Research Roundup – October 16, 2021

This Week in Mental Health Research

This is the first installment of a new weekly column reviewing recent mental health research and reports.  The articles cited are chosen from the peer-reviewed literature, prioritizing reports that can inform policy or new directions in research.  This column does not claim to be comprehensive nor does it promote the science cited.  It will appear on the MindSite News website and will be sent to subscribers of our Research Roundup newsletter. You can sign up for our newsletters here. 

By Tom Insel, MD

Community College Students: More Mental Health Problems and Less Care

The Covid-19 pandemic has been difficult for college students. But even before Covid, mental health issues were a major concern on college campuses, with eating disorders, anxiety, and mood disorders affecting as many as half of the students on many campuses. The consequences were clear: Depression doubled the rate of dropout and 24,000 students attempted suicide each year. 

But while reports of Ivy League suicides often draw headlines, one large group that gets relatively little attention is the one-third of students that attend community colleges, a group that includes far more students of color and students from low-income families.

To compare community college students to students at four-year universities, a team led by Sarah Ketchen Lipson of Boston University School of Public Health used the Healthy Minds Survey, an annual survey of mental health in college students. The team pulled survey data from 2016 to 2019 on more than 10,000 community college students and 95,000 students from four-year institutions and found that about half of each group met criteria for at least one mental health condition. 

For those aged 18-22, however, community college students had significantly higher rates of depression, anxiety, and suicidal ideation. And among those with a mental health condition, community college students of all ages were less likely to receive therapy (30% for community college students vs 39.5% for four-year college students) and far less likely to receive on-campus services (5.4% community college students vs 23.4% for four-year college students). The groups made equivalent use of psychotropic medication (32%). Community college students were more likely to cite financial stress as both a source of mental health issues and a reason for not receiving care.

While these results from before the pandemic don’t reflect the impact of Covid, they do reveal the importance of focusing on the mental health needs of community college students. Nearly half of graduates of four-year institutions have been in a community college, but many promising students drop out of community college without making that leap due to mental health challenges. This report, the largest to date, shows these issues are prevalent — and poorly addressed.

See: Mental Health Conditions Among Community College Students: A National Study of Prevalence and Use of Treatment Services. Psychiatric Services, Oct. 2021

Covid-19 and Schizophrenia: Dying from Double Jeopardy

We all know by now that people with pre-existing health conditions, the elderly, and people of color have been hit the hardest when it comes to Covid-19 and are far more likely to be hospitalized and to die. But what about people with serious mental illness? 

In an analysis of 16 studies across seven countries published in July, a team of French scientists reported a stunning 2.26-fold increase in mortality from Covid-19 in people with serious mental illness. This finding, if verified, would make serious mental illness a major risk factor for death from Covid-19, equivalent to pre-existing respiratory or cardiovascular disorders. But not all 16 studies found this degree of increased risk, and few looked at any specific diagnosis.

That’s why a new report on people with schizophrenia is important. Dana Tzur Bitan of Ariel University and her colleagues used an Israeli database to compare Covid outcomes in more than 25,000 people with schizophrenia to a control group of people matched by age and sex. The consistent way that Israel diagnoses both schizophrenia and Covid-19 makes this an ideal setting to answer questions about the consequences of having both disorders. 

Curiously, people diagnosed with schizophrenia were less likely to test positive for Covid-19 compared to the control population. But once infected, they were twice as likely to be hospitalized and three times as likely to die. People with schizophrenia also had higher rates of obesity, smoking, diabetes, pulmonary disease, and poverty, all of which could contribute to more serious outcomes with Covid-19. 

Yet these factors did not fully explain the outcomes. The authors suggest that something about schizophrenia itself made the difference. Perhaps people with schizophrenia had more trouble asking for help or following medical protocols. Or maybe they have a less robust immune response, leaving them less able to fight off the infection. Either way – behavioral or biological factors or both, the end result was dire: During the Covid-19 pandemic, people with schizophrenia appear to be in double jeopardy.

See: COVID-19 Prevalence and Mortality Among Schizophrenia Patients: A Large-Scale Retrospective Cohort Study, Schizophrenia Bulletin, Sept. 2021

Preschool Children on Antipsychotics: Multiple Drugs, Multiple Years

For years, controversy has raged over the use of powerful antipsychotic medications in children. In 2010, researchers at Columbia University found that prescribing to young children aged 2 to 5 had doubled over a period of several years, even though there was little evidence that they were safe or effective. 

In the years that followed, such prescribing declined markedly, remaining higher for children in low-income families and in foster care.

W. David Lohr and his colleagues at the University of Louisville School of Medicine wanted to learn more about the ways these drugs are used in low-income children. They examined Medicaid records for 316 children under age 6 who were prescribed antipsychotics in a single southern state between 2012 and 2017. The mean duration of treatment was 2.6 years, and more than a quarter of the kids were on the medications for more than 4 years. Most were prescribed more than one medicine and nearly a third received four or more different medications concurrently.

Although autism spectrum disorder is the only condition for which FDA approval of an antipsychotic has been granted for young children, just under half of the kids had that diagnosis. Almost all of them were said to have attention deficit hyperactivity disorder (ADHD) and nearly two-thirds were diagnosed with anxiety or trauma. 

The patterns of prescribing were similar in Black and white children but boys, especially those in foster care, were more likely to be in the group that took the drugs for a long time. The findings don’t define the rate of antipsychotic use among kids in Medicaid, but they do show that preschoolers from Medicaid families, especially those in foster care, are receiving antipsychotics along with many other kinds of psychiatric medication through critical years of development. The long-term impact of this treatment is unknown. 

