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222 Laboratory Medicine in Psychiatry and Behavioral Science
Prolactin (continued)
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed August 2021.
Park YM: Serum prolactin levels in patients with major depressive disorder receiving selective serotonin-
reuptake inhibitor monotherapy for 3 months: a prospective study. Psychiatry Investig 14(3):368–371,
2017
Richa V, Rahul G, Sarika A: Macroprolactin: a frequent cause of misdiagnosed hyperprolactinemia in clin-
ical practice.J Reprod Infertil 11(3):161–167, 2010
Torre DL, Falorni A: Pharmacological causes of hyperprolactinemia.Ther Clin Risk Manag 3(5):929–951,
2007
University of California San Francisco Health: Prolactin blood test. Medical Tests, August 19, 2018. Avail-
able at: https://www.ucsfhealth.org/medical-tests/prolactin-blood-test. Accessed August 2021.
https://t.me/med1917
223 Laboratory Tests
Prostate-specific antigen (PSA)
Type of test Blood
Background and explanation
of test
PSA is a protein found in both normal prostate epithelial
cells and prostate cancer cells that can be measured in the
blood in both free and bound forms. The sum of the two
forms—the total PSA—is variably increased in prostate car
-
cinoma, hyperplasia, and inflammation and with leakage of
prostatic fluid into the circulation. Use of PSA testing to de
-
tect clinically significant cancer has been a topic of contro-
versy over several decades. The low sensitivity and
specificity of the test has resulted in both missed diagnoses
and overdiagnoses, the latter
associated with morbidity
from unnecessary biopsy and surgery.
Attempts have been
made
to improve the test using PSA density and PSA change
measures such as velocity and doubling time, but there is
little agreement that these refinements have been successful.
Where PSA testing has been discouraged, both advanced-
stage diagnosis and mortality from prostate cancer have
increased. Even so, consensus is lacking as to how to risk-
stratify individual males for MRI study and biopsy. Detailed
guidelines have recently been published by the European
Association of Urology, noted in the reference list below.
The American Cancer Society makes the following recom-
mendations: males should be informed about the uncertain-
ties, risks, and potential benefits of prostate cancer
screening and then decide whether to be screened, in con
-
sultation with their health care provider. This discussion
should take place at age 50 for males at average risk of pros-
tate cancer who are expected to live another 10 years or lon-
ger. It should take place at age 45 for those at high risk,
including Black males and those with a first-degree relative
diagnosed at an early age (before age 65) with prostate can
-
cer. It should take place at age 40 for males with more than
one first-degree relative diagnosed at an early age. If testing
is negative, retesting should take place every 2 years for
those with a PSA level <2.5 ng/mL and yearly for those
with a level ≥2.5 ng/mL.
Relevance to psychiatry and
behavioral science
Psychiatrists who provide primary care for patients age
≥40 years need to be informed about the appropriate use
of PSA testing and the interpretation of test results.
Preparation of patient Blood sample should be collected prior to digital rectal exam
and prior to prostate biopsy. Patients should avoid ejacula-
tion and vigorous exercise in 48 hours before test.
Indications • Screening for prostate cancer, as described above
• Selecting patients for prostate biopsy or MRI
• Workup for males with signs/symptoms suggestive of
prostate cancer
• Monitoring effectiveness of treatment for prostate
cancer
• Detecting recurrence of prostate cancer
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224 Laboratory Medicine in Psychiatry and Behavioral Science
Prostate-specific antigen (PSA) (continued)
Reference range Age 40–49 years: 0.0–2.5 ng/mL
Age 50–59 years: 0.0–3.5 ng/mL
Age 60–69 years: 0.0–4.5 ng/mL
Age 70–79 years: 0.0–6.5 ng/mL
A single elevated PSA level should be confirmed with a sec-
ond test several weeks later, before biopsy or other testing.
Critical value(s) Total PSA levels >10 ng/mL indicate high risk of prostate
cancer.
