Living in Lockdown by Choice: Immune Disorder Patients Show Hidden Depression and Anxiety

People born with faulty immune systems often live by a rule most of us abandoned after the pandemic: avoid other people, because any infection could be dangerous. A new study from Hannover Medical School in Germany now shows that this constant, self-imposed isolation carries a heavy psychological price. In a cross-sectional study published in BMC Psychiatry, researchers found that patients with inborn errors of immunity who isolated themselves out of fear of infection scored significantly higher on standardized measures of both depression and anxiety than those who did not. The work is among the first to systematically quantify the mental health burden in this rare and heterogeneous patient population, and it points to a striking gap in care: many patients with clinically relevant symptoms had never received a psychiatric diagnosis or treatment.

Inborn errors of immunity, abbreviated IEI, are a group of more than 400 genetically determined disorders in which components of the immune system are missing, malfunctioning, or misdirected. The spectrum ranges from well-known conditions such as Common Variable Immunodeficiency, in which the body fails to produce adequate levels of protective immunoglobulin G antibodies, to rare monogenic defects affecting single signaling pathways. Because the immune defect is written into the genome, these are lifelong conditions. Patients typically experience recurrent, severe, or unusual infections, and many require regular immunoglobulin replacement therapy delivered intravenously or subcutaneously. What has received far less attention is the psychological dimension of living with such a vulnerability, and the new study was designed to address exactly that gap.

The research team, led by Luca J. Wolff and Thea Thiele of the Department of Rheumatology and Immunology at Hannover Medical School, together with psychiatrist Kai G. Kahl, recruited 143 adults from their clinic. The cohort included 88 women and 55 men with a mean age of 45.4 years, spanning ages 21 to 85. Each participant completed two widely validated screening instruments: the Patient Health Questionnaire-9, or PHQ-9, which quantifies depressive symptoms across nine diagnostic criteria, and the Generalized Anxiety Disorder-7, or GAD-7, which does the same for anxiety. Scores of 10 or higher on either instrument are conventionally interpreted as indicating at least moderate symptoms that warrant clinical attention. The researchers also collected routine clinical data, including the underlying diagnosis, documented psychiatric comorbidities, susceptibility to infections, and whether patients deliberately self-isolated because of infection-related concerns.

The headline numbers reveal a population under measurable strain. The median PHQ-9 score in the cohort was 5, with an interquartile range of 8, and the median GAD-7 score was 5, with an interquartile range of 7. On both scales, a score of 5 marks the threshold for mild symptoms, meaning that the typical patient in this study was already reporting noticeable, if subclinical, levels of depressive and anxious symptomatology. More concerning was the distribution above the clinical threshold. Among the 140 patients with valid PHQ-9 scores, eleven had scores of at least 10 despite having no documented psychiatric diagnosis. Taken together, roughly a quarter of patients with clinically relevant symptoms, 26 percent, had never been diagnosed or treated for a mental health condition.

The most statistically robust finding concerned self-isolation. Patients who reported isolating themselves because of concerns about infection had markedly higher symptom scores than those who did not. The association was quantified using Spearman’s rank correlation, a non-parametric measure of monotonic association suitable for ordinal questionnaire data. For depression, the correlation coefficient was 0.52, and for anxiety it was 0.48, both statistically significant at p less than 0.001. In behavioral science, correlations of this magnitude are considered moderate to strong, and they suggest that the degree of voluntary social withdrawal tracks closely with psychological distress. The authors emphasize that the cross-sectional design cannot determine whether isolation drives the symptoms, whether depressed and anxious patients withdraw more, or whether both are fed by a common cause such as fatigue, pain, or the cumulative burden of chronic illness.

