episode in MDD and BD as well as...

The menstrual cycle is characterized by various hormonal alterations and associations with mental and physical conditions have been postulated. Among endocrine factors, the androgen system has been a target of major interest in males and to a lesser extent in females and may influence emotion, cognition, behavior and somatic factors. Only few studi...

Apart from Alzheimer’s disease (AD), no biomarkers for the differential diagnosis of dementia have been established to date. Inflammatory processes contribute to the pathogenesis of dementia subtypes, e.g., AD or frontotemporal dementia (FTD). In the context of cancer or cardiovascular diseases, white blood cell (WBC) populations and platelet count...

Adverse drug reactions (ADRs) constitute a frequent cause of hospitalization in older people. The risk of ADRs is increased by the prescription of potentially inappropriate medications for older people (PIMs). The PRISCUS list and the FORTA classification represent established tools to detect PIMs. The aim of the present study was to examine the pr...

Background Prader–Willi syndrome (PWS) is a rare neurodevelopmental disorder based on a loss of paternally expressed genes in chromosome segment 15q11-13. Behavioral traits such as temper outbursts, stereotypic, and ritualistic behavior, as well as an increased risk of psychosis accompany the syndrome, representing a major issue in the treatment of...

Objectives: Information on medication-related problems (MRPs) in elderly psychiatric patients is scarce. In the present study, we analyzed the frequency and characteristics of MRPs in patients ≥60 years treated on the gerontopsychiatric ward of Hannover Medical School in 2019. Methods: Taking advantage of an interdisciplinary approach, two indep...

Die Ätiologie der Adipositas ist multifaktoriell. Soziale Umweltfaktoren, wie Werbung oder Konsumdruck, und stoffliche Umweltfaktoren, wie Fortbewegungsmittel, Architektur und die ständige Verfügbarkeit hochkalorischer Nahrung haben eine „obesogene“ Umwelt geschaffen, die adipogene Verhaltensweisen fördert. Dazu zählen Verzehr großer, hochkalorisch...

Obwohl über lange Jahre hinweg die Ätiologie der Essstörungen und speziell der Anorexia nervosa (AN) als überwiegend psychosozial determiniert angesehen wurde, zeigten formal- und molekulargenetische Untersuchungen der letzten Jahre (Exkurs: Molekulargenetische Forschungsansätze), dass erblichen Einflüssen ebenfalls eine erhebliche Bedeutung zukomm...

BACKGROUND Prader-Willi syndrome (PWS), a neurodevelopmental disorder resulting from the loss of paternally derived but maternally imprinted genes in chromosomal region 15q11-13, is typically associated with marked hyperphagia leading to massive obesity if food intake is not controlled. The hyperphagia-related behavior is currently attributed mainl...

Prader-Willi syndrome (PWS) is associated with severe hyperphagia, a specific behavioral phenotype and a high risk for developing psychotic episodes. Despite intense research, how genes within the PWS locus contribute to the phenotype remains elusive. In this study, we sequenced the whole genomes of 20 individuals with PWS using long-read nanopore...

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder based on a loss of paternally expressed but maternally imprinted genes in chromosome region 15q11-13. PWS individuals typically show insatiable appetite with subsequent obesity representing the major mortality factor unless food intake is inhibited. The neurobiological basis of PWS-t...

This study investigated the recently reported association between alcohol dependence and accelerated ageing and the potential effects of abstinence and relapse on DNA methylation status using Levine's epigenetic clock to estimate DNA methylation age in two independent cohorts. The first sample comprised 88 (15 female) detoxi-fied patients with alco...

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder caused by a loss of usually paternally expressed, maternally imprinted genes located on chromosome 15q11-q13. Individuals with PWS display a specific behavioral phenotype and have a higher susceptibility than the general population for certain psychiatric conditions, especially psych...

IntroductionSeveral studies reported dysregulated protein levels of brain-derived neurotrophic factor (BDNF) in smokers and during cessation. However, the epigenetic regulation of the BDNF gene has not yet been investigated. We measured the plasma levels of BDNF and the epigenetic regulation of exon IV of the BDNF gene in smokers compared to health...

Background: BDNFIV promoter methylation is a potential biomarker for treatment response to antidepressants in MDD. We have previously shown CpG-87 methylation as a successful biomarker for prediction of non-response to monoaminergic antidepressants like the SSRI Fluoxetine or the SNRI Venlafaxine. This study aimed to dissect the biological evidenc...