Increased levels • Prostate cancer
• Prostatic hypertrophy
• Prostatic inflammation
• Leakage of prostate fluid into circulation
Decreased levels Not applicable
Interfering factors PSA levels increase with age.
In the absence of disease, Black males may have mildly to
moderately increased PSA levels.
Palpation of prostate on digital rectal exam increases PSA
level. Both ejaculation and vigorous exercise involving the
pelvis (e.g., cycling) may transiently increase PSA levels.
High doses of chemotherapeutic drugs, such as cyclophos-
phamide and methotrexate, may increase or reduce PSA.
Cross-references None
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed September 2021.
Eyrich NW, Morgan TM, Tosoian JJ: Biomarkers for detection of clinically significant prostate cancer: con-
temporary clinical data and future directions. Transl Androl Urol 10(7):3091–3103, 2021
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Haverfield EV, Esplin ED, Aguilar SJ, et al: Physician-directed genetic screening to evaluate personal risk
for medically actionable disorders: a large multi-center cohort study. BMC Med 19(1):199, 2021
Van Poppel H, Roobol MJ, Chapple CR, et al: Prostate-specific antigen testing as part of a risk-adapted
early detection strategy for prostate cancer: European Association of Urology position and recom-
mendations for 2021. Eur Urol 80(6):703–711, 2021
https://t.me/med1917
225 Laboratory Tests
Protein, serum
Type of test Blood
Background and explanation
of test
Proteins have critical roles in the body as enzymes, hor-
mones, and transporters and as constituents of cells, tissues,
and organs. Two classes of protein are measured in blood:
albumin and globulins.
Albumin, which represents 60% of total protein, functions to
maintain colloidal osmotic pressure within the vasculature
and to transport drugs, hormones, and enzymes. It is pro
-
duced in the liver, and its level can be dramatically reduced
by liver disease, such as cirrhosis. The serum albumin level
can also be reduced in kidney disease, when the nephron is
no longer able to prevent loss of albumin in the urine.
Globulins include antibodies, enzymes, and other essential
proteins. Although measurement of total protein aids in the
evaluation of nutritional status and can be helpful in screen
-
ing for liver or kidney disease, it is more useful to know
which component—albumin or globulins—is present in ab
-
normal concentration.
Relevance to psychiatry and
behavioral science
Total protein may be low in anorexia nervosa, failure to
thrive in elderly patients, alcohol use disorder, and liver dis-
ease and postoperatively. Low protein values are frequently
encountered among patients on medical/surgical units in
the general hospital and represent a risk factor for the devel
-
opment of delirium. It is a commonly held misconception
that a low protein level and correspondingly low protein
binding of drugs result in increased drug action. In fact, re
-
duced protein binding of drugs has little clinical effect, even
among elderly patients. Unbound drug is available not only
for distribution to the target organ but also for metabolism
and excretion. What lowered protein binding does affect is
the interpretation of the laboratory measurement of the total
drug concentration; it is of potential concern that patients
might develop symptoms of toxicity at apparently therapeu
-
tic drug levels when protein levels are low.
Preparation of patient None needed
Indications • Component of CMP
• Evaluating nutritional status
• Workup of signs/symptoms of liver or kidney disease
• Evaluating edema
Reference range 6.0–8.0 g/dL
Critical value(s) ≤ 3 g/dL or ≥12 g/dL
Increased levels • Dehydration
• Viral infection (e.g., HIV, hepatitis B or C)
• Multiple myeloma, other gammopathies
• Waldenström’s macroglobulinemia
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226 Laboratory Medicine in Psychiatry and Behavioral Science
Protein, serum (continued)
Increased levels (continued) • Granulomatous diseases such as sarcoidosis
• Collagen vascular diseases such as SLE and rheumatoid
arthritis
• Chronic inflammatory states
• Chronic infections
Decreased levels • Malnutrition
• Malabsorption (celiac disease, inflammatory bowel dis-
ease)
• Chronic or severe diarrhea
• Postoperative state
• Liver disease
• Alcohol use disorder
• Kidney disease
• Burns, severe skin diseases
• Protein-losing enteropathy or uropathy
• Severe hemorrhage, with volume replacement
• Heart failure
• Hypothyroidism
• Prolonged immobilization
• Third trimester of pregnancy
Interfering factors Spurious elevation in protein can be caused by specimen he-
molysis, prolonged tourniquet application, or use of drugs
such as anabolic steroids, androgens, corticosteroids, dex
-
tran, growth hormone, insulin, phenazopyridine, or proges-
terone.
