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152 Laboratory Medicine in Psychiatry and Behavioral Science
High-sensitivity C-reactive protein (hsCRP)
Type of test Blood
Background and explanation
of test
CRP is an acute-phase reactant secreted by the liver in re-
sponse to inflammation or tissue injury when cytokines
such as interleukin-6 are present in the circulation. CRP lev
-
els are very low or undetectable in the serum of healthy in-
dividuals. CRP levels rise within hours when the
inflammatory response is stimulated and fall rapidly when
inflammation subsides.
Two separate CRP assays are available, both measuring the
same molecule in blood, although using different assays:
• CRP measures the molecule in the range 10–1,000 mg/L
• hsCRP measures the molecule in the range 0.5–10
mg/L
Because persistent, low-level inflammation is known to pro-
mote atherosclerosis, hsCRP testing is used to assess the risk
of heart attack or stroke. Moreover, drugs used to prevent
these outcomes also affect the hsCRP level. In fact, aspirin
reduces the risk only in patients with elevated hsCRP levels.
Statin drugs lower not only lipid levels but also hsCRP.
Weight loss lowers hsCRP (and CRP) levels; for each kilo-
gram of weight lost, CRP is reduced by 0.13 mg/L.
Relevance to psychiatry and hsCRP may be of use to behavioral health specialists work-
behavioral science ing in cardiac or neurological rehabilitation settings, partic-
ularly in relation to risk reduction efforts such as weight
management programs.
Preparation of patient Patients should fast (no food or fluids) for 4 hours before
test.
Indications • Assessing cardiovascular risk
• Assessing stroke risk
• Assessing degree of vascular inflammation
Reference range In general, hsCRP ≥1 mg/L constitutes a positive test; exact
reference values depend on testing methods.
In the absence of inflammation, hsCRP
is <0.2 mg/L.
hsCRP cardiovascular risk stratification:
• Low risk: < 1.0 mg/L
• Average risk: 1.0–3.0 mg/L
• High risk: 3.1–9.9 mg/L
• Very high risk: >9.9 mg/L
Critical value(s) Values > 10 mg/L on repeated measurement indicate a non-
cardiovascular cause of inflammation.
Increased levels • Elevated risk of stroke
• Elevated risk of MI
• Postoperative state
Decreased levels Not applicable
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153 Laboratory Tests
High-sensitivity C-reactive protein (hsCRP) (continued)
Interfering factors Obesity and late-stage pregnancy affect results.
Chronic inflammatory conditions such as arthritis may in-
terfere with risk assessment.
Use of NSAIDs dampens CRP response.
Cross-references Cardiovascular Risk Assessment (Appendix C)
C-Reactive Protein
Metabolic Syndrome
Abi-Saleh B, Iskandar SB, Elgharib N, et al: C-reactive protein: the harbinger of cardiovascular diseases.
South Med J 101:525–533, 2008
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com
. Ac-
cessed July 2021.
Ben-Yehuda O: High-sensitivity C-reactive protein in every chart? The use of biomarkers in individual
patients. J Am Coll Cardiol 49:2139–2141, 2007
Lin MS, Shih SR, Li HY, et al: Serum C-reactive protein levels correlates better to metabolic syndrome de-
fined by International Diabetes Federation than by NCEP ATP III in men. Diabetes Res Clin Pract
77:286–292, 2007
Patel AA, Budoff MJ: Screening for heart disease: C-reactive protein versus coronary artery calcium. Ex-
pert Rev Cardiovasc Ther 8:125–131, 2010
Selvin E, Paynter NP, Erlinger TP: The effect of weight loss on C-reactive protein: a systematic review.
Arch Intern Med 167:31–39, 2007
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154 Laboratory Medicine in Psychiatry and Behavioral Science
HIV testing
Type of test Blood or oral fluid
Background and explanation
of test
HIV infection continues to be a global public health problem
with no cure but now with effective prevention, diagnosis,
and treatment that enables affected people to lead long and
healthy lives. In the United States, ~1.2 million people live
with HIV, and ~13% of them are not aware of this fact and
need testing. New cases disproportionately affect racial and
ethnic minorities and gay, bisexual, and other men who
have sex with men.
