A client is being screened for risk factors of depression. Which risk factor(s) is associated with the development of depression? (Select all that apply)

Choice A reason: Current substance use is a well-established and clinically significant risk factor for the development and perpetuation of major depressive disorder. Substances including alcohol, opioids, stimulants, and cannabis have direct neurobiological effects on monoamine neurotransmitter systems, including serotonergic, dopaminergic, and noradrenergic pathways, which are central to mood regulation. Chronic substance use leads to dysregulation of these systems, neuroinflammation, and disruption of the hypothalamic-pituitary-adrenal (HPA) axis, all of which predispose to or worsen depressive symptomatology. Comorbid substance use disorder and major depressive disorder represent a highly prevalent and bidirectionally reinforcing dual diagnosis. Choice B reason: A lack of coping ability is a recognized psychosocial risk factor for depressive disorders. Coping skills mediate the relationship between stressors and their psychological impact. Individuals who lack effective adaptive coping strategies — such as problem-solving, cognitive reframing, emotional regulation, and help-seeking — are more vulnerable to the persistent psychological distress that can precipitate and maintain clinical depression. Poor coping is associated with rumination, learned helplessness, and passive avoidance, all of which are cognitive and behavioral mechanisms strongly implicated in the etiology of depressive disorders. Building coping capacity is therefore a key component of both prevention and treatment. Choice C reason: A responsive support system is a protective factor against the development of depression, not a risk factor. Social support buffers the negative psychological effects of stressful life events, provides emotional validation and practical assistance, reduces feelings of isolation, and promotes adaptive coping. Research consistently demonstrates that individuals with strong, responsive social support networks have significantly lower rates of major depressive disorder compared to those who are socially isolated. A responsive support system therefore does not belong among the risk factors associated with depression and is correctly excluded from the correct answer set. Choice D reason: Prior episodes of depression represent one of the most robust and clinically significant risk factors for future depressive episodes. The concept of episode sensitization or "kindling" in affective disorders suggests that each successive episode of depression lowers the threshold for subsequent episodes, requiring progressively less severe external stressors to trigger recurrence. The number of previous episodes is directly correlated with recurrence risk, with individuals who have experienced 3 or more episodes of major depression having a recurrence rate exceeding 90%. This makes prior depressive episodes a critical factor in longitudinal risk assessment and treatment planning. Choice E reason: A family history of depressive disorder is a well-established genetic and epidemiological risk factor for major depressive disorder. Twin studies estimate the heritability of major depression at approximately 37%, with first-degree relatives of individuals with MDD having a 2 to 3 times higher lifetime risk than the general population. The specific genetic variants implicated include polymorphisms in the serotonin transporter gene (SLC6A4), brain-derived neurotrophic factor (BDNF) gene, and genes related to the HPA axis and circadian regulation. Family history also contributes to risk through shared environmental exposures and modeled behavioral patterns, making it both a genetic and environmental risk factor. Choice F reason: The presence of life and environmental stressors is a foundational risk factor in the biopsychosocial model of depression etiology. Adverse life events — including trauma, loss, financial hardship, interpersonal conflict, and occupational stress — activate the HPA axis, elevating cortisol levels and promoting neurobiological changes associated with depression, including hippocampal atrophy, reduced neurogenesis, and altered serotonergic and dopaminergic signaling. The diathesis-stress model proposes that environmental stressors interact with biological vulnerability to precipitate depressive episodes. Chronic and cumulative stressors are particularly harmful, as they sustain HPA axis activation beyond the individual's adaptive capacity.