Understanding Depression: Symptoms and Theories

• Depression is considered the leading cause of disability worldwide and despite available treatments, a high proportion of patients don't recover and face high relapse rates.
• According to the DSM-5, depression diagnosis requires experiencing five or more symptoms during a two-week period, with at least one being depressed mood or loss of interest/pleasure.
• Symptoms include depressed mood, diminished interest/pleasure, significant weight changes and insomnia or hypersomnia
• Further symptoms are psychomotor agitation/retardation, fatigue, feelings of worthlessness/guilt, impaired thinking/concentration/indecisiveness, and recurrent thoughts of death/suicide.
• These symptoms must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Neurotransmitter Deficiency Theory

• A well-known theory about the deficiency of neurotransmitters in the brain
• The first antidepressants (isoniazid and iproniazid) were initially tuberculosis medications in the 1950s
• Clinicians observed improved mood in patients with low mood and further studies showed that these medications inhibit the enzyme that breaks down monoamine neurotransmitters
• The increase in neurotransmitters led to the initial conclusion that depression was due to a deficiency of these neurotransmitters

Main Neurotransmitters

• Serotonin
• Dopamine
• Norepinephrine
• They are all monoamines

Neurogenesis Hypothesis

• For decades, it was believed that the number of neurons in the adult brain was fixed with the majority produced during prenatal and perinatal periods
• Plasticity was thought to be achieved by strengthening synapses
• Research focused on neurotransmitter receptors, release mechanisms, and synapse structure/number
• The idea of new neurons being produced in adulthood (neurogenesis) has led to additional theories about the biology of depression

Additional theories of depression

• Dysfunction in the hypothalamic-pituitary-adrenal axis
• Alterations in the inflammatory response
• Involvement of the oxidative stress system

Neurogenesis Importance

• Stress and raised glucocorticoids decrease neurogenesis in animal models, correlating with increased depressive-like behavior
• Antidepressants or exercise increase neurogenesis and decrease depressive-like behaviors
• Neurogenesis in the adult hippocampus may underlie the development or recovery from depression

Confirmation of Neurogenesis Importance

• Postmortem brains of depressed patients showed decreased levels of new neurons, while individuals taking tricyclic antidepressants had increased levels
• Neurogenesis in the adult brain occurs in neurogenic rations, specifically the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus
• Antidepressants, ECT, and increased exercise increase neurogenesis
• While antidepressants quickly increase neurotransmitter concentrations, patients typically feel better after several weeks
• Mood improves as neurons grow and form new connections, a process that takes weeks

Animal Studies and Neurogenesis

• Antidepressants induce growth and enhance branching of neurons in the hippocampus
• Increased neurogenesis also occurs after ECT treatment in animals
• Studies detected an increase in hippocampal volume in patients after ECT, potentially due to changes in neurogenesis

Oxidative Stress

• Oxidative stress, an imbalance between oxidants and antioxidants, reduces neurogenesis
• Excess reactive oxygen species (free radicals) decrease neurogenesis levels

Meta-Analysis

• Meta-analyses have shown a correlation between depression and different levels of oxidative stress
• Measurements of oxidative stress in circulation are examined, as neurogenesis cannot clearly be looked at in living individuals

Holistic Approach

• Remember that mood disorders are complex and not isolated in life
• A holistic approach is likely the most beneficial for helping individuals suffering from mood disorders

An overview of depression, the leading cause of disability worldwide, and its symptoms according to the DSM-5. It highlights the criteria for diagnosis, including mood changes, and other psychological and physical symptoms. Also it touches on the neurotransmitter deficiency theory.