Major Depressive Disorder (MDD) is a serious mental health condition that affects upwards of 17% of the population at some point in life. For women, the odds are about twice as likely. 

MDD is more than just about “feeling sad.” For many, it’s like carrying a constant heavy weight that can alter how you see and interact with the world. Things you used to enjoy might not feel the same, and sometimes, everything just seems a bit tougher and less hopeful.

As we will discuss, the causes of MDD can be widespread and multifactorial – necessitating a holistic approach to evaluation and treatment. In this article, we will cover what MDD is, common symptoms and causes, and top labs to run bi-annually on patients with this disorder. 

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What is Major Depressive Disorder?

MDD is a prevalent and debilitating mental health condition. In fact, the World Health Organization (WHO) forecasts MDD to be the predominant mental health disease worldwide by 2030. MDD manifests in a range of symptoms, which primarily include a continuous state of sadness or a depressed mood and anhedonia, a reduced ability, or a complete lack of interest in activities that were once found pleasurable. Additional manifestations can include persistent feelings of guilt or worthlessness, a discernible decrease in energy or vitality, challenges with concentration, fluctuations in appetite, changes in psychomotor function that can be observed as either retardation or agitation, disturbances in sleep patterns, and thoughts related to suicide or self-harm (1). 

In clinical settings, the diagnosis of MDD is often grounded in the guidelines set forth by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). To be formally diagnosed with MDD as per the DSM-5, an individual must exhibit at least five of the symptoms mentioned earlier, with at least one of these being either a depressed mood or anhedonia. Moreover, these symptoms must be of sufficient severity to cause noticeable social or occupational impairment. It's also essential to ensure that the individual has not had a history of manic or hypomanic episodes, as these can indicate a different diagnosis (1).

What Causes Major Depressive Disorder?  

MDD is a multifaceted mental health disorder with a variety of contributing factors:

Environmental and Psychosocial Triggers 

Childhood trauma can predispose individuals to depression in adulthood due to neuroendocrine changes and cerebral cortex modifications. Brain scans indicate abnormalities in those with depression, such as hyperintensities in subcortical regions and decreased anterior brain metabolism (1).

Genetic and Cognitive Factors 

Genetic evidence suggests hereditary risks for MDD, with monozygotic twin studies indicating high concordance rates. Life events and certain personality traits are significant in MDD's onset. Learned helplessness theory links depression to perceived uncontrollable events, while cognitive theory suggests predisposed individuals can develop depression from cognitive distortions (1).

Stress and HPA Axis 

Chronic stress exacerbates depressive symptoms by dysregulating the HPA axis and elevating cortisol. Around 50% of depressed patients exhibit HPA axis disturbances linked to cognitive impairments and varying symptom severity (3). 

Neurotransmitters 

The monoamine hypothesis associated depression with decreased monoamine neurotransmission, evidenced by the efficacy of specific antidepressants. Yet, many patients are resistant to first-line treatments like SSRIs, suggesting other mechanisms. Depression is marked by changes in glutamate levels, with ketamine offering rapid relief and disruptions in GABA neurotransmission, prompting exploration into GABAergic treatments (3).

Neurotrophin Family and BDNF 

Neurotrophins, vital for neuroplasticity, decrease in depression. The neurotrophic hypothesis suggests this decline contributes to the disorder. Stress and antidepressants affect BDNF, which often drops in depressed patients (3).

Neuroinflammation 

Inflammation has a role in depression. Autoimmune or infectious diseases elevate depression risk, and pro-inflammatory treatments can induce depressive symptoms. Cytokines, inflammatory messengers, impact brain cells, emphasizing the importance of microglial balance between pro-inflammatory and anti-inflammatory states (3).

Gut-Brain Axis 

Gut health impacts brain function. Gut microbiota imbalances correlate with depression. Gut microbes affect the brain via the HPA axis, neurotransmitter levels, and immunity (3). 

Other Factors 

Depression's pathogenesis may also include oxidative stress, mitochondrial dysfunction, nutritional deficiencies, and circadian rhythm disturbances (3).

Major Depressive Disorder Symptoms

Major depressive disorder symptoms may include:

• Ongoing feelings of sadness, emptiness, or hopelessness.
• Diminished enthusiasm or pleasure in activities previously enjoyed.
• Either insomnia or hypersomnia.
• Increase or decrease in appetite leading to weight gain or loss.
• Constantly feeling low on energy or tired.
• Reduced speech and movement speed.
• Feelings of worthlessness or excessive guilt.
• Trouble focusing or making decisions.
• Frequent or recurring thoughts of death or suicide.

What Are The Benefits of Regular Lab Testing For Patients With Major Depressive Disorder?

Regular lab testing plays a significant role in managing patients with MDD. First of all, monitoring the physiological effects of antidepressant medications is an important part of treatment. For example, paroxetine, a commonly prescribed SSRI, has been linked to weight gain. Metabolic screenings become invaluable in such cases, as they can pinpoint alterations in lipid or blood glucose levels that might stem from medication use. Furthermore, certain antidepressants, like fluoxetine, can impact liver function over extended use.  

In addition to tracking medication effects, lab tests can also reveal underlying medical conditions or imbalances influencing depressive symptoms. Conditions such as hypothyroidism or vitamin D deficiency can present as depression, and regular screenings facilitate early detection. Addressing imbalances, like B vitamin or omega-3 fatty acid deficiencies, can augment the effectiveness of depression treatments. Furthermore, regular lab testing serves as a barometer for the success of treatment strategies. For instance, by assessing cortisol and inflammation levels, clinicians can gauge the effectiveness of interventions for patients with stress-aggravated MDD. Similarly, tracking gut health offers insights into improvements and the mitigation of inflammation.

Top Labs To Run Bi-Annually On Patients With Major Depressive Disorder

Functional medicine labs offer a variety of tests that can help tailor treatment to patients, allowing providers to optimize management strategies.

Organic Acids + Micronutrients

This test can assess various contributors to MDD, such as nutrient deficiencies, mitochondrial dysfunction, oxidative stress, and neurotransmitter metabolites that may be contributing to neurotransmitter imbalances (3). 

Comprehensive Stool Analysis

As the gut-brain axis has an impact on depression, analyzing gut microbiota can provide insights into imbalances that might be contributing to depressive symptoms (3).

Metabolic Panel

Given that some antidepressants (e.g., paroxetine) can lead to weight gain and other metabolic disturbances, it's recommended to monitor liver function, glucose levels and/or lipid levels for patients on antidepressants who are experiencing related side effects (3).

Inflammation and Stress Testing

Chronic stress, by dysregulating the HPA axis, often leads to elevated cortisol levels, a marker not just of stress but also of inflammation. Both elevated cortisol and inflammation can exacerbate depressive symptoms. Hence, regularly testing for cortisol and C-reactive protein provides a comprehensive view of the intertwined roles of stress, inflammation, and their contribution to depression, allowing for more informed treatment approaches (3).

Additional Labs to Check

Depending on the patient profile, analyzing thyroid function may be indicated, as this can also be a contributing factor to MDD (3).

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Summary

Major depressive disorder is a severe mental health condition projected by the WHO to become the leading mental health disease globally by 2030. This complex disorder can arise from a blend of environmental, genetic, neurochemical, and physiological factors, with symptoms ranging from persistent sadness to significant disruptions in daily life. Regular lab tests, especially those related to metabolism, neurotransmitters, gut health, and stress markers, are critical in MDD management. They not only monitor the effects of antidepressant medications but also help uncover potential underlying conditions mimicking depressive symptoms, facilitating a more tailored and effective treatment strategy for patients.