Genetic factors clearly increase the risk for depression.1 Even though numerous estimates of heritability have been published, usually based on twin studies, the specific genetic pathways are still being studied. Until recently, behavioral geneticists estimated that genetic factors accounted for about 40% of the variance in both males and females, with most of the remaining variance explained
by individuals’ unique environment.2 One the main findings in recent twin studies is that hereditability for depression is greater in females than in males.3 For example, a large study of Swedish twins revealed that hereditability was 29% and 42% in males and females, respectively.4 Another recent finding is that at least some genetic pathways include genes that may interact with a variety of childhood stressful life events, especially with maltreatment.5,6 These interactions have so far been limited to the serotonin transporter gene, but others may emerge as more knowledge is gained. From a clinical viewpoint, the implication is that the same event (e.g., maltreatment in childhood) may have a large depressogenic impact on one adolescent and little on another.

Major depression is relatively rare before puberty and equally distributed between boys and girls or slightly more prevalent in boys. Two changes occur with puberty. First, major depression becomes more frequent in both genders. Second, major depression and depressive symptoms become two to three times more prevalent in girls than in boys, as is the case in adulthood.

Multiple explanations have been proposed for this phenomenon, including genetic, hormonal, and social theories.3 Even though there might be genetic differences, the evidence is not conclusive.7 Recurrent estrogen withdrawal, beginning with puberty, may interfere with one of the functions of estrogens (i.e., the neutralization of corticoids released during stress), thus increasing the risk of stress-related depressive episodes.8 Among the many psychosocial factors proposed to explain the higher prevalence of adolescent depression in girls, theories that posit dissimilar affiliative needs have received a lot of attention. Even though both genders seek friends, girls are more likely to become emotionally invested in a friendship network and to have a higher turnover of close friends than boys. Thus girls are more exposed to disappointments in their relationships, and these disappointments may increase the risk for depression in adolescence.3,9

An extensive literature suggests that stressful life events often precede the onset of depressive episodes.10,11,12 It is noteworthy, however, that such events precede other psychiatric disorders as well.13 Some events seem to precipitate depressive episodes, whereas others may create a vulnerability to depression. Child maltreatment may operate both ways. Sexual abuse in childhood may increase the risk for depression, anxiety, eating disorders, and self-injurious behaviors in adolescence14,15 and create a vulnerability for adult depression.16,17,18 Child maltreatment, including physical and sexual abuse, is one of the childhood events most consistently associated with higher rates of depression and anxiety in adolescence and adulthood.14,19 Losses, such as a death in the family or loss of a close friend, seem to precipitate depressive episodes, and this association has some specificity; that is, losses are more likely to be associated with depression than with other disorders.13

Abundant evidence indicates that the quality of early attachments contributes to later depressive and anxious symptoms.20 Early emotional deprivation, which may result from disrupted attachments, may increase the responsiveness of the hypothalamic-pituitary-adrenal axis, thus altering responses to later stress.21,22,23 Clinical evidence also shows that disrupted attachments may be associated with severe early deprivation.24

Cognitive theories of depression suggest that individuals who have negative beliefs about themselves or about the world perceive stressors—such as stressful life events and their consequences—negatively. This pessimistic outlook may in turn increase the risk of depression in these individuals.25 Empirical evidence from longitudinal studies shows that negative cognitions and a negative explanatory style predict depressive symptoms, and the association is stronger in older children and adolescents.26,27,28 Overall, the evidence that negative cognitions increase the risk for depression in youth is solid. What is not clear, however, is whether these cognitions are an early manifestation of
clinical depression or a causal factor. Additionally, if negative cognitions are indeed a causal factor, the question of why certain children develop negative cognitions remains unanswered.

Anxiety disorders are the most common co-occurring conditions among youth with depression.25 Furthermore, anxiety disorders often precede the onset of depression, which has been observed in high-risk family studies as well as in clinical samples. Typically, anxiety disorders in school-age children are followed by major depression in adolescence.29,30,31 Interpreting the meaning of the sequence, from anxiety to later depression, is complex. Anxiety in childhood and depression in adolescence could be sequential manifestations of a single disorder (heterotypic continuity), and anxiety disorders, and perhaps symptoms, may indeed be a risk factor for major depression. Disruptive behavior disorders may also precede the onset of depression.32,33 Peer rejection, academic failure, and social isolation may increase the risk of depression in these children.34