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122 Laboratory Medicine in Psychiatry and Behavioral Science
Cross-references Event-Related Potential Testing
Multiple Sclerosis
Evoked potential (EP) testing (continued)
Daube JR: Clinical Neurophysiology. Philadelphia, PA, FA Davis, 1996
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
https://t.me/med1917
123 Laboratory Tests
Fecal blood testing
Type of test Stool
Background and explanation
of test
Blood from the upper GI tract may appear as black tarry
stool, whereas blood from the lower GI tract may appear as
frank blood in stool. In the early stages of GI diseases such
as cancer, no visible signs of bleeding may be seen, but occult
blood may be present. This can be detected using a fecal oc
-
cult blood test (FOBT). A positive test may suggest the pres-
ence of gastric ulcer or early localized colon cancer.
There has been considerable controversy about the validity
of the FOBT, even for office-based sampling. Multiple sam
-
ples collected at home according to package instructions are
in fact superior to a single sample collected in the physician’s
office.
The fecal immunochemical test (FIT) is a newer test that uses
an antibody to detect human hemoglobin in stool. Only two
samples are needed for this test, and fecal material is col
-
lected with a brush, so the test has higher patient acceptance
in addition to having improved reliability. FIT testing is of-
ten combined with stool DNA testing (Cologuard) to im-
prove sensitivity.
Relevance to psychiatry and
behavioral science
Upper GI bleeding can occur during treatment with SSRIs or
SNRIs. The risk is increased when medications such as
NSAIDs are used concomitantly.
Preparation of patient Package instructions are provided for sample collection. For
the FOBT, patients should be instructed to avoid aspirin and
dental procedures before testing. Foods that should be
avoided for 2–3 days before testing are listed in the Interfer
-
ing Factors section below. For FIT and FIT-DNA, no dietary
or other restrictions are needed.
Indications •
Routine health screening (yearly, starting at age 50 years)
• Change in stool pattern or appearance
• Workup for anemia
Reference range Negative for blood
Positive test • Ulcer
• Cancer
• Trauma from swallowed objects
• Diverticular disease
• Colon polyps
• Inflammatory bowel disease
• Hemorrhoids
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124 Laboratory Medicine in Psychiatry and Behavioral Science
Fecal blood testing (continued)
Interfering factors False-positive FOBT results are seen when certain foods or
drugs have been ingested, including beets, broccoli, rad
-
ishes, grapefruit, carrots, turnips, horseradish, red meat,
fish, poultry, iron, colchicine, iodine, or boric acid.
False-negative FOBT results are seen when vitamin C has
been ingested.
For all tests, intermittent bleeding may not be detected.
Cross-references Anemia
Collins JF, Lieberman DA, Durbin TE, et al: Accuracy of screening for fecal occult blood on a single stool
sample obtained by digital rectal examination: a comparison with recommended sampling practice.
Ann Intern Med 142:81–85, 2005
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Imperiale TF, Ransohoff DF, Itzkowitz SH, et al: Fecal DNA versus fecal occult blood for colorectal-cancer
screening in an average-risk population. N Engl J Med 351:2704–2714, 2004
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125 Laboratory Tests
Ferritin
Type of test Blood
Background and explanation
of test
In healthy individuals, most iron is stored as ferritin, an in-
tracellular protein found mainly in the liver but also in the
bone marrow, spleen, and skeletal muscle. When iron is de
-
pleted from the body, iron stores are used first, then the fer-
ritin level falls, and then iron deficiency develops. Several
weeks may elapse before anemia can be detected. The ferri
-
tin level serves as an early indicator of iron deficiency.
In iron overload, serum ferritin is less useful. Serum iron,
total iron-binding capacity, and percent transferrin satura
-
tion are more sensitive tests.
Relevance to psychiatry and
behavioral science
Patients with either iron deficiency anemia or hemochroma-
tosis may present with fatigue, lethargy, and weakness that
could be mistaken for depression.
