Coeliac disease and risk of mood disorders — A general population-based cohort study

Abstract

Background

Earlier research has indicated a positive association between coeliac disease (CD) and some mental disorders. Studies on CD and depression have inconsistent findings and we know of no study of CD and the risk of bipolar disorder (BD).

Methods

We used Cox regression to investigate the risk of subsequent mood disorders (MD); depression and BD in 13,776 individuals with CD and 66,815 age- and sex-matched reference individuals in a general population-based cohort study in Sweden. We also studied the association between prior MD and CD through conditional logistic regression.

Results

CD was associated with an increased risk of subsequent depression (Hazard ratio (HR) = 1.8; 95% CI = 1.6–2.2; p < 0.001, based on 181 positive events in individuals with CD and 529 positive events in reference individuals). CD was not associated with subsequent BD (HR = 1.1; 95% CI = 0.7–1.7; p = 0.779, based on 22 and 99 positive events). Individuals with prior depression (OR = 2.3; 95% CI = 2.0–2.8; p < 0.001) or prior BD (OR = 1.7; 95% CI = 1.2–2.3; p = 0.001) were at increased risk of a subsequent diagnosis of CD.

Limitations

Study participants with CD and MD may have more severe disease than the average patient with these disorders since they were identified through a hospital-based register.

Conclusions

CD is positively associated with subsequent depression. The risk increase for CD in individuals with prior depression and BD may be due to screening for CD among those with MD.

Introduction

Coeliac disease (CD) affects up to 1% of all individuals in the Western world (Dube et al., 2005). The disease occurs mainly in individuals with HLA-DQ2 or DQ8 (Sollid, 2000) and is triggered by exposure to gluten (Kagnoff, 2005). CD is characterized by mucosal atrophy in the small bowel, but is also associated with extraintestinal complications (Green and Jabri, 2003), including neuropsychiatric disorders (Bushara, 2005).

Depression is a major cause of worldwide disability and is projected to become the second most important cause of disability in the Western world in the year 2020, only surpassed by ischemic heart disease (Murray and Lopez, 1997). Goldberg (Goldberg, 1970) and Hallert et al. (Hallert and Astrom, 1982a, Hallert et al., 1982b, Hallert and Derefeldt, 1982) were among the first to describe the association of CD with depression. Their papers have since been followed by a number of reports on CD and depression (Accomando et al., 2005, Addolorato et al., 2001, Addolorato et al., 1996, Carta et al., 2003, Ciacci et al., 2003, Ciacci et al., 1998, Cicarelli et al., 2003, Fera et al., 2003, Pynnonen et al., 2002, Siniscalchi et al., 2005) with varying results. Bipolar disorder (BD) is another mood disorder (MD). BD is characterized by swings in a person's mood and energy and will often lead to damaged relationship and poor performance at school or work. About 1% of the American population aged 18 years or more have, in any given year, BD (Regier et al., 1993). To our knowledge there are as yet no published studies focusing on CD and BD.

The prevalence of depression in CD varies between 6–57% (6.5% (Ciacci et al., 2003), 14% (Cicarelli et al., 2003), 17% (Siniscalchi et al., 2005), 19–24% (Fera et al., 2003), 32% (Ciacci et al., 1998), 42%(life-time risk) (Carta et al., 2002), 46–57% (Addolorato et al., 2001)), with the lowest prevalence occurring among individuals with gluten-free diet in one of the largest earlier studies (Ciacci et al., 2003). The 36 individuals with CD in the Carta et al. study were at a 2.7-fold increased risk of major depressive disorders (Carta et al., 2002) but also at an increased risk of recurrent brief depression (Carta et al., 2003). Most other studies have shown a statistically significantly positive association between CD and depression (Addolorato et al., 2001, Addolorato et al., 1996, Ciacci et al., 1998, Hallert and Astrom, 1982a, Hallert et al., 1982b, Hallert and Derefeldt, 1982, Siniscalchi et al., 2005), but not all (Accomando et al., 2005, Cicarelli et al., 2003, Fera et al., 2003, Roos et al., 2006). Despite an increased depression score in a modified version of the Zung Self-Rating Depression Scale, Fera et al found no increased risk of depression as defined by this instrument in individuals with CD (Fera et al., 2003). Neither did two recent Italian studies (Accomando et al., 2005, Cicarelli et al., 2003); or a Swedish study based on psychological general well-being scores in individuals with treated CD (Roos et al., 2006).

Several of the previous studies have been based on a limited number of patients with CD (Addolorato et al., 2001, Addolorato et al., 1996, Carta et al., 2003, Ciacci et al., 2003, Ciacci et al., 1998, Fera et al., 2003, Hallert and Astrom, 1982a, Hallert et al., 1982b, Hallert and Derefeldt, 1982, Siniscalchi et al., 2005), with only four studies including more than 100 patients with CD (Ciacci et al., 2003, Cicarelli et al., 2003, Fera et al., 2003, Siniscalchi et al., 2005) and among the three studies that used controls (Cicarelli et al., 2003, Fera et al., 2003, Siniscalchi et al., 2005), only one found an increased risk of depression in individuals with CD compared with the control population (17% vs. 0%)(Siniscalchi et al., 2005). In several of the studies, depression was identified solely through self-rating questionnaires (Accomando et al., 2005, Addolorato et al., 2001, Ciacci et al., 2003, Ciacci et al., 1998, Hallert and Astrom, 1982a, Hallert et al., 1982b, Siniscalchi et al., 2005), while the involvement of medical professionals in the diagnosis of MD is not clearly outlined in several other papers (Cicarelli et al., 2003, Fera et al., 2003). Most studies on CD and MD have been cross-sectional in nature (Accomando et al., 2005, Addolorato et al., 1996, Carta et al., 2003, Ciacci et al., 2003, Ciacci et al., 1998, Cicarelli et al., 2003, Fera et al., 2003, Goldberg, 1970, Hallert and Astrom, 1982a, Hallert et al., 1982b, Hallert and Derefeldt, 1982, Pynnonen et al., 2002, Siniscalchi et al., 2005) and when both pre- and post-CD diagnoses of psychiatric disease have been studied, temporal sequence has not been taken into account when calculating risk estimates (Addolorato et al., 2001, Carta et al., 2002). This study is designed to address some of the methodological limitations of earlier work and to examine differences in association by temporal sequence of CD and MD (depression and BD) using longitudinal data. Swedish national registers were used to conduct this research among over 13,000 individuals with CD and 66,000 individuals without the disease.