People with major depressive disorder or bipolar disorder whose brain activity increases when they see scary faces are at increased risk of being admitted to a psychiatric hospital within a year. This increased vulnerability is also accompanied by a complementary tendency to recognize negative facial expressions more quickly than positive facial expressions. These findings emerged from a recent study published in the journal Neuropsychopharmacology.
Major depression and bipolar disorder are two of the most common and persistent mood disorders worldwide. Both health conditions can seriously disrupt a person’s life and, in some cases, cause periods of severe mental distress. The economic costs to society resulting from occupational impairment and the need for intensive care are enormous. If symptoms worsen rapidly, inpatient psychiatric treatment may be required for stabilization and safety.
Predicting who will experience such severe relapse remains a major challenge for medical professionals. Clinicians typically estimate the risk of future hospitalization based on a patient’s medical history, severity of current symptoms, and medication status. Mental health experts suspect deeper biological and psychological markers may provide better clues about a patient’s long-term course. Areas of interest include how the brain processes emotional information over time;
People with mood disorders often exhibit subtle differences in how they interpret the social world around them. Previous research has linked depression and bipolar disorder to increased activity in the amygdala, a small structure deep in the brain that acts as a primary alarm system for detecting threats. Similarly, the fusiform gyrus, a brain region specialized in recognizing faces, is often overactive when people with this condition see emotional expressions.
This increased brain activity is thought to create a negative cognitive bias. Experts believe that poor regulation by the prefrontal cortex may cause the amygdala to overreact to benign situations. This dysregulation causes individuals to perceive neutral social interactions as hostile or upsetting. Consistently misinterpreting social cues can lead to persistent depression and increased anxiety.
To find out whether these neurological characteristics predict long-term clinical outcomes, a team led by Camila W. Miskowiak conducted a study. Miskoviak is a professor and clinical psychologist at the University of Copenhagen and the Danish Capital Region’s Mental Health Services. Her collaborative team sought to determine whether patients’ neurological and behavioral responses to faces could predict the likelihood of serious health problems. They reasoned that increased threat sensitivity might impair psychological resilience, making people more vulnerable to sudden spikes in symptoms.
The research team recruited 112 participants who had previously been diagnosed with major depressive disorder or bipolar disorder. At the beginning of the study, participants took tests to assess their mental state and collected baseline records of their emotional responses. The researchers used functional magnetic resonance imaging, a technique that measures changes in blood flow, to observe brain activity in real time. Participants lay motionless inside the machine while looking at a series of fleeting pictures depicting happy and frightened human faces.
While the scanner recorded brain activity, participants pressed a button to indicate the gender of the person in each photo. This task allowed the scientists to record continuous unconscious responses within participants’ amygdala and fusiform gyrus, without the subjects actively thinking about the emotions being displayed. Participants completed additional behavioral assessments on a standard computer outside the scanner. This secondary test required participants to recognize changing facial expressions as sadness, fear, anger, disgust, surprise, and happiness.
The computer program steadily increased the intensity of emotional expression during the testing phase. Participants were instructed to identify the emotion as quickly and accurately as possible by tapping labeled keys on the keyboard. Following the initial testing phase, researchers followed participants for a full year using Denmark’s National Health Register. These comprehensive population databases maintain extensive, centralized records of all hospitalizations and medical diagnoses nationwide.
By analyzing registry data, the researchers were able to pinpoint which subjects ended up in a psychiatric hospital in the 12 months following their brain scans. Only hospitalizations strictly associated with mood episodes were counted in the final data. After examining clinical timelines, scientists found a link between excessive brain activation and subsequent hospitalization. Patients who had higher levels of activity in the left amygdala when viewing fearful faces were much more likely to be admitted to a psychiatric facility.
The results of the registry showed that a proportionate increase in left amygdala reactivity increased the average probability of requiring hospital treatment by about 3 percentage points. Other brain regions assessed in the scans, such as the right amygdala and left and right fusiform gyri, showed no statistically significant relationship with future hospital visits. Behavioral data from computer tests provided parallel insight into patients’ psychological vulnerabilities. People who recognized negative faces faster than positive faces had a significantly higher risk of needing hospitalization.
For every small increase in this measure of facial recognition speed, participants increased their average baseline risk of hospitalization by about 3.5 percentage points. However, the accuracy with which specific emotions were identified had non-statistically significant consequences for future psychiatric visits. Miskowiak and colleagues propose that these specific neural and behavioral markers indicate an overactive stress response system. Hypersensitivity to threats can exhaust a person’s coping mechanisms for months.
Without proper mental control, continued negative cognitions can easily worsen a depressive or manic episode until it reaches an emergency threshold. The researchers emphasize that this test highlights the underlying vulnerability profile rather than the underlying mechanism that spontaneously causes the episode. Although this study provides new prognostic insights, there are several limitations that deserve consideration. Of the 112 participants monitored throughout the year, only 20 ultimately required psychiatric hospitalization.
This small number of serious clinical events means that large-scale validation studies are needed to confirm the exact pattern of risk. The participant group also included people taking a variety of psychotropic medications, which may have subtly influenced their individual brain responses. Because this study relied entirely on observational data from health registries, the design cannot determine whether negative cognitive bias directly causes hospitalization. This association simply indicates that exaggerated threat responses tend to coincide with worse clinical outcomes.
The researchers also combined patients with major depressive disorder and bipolar disorder into a single group to maintain sufficient statistical power. Future studies may separate these populations to see if predictive biomarkers behave differently depending on the specific diagnosis. In the future, the researchers hope to investigate whether these threat processing markers can actively guide treatment decisions in the clinic. If clinicians can identify patients with high amygdala reactivity early, they may be able to provide more targeted interventions.
Preventive psychotherapies designed to reduce negative cognitive biases could theoretically reduce the overall disease burden in the most at-risk populations. Changing the way these brains process emotional information could ultimately keep more patients safe and out of psychiatric emergency wards.
The study, “Amygdala reactivity to threat, negative face recognition, and risk of future psychiatric hospitalization: A longitudinal study in major depression and bipolar disorder,” was co-authored by Camila W. Myskowiak, Bryce Ozenne, Hanne L. Kjerstad, and Patrick M. Shah, Emily E. Beeman, Vibeke H. Dam, Alexander T. Isbek Nielsen, Gitte M. Knudsen, Lars V. Kessing, Julian Makovianu, Vaib G. Frokyal, and Anjali Sankar.
