In women with opioid addiction, these variants are linked to irregular menstruation, early menopause, worsened symptoms, and increased anxiety, depression, and chronic pain (65, 66); CAMK4, a kinase in calcium signaling, is linked to pain processing and synaptic plasticity (67); OSM, a cytokine, contributes to inflammatory and neuropathic pain (68); while TGFBR2, a receptor for TGF-β, is involved in pain-related cellular processes (69). This evidence concerns the gene CAMK4 and major depressive disorder.