Preparation of patient None needed
Indications Diagnosing iron deficiency
Reference range Adult males: 20–250 ng/mL
Adult females: 10–120 ng/mL
Critical value(s) Iron deficiency: <10 ng/mL (<10 μg/L)
Increased levels • Hemochromatosis
• Alcoholic liver disease (acute or chronic)
• Inflammation
• Certain cancers
• History of multiple transfusions
• Other anemias (hemolytic, megaloblastic, thalassemia)
• Iron administration (oral or parenteral)
• End-stage renal disease
Decreased levels Iron deficiency anemia
Interfering factors Spurious results seen with hemolyzed blood or with recent
intake of oral contraceptives or antithyroid drugs.
Ferritin levels generally increase with age and are higher in
those who consume red meat compared with vegetarians.
Injury to ferritin-containing organs such as the liver may
cause ferritin elevation.
Ferritin cannot be used to evaluate iron status in patients
with alcoholic liver disease, autoimmune disease, cancer, or
chronic infection.
Cross-references Anemia
Hemochromatosis
Iron Level
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126 Laboratory Medicine in Psychiatry and Behavioral Science
Cross-references (continued) Total Iron-Binding Capacity
Transferrin; Transferrin Saturation
Ferritin (continued)
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed June 2021.
ARUP Laboratories: Ferritin, in Lab Test Directory. Salt Lake City, UT, ARUP Laboratories, 2021. Avail-
able at: https://ltd.aruplab.com/Tests/Pub/0070065. Accessed June 2021.
Fauci AS, Braunwald E, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, 17th Edition.
New York, McGraw-Hill, 2008
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127 Laboratory Tests
Flurazepam level
Type of test Blood
Background and explanation
of test
Benzodiazepines are Schedule IV sedative-hypnotic drugs
used to treat anxiety and insomnia. Flurazepam is a fast act
-
ing drug with a negligible half-life for the parent compound
and a long half-life for the metabolite N-desalkylflurazepam.
In general, metabolite level could be checked when overdose,
noncompliance, or nonprescription use is suspected. Com-
monly used urine drug screens are not designed to detect
flurazepam or its metabolites, and blood tests are not often
ordered because this drug is rarely used today.
Relevance to psychiatry and
behavioral science
Toxicity with chronic benzodiazepine ingestion may mani-
fest as confusion, disorientation, memory impairment,
ataxia, decreased reflexes, and dysarthria. With acute over-
dose, patients may exhibit somnolence, confusion, ataxia,
decreased reflexes, vertigo, dysarthria, respiratory depres
-
sion, and coma. More serious consequences usually involve
co-ingestion of alcohol or other sedatives. Administration of
flumazenil does not affect flurazepam level. Activated char
-
coal is no longer recommended as a treatment because of the
high risk of aspiration. Supportive care, including intuba
-
tion as indicated, is the mainstay of treatment.
Preparation of patient None needed
Indications •
Screening for drug use
• Suspicion of overdose
• Signs of toxicity in treated patient
• Suspected noncompliance with prescribed therapy
Reference range N-desalkylflurazepam: 0.01–0.24 μg/mL
Critical value(s) N-desalkylflurazepam:
• Toxic > 0.30 μg/mL
•Lethal >0.50 μg/mL
Increased levels • Overdose
• Overuse
• Poor metabolism
Decreased levels Noncompliance
Interfering factors None
Cross-references Benzodiazepines
Urine Drug Screen
Chernecky CC, Berger BJ: Laboratory Tests and Diagnostic Procedures, 5th Edition. St. Louis, MO, WB
Saunders, 2008
Galanter M, Kleber HD (eds): The American Psychiatric Publishing Textbook of Substance Abuse Treat-
ment, 4th Edition. Washington, DC, American Psychiatric Publishing, 2008
Wu AHB: Tietz Clinical Guide to Laboratory Tests, 4th Edition. St. Louis, MO, WB Saunders, 2006
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128 Laboratory Medicine in Psychiatry and Behavioral Science
Folate level
Type of test Blood
Background and explanation
of test
Folate is a water-soluble vitamin with several important cel-
lular and metabolic functions. Regular intake of folate is re-
quired and is particularly crucial during the first trimester
of pregnancy to avoid neural tube defects in the developing
fetus.
