Neuroscience of Depression

Neuroscience of Depression


Depression, is a mental disorder characterized by two or more weeks of low mood (feelings of sadness) often accompanied by low self-esteem, loss of interest in previously enjoyed activities, low energy, and sometimes even pain without a clear cause. Symptoms can affect a person’s overall life and can manifest as periods of depression separated by normal years or can nearly always be present. Depression affects approximately 3% of the world’s population, with rates being higher in the developed world, and is after only lower back pain as a leading cause of years lived with disability.

Symptoms and Related Conditions

Patients typically have multiple episodes of depression throughout their lifetime, during which the following symptoms are severe enough to cause problems in everyday activities most of the day nearly every day:

  • Sadness, tearfulness, emptiness, or hopelessness.
  • Angry outbursts, irritability or frustration, even over small things.
  • Loss of interest/pleasure in normal activities, such as sex, hobbies, or sports.
  • Sleep disturbances, including insomnia or oversleeping.
  • Tiredness and lack of energy such that even small tasks require extra effort.
  • Reduced appetite and weight-loss, or increased food cravings and weight gain.
  • Anxiety, agitation, or restlessness.
  • Slowed thinking, speaking, or body movements.
  • Feelings of worthlessness/guilt, experienced from fixating on past failures or self-blame.
  • Trouble thinking, concentrating, making decisions, and remembering things.
  • Frequent and/or recurrent thoughts of death, including suicidal thoughts, suicide attempts, or actual suicide.

Other conditions related to major depressive disorder include dysthymia and bipolar disorder.

Causes and Risk Factors       `

Though it’s not completely clear what causes depression, a number of factors may be involved such as:

  • Physical/biological changes and thus susceptibility to the disorder.
  • Degenerative neurological conditions, such as Multiple Sclerosis, Lupus, Parkinson’s disease, Alzheimer’s disease, Huntington’s Chorea, brain insults (Traumatic Brain Injury, Stroke) etc.
  • Brain chemistry abnormalities involving neurotransmitters (chemical substances involved in brain signaling) such as dopamine and serotonin.
  • Hormonal changes such as in pregnancy, postpartum (the weeks/months after giving birth), and endocrine disorders (thyroid issues), erectile dysfunction etc.
  • Genetic traits as demonstrated by increased likelihood of the disorder in those with affect relatives.

Depression typically begins during the teenage years, 20’s, or 30’s and is more often diagnosed in women, but can occur at any age regardless of gender. Factors involved in triggering depression include:

  • Some personality dispositions (such as low self-esteem and being too dependent, self-critical or pessimistic, having low distress tolerance).
  • Traumatic/stressful events (such as physical or sexual abuse, the death or loss of a loved one, a difficult relationship, or financial problems).
  • Blood relatives with a history of depression, bipolar disorder, alcoholism, or suicide.
  • Sexual orientation/identity unresolved issues.
  • History of other mental health conditions (such as anxiety disorder, bipolar disorder, eating disorders, or post-traumatic stress disorder etc).
  • Alcohol or recreational drug abuse.
  • Sudden Hormonal Changes or history of Thyroid Issues.
  • Serious and/or chronic illness, including cancer, stroke, long-term pain, or heart disease.
  • Certain medications (such as some high blood pressure medications or sleeping pills).

Underlying Mechanisms

Depression is not yet clearly understood, but researchers have close ideas. Current theories explaining the disorder include the following:

  • The Monoamine Theory postulates that insufficient activity of monoamine neurotransmitters (a class of chemical substances involved in brain signaling), such as serotonin, dopamine, and other adrenergic neurotransmitters, is the primary cause of depression. Brain areas of interest related to this theory include the locus coeruleus, striatum, and raphe nuclei. However, more recent evidence calls into question some aspects of this dominant theory.
  • Corticotropin-Releasing Hormone Receptor 1’s (CRHR1) increase and an increased frequency of dexamethasone test non-suppression in depressed patients suggests a relationship of the HPA axis (hypothalamic-pituitary-adrenal axis) with depression. They are believed to be the causes of reduced volume of the hippocampus (a brain area related to memory, learning, and emotion) in this disorder. This process occurs when there are high stress levels for a prolonged amount of time. The implication of that theory is that chronic stress not only leads to chronic diseases, compromised immune system it can also trigger depression.
  • Several models of structural and/or functional abnormalities in emotional circuits also exist:
    • Limbic Cortical Model – proposes hyperactivity of the ventral paralimbic regions (fear/stress response) and hypoactivity of frontal regulatory regions in emotional processing (rationalizing, problem solving area).
    • Cortico-Striatal model – hypothesizes that abnormalities of the prefrontal cortex in regulating striatal and subcortical structures results in depression
    • Yet another model suggests hyperactivity of salience structures in identifying negative stimuli and hypoactivity of cortical regulatory structures results in negative emotional bias and depression.
  • Research has also shown that the hippocampus is smaller in some depressed people. It has been shown that higher number of bouts of depression correlates with smaller hippocampi. This finding is tied to the CRHR1 hypothesis described above since experts believe that stress can suppress the production of new neurons in the hippocampus. Researchers have found links between slow production of new neuronal connection in the hippocampus and low moods. They hypothesize that maybe this is the reason why antidepressants do take a lot time to have a positive effect on mood. Animal studies have shown that medications need several weeks to trigger neurogenesis.

Prevention, and Treatment Routes

Preventing depression is not entirely possible, but some strategies that may help are:

  • Controlling stress in order to increase resilience, distress tolerance and self-esteem,
  • Maintaining important social relationships to better endure stressful times,
  • Seeking treatment as soon as possible to prevent worsening of the condition,
  • Maintaining long-term treatment to prevent relapse.

Treatment options include medications and psychotherapy, specifically:

  • Medications:
    • Selective serotonin reuptake inhibitors (SSRI’s)
    • Selective norepinephrine reuptake inhibitors (SNRI’s)
    • Atypical antidepressants
    • Tricyclic antidepressants
    • Monoamine oxidase inhibitors (MAOI’s)
    • Mood stabilizers and antipsychotics or anti-anxiolytics and stimulants, which may respectively be used long- and short-term.
  • Psychotherapy:
    • Cognitive behavioral therapy
  • Other forms of therapy:
    • Hospital and residential treatment,
    • Brain stimulation techniques (electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS))


Depression is unfortunately an all-too-common debilitating condition. However, proper diagnosis and management can help sufferers lead a relatively normal life.

Add Comment