Secondary medical causes of depression

Major depressive disorder is a mood disorder defined by 5 or more of 9 major depressive episode symptoms, including depressed mood or anhedonia, present nearly every day for at least 2 weeks and causing significant functional impairment. Diagnosis is clinical, screened with the Patient Health Questionnaire. First-line treatment is cognitive behavioral therapy, a selective serotonin reuptake inhibitor (SSRI) such as sertraline, or both, escalating to augmentation, esketamine, or electroconvulsive therapy for refractory or acutely suicidal presentations.

Hypothyroidism is thyroid hormone deficiency, most commonly caused by autoimmune (Hashimoto) thyroid failure in iodine-sufficient countries, diagnosed by an elevated thyroid-stimulating hormone with a low or normal free thyroxine. First-line treatment is levothyroxine dosed at 1.6 mcg/kg lean body weight orally once daily, titrated using thyroid-stimulating hormone rechecked no sooner than 6 weeks after any dose change.

Cushing syndrome is the clinical state of chronic glucocorticoid excess from any cause, most often exogenous glucocorticoid use, diagnosed by demonstrating loss of normal cortisol suppression or diurnal rhythm with at least two of three screening tests. Treatment targets the underlying source: withdrawal or tapering of exogenous steroid, transsphenoidal surgery for a pituitary cause, or adrenalectomy for an adrenal or ectopic tumor, with steroidogenesis inhibitors reserved for persistent or unresectable disease.

Pernicious anemia is autoimmune atrophic gastritis that destroys gastric parietal cells and abolishes intrinsic factor production, causing vitamin B12 malabsorption, megaloblastic macrocytic anemia, and a potentially irreversible myelopathy and neuropathy. Diagnosis rests on a low or borderline B12 with an elevated methylmalonic acid, confirmed by anti-intrinsic factor antibody, and treatment is lifelong vitamin B12 replacement.

Parkinson disease is a slowly progressive neurodegenerative disorder from loss of substantia nigra dopaminergic neurons with alpha-synuclein Lewy body pathology, presenting with asymmetric rest tremor, bradykinesia, rigidity, and gait impairment. Diagnosis is clinical; first-line treatment is levodopa-carbidopa or a dopamine agonist.

Ischemic stroke is sudden focal neurologic deficit from arterial occlusion confirmed by infarction on neuroimaging. Diagnosis relies on urgent noncontrast head CT to exclude hemorrhage; treatment is IV alteplase within 4.5 hours and mechanical thrombectomy for large-vessel occlusion within an extended window, followed by antiplatelet therapy and risk-factor control.

Obstructive sleep apnea is repetitive upper airway collapse during sleep, diagnosed by an apnea-hypopnea index of 5 or more per hour with symptoms, or 15 or more per hour regardless of symptoms, and treated first with weight loss plus positive airway pressure.

Pancreatic ductal adenocarcinoma usually presents late, with painless obstructive jaundice from a head-of-pancreas mass, weight loss, and sometimes new-onset diabetes or migratory thrombophlebitis. Pancreas-protocol CT defines resectability, endoscopic ultrasound with fine-needle aspiration confirms tissue diagnosis, and only complete surgical resection with pancreaticoduodenectomy offers a chance of cure, which most patients cannot receive.

HIV-associated neurocognitive disorders (HAND) span a spectrum from asymptomatic neurocognitive impairment to HIV-associated dementia, caused by chronic HIV infection and inflammation of CNS microglia, and occur regardless of antiretroviral treatment status; diagnosis is one of exclusion after ruling out opportunistic and metabolic causes of cognitive decline, and antiretroviral therapy initiation or optimization is the primary treatment, with efavirenz avoided for its neuropsychiatric effects.

Alcohol use disorder is a chronic pattern of drinking meeting 2 or more of 11 DSM-5 criteria within a 1-year period, screened with the CAGE or AUDIT-C and confirmed by history. First-line management combines a brief behavioral intervention and cognitive behavioral therapy with naltrexone or acamprosate, reserving disulfiram for highly motivated patients who can maintain abstinence.

Persistent depressive disorder (formerly dysthymia) is chronic, low-grade depressed mood present more days than not for at least 2 years with at least two associated symptoms and no symptom-free interval longer than 2 months. First-line treatment is long-term individual insight-oriented psychotherapy or cognitive behavioral therapy (CBT); a selective serotonin reuptake inhibitor (SSRI) such as sertraline is added when psychotherapy alone fails.

Delirium is an acute, fluctuating disturbance of attention and awareness caused by an underlying medical, toxic, or metabolic insult. Diagnosis rests on the Confusion Assessment Method; management is identification and treatment of the precipitating cause plus withdrawal of deliriogenic drugs, reserving antipsychotics for safety only.