Common psychiatric disorders and caffeine use, tolerance, and withdrawal: an examination of shared genetic and environmental effects.

Common psychiatric disorders have consistently been shown to be comorbid with substance use disorders (Grant et al., 2005; O’Neil et al., 2011; Root et al., 2010; Salbach-Andrae et al., 2008). It has been estimated that worldwide caffeine is consumed daily by 80% of individuals (James, 1997) and can be considered a substance for potential abuse. Similar to other psychoactive substances with potential for abuse, caffeine use can be associated with symptoms of tolerance and withdrawal (Griffiths et al., 2003). The Diagnostic and Statistical Manual for Mental Disorders (DSM)-IV contains several caffeine use diagnoses (American Psychiatric Association, 1994). A genome-wide association study has suggested several genes may be associated with coffee drinking (Amin et al., 2011). Evidence suggested that caffeine dependence might be related to other substances with abuse potential. Caffeine dependence symptoms shared a common genetic factor with alcohol and nicotine dependence symptoms and a common unique environmental factor with alcohol, nicotine, cannabis, and cocaine dependence symptoms (Kendler et al., 2007). Given that there is a high comorbidity between other licit and illicit substance use and psychiatric disorders, studying the comorbidity between caffeine use, caffeine tolerance, and caffeine withdrawal and common psychiatric disorders, like anxiety disorders and depression, is of potential interest. Thus far, some research has explored the comorbidity between caffeine use and psychiatric disorders. Caffeine use in women was associated with an increased risk of poor mental health defined as scoring four or higher on the Japanese version of the general health questionnaire (Shimbo et al., 2005). Caffeine intake, heavy caffeine use, caffeine toxicity, and symptoms of caffeine dependence were associated with an increased risk for developing major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder, adult antisocial personality disorder, and illicit drug abuse and dependence (Kendler et al., 2006). In a separate study, some eating disorder symptoms (binge eating, concern about weight and shape, self-perception of being overweight, and expressing a fear of gaining weight) were associated with caffeine abuse (Baker et al., 2010). Results of studies have also indicated that caffeine consumption can trigger or worsen anxiety. Caffeine has been shown to have anxiogenic effects in individuals with panic disorder (Breier et al., 1986; Charney et al., 1985; Nardi et al., 2007, 2009), performance social anxiety disorder (Nardi et al., 2009), and major depression with panic attacks (Nardi et al., 2007). Despite consuming similar amounts of caffeine as individuals without psychological disorders, those with depression expressed higher sensitivity to the anxiogenic effects of caffeine (Lee et al., 1988). Taken together, there may be shared genetic or environmental factors between psychiatric disorders and caffeine use phenotypes. Twin studies have suggested that genetic factors play an important role in the etiology of all common psychiatric disorders that have been examined including GAD (Hettema et al., 1995; Hettema et al., 2001; Scherrer et al., 2000), phobias (Kendler et al., 2008; Kendler et al., 1999), panic (Hettema et al., 2001; Kendler et al., 2001; Middeldorp et al., 2005; Mosing et al., 2009), MDD (Bierut et al., 1999; Kendler & Prescott, 1999a; Sullivan et al., 2000), anorexia nervosa (AN; Dellava et al., 2010; Klump et al., 2001; Mazzeo et al., 2009), and bulimia nervosa (BN; Bulik et al., 2010; Kendler et al., 1991; Kortegaard et al., 2001). Fewer studies have been conducted on caffeine use phenotypes. Of the existing twin studies, the heritability of caffeine use was estimated between 0.36 and 0.58 (Kendler & Prescott, 1999b; Yang et al., 2010), caffeine tolerance at 0.40 (Kendler & Prescott, 1999b; Luciano et al., 2005), and caffeine withdrawal at 0.35 (Kendler & Prescott, 1999b). Despite the high comorbidity between psychiatric disorders and caffeine phenotypes, few twin studies have examined the nature of this comorbidity. Although no significant results were found, possibly due to sample size, in monozygotic (MZ) twins all odds ratios between caffeine use phenotypes and psychological disorders were non-significant; in the full sample including all twins, this relationship was significant. This indicated that these phenotypes likely share genetic liability (Kendler et al., 2006). The genetic correlation between caffeine abuse/dependence and BN symptom count was estimated at 0.37 (Baker et al., 2010). A genetic correlation of 0.40 was found between caffeine use and sleep disturbance (Luciano et al., 2007). Further research is needed to determine if there is shared genetic or environmental liability between specific psychiatric disorders and specific caffeine use phenotypes. The aim of the current study was to determine the magnitude of the genetic and environmental correlations between common psychiatric disorders (GAD, panic disorder, phobias, MDD, AN-like syndrome, and BN-like syndrome) and key caffeine phenotypes (caffeine use, caffeine tolerance, and caffeine withdrawal) in women. In conducting these analyses, the possibility of the existence of consistent patterns among all the psychiatric phenotypes and caffeine phenotypes was explored. In addition, analyses could illustrate if each specific psychiatric phenotype displayed the same general relationship with all caffeine phenotypes. For all psychiatric phenotypes, broad diagnoses were used to maximize power.