Blood Tests for Stress and Psychological Issues

Psychological issues are multi-faceted in etiology, stemming from biological, psychological, and sociological drivers. Underlying each of these drivers is the stress-reactive mechanism. Stress reactivity has served an important evolutionary role in human survival and is critically important on an acute basis in dealing with exogenous and endogenous threats. However, the effects of chronic stress are well-documented to cause, or exacerbate, most psychological disorders and many physiological diseases. Chronic exposure to stressors dysregulates endocrine and immune system functions, leading to sustained inflammatory responses, resulting in the pathogenesis of depression and other disorders (see my posts on psychoneuroimmunology and stress reactivity). Addressing chronic stress is one of the most important goals for psychologists.

By using results from key blood panels, psychologists, working with medical providers, can develop a much more comprehensive understanding of their patient’s needs, enabling them to craft more effective long-term treatment plans.

Blood tests for psychological treatment

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Three blood test panels that are well-validated in aiding clinical diagnosis and treatment of stress-reactive induced psychological (and physiological) disorders include:

1. Hormone
2. Cytokine
3. White Blood Count (including c-reactive protein panels).

Hormone Panels

Hormones are chemical messengers of the endocrine system released into the bloodstream from various glands. Many hormones are active throughout the body, but there is a manageable number that has been shown in research to be correlated with psychological disorders. These include testosterone, sex hormone-binding globulin (SHBG), dihydrotestosterone (DHT), estradiol, thyroid, and cortisol.

First, testosterone is an androgen (male sex hormone); however, testosterone is also present in females and is important for both men's and women’s psychological health. Testosterone is produced in the gonads (testes in men and ovaries in women) and to a lesser degree in the adrenal glands. Too high of a level of testosterone can lead to irritability, aggression, depression, and anxiety. Too low of a level can result in depression, low libido, poor cognitive functioning, lack of concentration, lethargy, sexual dysfunction, and anhedonia.

Often, blood results only consider total testosterone, which is the aggregate absolute value of testosterone in the blood. Total testosterone is not an adequate measure by itself, as it does not reflect how much testosterone is available to be used. Free testosterone indicates how much testosterone is bioavailable in the blood to be delivered to targeted receptors. Therefore, comparing free testosterone with total testosterone provides a more accurate overview of testosterone availability. For example, a person could have a high total testosterone level, but the majority of the testosterone could be bound and not free to exert influence and enact biochemical change.

Second, to evaluate the level that testosterone is bound, SHBG can be tested. SHBG is a protein produced by the liver, which attaches itself to three of the sex hormones found in men and women, including testosterone, DHT, and estradiol. SHBG controls how much of these hormones are bound or free. Although SHBG attaches to all three of these hormones, an SHBG test is most valuable from a psychological context to evaluate testosterone. Low levels of SHBG indicate that SHBG molecules may not be attaching themselves to enough testosterone. This allows more unattached testosterone to be available in the bloodstream, causing excessive free testosterone with related effects. High levels indicate that SHBG molecules may be attaching themselves to too much testosterone, causing low levels of free testosterone.

Third, DHT is a male sex hormone that is considered much more androgenic than testosterone. It is created when the 5 alpha-reductase enzyme converts testosterone to DHT as part of the testosterone hormonal pathway. High and low levels of DHT produce the same psychological effects as with testosterone but with much stronger results. Including DHT in blood results can be particularly helpful in identifying psychopathology due to DHT’s pronounced effects. This is particularly important for men on testosterone hormone replacement therapy and men and women using testosterone for performance-enhancing effects.

Fourth, estradiol is one form of estrogen. In women, the ovaries, breasts, and adrenal glands produce estradiol. Estradiol helps with the growth and development of female sex organs. Men also produce estradiol, although at significantly lower levels than women in homeostatic conditions. In males, the adrenal glands and testes make estradiol. Testosterone converts to estradiol through a chemical process involving the aromatase enzyme. This can be quite pronounced in men, particularly those who are under a regimen of testosterone replacement or are using performance-enhancing drugs with a testosterone-derived base. Therefore, it is important to evaluate estradiol values in men as well. Interestingly, estradiol levels that are too high and too low produce similar psychological results of depression, anxiety, decreased libido, sexual dysfunction, lethargy, anhedonia, and irritability.

Fifth, thyroid functioning is an important factor to consider in psychological well-being, particularly in women. Among other functions, the thyroid impacts metabolic activity. When stress is encountered the thyroid gland slows metabolism. The psychological effects of stress and thyroid disorders can often be indistinguishable and have a circuitous nature, meaning that stress can cause thyroid disease and thyroid disease can cause stress. Therefore, it is important to accurately diagnose if a stress-induced psychological disorder is discreet or indicative of thyroid pathology. Four measures of thyroid functioning are particularly relevant: thyroid-stimulating hormone (TSH), thyroxine(T4), triiodothyronine (T3), and antithyroid antibodies.