Spurious decrease in protein can be caused by sampling
proximal to an IV catheter, massive infusion of crystalloid
solution, or use of drugs such as ammonium ion, estrogen,
or oral contraceptives.
Cross-references Albumin
Anorexia Nervosa
Cerebrospinal Fluid Protein
Cirrhosis
Comprehensive Metabolic Panel
Urine Protein
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed September 2021.
Fuhrman MP, Charney P, Mueller CM: Hepatic proteins and nutrition assessment. J Am Diet Assoc
104:1258–1264, 2004
Jacobson SA, Pies RW, Katz IR: Clinical Manual of Geriatric Psychopharmacology. Washington, DC,
American Psychiatric Publishing, 2007
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227 Laboratory Tests
Pyridoxine (vitamin B
6
) level
Type of test Blood
Background and explanation
of test
Pyridoxine is a water-soluble vitamin and essential nutrient
involved as a coenzyme in a large number of reactions regu
-
lating the metabolism of proteins, glucose, lipids, DNA, and
neurotransmitters. It also has antioxidant and immune sys
-
tem functions. Research to date suggests that this vitamin has
a role in processes as varied as cognitive decline in older
adults, cancer risk, cardiovascular disease, late luteal phase
dysphoric disorder, and morning sickness i n pregnancy.
Food sources of pyridoxine include fish, organ meats, beef,
poultry, potatoes and other starchy vegetables, fortified cere
-
als, and fruits other than citrus. Risk of deficiency is higher in
pregnancy, in obese individuals, and in those with alcohol use
disorder, malabsorption syndromes, impaired renal function,
and autoimmune disorders such as rheumatoid arthritis and
inflammatory bowel disease. In addition, certain antiepilep
-
tic drugs used in psychiatric practice increase the breakdown
of pyridoxine, potentially causing deficiency; this is dis
-
cussed in the following section.
Adequacy of pyridoxine levels can be measured directly by
testing for pyridoxal 5′ phosphate, one of the vitamin’s active
forms. Values outside the reference range noted below are of
potential concern because both deficiency and toxicity are
seen. Deficiency is associated with dermatitis, cheilosis, glos
-
sitis, anemia, EEG abnormalities, depression, confusion, and
poor immune system function. Toxicity, resulting from ≥1 g
of oral pyridoxine daily for ≥12 months, can cause a severe,
progressive sensory neuropathy with marked ataxia. Other
toxic symptoms include photosensitivity, nausea, heartburn,
and serious dermatological lesions.
Relevance to psychiatry and
behavioral science
As noted above, pyridoxine levels outside the reference range
are associated with depression, confusion, EEG abnormali-
ties, and ataxia. Antiepileptic drugs known to increase the
breakdown of pyridoxine include valproate, carbamazepine,
and phenytoin.
Preparation of patient 8-hour or overnight fast is required.
Indications Clinical suspicion of pyridoxine deficiency
Reference range 5–50 ng/mL
Critical value(s) Deficiency: < 5 ng/mL
Toxici ty: > 50 ng/mL
Increased levels Excessive supplementation
Decreased levels • Pregnancy
• Obesity
• Alcohol use disorder
• Autoimmune disorders
• Cirrhosis
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228 Laboratory Medicine in Psychiatry and Behavioral Science
Pyridoxine (vitamin B
6
) level (continued)
Decreased levels (continued) • Hyperthyroidism
• Malnutrition, eating disorders
• Malabsorption
• Chronic kidney disease
• Congestive heart failure
• Drugs that antagonize pyridoxine or cause increased
requirements: TCAs, antiepileptic drugs, cycloserine,
disulfiram, isoniazid, penicillamine, hydralazine, estro-
gens (including birth control pills), and theophylline
Interfering factors Levels decrease with age, although age norms have not been
published.
