In Japan, neonatal cerebral depression is managed by neonatologists. Depression is a treatable medical illness in which persistently low mood or loss of interest, plus a cluster of cognitive, somatic, and energy changes, lasts at least two weeks and interferes with daily life. About 8% of US adults (21 million people) meet criteria for major depressive disorder in a given year, and roughly 280 million people are affected worldwide, making depression the leading global cause of disability.
Depression (ICD-10: F32 for major depressive disorder single episode, F33 for recurrent; DSM-5 305.xx codes) is a heterogeneous clinical syndrome characterized by a sustained negative emotional state combined with neurovegetative, cognitive, and behavioral changes. Major depressive disorder requires at least five of nine DSM-5-TR criteria for a minimum of two weeks, with at least one being depressed mood or anhedonia (loss of interest or pleasure). The remaining criteria are significant weight or appetite change, sleep disturbance (insomnia or hypersomnia), psychomotor agitation or retardation, fatigue, feelings of worthlessness or excessive guilt, impaired concentration or indecisiveness, and recurrent thoughts of death or suicide. The illness is staged by severity (mild, moderate, severe), by presence of psychotic, anxious, melancholic, atypical, or peripartum features, and by single versus recurrent episodes.
The key symptoms of Neonatal cerebral depression are: Persistently low or sad mood most of the day, nearly every day, present for at least two weeks; described as flat, empty, numb, or tearful., Marked loss of interest or pleasure (anhedonia) in activities that were previously enjoyable — hobbies, food, sex, social contact., Significant change in appetite or weight (more than 5% change in a month) without intentional dieting; can go either direction., Sleep disturbance — early morning awakening with inability to return to sleep is classic for melancholic depression; hypersomnia is typical of atypical depression., Psychomotor agitation (restlessness, hand-wringing, pacing) or retardation (slowed speech, movement, and thought) observable by others., Fatigue or loss of energy disproportionate to activity; small tasks like dressing or making a meal feel exhausting., Feelings of worthlessness or excessive, inappropriate guilt — not just self-criticism, but ruminative guilt about past events that is out of proportion..
Depression is diagnosed clinically through a structured interview, validated screening tools, and a focused medical workup to exclude conditions that mimic the syndrome. The DSM-5-TR requires at least 5 of 9 criteria for a minimum of 2 weeks, with at least one of those being depressed mood or loss of interest. Screening in primary care is recommended for all adults and adolescents and uses the PHQ-2 (two questions) followed by the PHQ-9 when positive — a score of 10 or higher on the PHQ-9 has 88% sensitivity and 88% specificity for MDD and grades severity from mild (5-9) to severe (20-27). For adolescents, the PHQ-A is the youth-adapted version. Suicide-risk assessment is mandatory at every visit (Columbia C-SSRS or the simpler PHQ-9 item 9). Medical workup excludes mimics: TSH for hypothyroidism, CBC for anemia, vitamin B12 and folate, vitamin D, comprehensive metabolic panel, and HIV/syphilis screening in higher-risk patients. Sleep apnea screening (STOP-Bang) is appropriate in patients with hypersomnia, snoring, or obesity. Substance use is screened with AUDIT-C, DAST, and direct questions about cannabis and stimulants. Bipolar disorder must be specifically excluded — every patient screened for depression should be screened with the Mood Disorder Questionnaire or directly asked about past hypomania/mania, because antidepressants prescribed for unrecognized bipolar depression can trigger mania or rapid cycling. Anxiety disorders, PTSD, eating disorders, ADHD, and personality features should be assessed because they alter treatment selection. Cultural and language-appropriate interviewing reduces under-diagnosis in minoritized populations.
About 60-80% of patients respond to first or second-line treatment within 12 weeks, and 30-40% achieve remission with the first adequate antidepressant trial (STAR*D). Median time to recovery from a single episode is 5-6 months. The illness recurs in 50-60% of patients after a first episode, 70% after a second, and 90% after a third — which is why continuation therapy for 6-9 months after remission and maintenance therapy after multiple episodes are standard. Untreated depression carries a 4-5% lifetime suicide mortality, more than 20-fold higher than the general population. Adequate treatment, including therapy plus medication and ongoing follow-up, reduces both relapse and suicide mortality substantially. Predictors of better outcome include earlier treatment initiation, treatment engagement, social support, absence of comorbid substance use, and prior treatment response. Treatment-resistant depression — failure of 2+ adequate trials — remains effectively treatable with esketamine, ECT, TMS, lithium augmentation, and combination strategies.
Refer to psychiatry for severe depression (PHQ-9 ≥20), suicidal ideation with plan or intent, psychotic features, catatonia, bipolar features (past hypomania/mania), treatment-resistant depression (failure of 2 antidepressant trials), perinatal depression, geriatric depression with cognitive symptoms, and complex comorbidity (substance use, eating disorder, severe personality disorder). Psychology referral is appropriate for evidence-based psychotherapy (CBT, IPT, behavioral activation, ACT) and for cases where therapy is the patient's preferred or primary modality.
Find specialists →Initial antidepressant effects (sleep, appetite, energy) emerge within 1-2 weeks; mood and motivation improvement typically by 2-4 weeks; full response by 6-8 weeks. Failure to achieve a 25% reduction in PHQ-9 by week 4 predicts non-response to that agent at week 8 and should prompt dose increase, switch, or augmentation. Psychotherapy (CBT, IPT) typically shows benefit by session 6-8 of a 12-16-session course. ECT response can occur within 1-2 weeks of starting a 3×/week course. Continuation-phase treatment for 6-9 months after remission reduces 1-year relapse from ~50% to ~25%.
Aim for 30-45 minutes of moderate-intensity aerobic exercise 3-5 days per week. Even 10-15 minutes of brisk walking can lift mood acutely. Resistance training twice weekly adds anxiolytic and cognitive benefits. Group-based exercise carries additional benefit from social connection. Effect sizes are largest in mild-to-moderate disease; severe depression still benefits but typically needs medication plus therapy alongside.
Most depression is well managed in primary care, especially with PHQ-9 monitoring and warm hand-off to therapy. For complex or treatment-resistant cases, look for a psychiatrist board-certified by ABPN and ideally trained in psychopharmacology, ECT, TMS, or perinatal psychiatry depending on need. Integrated behavioral-health clinics with psychiatry plus therapy plus care management deliver the best access and adherence outcomes. For severe and refractory illness, academic-medical-center programs with TMS, ECT, ketamine clinics, and DBS trials offer the full spectrum.
Medically reviewed by AIHealz Medical Editorial Board · May 12, 2026
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