Risk factors for depression
The prevalence of depression is determined by exposure to risk factors that precipitate or maintain episodes of depression. With few exceptions, the prevalence and incidence of depressive disorders are higher in females than males, beginning at mid-puberty and persisting through adult life, although the determinants of gender differences are far from being established . Socio-economic risk factors that might conceivably be addressed include low income and financial strain , unemployment , work stress , social isolation  and poor housing . Relative poverty and unemployment are associated with a longer duration of episodes of depression rather than their onset , and depressive symptoms are also associated with subsequent unemployment and loss of family income . Fixed factors such as a family history of depression  and personality  play a part but it is uncertain whether they act independently of other risk factors . Physical health has been related to the onset and persistence of depression . Stressful life events pose a greater risk for depression among women compared to men  and, like social support , these events also seem to be both a cause and a consequence of depression . Many other candidate risk factors for depression exist, including for example childhood social disadvantage , childhood maltreatment , cigarette smoking , alcohol and drug abuse , and anxiety disorders .
However, the study of risk factors for depression suffers from limitations: First, it is often difficult to distinguish between their effects on the onset and on the course of depression; second, several risk factors may interact and be either a cause or a consequence of depression; and finally, few studies have controlled for candidate risk factors with comprehensive models, possibly due to the many possible factors involved.
The predictD-Spain study
Drawing on our experience as part of the predictD international study , the predictD-Spain study aimed to improve certain methodological aspects, extending the follow-up for three years, considering genetic factors in the equation (the predictD-Gene study), and studying professional and organizational factors as contributors to both the onset and persistence of episodes of depression (the predictD-Services study).
A genetic predisposition to depression may be a potential risk factor in the development of depression. Although the neurobiological equivalent of the predisposition remains unclear, the brain's serotonin system appears to play an important mediating role. Individuals with the 5-HTTLPR s/s genotype are more prone to develop depression , and this genotype may determine stress coping mechanisms and thereby increase stress vulnerability .
A recent systematic review identified only 17 longitudinal studies of depression in primary care, most of which involved small sample sizes or were relatively short-term . The most usual risk factors for persistence of depression in primary care were severity and chronicity of the depressive episode, the presence of suicidal thoughts, poorer self-reported quality of life, lower self-reported social support, experiencing key life events, antidepressant use, lower education level and unemployment. However, whether differences exist in depression outcomes between patients whose depressive disorders are recognized and those whose disorders are unrecognised in primary health care is unclear .
In Spain, general practitioneers (GPs) failed to detect 30% of depressed patients , while only 30% of those diagnosed received appropiate treatment . The suitable use of antidepressants, medication adherence, and 'case management' between mental health specialists and primary care professionals might be some of the best predictors for the recovery from depression . Thus, the need to control for these factors in predictive models on the persistence of depression in primary care is clear .
Each anxiety disorder and panic attack appears to confer an independent risk for the onset of major depression  and an association between psychopharmacological treatment for generalized anxiety disorders and a lower risk of depression has been suggested . However, anxiety disorders are not always adequately detected and managed by GPs . Consequently, the detection and treatment of anxiety disorders might also condition the onset of depression.
Several GP factors are related with their ability to detect and manage psychosocial problems: gender, interview training, previous doctor-patient relationship or psychosocial orientation [39–42]. Concerning organizational factors, a recent meta-analysis showed that collaborative care for depression improved the outcome . The most commonly used intervention features in the collaborative care were patient education and self-management, monitoring of depressive symptoms and treatment adherence, decision support for medication management, a patient registry, and mental health supervision of care managers . Finally, one of the best professional-organizational factors associated with the recognition and good management of psychosocial problems in primary care is the length of interviews [42, 45].
Accordingly, we aim to develop comprehensive models to predict the onset and persistence of episodes of depression in primary care. As well as individual, genetic, and environtmental risk factors, we are also considering other professional and organizational factors. In this report we explain the general methodology of the study and evaluate the reliability of the questionnaires used.