About

The overarching purpose of the Nielson lab is to understand and treat trauma. Research projects in the Nielson lab utilize a multidisciplinary approach, merging the fields of neurobiology, psychiatry and informatics to identify more precise "bio-types" of trauma psychopathology than traditional diagnostic criteria, and potential novel targets for treatment. We use established and emerging machine learning methods with multi-modal data spanning across a diverse range of diagnostic categories for neuropsychiatric disorders. Our approach is part of the rapidly growing field of computational psychiatry, where mental health data can be used to run hypotheses on in silico models to understand the complexity involved in these disorders. An advantage of such approaches is the minimization for the need to test hypotheses in animal models (in vivo). Dr. Nielson received an Early Stage Investigator (ESI) award from NIMH to apply these methods to large datasets from trauma-exposed patients to identify and validate dimensions of post-traumatic stress (PTS), relevant biological predictors, and precision treatment response trajectories.

Other areas of focus in the Nielson lab are dedicated to psychedelic-assisted therapy (PATH) research and drug policy reform. Dr. Nielson has been collecting data through an anonymous online survey to assess benefits and risks of ayahuasca use in naturalistic settings to treat symptoms of trauma. Dr. Nielson is also investigating the therapeutic potential of psilocybin-assisted psychotherapy (PAP) to treat trauma-related mental health disorders. This work is funded by the newly created PATH Fund through the UMN Foundation, which was created thanks to a generous donation from the community. These, and other data, are part of a larger network of data supporting the potential for psychedelic therapies for the treatment of numerous mental health conditions (see network below). 

Donate to the PATH Fund!

 

Computational Psychiatry

Recent efforts to optimize diagnosis and treatment planning for psychiatric disorders through the Research Domain Criteria (RDoC) and ongoing clinical trials have generated large datasets housed in the NIMH Data Archive (NDA). The NDA is a valuable resource for data-driven discovery in mental health research. Data across multiple units of measure from a wide array of disorders are housed in the NDA. We will mine data from the NDA to characterize biotypes that span across diagnostic categories, and the complex constellation of symptoms and functional deficits that can be measured in individual patients.

Current computational psychiatry research projects include combining dimension reduction, causal analyses, machine learning and topological data analysis (TDA) to characterize subtypes and predictors of syndrome trajectories and treatment response.

Current datasets include:

1) De-identified data from the NIMH Data Archive (NDA)

  • Contains data from clinical research on a wide range of mental health disorders for transdiagnostic and precision treatment research (N > 250,000).
  • Standardized data can be queried across multiple domains for clinical/phenotype, neurophysiology, imaging, genomics, disorder-specific assessments and completed treatment trials.

2) Data from an anonymous online survey to assess the therapeutic uses of the plant medicine ayahuasca.

  • Contains structured data from questionnaire-based assessments related to symptoms of trauma, including PTSD, substance use, and depression.
  • Contains unstructured data from open-ended responses describing dangerous, beneficial and general experiences associated with ayahuasca use.

3) Neurotrauma datasets from animal models and de-identified observational clinical studies assessing complications associated with trauma exposure.

  • Preclinical (animal models) spinal cord injury (SCI) data from the Open Data Commons for SCI (ODC-SCI)
  • De-identified observational data from traumatic brain injury (TBI) patients through the TRACK-TBI study.
  • De-identified observational data from patients with post-traumatic stress disorder (PTSD), monitoring cardiovascular health during disease progression from the Mind Your Heart (MYH) study.

4) De-identified data from cognitive training interventions for schizophrenia

  • Assessments before and after training for cognitive and symptom changes
  • ELISA data from serum samples before and after training for blood-based biomarker discovery

5) De-identified data from the The National Survey on Drug Use and Health (NSDUH).

  • NSDUH contains data about the use of illegal drugs, alcohol, and tobacco, diagnosed mental disorders and related treatments within the U.S. population, ages 12 or older.  
  • Data tables available from 1979 to 2016.

 

The figure below illustrates a data-driven hypothesis that was found regarding functional decline in patients with PTSD following traumatic brain injury (TBI). Using a machine learning method known as topological data analysis (TDA), a gene involved in DNA repair was uncovered to have predictive value on functional outcome trajectories in a subgroup of patients with co-morbid PTSD and mild TBI.

PTSD TDA

Figure Legend. Network topology of patients with traumatic brain injury differentiates severity of brain pathology measured by both CT (A) and MRI (B), where most patients with a PTSD diagnosis 6 months (C) after injury have little to no obvious brain pathology (circled nodes). Highlighted patients show a decline in function between 3 (D) and 6 months (E) after injury, which was significantly predicted by enrichment for the A/T genotype of the PARP1 SNP (F, green nodes), a gene involved in DNA repair. Published in Nielson et al., 2017, PLoS One.

