Depression and Suicide _ ______________________________________________________________________
Early-Life Adversity Early-life adversity (ELA) describes childhood trauma, abuse, or caregiver abandonment, and research demonstrably links ELA with inflammation and later depression. The brain and immune system are incompletely formed at birth; maturation is shaped by interaction with the postnatal environment. ELA can affect immune development, which can adversely affect development of brain regions involved in mood, cognition, and behavior [50]. ELA can also promote neuroendocrine, physiologic, behavioral, and psychologic changes that impair normal development of brain systems involved in learning, motivation, and stress response. A chronically over-reactive stress response system can impair stress response, emotional regulation, and impulse control in adulthood—a biologic prim- ing for later depression [51; 52; 53; 54; 55]. The neurobiologic correlates of ELA and inflammation are striking, and impact on adverse clinical outcomes is demonstrated across psychiatric disorders [56]. Depression as Systemic Illness More than 80% of patients with depression have medical comorbidity, and depression is viewed as a systemic illness [57]. Chronic inflammatory states and hyper-reactive immune response to stress in patients with MDD and ELA likely con- tribute to the high prevalence of inflammatory medical disor- ders in this population. The relationship between inflamma- tion, inflammatory disorders, and depression is bidirectional; as these medical disorders persist, the chronic inflammatory state promotes the onset of depression [58; 59]. Patient-Treatment Matching The limitations of standard pharmacotherapy for MDD have prompted efforts to identify patient subtypes for effective treatment matching. In a 2017 study, functional magnetic reso- nance imaging (fMRI) brain scans of 1,200 patients with MDD were analyzed and four unique biotypes (subtypes), distinct by patterns of abnormal functional connectivity in limbic and frontostriatal networks, were identified. For example, patients with biotype 1 showed severely impaired connectivity in brain regions that regulate fear-related behaviors and reappraisal of negative emotional stimuli. Treatment response to repetitive transcranial magnetic stimulation differed by subtype and was predicted with very high accuracy [60].
disorders are categorized into depressive (unipolar) and manic depressive (bipolar) conditions. Unipolar mood conditions are divided into MDD and persistent depressive disorder [21]. Biologic measures of depression are not available for clinical practice, and diagnosis is made through psychometric findings, fulfillment of diagnostic criteria, patient history, and clinical impression [61]. SIGNS AND SYMPTOMS OF DEPRESSION Depression is often difficult to diagnose because patient pre- sentation is diverse, and a mood disorder may not be obvious. Patients with MDD may not seek help for mood problems, but their presentation can reflect current depression. Presentations associated with depression in patients not complaining of depressed mood or anhedonia include [10; 62]: Clinical Factors • Previous personal or family history of depression • Psychosocial adversity (divorce, domestic violence) • High healthcare system utilizers • Chronic medical conditions (especially cardiovascular disease, diabetes, neurologic disorders) • Other psychiatric conditions • Times of hormonal challenge (e.g., peripartum)
Symptom Factors • Unexplained physical symptoms • Chronic pain
• Fatigue • Anxiety • Substance abuse
• Weight gain or loss • Sleep disturbance • Dampened affect • Complaints about memory, concentrating, making decisions Assessment of the presence of depression can also be made through signs and symptoms of the following cognitive, affec- tive, and behavioral domains [10; 21; 22]. Appearance and Affect Although most patients with MDD appear normal upon initial presentation, patients with severe symptoms can exhibit poor grooming and hygiene and changes in weight from previous contact. Psychomotor retardation may be present, reflected by a slowing or absence of spontaneous movement, flat affect, and sighs and long pauses. This represents a diminished reactivity in emotional expression. Some patients with MDD may display psychomotor agitation, reflected by pacing, hand wringing, or hair pulling [10; 21; 22].
ASSESSMENT AND DIAGNOSIS OF DEPRESSION
As noted, depression is a disorder of mood involving distur- bances in emotional, cognitive, and behavioral regulation. The mood disorder is considered secondary if it occurs in association with substance abuse or withdrawal and/or certain medications. The mood disorder is called primary if it does not occur in association with these conditions. Primary mood
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