Introduction: The heat and redox-sensitive ion channel TRPM2 was reported to be a causative mechanism for depression in a mouse model and to be upregulated in the hippocampus in patients suffering from depressive disorders. TRPM2 may thus be a novel target for antidepressants, but so far, selective TRPM2-inhibitors have not yet been developed. In...

Major depressive disorder (MDD) is frequently associated with poor response to treatment. Common antidepressants target neurotransmission and neuronal plasticity, which require adequate energy supply. As imaging studies indicate disturbances in central energy metabolism, and caloric restriction improves neuroplasticity and impacts mood and cognitio...

Drug-inducible suicide systems may help to minimize risks of human induced pluripotent stem cell (hiPSC) therapies. Recent research challenged the usefulness of such systems since rare drug-resistant subclones were observed. We have introduced a drug-inducible Caspase9 suicide system (iCASP9) into the AAVS1 safe harbor locus of hiPSCs. In these cel...

We investigated stability and change of plasma and urinary oxytocin as well as OXTR DNA methylation patterns through psychotherapy. Furthermore, we explore the potential impact of inpatient psychotherapy on oxytocin-related biomarkers and vice versa by differentiating patients who remitted from depression versus non-remitters. Blood and urine sampl...

Obesity is often accompanied by major depressive disorder (MDD), and vice versa. Latest research findings suggest the body mass index (BMI) to play a role in antidepressant treatment response in general. Our study aims to examine whether adiposity-related parameters such as BMI, glucose homeostasis, or serum lipids are associated with remission to...

Psychotic disorders often run a chronic course and are associated with a considerable emotional and social impact for patients and their relatives. Therefore, early recognition, combined with the possibility of preventive intervention, is urgently warranted since the duration of untreated psychosis (DUP) significantly determines the further course...

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder based on a loss of paternally expressed but maternally imprinted genes in chromosome region 15q11-13. During child development, PWS usually results in insatiable appetite with subsequent obesity representing the major mortality factor. The neurobiological basis of PWS-typical hyperph...

Background: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder caused by a loss of usually paternally expressed, maternally imprinted genes located on chromosome 15q11-q13. Individuals with PWS display a specific behavioral phenotype and have a higher susceptibility than the general population for certain psychiatric conditions, espe...

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder based on a loss of paternally expressed genes in chromosome region 15q11-13. In addition to typical characteristics such as hyperphagia, PWS is evidenced by a certain behavioral phenotype. Common indicators are repetitive behaviors, temper tantrums, and self-injurious behaviors such...

An amendment to this paper has been published and can be accessed via the original article.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease leading to degeneration of motor neurons (MNs). Epigenetic modification of gene expression is increasingly recognized as potential disease mechanism. In the present study we generated motor neurons from induced pluripotent stem cells from ALS patients carrying a mutation in the fu...

Background Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder caused by the absence of paternally expressed and maternally imprinted genes on chromosome 15q 11.2–13. It is associated with a certain behavioural phenotype, especially temper outbursts with verbal and physical aggression towards others. Recent studies show a promising th...

Background Based on findings in the brain stems of SIDS victims, the serotonin transporter (5-HTT) gene has been discussed to be associated with SIDS. Methods In the largest study to date, we investigated the promoter length (5-HTTLPR) and intron 2 VNTR polymorphisms in 274 cases and 264 controls and the Ile425Val polymorphism in 65 cases and 64 c...

Numerous studies have shown associations between anomalies of the serotonergic system and impulsive behavior, depression, or traumatic life events. However, it is currently unknown, whether pedophilia or child sexual offending (CSO) is also related to alterations of the serotonergic system. Using a two by two factorial paradigm within a multisite c...

Bisulfite sequencing has long been considered the gold standard for measurement of DNA methylation at single CpG resolution. In the meantime, several new approaches have been developed, which are regarded as less error-prone. Since these errors were shown to be sequence-specific, we aimed to verify the methylation data of a particular region of the...

We examined potential changes in catecholamine plasma levels and cortisol serum levels in 29 patients with treatment-resistant Major Depressive Disorder (MDD) during a course of electroconvulsive therapy (ECT). Blood samples were taken at three different time points: directly before (T1) and 15 min after (T2) the first ECT, and directly before the...

Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially met...

Background Both atrial natriuretic peptide (ANP) and vasopressin (VP) influence alcohol intake and withdrawal as well as craving and are also regulated by epigenetic factors. Disturbances in expression and promoter methylation status have been described in patients suffering from alcohol use disorder and alcohol withdrawal therapy. Objectives In t...