When thyroid levels are lower than the homeostatic level, TSH is secreted, causing the production of T4 and T3 to occur. T3 is the active form of thyroid hormone and 80% of T3 is converted from T4. Low levels of TSH can be indicative of high levels of cortisol and inflammatory stress-induced responses. Cortisol has also been shown to suppress TSH (Hage and Azar, 2012). The resulting lower TSH values can lead to a hypothyroid condition. Regardless of whether the thyroid is in a hypo or hyper state, numerous psychological conditions have been correlated, including depression, lethargy, affective disorders, cognitive impairment, memory loss, sleep disorders, anxiety, dysphoria, irritability, and even psychosis (Hage and Azar, 2012). One final measure of value when analyzing thyroid results is antithyroid antibodies, which when elevated, can indicate a potential autoimmune disorder (such as Hashimoto’s disease). From a psychological perspective, higher than normal antibodies have significantly increased correlations with depression (Hage and Azar, 2012).

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Sixth, cortisol is often considered to be the stress hormone. This is a great oversimplification as the stress-reactive process is quite complicated (see my post on stress reactivity), involving multiple psychophysiological systems, neurotransmitters, hormones, cytokines, immune functions, personal history, habituated patterns to stressors, environmental conditions, and many other factors. Nonetheless, cortisol assessment can provide valuable information on stress levels. Reliable and valid cortisol tests can be difficult to obtain, as cortisol fluctuates considerably throughout the day and is closely influenced by co-occurring hormones, neurotransmitters, and other sympathetic nervous system influences. Baseline longitudinal patterns of cortisol can be particularly effective at increasing validity. High levels of cortisol indicate active stress-reactive processes with the accompanying symptoms, including psychophysiological pathologies.

Cytokine Panel

Cytokines are pro- and anti-inflammatory markers that are released during the stress-reactive process. Inflammation has become well documented as a potential biomarker for psychopathology, especially with depressive disorders (Maydych, 2019). Additionally, authors have reported that depressive symptoms and negative cognitive bias may be reversible through the use of anti-inflammatory drugs (Kojima et al., 2009; Köhler et al., 2014; Maydych, 2019; Rohleder, 2014).

Research has found that patients diagnosed with depression exhibit higher levels of the specific cytokines interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) (Howren et al., 2009; Dowlati et al., 2010). Interleukins are naturally occurring proteins and are particularly important in stimulating immune responses, including inflammation.

• IL-1 is a pro-inflammatory cytokine responsible for activating lymphocytes (white blood cells that increase immune responses). IL-1 has been shown to be correlated with depression and serotonin inhibition (Farooq et al., 2017).
• IL-6 is released by macrophages (a type of white blood cell) and acts as a pro-inflammatory and anti-inflammatory molecule. High levels of IL-6 have been shown to be correlated with major depressive disorder (MDD), guilt, suicidal ideation, and schizophrenia (Brymer et al., 2019; Kundakovic et al., 2009; Sharma, Tun, & Graceson, 2008).
• TNF-α is a naturally occurring pro-inflammatory cytokine and has been shown to be correlated with MDD, mood disorders, anxiety, and other neurodevelopmental disorders (Postal et al., 2016).

White Blood Count (and C-Reactive Protein) Panel

White blood count (WBC) and c-reactive protein (CRP) tests provide a solid basis for immune system functioning. The immune system is quite active during chronic stress-reactive processes—particularly regarding inflammatory excitation, which contributes to virtually all psychological disorders. White blood cells fight infection; therefore, a WBC can detect hidden infections within your body and give a good proxy to immune system functioning. High and low values of white blood cells have been shown to be correlated with psychological disorders, including depression, mood disorders, and anxiety (Beydoun et al., 2016; Shafiee et al., 2017).

CRP is produced in the liver and released into the bloodstream in response to inflammation. CRP provides an indication of stress levels within the body and can be particularly valuable when evaluated at periodic time intervals during psychological treatment. Considerable research has indicated that high CRP values are correlated with depression and stress overall, and can in fact be used as a biomarker for depressive assessment (Pitharouli et al., 2021; Yungsheng, et al., 2011).

Conclusion

Psychological disorders entail a complicated range of psychopathology, involving causal factors of a biological, psychological, and sociological nature. Underlying these factors are stress-reactive psychoneuroimmunoendocrinological processes that involve many physiological systems. Understanding the dynamics of these neurochemical interactions can be tremendously complicated for the practicing psychotherapist. However, by using common blood panels in collaboration with medical providers, information can be readily ascertained, providing clinical value in developing treatment methodologies in conjunction with psychotherapeutic techniques, leading to better symptomatic understanding and more effective outcomes.