7.2. Research implications

Due to the fact that in females, the association between atopy and depression was apparent independently of the severity of the depressive symptoms, and that in males, the association was seen only in the most severe manifestations of depression, it can strongly be suggested that in future studies the gender difference and the level of depression should be taken into account while investigating the association between these two disorders. Whether the occurrence of depression is more prevalent during the allergy seasons of atopic patients should also be taken into account in further studies, since it was very recently shown that subjects with allergic rhinitis reported to have had higher levels of general and mental fatigue during ragweed seasons (Marshall et al. 2002).

The finding of this thesis that maternal atopy increases the likelihood of a female proband’s depression needs to be replicated and further investigated by using other databases. Given that genetic factors might play a greater role in the etiology of depression in women than in men (Bierut et al. 1999, Kendler et al. 2001a), and that earlier twin-studies have preferred to accept that a common genetic rather than an environmental etiology exists behind these two disorders (Wamboldt et al. 1998, 2000), genetic investigations are recommended. Since maternal inheritance has been postulated to be one possible etiological factor in bipolar disorders via an association with mitochondrial DNA mutations, and because mitochondrial DNA mutations have also been found in persons with atopic disorders (Karvonen et al. 1999), it could be recommended that mitochondrial DNA would be worth an investigation to determine whether it has a role in the pathophysiology of unipolar depression as well. The other possible explanatory genetic mechanisms for the “parent-of origin” effect, such as the phenomenon of genomic imprinting (Davies et al. 2001, Strauch et al. 2001), should also not be overlooked while studying the genetic etiology behind the atopy-depression association.

The association of stress with stress hormones and cytokine secretion, in general, is complex and not fully understood (Kronfol & Remic 2000). There is, however, some evidence that stress is not uniform and non-specific reaction (Elenkov & Chrousos 1999); Stress has various dimensions (e.g., psychological vs. biological) and it may be considered in terms of its duration, quantity and quality as reviewed by Maddock and Pariante (2001). Different types of stressors might also have different effects on the immune response (Elenkov & Chrousos 1999). In addition, stress systems have different regulatory effects at systemic level than at local level in the body (Elenkov & Chrousos 1999). Thus, further investigations have been called for to clarify these complex interactions between the neuroendocrine and the immune body systems (Elenkov & Chrousos 1999, Kronfol & Remic 2000).

With regard to cytokine secretion, particularly during allergic inflammation, there is also a need for further investigations to deepen our understanding about the underlining profound immunological patterns and their putative associations with immunopathological changes in depression. Since there is evidence that the Th cell response pattern differs during different states of atopic disorders, it should be investigated in forthcoming studies, whether or not these Th response differences have an influence on the association between atopy and depression. As proposed by Schwarz et al. (2001), it is premature in major depression to formulate either a Th1- or a Th2-related hypothesis for all patients suffering from this disorder: There is some evidence that Th1 cytokines are associated with the pathophysiology of suicidality in major depression, whereas the cytokine profile might be towards Th2 dominance among non-suicidal depressive patients (Schwarz et al. 2001). Thus, the possibility that different types of depression might have different immunological features should also not be overlooked in any future studies.

The HPA-axis activation and the resultant hypercortisolemia could be, in general, seen as a negative feedback mechanism to suppress an otherwise exaggerated inflammatory response. Most probably, the HPA axis is also involved with the body-mind interactions between atopic disorders and depression. Since it is still unknown, what the exact mechanisms of altered HPA axis activity in the association between atopic disorders and depression might entail, additional investigations are needed. In addition to immunomediators of the HPA axis and the SNS, also several other hormones, e.g., sex steroids, growth hormones, and opioid peptides have been implicated in immunomodulatory processes (Buske-Kirschbaum et al. 2001). This should be kept in mind in further investigations.

In its entirety, the association between atopy and depression is in all likelihood multifactorial in its origin. Most probably this phenomenon is caused by complex associations between biological, psychological, environmental, and social processes during human development. In order to gain a deeper understanding about the association between these two disorders, controlled experimental studies using multidisciplinary research strategies are needed. In addition, large epidemiological studies are called for when the goal is to investigate, whether the association between atopic disorders and depression is specific to atopic disorders, or whether depression is related to other physical disorders as well. In addition, the strength of the association between atopic disorders and depression compared with that between other physical disorders and depression should also be assessed.

Finally, it has also been suggested that the association between various physical diseases – such as coronary artery disease, diabetes mellitus, and some immune-mediated illness – and depression might be explained by disturbed fatty acid and phospholipid metabolisms (Horrobin & Bennet 1999). Further studies are, however, needed to ascertain the pathophysiological mechanisms behind the association of atopic disorders and depression as well as behind the association of other physical disorders and depression. This would facilitate the search of whether there exist fundamental differences in relation to the mechanisms that govern the associations between different types of physical disorders and depression.