3. Comorbid diagnoses in children with MDD. 60%-80% of children meeting criteria for MDD have additional or comorbid disorders, such as anxiety, attention deficit disorder, substance abuse, and conduct problems, including lying, stealing, vandalism, and truancy. Comprehensive treatment planning must include and integrate comorbid disorders.

1. Genetic. The biologic offspring of depressed adults are up to three times more likely to have MDD, which may present earlier and recur more frequently. Research in the past decade implicated a polymorphism in the serotonin transporter promoter region (5-HTTLPR) as contributing to vulnerability to depression, although a recent meta-analysis has called this into question. Genome-wide linkage scan studies have identified areas of interest on chromosomes 15q, 17p, and 8p. There is also emerging evidence that adverse early life events can exert epigenetic effects, such as methylation status of gene regulatory regions. If confirmed, this study suggests a pathway for interaction between environmental and genetic factors influencing behavior and mood. In general, research suggests polygenetic inheritance, and interaction between genetic factors and life stress, in the development of depression.

2. Environmental. Distinguishing etiologic environmental factors that cause MDD from those that are coincidental to or a consequence of MDD is difficult. Children identify with, learn from, and share the mood of their parents and siblings. They are greatly affected by losses, especially parental death and divorce, and other stresses including trauma and abuse. The boundary between extended bereavement and MDD requires careful monitoring. From a neurobiological perspective, environmental factors affect stress hormone reactivity along the hypothalamic-pituitary-adrenal axis and may thereby exert an influence on the development of depression.

3. Organic. It is hypothesized that a biochemical imbalance in norepinephrine may contribute to the fatigue of MDD; an imbalance in serotonin may cause the problems of irritability and anxiety. Many acute medical conditions (including toxic ingestions, metabolic disturbances, and central nervous system infections) and several chronic medical illnesses can lead to changes in appetite, weight loss, decreased energy, or irritable mood.

4. Developmental. Adolescence is a time of change, of puberty, of separation, of transition from the familiar childhood family unit in the context of evolving autonomy. Intrapsychic depressive experiences become more differentiated and specific as emotional, language, cognitive, and social development proceed. Depressive symptoms are more common and the adolescent’s increasing self-centered perspective and sense of autonomy sometimes interferes with a clinical relationship. Young children with MDD may simply experience a vague and overwhelming discomfort, whereas older children may come to use stomachache, headache, or feeling fearful as words for internal mood states. Such abstract terms as depression and age-appropriate symptoms like blue, bored, empty, down and bothered, angry, or irritable are more likely to be used in early adolescence.

5. Transactional. The interaction of environmental contributions from school, home, and peers differs at different developmental stages and is influenced by genetic and organic factors. Some factors such as a special skill, relationship, or intellectual strength may foster resiliency; other factors such as family tension may act as a stressor. Some school-aged children with MDD lose their ability to concentrate in school, causing performance and peer relationships to suffer. Other children are able to control their mood swings while at school, only to collapse into a depressed or irritable mood on safe arrival home.

1. Infant/toddler. Both the persistently passive, unresponsive infant and the irritable, unsoothable, crying infant may suffer from the mood dysregulation associated with depression. Their clinical presentations may evolve into a quiet, inhibited toddler with arrested social development or an overactive, impulsive, and irritable preschooler. Key features may include anhedonia, fatigue, excessive guilt, and diminished cognitive abilities.

2. School age. In school-aged children with MDD, the expected pride associated with industry and enthusiasm may be overwhelmed by humiliation, defeat, irritability, and self-doubt. The child may become sad, isolated, rejected, and accident prone. Temper tantrums or morbid preoccupations with bodily injury, illness, abandonment, or death might emerge. There may be pediatric office visits for multiple somatic complaints. Bereavement may not gradually ease to normal functioning, but instead persist to a full depressive state.