Treatment-Resistant Depression: Could Personalized Brain Stimulation Ease Depression and OCD?

What’s happening – Two recent papers published in Nature Medicine explored the potential of personalized brain stimulation to treat depression and obsessive-compulsive disorder (OCD). A team from the University of California San Francisco (UCSF) used deep brain stimulation (DBS) – which requires surgery to implant electrodes in the brain – to deliver targeted neuromodulation to a woman with severe treatment-resistant depression.

Researchers mapped the effects of targeted stimulation to different brain regions and different symptoms, which could change depending on the woman’s mood at the time. The stimulation took a few minutes and the results lasted hours; the woman’s symptoms improved significantly during the 10-day study and she was in remission for 6 weeks. Next, a device was implanted in her brain that monitors for depressed mood and delivers mild stimulation to reverse any perceived symptoms. This case study is one step in a larger clinical trial called PRESIDIO that aims to test a personalized treatment for major depression.

In the second recently published study, researchers from Boston University explored ways to deliver non-invasive electrical current to the brain’s reward processing center to help alleviate OCD. The team applied transcranial alternating current stimulation (tACS) to the study’s 60 participants which were split into three groups: one received personalized stimulation, one got stimulations at a lower frequency, and the placebo group received no electrical current. After a 30-minute application for 5 consecutive days, subjects who received the personalized stimulation experienced an average reduction in OCD symptoms of 28% that lasted roughly 3 months.

The details – Read the full study on depression by Scangos et al and the study on OCD by Grover et al.

The perspectives

Why it’s noteworthy – The ability to provide customized patterns of brain stimulation based on an individual’s needs is a breakthrough for the field. A study in Nature Biomedical Engineering  by Shanechi et al described a way to predict the effect of stimulation on a person’s brain based on two tools that the researchers created: one is a stimulation waveform that maps brain activity and the other is a machine-learning model. Together, they can personalize electrical stimulation to achieve the desired effects on the brain for any patient.

Additional research on brain stimulation:

  • The future of personalized brain stimulation research and the hope for future treatments
  • An article from Nature Reviews Neurology explores the state of DBS research and its future directions
  • The VA conducted a pilot study that found that a type of brain stimulation called repetitive transcranial magnetic stimulation (rTMS) reduced apathy in Alzheimer’s patients
  • FDA recently approved a DBS system to treat Parkinson’s disease
  • A neurology review explores whether DBS can help with chronic pain

The conversation

  • @UCSFimaging tweeted “A new study by scientists at the UCSF Dolby Center for Mood Disorders found that personalized neuromodulation can selectively improve symptoms of severe, treatment resistant depression. Great work by all!”
  • @NeuroTransmitOz, Nature Medicine editor Jerome Staal, tweeted “Great new study from #ReinhartLab shows that #neuromodulation of orbitofrontal beta–gamma rhythms in humans reduces obsessive–compulsive behaviors. #OCD @buCSNneuro @NeurosciBU.”
  • @MaryamShanechi, lead author of the Nature Biomedical Engineering study on personalized deep brain stimulation, tweeted “@USCViterbi story about our recent @natBME paper on modeling large-scale #brain network dynamics in response to stimulation, and its broader implications for #personalized closed-loop #DBS therapy in neurological & mental disorders.”
  • @dongsong, a colleague of Dr. Shanechi at USC Viterbi, replied “Beautiful work! Great computational framework for brain stimulation.”

In practice – More on OCD treatments including troriluzole for residual symptoms, and what future depression screenings may look like.

 Phobias and Exposure Therapy: VBE May Offer Best Approach for Treatment Adherence

 What’s happening – Non-conscious exposure to images of spiders reduced arachnophobia

in women, according to a study published in Lancet Psychiatry. Very brief exposure (VBE) to masked images of spiders (images appeared for 30 ms) produced neural activity in regions supporting automatic fear extinction, emotion regulation, and attention systems – all observed with fMRI. After VBE, 52% of the women with spider phobia were able to get closer to a live tarantula.

Exposure therapy is a well-established technique to treat specific phobias, but for some people it can be too distressing to begin or complete treatment. The researchers suggest that VBE may help people complete treatment if used as an adjunct to – or as a pretreatment to – full exposure therapy. The team wrote that their findings on how non-conscious exposure to a feared stimulus could reduce fear while not eliciting an experience of fear or distress challenges conventional clinical thinking that fear must be experienced via direct confrontation of the feared stimulus in order to reduce fear. Future research, they recommend, should investigate the use of VBE in other fear-based disorders such as PTSD and social anxiety disorder.