Specimen handling affects results; the specimen must be re-
ceived in the lab within 30 minutes of collection. Prolonged
light exposure invalidates the results.
Cross-references Pyridoxine Deficiency
ARUP Laboratories: Vitamin B
6
(pyridoxal 5-phosphate), in Lab Test Directory. Salt Lake City, UT, ARUP
Laboratories, 2021. Available
at: https://www.aruplab.com/Tests/Pub/0080111. Accessed Septem-
ber 2021.
Minovic I, Kieneker LM, Gansevoort RT, et al: Vitamin B
6
, inflammation, and cardiovascular outcome in
a population-based cohort: the Prevention of Renal and Vascular End-Stage Disease (PREVEND)
study. Nutrients 12(9):2711, 2020
National Institutes of Health Office of Dietary Supplements: Vitamin B6: Fact Sheet for Health Profession-
als. Bethesda, MD, National Institutes of Health, 2021. Available at: https://ods.od.nih.gov/
factsheets/VitaminB6-HealthProfessional. Accessed September 2021.
Odai T, Terauchi M, Suzuki R, et al: Depressive symptoms in middle-aged and elderly women are asso-
ciated with a low intake of vitamin B6: a cross-sectional study. Nutrients 12(11):3437, 2020
Peterson CT, Rodionov DA, Osterman AL, Peterson SN: B vitamins and their role in immune regulation
and cancer. Nutrients 12(11):3380, 2020
Romoli M, Perucca E, Sen A: Pyridoxine supplementation for levetiracetam-related neuropsychiatric ad-
verse events: a systematic review.Epilepsy Behav 103(Pt A):106861, 2020
Schorgg P, Bärnighausen T, Rohrmann S, et al: Vitamin B
6
status among vegetarians: findings from a pop-
ulation-based survey. Nutrients 13(5):1627, 2021
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229 Laboratory Tests
Quantitative electroencephalogram (qEEG)
Type of test Neurophysiology
Background and explanation
of test
The qEEG represents a refinement and extension of conven-
tional electroencephalography made possible by the intro-
duction of digital data capture. The patient interface for a
qEEG is the same as for an EEG, with the 10–20 electrode
placement system used for both. qEEG can process raw EEG
data to create new parameters, such as absolute and relative
power in different frequency bands, spectral edge frequency,
and signal coherence. Although qEEG has in the past been
used largely in research settings, most new clinical EEG sys
-
tems are now digital, with at least the theoretical potential to
generate more sophisticated responses to referring questions.
Digital systems retain the ability to generate analog displays
of EEG data in real time, so that visual examination (“read
-
ing”) can still take place as a check on qEEG findings. Digital
systems can also generate spatial displays of data, often su
-
perimposed on an outline of the brain (“brain maps”). De-
pending on the referring question, qEEG may be analyzed
and reported as numerical data, a series of brain maps, or a
real-time tracing that includes activation procedures (hyper
-
ventilation and photic stimulation). Moreover, for conditions
with persistent (nonperiodic) EEG correlates such as delir
-
ium, it would be possible to capture only a few seconds of
qEEG for analysis, making this a preferred modality for pa
-
tients who are unable to cooperate.
Relevance to psychiatry and
behavioral science
See discussion in the Electroencephalogram entry. With
qEEG, additional information can be obtained that allows
three-dimensional dipole localization in seizure evaluation.
In research settings, other data obtained include coherence of
electrical signals among brain areas, providing a measure of
functional connectivity that is particularly useful in the study
of cognitive tasks and state changes.