Three types of tests are used to diagnose HIV:
• Antibody tests—use blood or oral fluid. Most rapid tests
and home-use tests are of this type.
• Antigen/antibody tests—detect parts of the virus itself
as well as the body’s response to it.
• Nucleic acid tests—detect HIV virus in blood.
Initial testing is with either an antibody test or an antigen/
antibody test. Nucleic acid tests are costly and are not used
for screening except for high-risk exposure or possible expo
-
sure with early HIV symptoms.
If the initial test is positive, a follow-up test is conducted. A
second positive test confirms HIV.
Relevance to psychiatry and
behavioral science
Psychiatrists should be aware of the rate of HIV infection in
their catchment areas and that homeless and drug-abusing
populations have greatly increased risk. Where patients
with chronic mental illness use their mental health profes-
sional as a primary care provider, knowledge about testing
and follow-up is essential.
Preparation of patient Patient counseling is mandatory for HIV testing. The fol-
lowing information should be provided to the patient,
whether for an office-based or a laboratory-based test: infor-
mation about the HIV test, its benefits and consequences,
ways HIV is transmitted and how it can be prevented, the
meaning of the test results, and where to obtain further in
-
formation and other services, including treatment. Those
tested with rapid tests should be informed that results will
be available during the visit and that confirmatory testing
will be needed if the rapid test is positive. In this case, a
return visit should be scheduled to discuss the confirmatory
test results.
Indications HIV testing should be performed:
• At least once for all patients ages 13–64 years as part of
routine medical care
• Yearly for those at higher risk
• Every 3–6 months for sexually active gay and bisexual
men
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155 Laboratory Tests
HIV testing (continued)
Indications (continued) Factors that increase risk include the following:
• Having vaginal or anal sex with someone who is HIV
positive or whose HIV status is unknown
• Injecting drugs and sharing needles, syringes, or other
drug equipment with others
• Exchanging sex for money or drugs
• Having a sexually transmitted disease, such as syphilis
• Having hepatitis or tuberculosis
• Having sex with anyone who has any of the above risk
factors
Negative test Either no HIV infection is present or the test was performed
outside window of detection. No test can detect HIV imme
-
diately after infection. Antibody tests can take 23–90 days to
detect infection, with oral fluid or finger-prick samples tak-
ing longer than venous blood. Antigen/antibody tests can
take 18–45 days, with finger-prick samples taking longer
(up to 90 days). Nucleic acid testing can detect infection 10–
33 days after exposure.
Positive test A positive test is followed up by a confirmatory test. If the
second test is positive, HIV infection is presumed present.
Indeterminate test Usually caused by cross-reacting antibodies in an unin-
fected patient. The patient should be retested in 4–8 weeks
and then again in 6 months.
Interfering factors As noted above, if the patient tested too soon after exposure,
the test may be falsely negative.
Cross-reacting antibodies may cause a false-positive result.
Cross-references HIV and AIDS
Centers for Disease Control and Prevention: Types of HIV tests. Atlanta, GA, Centers for Disease Control
and Prevention, 2021. Available at: https://www.cdc.gov/hiv/basics/hiv-testing/test-types.html
.
Accessed July 2021.
HIV.gov: U.S. Statistics. Washington, DC, U.S. Department of Health and Human Services, 2021. Avail-
able at: https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics
. Accessed July 2021.
National Institutes
of Health: HIV overview. HIVinfo, 2021. Available at: https://hivinfo.nih.gov/
understanding-hiv/fact-sheets/hiv-testing. Accessed July 2021.