We describe the case of a 59‐year‐old woman who exhibited psychotic symptoms, cognitive dysfunction, and restlessness. While the clinical picture and 18F‐FDG PET/CT suggested the presence of a tauopathy, especially frontotemporal dementia or progressive supranuclear palsy, genetic testing eventually revealed Huntington's disease. We describe the ca...

Studies show that psychiatric symptoms in adults and children are sometimes associated with serum neural autoantibodies. The significance of serum neural autoantibodies associated with psychiatric symptoms in children remains often unclear, but might be relevant for the extent and occurrence of psychiatric disease manifestation in later life, as we...

Background: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder caused by the absence of paternally expressed and maternally imprinted genes on chromosome 15q 11.2-13. It is associated with a certain behavioural phenotype with repetitive and ritualistic behaviours, skin-picking and temper outbursts. Temper outbursts are characterized...

Viral encephalitis often presents with severe illness, headache, fever, behavioral changes, altered level of consciousness, and focal neurologic deficits. One of the most feared kind of virus encephalitis is herpes simplex encephalitis; however, other central virus infections are also capable of presenting with psychiatric symptoms. Here, we report...

ZUSAMMENFASSUNG Während interdisziplinäre Visitenmodelle in operativen Disziplinen wie der Unfallchirurgie nachweislich die Patientenversorgung verbessern, sind vergleichbare Visitenkonzepte in der klinischen Psychiatrie bisher nicht regelhaft etabliert. In der vorliegenden Arbeit präsentieren wir Ergebnisse der an unserer Klinik als Pilotprojekt i...

Structural and functional abnormalities in the cerebellar midline region, including the fastigial nucleus, have been reported in neuropsychiatric disorders, also comprising the cerebellar cognitive affecting syndrome. In rats, early fastigial lesions reduce social interaction during development and lead to cognitive and emotional deficits in adults...

Background Prader–Willi syndrome (PWS) is a rare genetic disorder that in many cases is associated with mental health disorders, in addition to characteristic symptoms such as hyperphagia. The current Sars‐CoV‐2 coronavirus pandemic has led to massive restrictions in health care and social life worldwide. People with PWS represent a particularly vu...

Background: The model of neuroinflammation has been proposed as a possible explanation of depression. Investigations of serum levels of tumor necrosis factor-α (TNF-α) in depressed patients have previously shown contradictory results of increased and decreased levels of TNF-α during the treatment of depression. Methods: We compared the serum lev...

Introduction: DNA methylation constitutes one important epigenetic mechanism that regulates gene expression in human cells. With regard to obesity, bariatric surgery-induced weight loss has been associated with promoter methylation changes in several genes. Hyperleptinemia is a characteristic feature of obesity. The underlying regulating mechanism...

Prader–Willi syndrome (PWS) is a rare neurodevelopmental disorder caused by lack of the paternal copy of maternally imprinted, paternally expressed genes at the chromosome 15q11‐13 region. In most cases, it is caused by a paternal deletion or a maternal disomy of chromosome 15. Behavioral problems with temper outbursts are common and often combined...

Background: Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract associated with abdominal pain and diarrhea. Pain caused by Crohn's disease likely involves neurogenic inflammation which seems to involve the ion channel transient receptor potential ankyrin 1 (TRPA1). Since the promoter methylation of TRPA1 was shown to...

Background Autoimmune-mediated encephalitis is a disease that often encompasses psychiatric symptoms as its first clinical manifestation’s predominant and isolated characteristic. Novel guidelines even distinguish autoimmune psychosis from autoimmune encephalitis. The aim of this review is thus to explore whether a wide range of psychiatric symptom...

Background The benefits and risks of treatment with antipsychotics during pregnancy must be weighed up carefully and individually because antipsychotics can penetrate the placental barrier and prescription is off-label.Objective Evaluation of the risks and benefits of administering antipsychotics during pregnancy or for women who wish to become pre...

Epigenetic mechanisms, which modulate gene expression, are becoming increasingly important in the research on anorexia nervosa (AN). Patients with AN have difficulties with the perception of hunger even though hormones like high ghrelin and low leptin signal the need for energy intake. Given the prominent role of the growth hormone secretagogue rec...

Background: Major depressive disorder (MDD) represents a serious global health concern. The urge for efficient MDD treatment strategies is presently hindered by the incomplete knowledge of its underlying pathomechanism. Despite recent progress (highlighting both genetics and the environment, and thus DNA methylation, to be relevant for its develop...