The Causes of Depression and Available Treatments

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Depression TreatmentWhat Causes Depression?

Mood naturally fluctuates and everyone experiences highs and lows in their lives, but in some cases changes in mood can become long-lasting, debilitating and can impair someone’s ability to hold down a job or sustain meaningful relationships.

It’s estimated that 10% of people will at some points in their lives suffer from depression, a mood disorder characterized by several symptoms such as:

    • feeling sad
    • distressed
    • unmotivated
    • excessively tired
    • losing interest in once-pleasurable activities known as anhedonia.

 

Many people with depression also suffer from anxiety.

“It’s estimated that around 10% of people will at some points in their lives suffer from depression”

what a depressed brain looks like
Neuro-imaging studies reveal that many brain circuits that normally regulate mood are dis-regulated in depression.

Neuro-imaging studies reveal that many brain circuits that normally regulate mood are dis-regulated in depression.

Located deep within the brain, the amygdala processes highly salient stimuli such as rewards and potential threats.

In depression, the amygdala is overactive and responds excessively to negative events.

In turn, the amygdala connects to a set of brain regions that hone the physiological and behavioral response to emotional stimuli.

These areas include the medial prefrontal cortex, the nucleus accumbens, the hippocampus and the insula.

“In depression, the amygdala is overactive and responds excessively to negative events.”

The hippocampus is involved in memory formation and along with a [highlight]prefrontal cortex is particularly vulnerable to the effects of stress.

Depressed people are more susceptible to stress, which can cause physical changes in the brain, including atrophy of the hippocampus.

“…Depressed people are more susceptible to stress…”

These changes in depressed people may cause inappropriate responses to emotional events.

The medial prefrontal cortex is involved in regulating how strongly we react to emotional stimuli.

Treatment such as antidepressant drugs, cognitive behavioral therapy and electroconvulsive therapy affect the structure and function of these and other brain regions.

Animal models such as mice are critical in helping us understand the cellular and molecular changes underlying depression and develop better treatments.

Chronic stress can reduce normal brain plasticity

Although it’s impossible to know if a mouse is depressed, mice subjected to chronic stress show some symptoms similar to depressed humans, such as anxiety-like behavior, less social interaction and a lack of interest in normally pleasurable activities.

While not all human depression is triggered by stress, these models may still shed light on the biology of depression and they’re the closest scientists can get while studying mice.

As with humans, chronic stress in mice can lead to atrophy of the hippocampus and prefrontal cortex.

Mouse studies have also shown altered neuronal plasticity in various brain regions, including the hippocampus, prefrontal cortex, amygdala and nucleus accumbens.

In a healthy hippocampus, experiences can lead to changes in the connections between neurons resulting in learning.

These changes are referred to as plasticity. Chronic stress can reduce this plasticity.

Healthy brains also continue to produce new neurons in one part of the hippocampus. These new neurons slowly mature and integrate into the circuitry where they have a strong effect on hippocampal activity and behavior.

New neurons are also affected by stress.

They’re reduced in number in stressed brains. These effects may result from reduced levels of neurotrophins, proteins that increase neuronal growth and plasticity.

Reduced plasticity may stop the hippocampus from being able to properly regulate the stress response which may lead to a vicious cycle where stress perpetuates more stress.

“Reduced plasticity may stop the hippocampus from being able to properly regulate the stress response which may lead to a vicious cycle where stress perpetuates more stress.”

The hippocampus is particularly affected but there can be reductions in plasticity elsewhere in the brain, and together these changes could contribute to other symptoms of depression like anhedonia.

Whether these cellular changes seen in mice are involved in human depression remains unclear.

Most antidepressants available today rapidly increase the amounts of the neurotransmitters serotonin and/or norepinephrine in the synapse.

However, improvements in symptoms in patients and mice usually don’t occur until weeks after starting the treatment.

While the reasons for this delay aren’t fully understood, prolonged treatment with antidepressants can over time act to reverse some of the changes induced by chronic stress: increasing neurotrophin expression and rebooting hippocampal plasticity.

Non-chemical treatments for depression including electroconvulsive shock also promote hippocampal plasticity in mice.

Antidepressant treatment

Antidepressant treatment can also reverse stress-induced changes in other areas of the brain including the prefrontal cortex and reward circuitry.

Different treatments may target different regions to improve symptoms.

Recently, the drug ketamine was found to have rapid antidepressant effects in patients with depression as well as in rodent models with effects lasting for days. The mechanism behind this is an area of active research.

Different treatments may target different regions to improve symptoms.

Treating Depression with Ketamine

Ketamine blocks a type of synaptic transmission leading to activation of a number of signaling pathways and increasing neurotrophin expression.

These molecular changes result in increased plasticity in the prefrontal cortex and hippocampus and likely contribute to ketamine’s behavioral effects.

By studying the changes in the brain caused by chronic stress and how antidepressants like ketamine work to reverse them, researchers may find new targets for treatment or new drugs that could act more quickly, more specifically, or more effectively than currently available treatments.

If you or someone you know needs help with depression then call our Depression Center Hotline.

Did you know: We offer a free referral service that educates and helps you pick the best rehab for you or a loved one? Speak to a care specialist who can answer all your treatment-related questions, review your health insurance or out of pocket eligibility and locate a facility that is perfect for your needs. All you have to do is visit our drug treatment centers page to get started.