 

Psychedelic Therapy

Psychedelic therapy is undergoing a renaissance within the scientific arena, where an astounding volume of literature and data are emerging to support this new frontier in medicine. There is also increasing attention being paid in the popular press towards their therapeutic potential, including notable mediums like The New Yorker, NY Times, and Rolling Stone. While this added attention has helped in the re-birth of the scientific inquiry of psychedelics, it has also given rise to increased "underground" facilities that lead to exploitation of resources and harm to those seeking them out for psychological and spiritual support. 

Psychedelic therapy research in my lab focuses on collecting data from completed and ongoing psychedelic research studies to develop an evidence base for drug policy reform and treatment planning. Current projects include the development of a pilot study of psilocybin-assisted psychotherapy for treating trauma-related mental health disorders, and analysis of data from an anonymous online survey of ayahuasca users in naturalistic settings.

The network below is a model of overlapping symptoms of trauma, and the respective psychedelic therapies that have published research (red numbers and reference list) suggesting a therapeutic benefit.

Treatment network

 

References for psychedelic therapy network

 

1. LSD and psilocybin for end of life anxiety

Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review

Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer

Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases

LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy

 

2. LSD and psilocybin for cluster headaches

Response of cluster headache to psilocybin and LSD

Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey

Psychoactive substances as a last resort—a qualitative study of self-treatment of migraine and cluster headaches

 

3. Psilocybin for depression:

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression

Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression

Psilocybin with psychological support for treatment-resistant depression: six-month follow-up

Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression

 

4. Ayahuasca for depression:

Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study

Cortisol Modulation by Ayahuasca in Patients With Treatment Resistant Depression and Healthy Controls

Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

 

5. Ayahuasca for addiction:

Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada

Therapeutic effects of ritual ayahuasca use in the treatment of substance dependence--qualitative results.

Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans.

 

6. Ayahuasca for PTSD:

Ayahuasca as a Candidate Therapy for PTSD

 

7. Ibogaine for addiction:

Ibogaine: Complex Pharmacokinetics, Concerns for Safety, and Preliminary Efficacy Measures

Noribogaine reduces nicotine self-administration in rats

Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents

Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study

Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes

 

8. Psilocybin for addiction:

Pilot Study of the 5-HT2AR Agonist Psilocybin in the Treatment of Tobacco Addiction

Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study

Psilocybin-occasioned Mystical Experiences in the Treatment of Tobacco Addiction

Long-term Follow-up of Psilocybin-facilitated Smoking Cessation

Clinical Interpretations of Patient Experience in a Trial of Psilocybin-Assisted Psychotherapy for Alcohol Use Disorder

The Psychedelic Debriefing in Alcohol Dependence Treatment: Illustrating Key Change Phenomena through Qualitative Content Analysis of Clinical Sessions

 

9. Psilocybin for OCD:

Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder

Psilocybin and Obsessive Compulsive Disorder

 

10. MDMA for PTSD:

MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder

The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study

A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD)

Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study

Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy

MDMA-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial

 

11. MDMA for social anxiety in autistic adults:

MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults

Reduction in social anxiety after MDMA-assisted psychotherapywith autistic adults: a randomized, double-blind, placebo-controlledpilot study.

 

12. Cannabidiol for Dravet's syndrome:

Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial

Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome

 

13. Marijuana for PTSD:

On Disruption of Fear Memory by Reconsolidation Blockade: Evidence from Cannabidiol Treatment

Δ9-Tetrahydrocannabinol alone and combined with cannabidiol mitigate fear memory through reconsolidation disruption

Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders

Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety‐related and substance abuse disorders

Preliminary, Open-Label, Pilot Study of Add-On Oral Δ9-Tetrahydrocannabinol in Chronic Post-Traumatic Stress Disorder

PTSD Symptom Reports of Patients Evaluated for the New Mexico Medical Cannabis Program

 

14. Ketamine for depression:

Augmentation of response and remission to serial intravenous subanesthetic ketamine in treatment resistant depression

The Effect of Repeated Ketamine Infusion Over Facial Emotion Recognition in Treatment-Resistant Depression: A Preliminary Report

Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial

Persistent antidepressant effect of low-dose ketamine and activation in the supplementary motor area and anterior cingulate cortex in treatment-resistant depression: A randomized control study

Intravenous ketamine infusion for a patient with treatment‐resistant major depression: a 10‐month follow‐up

Impact of oral ketamine augmentation on hospital admissions in treatment-resistant depression and PTSD: a retrospective study

Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression

Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial.

 

15. Ketamine for PTSD:

Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic

Impact of oral ketamine augmentation on hospital admissions in treatment-resistant depression and PTSD: a retrospective study

Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression