Table 5 Summary of potential testing parameters established via expert heuristic evaluation

Thiamine (vitamin B1)

In thiamine deficiency, the activity of the oxidative decarboxylation of pyruvate and α-ketoglutarate is decreased, resulting in impaired cellular function because of decreased production of ATP (adenosine triphosphate) [34]

Riboflavin (vitamin B2)

Riboflavin is involved in tryptophan and iron metabolism [10, 52]. Deficiency is rare

Niacin (vitamin B3)

Essential cofactor of dopamine and serotonin biosynthesis (Figs. 2 and 3)

Pantothenic acid (vitamin B5)

Involved in the development of the CNS and in the formation of acetylcholine, which is linked to depression [10]. Deficiency is rare

Pyridoxine (vitamin B6)

Essential cofactor of dopamine and serotonin biosynthesis (Figs. 2 and 3)

Biotin (vitamin B7)

Essential enzyme cofactor in the metabolism of fats and amino acids [53]. Deficiency is rare

Folate (vitamin B9)

Essential cofactor of dopamine and serotonin biosynthesis as a precursor of SAMe (see 2.3.1) (Figs. 2 and 3)

Cobalamin (vitamin B12)

Vitamin B12 deficiency is a common cause of various neuropsychiatric symptoms [31]. Higher levels correlate with improved depression treatment outcomes [10]

Ascorbic Acid (vitamin C)

Essential cofactor of dopamine, adrenaline (Fig. 2) and serotonin (Fig. 3) biosynthesis and essential in iron metabolism (see 2.3.1)

Ergocalciferol, cholecalciferol (vitamin D)

Essential cofactor of dopamine and serotonin biosynthesis. One of the most prevalent vitamin deficiencies (see 2.3.1)

Iron (Fe)

Essential cofactor of dopamine and serotonin biosynthesis (Fig. 3)

Magnesium (Mg)

Essential cofactor of adrenaline biosynthesis (Fig. 2)

Copper (Cu)

Essential cofactor of adrenaline biosynthesis (Fig. 2)

Zinc (Zn)

Essential for methylation [54]. Deficiency is common in patients with depression [55]

Potassium (K)

Essential for the proper functioning of the nervous system

Phosphate (PHOS)

Will be elevated when vitamin D is overdosed [56]

Dopamine

Classic target of some antidepressant medications. Not usually tested

Serotonin

Classic target of some antidepressant medications. Not usually tested

Oxytocin

Involved in biological processes that are altered in patients with depression. Mechanisms involved with depression part of ongoing research [57]. Not usually tested

β-endorphin

A growing body of evidence points to a strong link between opioid system dysfunction and psychopathology [58]

SAMe (S-Adenosyl-methionine)

Essential for methylation, e.g., in the metabolism of folate and cobalamin metabolism. Essential cofactor for biosynthesis of adrenaline and melatonin (Figs. 2 and 3)

PUFAs: fatty acids

Omega 3/n-3

EPA, DHA

Essential cofactor of dopamine and serotonin biosynthesis (see Figs. 2 and 3). Typically analyzed together with Omega 6/n-6. Varying standards for testing [42]

(essential) amino acids

Essential cofactors of dopamine and serotonin biosynthesis and profound impact on neurotransmitter synthesis and metabolism (Figs. 2 and 3)

DHEA-S (+ cortisol)

Most abundant steroid hormone in the circulation. Converted to sex steroid hormones. Important indicator of hormone health

Sex steroid hormones: E2, E1, P4, TTBF

Significant influence on brain physiology, modulating and stimulating effect on neuronal activity in cognition, behavior and agonistic or antagonistic effects toward various neurotransmitters

Thyroid panel: TSH, T4, T3, rT3  + autoimmune conditions

Thyroid conditions are frequently associated with depression. Hypothyroidism is considered a cause of or strong risk factor for depression, mainly in women

PRL

Prolactin (PRL) is regulated by dopamine in the brain, which makes it a possible indicator of dopamine function

HGH, IGF-1

Promising research links deficiency in HGH and its product IGF-1 to depression

Homocysteine

Indicator of methylation-related polymorphisms (e.g. MTHFR) (48, 49)

CRP

Indicator of inflammatory comorbidities that can trigger or aggravate depression

Standard blood count

Standard starting point for diagnosis