Price RW, Epstein LG, Becker JT, et al: Biomarkers of HIV-1 CNS infection and injury. Neurology 69:1781–
1788, 2007
Syed Iqbal H, Balakrishnan P, Murugavel KG, et al: Performance characteristics of a new rapid immuno-
chromatographic test for the detection of antibodies to human immunodeficiency virus (HIV) types 1
and 2. J Clin Lab Anal 22:178–185, 2008
Taylor MM, Hawkins K, Gonzalez A, et al: Use of the serologic testing algorithm for recent HIV serocon-
version (STARHS) to identify recently acquired HIV infections in men with early syphilis in Los An-
geles County. J Acquir Immune Defic Syndr 38:505–508, 2005
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156 Laboratory Medicine in Psychiatry and Behavioral Science
Homocysteine level
Type of test Blood
Background and explanation
of test
Homocysteine is an intermediate product of methionine
metabolism that can be elevated with certain nutritional
deficiencies, including vitamin B
12
, vitamin B
6
, and folate. Se-
rum homocysteine is toxic to vascular endothelial cells, and
elevations have been found to be associated with a range of
diseases: cardiovascular disease, hypertension, stroke, cogni
-
tive dysfunction, dementia (Alzheimer’s disease [AD] and
vascular dementia), chronic kidney disease, cancer, and bone
tissue damage. A recent prospective study found that an in
-
crement in the homocysteine level of 5
μmol/L increased the
risk of developing AD by 40%.
Serum homocysteine levels can also be used to detect vitamin
B
12
and/or folate deficiency. Supplementation with these vi-
tamins can lower the homocysteine level.
Relevance to psychiatry and
behavioral science
As noted above, elevation of the serum homocysteine level
increases the risk of various diseases of interest to psychia
-
trists. In addition to the established use of serum homocyste-
ine to detect folate or early vitamin B
12
deficiency, compelling
evidence suggests that serum total homocysteine should be
checked as part of the evaluation for dementia or cognitive
impairment and that, for this patient population, supplemen-
tation should be considered for homocysteine levels
≤10 μmol/L. These vitamins are not stored by the body; any
excess is excreted in urine. Although understudied in psychi
-
atry generally, serum homocysteine is thought to be elevated
in alcohol use disorder, schizophrenia, epilepsy, and hypothy-
roidism.
Preparation of patient Patients should fast for ≥8 hours before testing.
Indications • Patients with poor nutritional status, in whom vitamin
deficiency is suspected: elderly patients, patients with al-
cohol use disorder and/or substance abuse/dependence
• Patients with peripheral neuropathy or myelopathy
• Vegetarians not taking vitamin B
12
supplements
• Patients using medications known to interfere with folate
metabolism (e.g., antiepileptic drugs, methotrexate)
Reference range 0–15 μmol/L
A slightly lower upper limit of normal (8–10 μmol/L) may be
appropriate for prevention of cognitive impairment in elderly
patients.
Critical value(s) >15 μmol/L
Increased levels •
Vitamin B
12
deficiency
• Folate deficiency
• Vitamin B
6
deficiency
• Inherited disorders of methionine metabolism
• Chronic kidney disease
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157 Laboratory Tests
Homocysteine level (continued)
Decreased levels Not applicable
Interfering factors False elevation may be seen if serum is not promptly sepa-
rated from cells when specimen is collected.
Medications that affect homocysteine levels include azari-
bine, carbamazepine, methotrexate, nitrous oxide, and
phenytoin.
Cross-references Folate Deficiency
Folate Level
Methylmalonic Acid Level
Vitamin B
12
Deficiency
Vitamin B
12
Level
ARUP Laboratories: Homocysteine, total, in Lab Test Directory. Salt Lake City, UT, ARUP Laboratories,
2021. Available at: https://ltd.aruplab.com/Tests/Pub/0099869. Accessed July 2021.
Chen S, Honda T, Ohara T, et al: Serum homocysteine and risk of dementia in Japan.J Neurol Neurosurg
Psychiatry 91(5):540–546, 2020
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Jiang B, Yao G, Yao C, Zheng N: The effect of folate and VitB12in the treatment of MCI patients with hy-
perhomocysteinemia. J Clin Neurosci 81:65–69, 2020
Li S, Guo Y, Men J, et al: The preventive efficacy of vitamin B supplements on the cognitive decline of el-
derly adults: a systematic review and meta-analysis. BMC Geriatr 21(1):367, 2021
Mielech A, Puscion-Jakubik A, Markiewicz-Zukowska R, Socha K: Vitamins in Alzheimer’s disease: re-
view of the latest reports. Nutrients 12(11):3458, 2020
Seshadri S, Beiser A, Selhub J, et al: Plasma homocysteine as a risk factor for dementia and Alzheimer’s
disease.N Engl J Med 346(7):476–483, 2002
Smith AD, Refsum H, Bottiglieri T, et al: Homocysteine and dementia: an international consensus state-
ment.J Alzheimers Dis 62(2):561–570, 2018
Sun J, Han W, Wu S, et al: Associations between hyperhomocysteinemia and the presence and severity of
acute coronary syndrome in young adults≤35years of age.BMC Cardiovasc Disord 21(1):47, 2021
Yang Q, Lu Y, Deng Y, et al: Homocysteine level is positively and independently associated with serum
creatinine and urea nitrogen levels in old male patients with hypertension.Sci Rep 10(1):18050, 2020
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158 Laboratory Medicine in Psychiatry and Behavioral Science
Human chorionic gonadotropin (hCG)
Type of test Urine (hCG), blood (β-hCG)
Background and explanation
of test
hCG is a hormone produced by the developing placenta that
is excreted in urine. Its level is elevated in pregnancy and in
the presence of trophoblastic or germ cell tumors. An ele
-
vation at menopause also occurs in which the hCG is of
pituitary origin. Of the two subunits of hCG (α and β), the
β subunit is the more sensitive and specific for early preg
-
nancy.