Four stages of folate deficiency are recognized. In Stage 1,
the plasma or serum folate level drops. If folate is not re
-
placed, then the RBC folate level falls. In Stage 2, RBC folate
level falls. In Stage 3, hypersegmented granulocytes are
seen. In Stage 4, a frank anemia develops, with hemoglobin
<10 g/dL and macrocytic RBCs seen.
In the general North American population, folate deficiency
is now less common because cereals, breads, and grain
products are folate-enriched, but the deficiency can still be
seen in those with low intake of these foods as well as inad
-
equate intake of fresh green vegetables and beans. Folate
deficiency is still common in developing countries. This
deficiency is also seen in specific patient populations.
Malabsorption of folate (along with vitamin B
12
) can affect
individuals with disease or surgical conditions involving
the small intestine, such as celiac disease or gastric bypass
surgery. Accelerated loss of folate can occur in patients with
liver disease, alcoholism, or kidney disease. Medications
that can decrease folate levels include phenytoin, metfor-
min, carbamazepine, oral contraceptives, trimethoprim, tri-
amterene, and methotrexate.
Folate can be measured in serum/plasma or in RBCs. Se-
rum/Plasma measurements are cheapter and more widely
available. It was once thought that RBC folate was superior
because it was more closely correlated with tissue stores,
but more recent studies suggest that the two measures are
clinically comparable. When folate is checked, vitamin B
12
should also be checked because the two deficiencies can oc-
cur together. When folate and vitamin B
12
are both low, B
12
should be replaced first to avoid the serious neurological
complication of subacute combined degeneration of the spi
-
nal cord.
Relevance to psychiatry and
behavioral science
Low folate levels are often found in community-dwelling
individuals with an unhealthy diet and are correlated with
depression and a poor response to antidepressant medica-
tion. Some patients with depression respond to folate aug-
mentation of antidepressant medication even when their
folate levels are in the normal or low-normal range. Folate
levels are also correlated with dementia in certain patient
populations, so folate is one of the laboratory tests routinely
ordered in the evaluation of cognitive impairment. Newly
admitted psychiatric patients with a variety of diagnoses
are more likely than the general population to have low fo-
late levels.
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129 Laboratory Tests
Folate level (continued)
Preparation of patient Patients should fast for 6–8 hours before test.
Indications • Physical symptoms of folate deficiency
• Mental or behavioral changes, especially in elderly
patients
• Suspected malnutrition or malabsorption in patients
with conditions such as alcoholism, celiac disease,
Crohn’s disease, or cystic fibrosis
• Evaluation of megaloblastic anemia
Reference range Serum folate: ≥5.9 ng/mL
RBC folate: ≥366 ng/mL
Critical value(s) Serum folate ≤ 3.9 ng/mL indicates deficiency.
Increased levels • Supplementation
• Acute renal failure
• Active liver disease
Decreased levels • Malabsorption: liver disease, alcoholism, gastric bypass,
celiac disease
• Use of certain medications noted in Background section
above
• Inadequate dietary intake
• Increased metabolism
• Increased requirements (e.g., pregnancy)
• Renal dialysis
• Malignancy (e.g., lymphoproliferative disease)
• Increased hematopoiesis (e.g., thalassemia major)
Interfering factors RBC hemolysis
Radioactive scan within 48 hours of testing
Specimen handling (must be protected from light)
Ethnicity (values higher in Whites than in other ethnic
groups)
Cross-references Alcohol Use Disorder
Anemia
Depressive Disorder Due to Another Medical Condition
Folate Deficiency
Vitamin B
12
Deficiency
Vitamin B
12
Level
ARUP Laboratories: Folate, RBC, in Lab Test Directory. Salt Lake City, UT, ARUP Laboratories, 2021.