Preparation of patient Patients may need reassurance that qEEG only records elec-
trical activity and does not deliver an electrical stimulus. The
process of electrode application should be explained; applica
-
tion often includes use of collodion, an adhesive gel that re-
quires vigorous cleansing for removal. Patients should avoid
sedatives before testing. Sleep deprivation may be needed to
ensure an adequate sleep sample is obtained (e.g., in the case
of suspected seizures). Sleep deprivation protocol is to
awaken the patient at 4:00
A.M. and then keep the patient
awake without naps or stimulants until the time of testing.
Indications •
Detecting presence of epileptiform or ictal activity
• Confirming diagnosis of delirium and monitoring
course of delirium (serial studies)
• Evaluating suspected functional neurological symptom
presentations
• Various research applications
See
Electroencephalogram
entry for other indications.
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230 Laboratory Medicine in Psychiatry and Behavioral Science
Quantitative electroencephalogram (qEEG) (continued)
Reference range • Alpha power (absolute and relative) highest over occip-
ital areas; symmetric
• No appreciable slow-wave (delta or theta) power in
wakefulness
• Other reference values per laboratory report
Critical value(s) None
Abnormal test findings • Increased delta and theta power in a generalized distri-
bution may be consistent with delirium or medication
effects.
• Reduced alpha power in occipital areas may be consis-
tent with dementia or medication effects.
• Increased beta activity may be consistent with anxiety or
sedative-hypnotic use or withdrawal.
• Reduced coherence may indicate areas of neuronal loss
or injury.
Interfering factors Motion artifacts from eye movements may introduce delta
power to frontotemporal areas. Muscle activity may intro
-
duce beta power.
An EEG study that does not explicitly produce and docu-
ment alerting stimuli for a patient with a depressed level of
consciousness (e.g., suspected delirium) is considered in-
complete.
Many psychotropic drugs affect the EEG, usually introducing
either slow-wave power (e.g., antipsychotics or mood stabi
-
lizers) or beta power (e.g., sedative-hypnotics or alcohol).
Cross-references Delirium
Electroencephalogram
https://t.me/med1917
231 Laboratory Tests
Red blood cell (RBC) count
Type of test Blood
Background and explanation
of test
RBCs are the most numerous blood cells in the circulation.
They are formed in bone marrow and have a life cycle of
~120 days. These cells function to carry hemoglobin bound
to oxygen from the lungs to tissues and carbon dioxide from
the tissues to the lungs.
Relevance to psychiatry and
behavioral science
A low RBC count is associated with symptoms of fatigue,
weakness, somnolence, anhedonia, and depression.
Preparation of patient Fasting is not required. Patients should avoid dehydration
and overhydration. Signs of severe anemia should be noted
before blood is drawn. Note on requisition if the patient is
receiving IV fluids.
Indications • Routine component of CBC
• Clinical suspicion of anemia or polycythemia
Reference range Adult males: 4.5–5.5×10
6
/mm
3
Adult females: 4.0–5.0×10
6
/mm
3
Critical value(s) None
Increased levels Primary erythrocytosis (increase in RBCs)
• Polycythemia vera (a myeloproliferative disorder)
• Erythremic erythrocytosis (increased RBC production in
bone marrow)
Secondary erythrocytosis
• Renal disease
• Extrarenal tumors
• High altitude
• Pulmonary disease
• Cardiovascular disease
• Alveolar hypoventilation
• Hemoglobinopathy
• Tobacco use, carboxyhemoglobin
Relative erythrocytosis (decreased plasma volume)
• Dehydration (from vomiting, diarrhea)
• Gaisböck syndrome
Decreased levels • Anemia secondary to RBC destruction, blood loss, or di-
etary insufficiency of iron or vitamins essential to RBC
production
• Lymphoma, leukemia, or multiple myeloma
• Hemorrhage
• Chronic disease or infection
•
SLE, Addison’s disease, rheumatic fever, and other dis-
eases
https://t.me/med1917
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