For routine pregnancy testing, a qualitative test is per-
formed on a urine specimen. The test becomes positive
within 3 days of egg implantation, just after the first missed
period. A urine home pregnancy test can be used for this
purpose; these tests are accurate if used according to pack-
age instructions. For nonroutine pregnancy testing and for
testing of conditions other than pregnancy, quantitative
testing of β-hCG in blood is performed. This is the most sen
-
sitive and specific test to detect early pregnancy, estimate
gestational age, and diagnose ectopic pregnancy or threat
-
ened abortion. This test is also used to diagnose and monitor
various hormone-producing tumors.
Relevance to psychiatry and
behavioral science
Pregnancy tests are performed in females of reproductive
age being considered for procedures such as ECT or before
initiation of potentially teratogenic medications (including
psychotropics such as valproate, carbamazepine, and lith
-
ium). Pregnancy itself can precipitate psychiatric symptoms
in some patients, and when this is suspected, pregnancy
testing is part of the diagnostic workup.
Preparation of patient For urine testing, instruct patient to collect their first morn-
ing urine specimen, which contains the highest concentra-
tion of β-hCG. If a random specimen is used, the specific
gravity must be >1.005 for the result to be valid. Specimens
containing gross blood should not be used.
Indications •
Confirming or ruling out pregnancy
• Diagnosing ectopic pregnancy
• Diagnosing and monitoring gestational trophoblastic
tumors
• Ruling out pregnancy before initiating ECT
• Ruling out pregnancy before initiating that is potentially
teratogenic medications
• Ruling out pregnancy before procedures involving ion-
izing radiation or contrast media potentially harmful to
fetus
Reference range Urine
• Positive: pregnant
• Negative: not pregnant
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159 Laboratory Tests
Human chorionic gonadotropin (hCG) (continued)
Reference range (continued) Blood, quantitative
• Males and nonpregnant females: <5.0 IU/L
• Pregnant females: wide variation, dependent on gesta-
tional age
Critical value(s) None
Increased levels Positive urine results also occur in choriocarcinoma, hy-
datidiform mole, testicular and trophoblastic tumors in
males, chorioadenoma destruens, or ectopic pregnancy.
Increased blood values also occur in hydatidiform mole,
choriocarcinoma, seminoma, ovarian and testicular terato-
mas, ectopic pregnancy, certain cancers (lung, stomach,
pancreas), or Down syndrome.
Decreased levels Negative urine results also occur in fetal demise, abortion,
or threatened abortion.
Decreased blood values also occur in ectopic pregnancy,
trisomy 18.
Interfering factors Urine false-positive: proteinuria, hematuria, excess pituitary
gonadotropin, certain drugs (including phenothiazines and
methadone)
Urine false-negative: specimen obtained too early in preg-
nancy or urine too dilute
Blood factors: lipemia, hemolysis, radioisotope administra-
tion within 1 week. Positive result persists for 1 week after
completed abortion. Presence of heterophile antibodies may
increase or decrease quantitative results.
