The severity and progression of alpha-1 antitrypsin deficiency (AATD) may be contributing to the prevalence of psychological disorders among patients, according to researchers in the UK.

“This implies that patients who are declining rapidly should be actively monitored for psychological comorbidity and treated by relevant cognitive or pharmacological means,” wrote the authors of the study that was published in the Journal of Chronic Obstructive Pulmonary Disease.

The psychological aspect of AATD is not well studied. Here, a team of researchers led by Alice M. Turner, MBChB, MRCP, PGCE, PhD, investigated the prevalence and clinical impact of anxiety and depression in patients with AATD.

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They analyzed a total of 746 patients. Of those, 635 had the PiZZ/PiZnull genotype while 111 had the PiSZ genotype. The researchers grouped the patients as either having a diagnosis of anxiety and/or depression or not. 

Statistical analyses revealed that 16.4% of all patients regardless of genotype had anxiety and/or depression. This was associated with a lower baseline pulmonary function and worsened health status.

Read more about AATD comorbidities

Patients with the PiZZ/PiZnull genotype and anxiety and/or depression had a greater average decline in FEV1% predicted, which is a measure of disease severity and progression, compared to those without mental health issues. However, there was no difference in the decline in health status. This observation was not valid in patients with the PiSZ genotype.

The researchers also noted that shortness of breath was worse among patients with anxiety and/or depression, but comorbidity burden did not differ between patients regardless of the presence of mental health issues. 

“Disease severity and progression may be contributing to the prevalence of psychological factors in PiZZ/PiZnull patients,” the researchers concluded.

The most common form of AATD is found in individuals with the PiZZ genotype. The PiSZ, PiNull, and PiZnull genotypes are associated with a more severe presentation of the disease. 


Mobeen F, Edgar RG, Pye A, Stockley RA, Turner AM. Relationship between depression and anxiety, health status and lung function in patients with alpha-1 antitrypsin deficiency. J Chron Obstruct Pulmon Dis. 2021;22:1-9. doi:10.1080/15412555.2021.1991904