Available at: https://ltd.aruplab.com/Tests/Pub/0070385. Accessed June 2021.
ARUP Laboratories: Folate, serum, in Lab Test Directory. Salt Lake City, UT, ARUP Laboratories, 2021.
Available at: https://ltd.aruplab.com/Tests/Pub/0070070. Accessed June 2021.
https://t.me/med1917
130 Laboratory Medicine in Psychiatry and Behavioral Science
Folate level (continued)
Bender A, Hagan KE, Kingston N: The association of folate and depression: a meta-analysis.J Psychiatr
Res 95:9–18, 2017
Khosravi M, Sotoudeh G, Amini M, et al: The relationship between dietary patterns and depression me-
diated by serum levels of folate and vitamin B
12
.BMC Psychiatr 20(1):63, 2020
Kim JM, Stewart R, Kim SW, et al: Predictive value of folate, vitamin B
12
and homocysteine levels in late-
life depression. Br J Psychiatry 192:268–274, 2008
Lerner V, Kanevsky M, Dwolatzky T, et al: Vitamin B
12
and folate serum levels in newly admitted psychi-
atric patients. Clin Nutr 25:60–67, 2006
Morris DW, Trivedi MH, Rush AJ: Folate and unipolar depression. J Altern Complement Med 14:277–285,
2008
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131 Laboratory Tests
Follicle-stimulating hormone (FSH)
Type of test Blood
Background and explanation
of test
FSH is an anterior pituitary hormone that acts on the ovaries
to stimulate follicle maturation and on the testes to stimulate
sperm development. FSH is regulated by gonadotropin
-
releasing hormone (GnRH) from the hypothalamus as well
as estrogen and progesterone in females and testosterone in
males.
The menstrual cycle is divided into two phases—follicular
and luteal—by a midcycle surge of FSH and LH, which is
followed by ovulation. In the follicular phase, FSH stimu
-
lates estradiol production by the egg follicle, and these two
hormones promote follicle maturation. In the luteal phase,
FSH stimulates progesterone production. FSH also facilitates
the ovaries’ response to LH. At menopause, when the ovaries
cease to function, FSH levels rise.
FSH is used in combination with LH to diagnose primary
ovarian failure, in which both hormone levels are elevated.
Hormone levels are not needed to confirm ovarian failure in
females 45 years or older who have typical symptoms of
menopause; in these cases, a clinical diagnosis is the stan-
dard. The FSH assay can be useful in females <45 years with
possible early menopause and females <40 years with sus
-
pected premature ovarian failure. In these cases, two sepa-
rate FSH values >40 IU/L obtained 4–8 weeks apart would
be consistent with ovarian failure.
Fertility declines with FSH values >25 IU/L, but the assay
provides no guarantee of infertility. Advice about discontin
-
uation of contraception should be based on the duration of
amenorrhea.
In males, FSH promotes production of androgen-binding
proteins in addition to promoting sperm development. Once
puberty is reached, FSH levels in males are stable.
Relevance to psychiatry and
behavioral science
FSH levels are influenced by various conditions encountered
in psychiatric practice, including alcohol use disorder, an-
orexia nervosa, Klinefelter’s syndrome, precocious or de-
layed puberty, and pituitary or hypothalamic disease. In
addition, medications such as phenothiazines and megestrol
act to lower FSH levels.
Preparation of patient None needed
Indications • Component of infertility workup in both males and
females
• Determining cause of a low sperm count in males
• Workup of menstrual irregularities
• Confirming onset of menopause (not recommended for
routine use; duration of amenorrhea is more reliable)
• Confirming onset of menopause in females taking oral
contraceptives and those who have undergone hysterec-
tomy (if oligomenorrhea or amenorrhea do not apply)
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