The Four-Item Patient Health Questionnaire for Anxiety and Depression: A Validation Study in Infertile Patients

Document Type : Original Article


1 Department of Diabetes, Obesity and Metabolism, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

2 Department of Medical Ethics and Law, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

3 Department of Biostatistics and Epidemiology, School of Public Health, Babol University of Medical Sciences, Babol, Iran

4 Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Biostatistics, School of Nursing and Midwifery, Guilan University of Medical Sciences, Rasht, Iran


Background: The most common mental disorders in infertile patients are depression and anxiety. The four-item
Patient Health Questionnaire-4 (PHQ-4) is a widely used tool that consists of the PHQ-2 depression and Generalized
Anxiety Disorder-2 (GAD-2) scales. Given that PHQ-4 has not been validated in infertile patients, this study aimed to
examine its reliability and validity in this population.
Materials and Methods: Participants in this cross-sectional study consisted of 539 infertile patients from a referral
fertility centre in Tehran, Iran. The PHQ-4, Hospital Anxiety and Depression Scale (HADS), World Health Organisation-
Five Well-Being Index (WHO-5), Penn State Worry Questionnaire (PSWQ) and demographic/infertility questionnaires
were administered to all participants. Factor structure and internal consistency of PHQ-4 were evaluated
via confirmatory factor analysis (CFA) and Cronbach’s alpha, respectively. The convergent validity of this scale was
examined by its relationship with HADS, WHO-5 and PSWQ.
Results: CFA results provided support for a two-factor model of PHQ-4. Internal consistency of the PHQ-4 and its subscales
both were elevated with Cronbach’s alpha coefficients of 0.767 (PHQ-4), 0.780 (PHQ-2) and 0.814 (GAD-2). Inter-item
correlations were between 0.386 and 0.639, and corrected item-total correlations were between 0.576 and 0.687. PHQ-4,
PHQ-2 and GAD-2 showed positive correlations with measures of HADS-anxiety, HADS-depression, and PSWQ and negative
correlations with WHO-5, which confirmed convergent validity. Among demographic/fertility variables, we observed
that gender, infertility duration, and failure in previous treatment were correlated with PHQ-4 and its subscales scores.
Conclusion: The PHQ-4 is a reliable and valid ultra-brief screening instrument for measuring both anxiety and depressive
symptoms in infertile patients.