Initial Presentation

Katie initially presented with complaints of severe depression, including persistently low mood, anhedonia, feelings of worthlessness, difficulties initiating and maintaining sleep and anxiety. She reported a long history of anxiety dating back to adolescence. Onset of depression, however, was more recent, approximately 6 months ago in the context of multiple significant psychosocial stressors, including a recent move to the United States from England, work-related stress and recent termination of a long-term romantic relationship.

After seeing a new primary care provider and expressing inability to get out of bed in the morning due to the severity of her depressive and anxiety symptoms, she was started on Zoloft (sertraline), which was titrated up to 150 mg/day. Additionally, she started weekly psychotherapy. At her initial visit, she expressed feeling unable to work and requested a four-week medical leave which was granted. Baseline blood work was ordered. She reported a past history of anemia but had not had any blood work done in years. No other significant medical history was noted by the patient and she was not taking any medications other than Zoloft.

Initial Relevant Labs

• Ferritin low at 19 ng/mL
• Iron, hemoglobin, hematocrit, red blood cell (RBC) count within normal limits
• Mean corpuscular volume (MCV) within the lab’s normal range, however functionally low at 82 fL
• Mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) trending low, but within the lab’s normal range
• Red cell distribution width (RDW) trending high, but within the lab’s normal range
• Total iron binding capacity (TIBC) elevated at 456 mcg/dL
• Unsaturated iron binding capacity (UIBC) elevated at 354 mcg/dL
• Transferrin saturation low at 14%

Working Diagnosis:

• Major Depressive Disorder, Single Episode, Severe
• Generalized Anxiety Disorder
• Iron deficiency without anemia

Initial Treatment

• Iron bisglycinate 27 mg twice daily with meals
• Vitamin C 250 mg twice daily with iron supplement
• Recommended to increase intake of the following heme and non-heme food sources of iron
  • Organic, grass-fed red meat
  • Organic beef or chicken liver
  • Clams, oysters, mussels and sardines
  • Spinach, beans and lentils paired with Vitamin C-rich foods like bell peppers for better absorption

Explanation

Iron deficiency is the most common micronutrient deficiency worldwide, according to the World Health Organization (Kumar et al., 2022). While iron status is most often assessed via a complete blood count (CBC) which measures hemoglobin and RBC levels, these tests often miss subtler forms of deficiency that can significantly impact brain health. Iron deficiency, even before it progresses to full-blown anemia, can exert profound effects on cognitive function, mood regulation and overall mental well-being. This is because iron serves as a vital cofactor in the synthesis of neurotransmitters crucial for proper brain function, including dopamine, serotonin and norepinephrine (Wu et al., 2023). Additionally, iron plays a pivotal role in supporting optimal thyroid function, another essential component of mental health (Soliman et al., 2017).

Failing to identify and treat subtler iron deficiencies can lead to a spectrum of neuropsychiatric symptoms, ranging from cognitive impairments to mood disorders (Lee et al., 2020). A comprehensive evaluation for iron deficiency should incorporate measures such as serum ferritin, serum iron, transferrin saturation, TIBC and UIBC, providing a more complete look at a given patient’s iron status. Ferritin reflects iron stores in the body and is arguably the most sensitive marker for iron deficiency (Bouri & Martin, 2018). However, ferritin is also an acute phase reactant, and can be elevated in cases that include inflammation or chronic disease, clouding the diagnosis of deficiency. In such cases, low transferrin saturation can be diagnostic (Al-Naseem et al., 2020).

Since the brain’s demand for iron is exceptionally high due to its involvement in various metabolic processes and neurotransmitter synthesis, even marginal deficiencies can have significant repercussions.

In Katie’s case, while her hemoglobin, RBC, and even serum iron values were in the normal range, other more sensitive markers like ferritin, transferrin saturation, TIBC, UIBC and MCV all painted the picture of a significant iron deficiency. She followed up with her primary care provider who was dismissive of the results. Considering the myriad roles of iron in the body and brain, Katie was recommended to start an iron supplement and begin incorporating more iron-rich foods into her diet in order to improve her iron status.

Follow-up Presentation

After two months of supplementation, Katie’s iron markers had started to rise into the normal range. Her symptoms of depression diminished to the point where she returned to work and felt she was performing well. She was sleeping through the night and feeling energetic throughout the day without needing to lean on excessive amounts of caffeine. She also noticed that her motivation to exercise and initiate activities with friends was significantly improved.

Follow-up Testing

• Ferritin; 32 ng/mL
• Iron, hemoglobin, hematocrit, RBC; within normal limits
• MCV; 88 fL
• MCH, MCHC, RDW; within normal limits
• TIBC; 378 mcg/dL
• UIBC; 319 mcg/dL
• Transferrin saturation; 25%

Follow-up Treatment

• Reduce Iron bisglycinate to 27 mg once daily with a meal
• Reduce Vitamin C 250 mg to once daily with iron supplement

Explanation

Katie’s depression was strongly rooted in a simple deficiency of iron and responded robustly to iron supplementation combined with vitamin C to aid in absorption and the incorporation of iron-rich foods into her diet. As optimal ferritin levels are closer to 50 ng/mL, we decided to continue the iron supplement but at a lower dose. Research continues to underscore the critical nature of iron sufficiency, with reported benefits in a number of different mental health conditions (Lee et al., 2020).

Case Summary

One of the core nutrients that should be evaluated in patient’s struggling with psychiatric and sleep disorders is iron. Iron deficiency, with and without anemia, is common, especially in menstruating women and those eating vegan or vegetarian diets. Fortunately, treatment for iron deficiency is usually straightforward, although tracking levels over time is advised to make sure patients maintain their levels in an appropriate therapeutic range. Once levels are optimized, providers should attempt to maintain levels with iron-rich foods as iron is a “goldilocks” mineral with both too little and too much causing potential problems.

In summary, recognizing the impact of iron deficiency on brain health is paramount in functional psychiatry. Beyond its role in oxygen transport, iron serves as a critical micronutrient for synthesizing neurotransmitters and supporting thyroid function, both of which are integral to optimal brain function. Relying solely on conventional measures like a CBC may overlook subtle deficiencies that can contribute to a spectrum of neuropsychiatric symptoms. Therefore, a comprehensive assessment of iron status, including serum ferritin levels, is essential for effectively managing mental health conditions and promoting overall well-being in psychiatric patients.