The details – Read the full study by Siegel et al in Lancet Psychiatry.

The perspectives

Other Research Approaches – VBE is an emerging approach to treating specific phobias, and research is underway for how to best utilize this exposure technique. A review article examined approaches in psychotherapy, virtual reality, pharmacology, for instance, for specific phobias in adults. Additional examples:

  • A qualitative study examined an automated, gamified virtual reality exposure therapy program for spider phobia and found that the users reacted favorably to the intervention.
  • A study in Nature’s Scientific Reports looking at the neuronal correlates of spider phobia was the first to combine functional near-infrared spectroscopy (fNIRS) and EEG to examine specific phobia and was the first to use video of spiders rather than static images.
  • Considering the worldwide popularity of superhero movies such as Spider-Man and Ant-Man, a study by Hoffman et al used exposure to clips from those films to help reduce insect phobia. The researchers predicted that exposure through a leisure activity such as watching a film might be less distressing than insect exposure in a therapeutic environment.

The conversation

  • @RyanSmith_LIBR, author of the Lancet Psychiatry commentary on the VBE study, tweeted about his article “It’s in relation to a really cool study where repeated unconscious exposure to spider images reduced spider phobia symptoms.”
  • @JCedernaes (Jonathan Cedernaes, sleep and circadian researcher at Northwestern University) tweeted “#Subconscious (very brief) exposure to stimuli reduces avoidance in women with #phobias, here against spiders, ‘by recruiting brain regions supporting automatic fear extinction, emotion regulation & top-down attentional processing’” and linked to the VBE study.
  • @EntSocOnt (Entomological Society of Ontario) tweeted “We know art can be therapeutic, but did you know that exposure to insects in movies can reduce symptoms of phobia?” and linked to the study about superhero movies by Hoffman et al.

In practice – Some mental health apps for PTSD focus on exposure therapy.

Psy-Q: This Week's Challenge

Can unconscious exposure to a phobia reduce phobia symptoms and/or improve treatment adherence? Bradley S. Petersen, MD, answers, using arachnophobia as an example.

Get the Answer

Social Support Can Benefit Youth with Mental Health Disorders, But Perceptions Matter

What’s happening – Perceived social support appears to have a protective effect on the mental health of young people as they enter adulthood. In a population-based study, a cohort of 19-year-olds (n=1,174) were measured for self-reported social support and followed up at 1 year. At age 20, young adults with higher perceived social support reported fewer symptoms of depression, anxiety, and had a lower risk of suicide-related outcomes – even when participants had a history of mental illness in adolescence.

The researchers, based in the University of Montreal and McGill University, highlighted the potential protective effect of perceived social support on the mental health of emerging adults, which they identify as a period of life “marked by a high prevalence” of mental health problems. They suggested that emphasizing social support in prevention and treatment programs, as well as considering perceptions of social support, may help young people.

The details – Read the full study by Scardera et al in JAMA Network Open.

Why it’s complicated – The study was completed before the COVID-19 pandemic, and the researchers do not know how their results on perceived youth social support and mental health will extend to today’s new normal. The research team plans to investigate whether the same associations have remained during the pandemic, according to an article by McGill University.

The perspectives

  • Perceived parental support was the subject of another cohort study involving 4,463 students aged 18 to 24. Lower perceived parental support was associated with higher risk of mental health disorders, and the researchers suggested the potential use of a person’s perceived parental support as a screening tool for mental health.
  • A study of social support and mental health in late adolescence concluded that the quality of social support was more important than the quantity (ie, the size of a person’s social network).
  • In a cohort study of twins, researchers found that greater perceived social support was associated with a reduced likelihood of psychotic experiences in adolescents.

The conversation

  • @namimaine (NAMI Maine) linked to this new report, tweeting “Young adults who believe they have strong social support experience fewer problems later in life…”
  • Neuroscientist @hassaan_tohid tweeted “The power of perception. A team of McGill University researchers has found that young adults who perceived higher levels of social support reported fewer mental health problems.”
  • @StopStigma_Now and @MoodDisordersCa (MoodDisorders Canada) were among others who tweeted their support of the study

In practice – Additional perspectives on mental health in adolescence from AACAP, including Identifying and Preventing Mental Disorders in ChildrenOverlapping Autism, ADHD, and Psychosis; the Hidden Benefits of Stimulants for ADHD; Measuring and Coding Emotional Dysregulation.

Last Updated: Apr 20, 2021