See: Antipsychotic Medications for Low-Income Preschoolers: Long Duration and Psychotropic Medication Polypharmacy, Psychiatric Services, Sept. 2, 2021

Most Youth with Serious Mental Illness Have Crossed the Digital Divide

The explosion of investment and innovation in digital mental health has largely focused on people with mild to moderate mental disorders, neglecting those with serious mental illness (SMI). The assumption seems to be that someone with a diagnosis of schizophrenia or bipolar disorder wouldn’t benefit from smartphone-based apps even though many small studies have shown the value of technology for tracking symptoms, managing medications, and linking seriously ill people to social supports that might help them. 

John A. Naslund and Kelly A. Aschbrenner from Harvard University explored these issues with a diverse group of 150 young adults 35 and under (26% self-identified as Black, 30% as Latino) being treated in community mental health centers. Of the total group, 65 (43%) had a diagnosis of a psychotic illness; the rest had a mixture of diagnoses, including depression, anxiety and post-traumatic stress disorder. 

Despite concerns about unequal access to technology – the “digital divide” – 92% of young adults with a serious mental illness owned a mobile phone and 95% used social media (most often YouTube and Facebook). Roughly three-fourths searched online for information about mental health or general health. And more than half were interested in apps for depression or anxiety, although there was less interest in crisis helplines.

The overall picture revealed few differences between those with psychotic disorders and those without, as both groups were interested and engaged in the use of digital technologies for mental health. Indeed, rather than being a bridge too far, these young people seem already to have crossed. More evidence that should encourage development of innovative tools for this population.

See: Technology Use and Interest in Digital Apps for Mental Health Promotion and Lifestyle Intervention Among Young Adults with Serious Mental Illness, Journal of Affective Disorders Reports, Sept. 7, 2021

Genes Fail – Again – to Predict the Course of Schizophrenia

Studies of the genetics of schizophrenia have revealed hundreds of variations in DNA associated with the disorder. Each one alone has little impact but what if they were combined to create a profile of risk? That’s the concept behind the polygenic risk score, or PRS, a popular approach to defining genetic risk for common disorders for a given individual. 

A person with 50 variants for schizophrenia risk would presumably be at greater risk than an individual with only five. This approach has been used (with mixed results) to predict who will develop schizophrenia. Could this elegant tool, derived from genetic studies of hundreds of thousands of people with schizophrenia, be used to predict prognosis? 

A team of geneticists from eight institutions, led by Isotta Landi of Mt Sinai’s Icahn School of Medicine, compared the predictive power of PRS to standard clinical assessments in over 8,500 patients. The result: the PRS does not predict clinical outcome any better than clinical assessment. Even though the magnitude of the PRS for schizophrenia exceeds the genetic signal for most common diseases and the PRS has been one of the cornerstones of precision medicine in other areas, it does not yet appear to have value for clinical care for individuals with schizophrenia. 

See: Prognostic value of polygenic risk scores for adults with psychosis, Nature Medicine, Sept. 6, 2021

Neuromodulation: Closing the Loop for Depression

Over the past two decades, neuroscientists using imaging techniques and armed with a deeper understanding of the functional wiring of the brain have shifted their view of depression from a “chemical imbalance” to a “circuit disorder” – essentially a kind of brain arrhythmia. There’s no specific lesion or injury but specific circuits might be overactive, underactive, or disconnected. 

So if depression is a circuit disorder, could we use a brain pacemaker to treat depression the way cardiac pacemakers fix arrhythmias? In 2005, Helen Mayberg and her colleagues showed that the pacemaker approach – which neuropsychiatrists call “deep brain stimulation” – could reduce the symptoms of depression, sometimes almost immediately. In fact, deep brain stimulation had already been used extensively and successfully for epilepsy and Parkinson’s disease. While the initial finding and subsequent research appeared to support the idea that depression can be treated as a circuit disorder, the results were inconsistent. Variation in the placement of electrodes, the pattern of brain activation, and perhaps even the biology of depression seemed to confound many of the studies.

A new report takes this field a big step forward. Katherine Scangos and her colleagues at the University of California San Francisco studied a 36-year-old woman with childhood onset, unremitting depression that had not responded to medications or electroconvulsive therapy. The team implanted multiple electrodes and mapped changes in brain activity to the woman’s self-reported ratings of her own mood for 10 days. With this map, the team developed a “personalized symptom-specific biomarker” – a reproducible pattern of circuit activity that predicted her deteriorating mood. 

Using this biomarker, they developed sequences for brain stimulation to reverse both the circuit activity and the symptoms of depression. Just as neurologists have learned to stimulate brain regions to preempt a seizure, Scangos and her colleagues created the first closed-loop intervention for depression, buzzing the precise circuit just as it is manifesting the arrhythmia associated with depressed mood.

This report is a proof of concept, not a controlled study. Still, it is important for at least three reasons. First, describing an individualized or personalized biomarker for depression points the way to solving the problems of variable results from the first generation of deep brain stimulation research. Second, this is the first use of a closed-loop approach that ties the intervention specifically to the time and place of concern. And finally, while it’s too early to know how this approach will work in others, it points to a new potential intervention for people with depression. More than 160,000 people have undergone deep brain stimulation, mostly for Parkinson’s disease, a disorder for which the targets are known. For them, the stimulation has proven lifechanging. In the future, will closed-loop deep brain stimulation bring a similar benefit to the 30% of people with major depression who are not helped by other treatments?

See: Closed-loop neuromodulation in an individual with treatment-resistant depression Nature Medicine, Oct 4, 2021.

Tom Insel, MD, is a psychiatrist, neuroscientist, and former director of the National Institute of Mental Health (NIMH). He is a donor to MindSite News and chair of its Editorial Advisory Board. Dr. Insel’s financial conflict of interest statement, which includes equity and advisory roles in several early-stage mental health technology companies, can be found here.