Skip to main content
Family of four plays at the beach with coastline in background

How untreated depression changes the brain

May 06, 2024 | Heather Shannon
a young man and his therapist sit near a window at a table in chairs and discuss his depression
The gold standard of treatment for major depressive disorder is a combination of medication and psychotherapy.

Feelings of sadness, moodiness and distress are common. But when they persist for more than a few weeks and intensify, these feelings can develop into clinical depression if left untreated.

Also called major depressive disorder (MDD), this condition can disrupt vital aspects of a person’s life, including sleep, alertness, temperament, mood and even cognition, says UCI Health Memory Disorder Services neuropsychologist Hayley B. Kristinsson, PsyD. Recent studies suggest that MDD may also alter the brain.

“MDD is associated with a number of neurological changes, including disrupted activity in certain regions, atrophy and cortical thinning,” notes Kristinsson, who treats people with a variety of neurological and cognitive disorders, including memory loss, dementia, stroke and Alzheimer’s disease.

How major depression alters the brain

Functional imaging studies of people with MDD have shown abnormal activity in the ventral limbic system, which primarily regulates emotions and involuntary physical processes, such as breathing and digestion.

The studies vary, but Kristinsson says all show that patients with MDD have both structural and functional brain differences.

“The amount of atrophy, or shrinkage, in the hippocampus, thalamus, amygdala and prefrontal cortex is related to the severity and length of the episode of depression.”

MDD also appears to alter the neurotransmission process in the brain, potentially making it more difficult for different regions to communicate with one another. Whether this is a cause or effect of serious depression is unclear.

Depression also may lead to decreased volume in the hippocampus, the part of the brain involved in memory. “Research has shown that the number of days of untreated depression has a direct impact on hippocampal size,” she says.

Signs of clinical depression

Not everyone who is unhappy and feeling depressed will experience MDD.

“The key difference is that feelings of sadness don’t cause significant impairment in an individual’s ability to function,” says Kristinsson, an assistant professor in the UCI School of Medicine Department of Neurology.

In fact, many depressed people may have no problem continuing to work, participating in hobbies or maintaining personal hygiene.

However, signs that depression has morphed into MDD include:

  • Depressed mood for more than two weeks
  • Loss or diminished pleasure in activities one previously enjoyed
  • Appetite changes
  • Sleep changes
  • Cognitive difficulties
  • Thoughts of death
  • Feelings of guilt or worthlessness

Kristinsson says some people may also have somatic symptoms, physical manifestations such as fatigue or body aches and pains. Children and adolescents suffering from severe depression more often display irritability or agitation instead of a depressed mood.

Just who is likely to develop MDD is a complex question, one that researchers are continuing to study. “But a number of temperamental, genetic, physiological and environmental factors can increase the risk for developing MDD,” she says.

Treatment for MDD

Despite the effects MDD has been shown to have on the brain, there is good news.

“When depression is treated effectively, many people experience a resolution of the cognitive changes, suggesting that these changes may not be permanent,” Kristinsson says.

The gold standard of treatment is a combination of medication and psychotherapy.

Medications known as antidepressants fall into several categories: selective serotonin reuptake inhibitors (SSRIs), serotonin/norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), atypical antidepressants, monoamine oxidase inhibitors (MAOIs) and N-methyl-D-aspartate (NMDA) antagonists.

Psychiatrists are extensively trained in the pharmacological management of mood disorders and can help identify which antidepressants are most appropriate for treatment.

To find a qualified therapist, Kristinsson suggests using the directory of the American Psychological Association. There are a number of therapy types for depression, including cognitive behavioral therapy and, in more severe cases, electroconvulsive therapy, vagal nerve stimulation and repetitive transcranial magnetic stimulation.

“Many therapists have websites where you can read about their approach to therapy and see if it fits your needs. The key is to find a therapist who practices in a style that suits you.”

Related stories