Do mental health disorders change antibody responses to vaccination, and does insomnia explain part of that difference?

Which mental health conditions are linked to lower antibody levels after vaccination?

The strongest signal comes from mood disorders. In a study of 939 vaccinated adults in Catalonia, people with mood affective disorders had IgG antibody levels against the SARS-CoV-2 receptor-binding domain about 26% lower than people without such diagnoses, after accounting for demographics, other health conditions, and lifestyle factors [1]. A systematic review of 13 studies across different vaccines also found that people with major depressive disorder or schizophrenia showed either weakened immune responses or no statistical difference compared with controls [2].

Not every condition shows the same pattern. The Catalonia study found no association between anxiety disorders and antibody levels [1]. The systematic review reported that people with anorexia nervosa or post-traumatic stress disorder did not show weakened antibody levels after vaccination [2]. This matters because it suggests the link is not simply 'mental illness' in general but may depend on the specific condition.

Insomnia appears as its own signal, not as the explanation

Insomnia shows up in the evidence as a condition associated with lower antibody levels, but not as a mediator that explains why people with other mental health disorders have weaker responses. In the Catalonia study, the group of 'other diagnoses'—mainly insomnia and nicotine dependence—had IgG antibody levels about 22% lower than people without those diagnoses, and recent-onset cases showed a greater decline in antibodies [1]. The systematic review likewise reported that individuals with insomnia had lower antibody levels after vaccination, while those with obstructive sleep apnea showed no difference [2].

However, neither study tested whether insomnia statistically accounts for the antibody differences seen in people with mood disorders or other conditions. The Catalonia study's verification summary explicitly notes that it does not explore whether insomnia mediates the differences in antibody responses among those with mental health disorders [1]. The systematic review similarly does not directly assess whether insomnia explains differences in antibody responses among individuals with mental disorders [2]. So insomnia is a separate risk signal, not a demonstrated bridge.

Why might mental health conditions affect antibody responses?

One proposed explanation is immune dysregulation: mental disorders have been associated with altered levels of biological markers of immunity, which could in turn affect how well the body produces antibodies after vaccination [2]. The Catalonia study also points to factors beyond diagnosis alone. People taking second-generation antipsychotics or multiple classes of psychotropic drugs in the previous six months had lower antibody levels [1]. That suggests medication and treatment intensity may matter alongside the diagnosis itself.

Genetic liability may also play a role. In a genotyped subset of 247 participants, higher polygenic risk scores for schizophrenia were associated with lower IgG antibody levels against the receptor-binding domain, and a Mendelian randomization analysis—a method that uses genetic variants to probe causality—suggested a causal relationship between genetic liability to major depression and lower antibody levels [1]. These are statistical and genetic signals, not direct measurements of immune function, so they point toward possible mechanisms rather than proving them.

How reliable is this, and what would it take to know whether insomnia matters?

The evidence is suggestive but not conclusive. The systematic review included only 13 articles, most with fewer than 30 subjects, and concluded that vaccine response in adults with mental disorders remains inconclusive [2]. The Catalonia study is larger and population-based, but it is one study in one country, and its genetic analyses used a subset of only 247 people [1]. Neither study followed people forward to see whether lower antibody levels translated into more breakthrough infections, which is the outcome that would matter most for vaccine policy [1].

To answer whether insomnia explains part of the difference, researchers would need studies that measure insomnia and antibody levels in the same people with other mental health disorders and formally test whether insomnia accounts for part of the association—something neither of these studies did [1][2]. For now, the practical takeaway is that mood disorders and insomnia are each associated with lower antibody levels after vaccination, but they appear to be separate signals rather than one explaining the other.

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