dr. B.C.M. (Benno) Haarman

Innovative treatment for Mood Disorders

The University Medical Center Groningen is the tertiary health care facility for more than 4 million people in the northern region of the Netherlands. The hospital hosts a unique combination of world-wide renowned excellent research centers in the fields of molecular and neuroimaging, microbiota-host interaction and microbiome. As Head of the Mood and Anxiety Disorder Program of the Department of Psychiatry of the UMCG, I strive every day to bring out the best in our clinical and research teams to face up to challenge the gap between basic neuroscience and clinical psychiatry. My desire to constantly improve my academic skills and energizing those of my colleagues, has led to important new insights into the pathophysiology of mood disorders, and has contributed significantly to expand our center’s innovative excellence. Under my leadership, the Program now bridges the gap between scientific research and patient care on cutting edge psychotherapeutic (CBASP), psycho-stimulating (ketamine, psylocybin), neurostimulating (rTMS, DBS) and chronotherapeutic treatment modalities. With the ambition to cater for the unmet needs of suffering patients, we develop and refine novel treatments for subsequent dissemination into the general field of psychiatry.

Psychosurgery

In a joint collaborative effort the departments of neurosugery and psychiatry of the UMCG will add deep brain stimulation (DBS) to the existing treatment arsenal for patients with severe obsessive compulsive disorder later this year. Within this collaboration we currently explore other psychosurgical treatment options for future  implementation.

MOODINFLAME / PSYCHAID / MOODSTRATIFICATION consortium

MOODINFLAME

In MOODINFLAME a new model of the origin, development and progress of mood disorders was constructed, based on studies of animal model systems and advanced assays to detect immune imbalances in patients and individuals at risk for major mood disorders. The imbalances reflect an abnormal equilibrium between neuronal cells, hormones and cells of the immune system in the brain (including microglia, macrophages and T cells), resulting in an abnormal proneness to inflammation in both the brain as well as in peripheral tissues (since the equilibrium is also disturbed in all sorts of organs and tissues outside the brain). In the model the investigators identify two stages in the development of a severe mood disorder. In the first stage there are not yet symptoms of a mood disorder, but there are already biological markers of an abnormal equilibrium of the T cell system in general, which disturbs the interaction between the endocrine (=hormone) system, the immune system and the neurological system. This results in a disturbed development of the brain, in particular in areas important for mood regulation, learning and an adequate responsiveness to stress. 

Research in Groningen contributed to relevant publications that demonstrated (1) An increased monocyte gene expression in BD patients while having a mood episode; (2) A possible relation between monocyte gene expression and manic symptomatology in BD; (3) Patients with BD demonstrated increased [11C]-(R)-PK11195 (microglia activation) in the hippocampus, compared to healthy controls; (4) Using DTI scans, patients with BD taking lithium demonstrated a higher fractional anisotropy and lower radial diffusivity, compared to patients not taking lithium.

PSYCHAID

The immune and endocrine (=hormone level) tests used in MOODINFLAME were further refined, validated and sometimes already registered in PSYCH-AID, in combination with the results of another EU-FP7 project: SchizDX. These laboratory tests focused on immune functions reflecting the imbalanced immune system and the activated inflammatory response system in conjunction with an abnormal neuro -endocrine equilibrium. The aim of PSYCH-AID was the development of clinically applicable blood assays identifying patients and other individuals with such altered neuro-immuno-endocrine profile and at risk for major depressive disorder and bipolar disorder. To realize this, the efforts of academia and industry were combined in a cooperation with 9 European partners, excelling in this field: 5 academia and 4 SME’s.

MOODSTRATIFICATION

At the moment 12 European research institutes cooperate in the project MOODSTRATIFICATION (https://moodstratification.eu). The research teams look for refined immune signatures in patients with unipolar and bipolar depressions, by further exploring the MOODINFLAME data and other datasets in more detail. The background hypothesis in this project is that a large proportion of recurrent and severe mood disorders are caused by the single action or the combination of:

1. (Inborn and acquired) T cell imbalances which result in mal development and functioning of the brain, and lead to flares of chronic inflammation, further impacting brain function
2. Childhood trauma (mainly emotiona and sexual) leading to a high inflammatory state of the immune system.

The aim of the MOODSTRATIFICATION project is to develop further evidence for this hypothesis and to develop simple blood tests to measure the above mentioned immune imbalances in clinical practice. Also various therapy trials will take place with T cell enforcing and anti-inflammatory treatments on patients with mood disorders and T cell imbalances.

In a novel RCT starting in 2021, we will explore the effect of an 8 week moderate intensity indoor cycling intervention on the aging of the immune system in patients with bipolar disorder.

ENIGMA - BD

The ENIGMA Consortium is an international effort by leaders worldwide. The Network brings together researchers in imaging genomics, neurology and psychiatry, to understand brain structure and function, based on MRI, DTI, fMRI, genetic data and many patient populations. The ENIGMA-BD working group (http://enigma.ini.usc.edu/ongoing/enigma-bipolar-working-group/) coordinates the execution of these analyses for bipolar disorder.

GUTS / No Guts, No Glory

For patients with a bipolar or psychotic disorder, recent investigations have pointed to the gut-brain axis as a new venue for treatment, with increased inflammation stemming from increased intestinal permeability to further affect brain functioning in a significant subset of patients. Probiotics are promising candidates to improve patients’ symptomatology and functioning and there are rational methods to personalize its application with accessible and tolerable predictive biomarkers.

In a double blind randomized controlled trial, funded by Stanley Medical Research Institute (18T-004) and ZonMW (636320010); GUTS RCT, having started in 2019, we examine the effect of the probiotic product Ecologic Barrier (Winclove Probiotics, Amsterdam, the Netherlands) on symptom improvement in 145 patients with a psychotic disorder or with BD (approx. n=72). Ecologic Barrier is a probiotic formulation consisting of 9 bacterial strains, known to decrease intestinal permeability and to have an effect on the immune system in humans. Patients will be treated 12 weeks either with this probiotic formulation or placebo. Part of this study, intestinal permeability, intestinal inflammation and immunological measurements will be performed.

In the novel No Guts, No Glory study we will additionaly investigate the impact of a dietary intervention on the functioning of patients with bipolar disorder, psychotic disorders, Alzheimer's disease and Parkinson's disease. A personalized probiotic formulation will also be investigated, base on individual participant's organoids.

Combined chronotherapy in clinical practice

We recently published an article of a study from 26 depressed patients with major depressive disorder or bipolar disorder who received chronotherapy. In a follow-up study drs. S. Druiven investigates whether clinical treatment success can be predicted using actiwatch activity measurements and a patient diary, using both basic group statistical methods as more complex n=1 approach.