Cross-references Medical Evaluation for Electroconvulsive Therapy
(Appendix C)
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Wu AHB: Tietz Clinical Guide to Laboratory Tests, 4th Edition. St. Louis, MO, WB Saunders, 2006
https://t.me/med1917
160 Laboratory Medicine in Psychiatry and Behavioral Science
Human growth hormone level
Type of test Blood
Background and explanation
of test
Growth hormone (GH) released by the anterior pituitary
gland is critical for normal growth in children. During the
growth years, if too little GH is secreted, children grow more
slowly and are small for their age. In extreme cases, dwarf
-
ism results. If too much is secreted, children may develop
gigantism, with long bones growing beyond puberty, thick
-
ened facial features, weakness, headaches, and delayed pu-
berty.
In adults, GH subserves metabolic functions such as muscle
protein synthesis and lipolysis (especially of visceral fat)
and has beneficial effects on the lipid profile. GH defi-
ciency—associated with TBI, pituitary disease, vascular
compromise, or cranial irradiation—is associated with cen
-
tral obesity, decreased bone density and muscle mass, and
elevated lipid levels in addition to the psychiatric symp-
toms noted below.
GH excess in adults, which can result
from pituitary tumors, is associated with acromegaly.
GH is released in pulses, primarily at night, and daytime
levels may be undetectable, especially in elderly or obese
individuals. In determining deficiency, random GH levels
are not useful, so biomarkers such as insulin-like growth
factor (IGF)-1 (a downstream product of GH) are used. De-
finitive diagnosis is made by a blunted GH response to two
or more validated provocative tests that induce GH release.
Insulin-induced hypoglycemia is the gold standard for di-
agnosis.
A separate issue relating to GH is that its effects on muscle
strength and endurance have made this hormone popular as
a performance-enhancing supplement for athletes. This is a
different situation from GH replacement in patients with GH
deficiency. In general, this practice of supplementing GH is
not safe because of myriad adverse effects, including diabe-
tes, osteoporosis, and increased risk of cancer. Use of GH is
prohibited by the World Anti-Doping Agency, and testing
for GH ingestion is now routine. Use of GH to increase en-
ergy and drive in elderly patients, whose GH levels are nat-
urally low, is similarly ill-advised.
Relevance to psychiatry and
behavioral science
Children with GH abnormalities may come to clinical atten-
tion because of concerns about stature or physical anomalies.
These patients should be referred promptly for endocrino-
logical evaluation. In adults, GH deficiency is associated
with social isolation, reduced quality of life, low self-esteem,
low energy, and reduced drive, symptoms that could be mis
-
taken for depression. Adults and children with Prader-Willi
syndrome have reduced GH secretion and have signs and
symptoms like those of other causes of GH deficiency, such
as TBI. In these cases, GH replacement may be indicated.
Preparation of patient Patients should fast and limit physical activity for
10–12 hours before testing.
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161 Laboratory Tests
Human growth hormone level (continued)
Indications • Evidence of pituitary or parasellar mass
• Characteristic symptoms in patients with a history of
hypothalamic-pituitary insult (surgery, radiation ther
-
apy, TBI, brain tumor, stroke)
• Slow growth in children
• Gigantism in children
• Acromegaly in adults
Reference range See laboratory reference ranges for various test protocols.
Critical value(s) None
Increased levels • Pituitary tumor/hyperpituitarism
• Acromegaly
• Gigantism
• Anorexia nervosa
• Diabetes in adolescents
• Hypoglycemia, starvation
• Surgery
• Deep sleep states
• Drugs: gamma-hydroxybutyrate (GHB), gamma-
butyrolactone (GBL), amphetamines, β-blockers,
estrogens, oral contraceptives, histamine, insulin,
niacin, levodopa, arginine, glucagon, St. John’s wort
Decreased levels • Congenital hypoplasia; lesions of hypothalamus or pitu-
itary
• Congenital GH deficiency
• Prader-Willi syndrome
• Dwarfism
• Failure to thrive
• Acute lymphoblastic leukemia
• Chronic atrophic gastritis
• Hyperglycemia
• Urban pollutants
• Drugs: corticosteroids, phenothiazines, SSRIs
Interfering factors Stress and exercise affect GH levels.
Use of radioactive contrast material in the week before
testing may affect the results.
Obesity and advanced age may cause a blunted GH
response to provocation.
Cross-references Anorexia Nervosa
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