That ambiguity is important, because the study also measured fatigue, pain, and quality of life using visual analogue scales, simple instruments in which patients rate their subjective experience on a continuous line. Chronic fatigue and pain are well-documented companions of immune deficiency, arising from repeated infections, inflammatory activity, and the physical toll of therapy schedules. Both are also established risk factors for depression in virtually every chronic disease studied, from rheumatoid arthritis to multiple sclerosis. In patients with IEI, these somatic symptoms may create a vicious circle: feeling exhausted and unwell discourages social engagement, social withdrawal deepens low mood, and low mood further reduces the motivation to maintain contact with friends, family, and even medical services.

The pandemic made this dynamic vividly familiar to the general population. Healthy people experienced only a compressed version of what immune-deficient patients navigate permanently: the calculation before every meeting, the weighing of a dinner party against a respiratory infection, the slow erosion of social confidence. Research from the pandemic years consistently showed that prolonged isolation increased rates of depression and anxiety even in people with no underlying medical vulnerability. The Hannover findings extend that lesson to a group for whom isolation is not a temporary public health measure but a rational, ongoing response to a genuine medical threat. The psychological cost, the study suggests, is real and quantifiable, even when the isolation is medically sensible.

Why did so many symptomatic patients go undiagnosed? The authors point to the structure of specialist care. Adults with inborn errors of immunity are typically managed by immunologists and rheumatologists whose consultations focus on infection history, antibody levels, and replacement therapy dosing. Mental health screening is not routinely embedded in these visits, and patients themselves may not volunteer psychological complaints when their medical agenda is dominated by physical symptoms. The PHQ-9 and GAD-7 take only a few minutes to complete, and the study’s results argue that administering them at regular intervals in immunology clinics could surface a substantial hidden burden. Eleven patients with PHQ-9 scores of 10 or above and no psychiatric diagnosis is a small absolute number, but in a cohort of only 143 it represents a meaningful fraction, and the 26 percent treatment gap among symptomatic patients suggests the problem scales beyond this single center.

The study’s conclusions carry practical implications for how care for these patients is organized. The authors call for greater awareness of mental health issues and for multidisciplinary care models in which immunologists, primary care physicians, and mental health professionals collaborate. Such models are already standard in oncology and increasingly in chronic inflammatory diseases, where the interplay between immune function and mood is well recognized. Interestingly, the biology may run in both directions: chronic psychological stress alters cortisol and inflammatory signaling, and in patients whose immune regulation is already genetically compromised, the clinical consequences of that interaction remain an open research question. The Hannover team did not test mechanistic hypotheses, but their data provide the epidemiological foundation for such work.

For patients and families, the message is that the emotional weight of living with an immune defect deserves explicit attention, not quiet endurance. Feeling persistently down, tense, or exhausted is not an inevitable part of having a rare disease that must simply be accepted; it is a treatable component of the illness experience. For clinicians, the message is that a two-questionnaire screen and a conversation about social isolation could identify patients who are suffering invisibly. And for the broader public, the study is a reminder of a lesson the pandemic taught and then faded: that protecting the body from infection by withdrawing from the world exacts a measurable toll on the mind, and that toll deserves the same seriousness as any laboratory value on a patient’s chart.

Subject of Research: Depression and anxiety in patients with inborn errors of immunity and their association with infection-related self-isolation

Article Title: Frequency of depression and anxiety in patients with inborn errors of immunity: a cross-sectional study

Article References: Wolff, L. J., Witte, T., Kahl, K. G., Meinecke, A., Ahrenstorf, G., Sogkas, G., Hillmer, S., & Thiele, T. (2026). Frequency of depression and anxiety in patients with inborn errors of immunity: a cross-sectional study. BMC Psychiatry, 26(1), Article 721. https://doi.org/10.1186/s12888-026-08654-1

Image Credits: AI Generated

DOI: 10.1186/s12888-026-08654-1

Keywords: inborn errors of immunity, depression, anxiety, self-isolation, PHQ-9, GAD-7, common variable immunodeficiency, mental health, quality of life, immunodeficiency, cross-sectional study, multidisciplinary care