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52 Laboratory Medicine in Psychiatry and Behavioral Science
Carbamazepine level
Type of test Blood
Background and explanation
of test
Carbamazepine is an antiepileptic drug used for a range of
psychiatric indications, including bipolar disorder, aggres
-
sion, agitation in the context of dementia and TBI, mood sta-
bilization in patients with personality disorders, neuropathic
pain, and adjunctive treatment for patients with depression,
schizophrenia, and schizoaffective disorder.
Therapeutic drug monitoring with carbamazepine is re-
quired because of the drug’s narrow therapeutic index. It has
numerous significant drug interactions and adverse effects,
the latter including Stevens-Johnson syndrome/toxic epider
-
mal necrolysis, which can be fatal. This syndrome particularly
affects patients of Asian descent carrying the HLA-B*1502 al-
lele, and this has prompted the FDA to recommend genotyp-
ing of all Asian patients before carbamazepine is used. The
HLA-A*3101 allele, which is more widely distributed in the
world population, has also been associated with hypersensi
-
tivity reactions.
Carbamazepine’s major active metabolite carbamazepine-
10,11-epoxide has the same potency as the parent drug and
contributes to both therapeutic and adverse effects. If carba-
mazepine toxicity is suspected, levels of both the parent
drug and the epoxide should be checked. Further informa
-
tion about this drug can be found in the Psychotropic Med-
ications chapter.
Relevance to psychiatry and
behavioral science
See above.
Preparation of patient Patients should be instructed to hold the dose of medication
until blood is drawn for testing. Trough level is checked just
before morning dose.
Indications • Therapeutic drug monitoring
• Signs and symptoms of toxicity
• Question of noncompliance
Reference range Total carbamazepine: 4–12 μg/mL
Free carbamazepine: 1–3 μg/mL
% free carbamazepine: 8%–35% (calculated)
Carbamazepine-10,11-epoxide: 0.5–2 μg/mL
Critical value(s) Total carbamazepine >15 μg/mL
Free carbamazepine >3.8 μg/mL
Increased levels • Renal failure increases the level of carbamazepine-
10,11-epoxide.
• Drugs: many, particularly coadministered drugs that are
CYP3A4 inhibitors
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53 Laboratory Tests
Carbamazepine level (continued)
Decreased levels • Noncompliance
• Drugs: many, particularly coadministered drugs that are
CYP3A4 inducers
Interfering factors None
Cross-references Bipolar and Related Disorder Due to Another Medical
Condition
ARUP Laboratories: Carbamazepine, total, I Lab Test Directory. Salt Lake City, UT, ARUP Laboratories,
2021. Available at:
https://ltd.aruplab.com/Tests/Pub/0090260. Accessed November 2021.
Brahmi N, Kouraichi N, Abderrazek H, et al: Clinical experience with carbamazepine overdose: relation-
ship between serum concentration and neurological severity.J Clin Psychopharmacol 28(2):241–243,
2008
Ferrell PB Jr, McLeod HL: Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic
epidermal necrolysis: US FDA recommendations. Pharmacogenomics 9(10):1543–1546, 2008
Hiemke C, Bergemann N, Clement HW, et al: Consensus guidelines for therapeutic drug monitoring in
neuropsychopharmacology: update 2017.Pharmacopsychiatry 51(1–2):9–62, 2018 [published correc
-
tion appears in Pharmacopsychiatry 51(1–2):e1, 2018]
Karazniewicz-Łada M, Główka AK, Mikulska AA, Główka FK: Pharmacokinetic drug-drug interactions
among antiepileptic drugs, including CBD, drugs used to treat COVID-19 and nutrients.Int J Mol Sci
22(17):9582, 2021
Petit P, Lonjon R, Cociglio M, et al: Carbamazepine and its 10,11-epoxide metabolite in acute mania: clin-
ical and pharmacokinetic correlates. Eur J Clin Pharmacol 41(6):541–546, 1991
https://t.me/med1917
54 Laboratory Medicine in Psychiatry and Behavioral Science
Carbohydrate-deficient transferrin (CDT)
Type of test Blood
Background and explanation
of test
Transferrin is a protein that carries iron through the circula-
tion to the bone marrow, where RBCs are produced. Several
forms of transferrin exist, with differing numbers of resi
-
dues of the carbohydrate sialic acid attached. Normally, each
transferrin molecule has four sialic acid chains attached. In
people who drink significant amounts of alcohol (more than
four or five drinks daily for several weeks or more), the
number of transferrin molecules with only one, two, or
three sialic residues is increased. These CDTs can be mea
-
sured in the blood, providing a useful indicator of problem
drinking.
Studies have shown the CDT test to be positive in people
drinking 50–80 g of ethanol daily for a minimum of several
weeks. In general, the specificity of the test is high (97%),
but the sensitivity is variable (65%–95%). Sensitivity can be
improved without loss of specificity when GGT is measured
in conjunction with CDT, because the combined test is pos
-
itive in people drinking ≥40 g of ethanol daily.
CDT value normalizes with 2–4 weeks of abstinence be-
cause the abnormal transferrin has a half-life of 14–17 days.
Relevance to psychiatry and
behavioral science
This is a useful test to supplement other measures in the
evaluation of drinking behavior when the patient has not
admitted a problem. It can also be used to detect relapse in
patients who are in treatment for alcohol dependence. In the
latter case, the patient’s own serial CDT values can provide
a sensitive indicator of change in drinking status.
Preparation of patient None needed
Indications Detection of recent heavy alcohol consumption
Reference range ≤2.5%
Critical value(s) ≥ 2.6% suggests active drinking
Increased levels • Recent heavy drinking
• Transferrin D protein variant
• Glycoprotein disorders
• Primary biliary cirrhosis
• Chronic active hepatitis
Decreased levels Not applicable
Interfering factors Differences in testing methods may render CDT results dif-
ficult to compare between laboratories.
Cross-references Alcohol Use Disorder
Bortolotti F, Sorio D, Bertaso A, Tagliaro F: Analytical and diagnostic aspects of carbohydrate deficient
transferrin (CDT): a critical review over years 2007–2017.J Pharm Biomed Anal 147:2–12, 2018
Chrostek L, Cylwik B, Szmitkowski M, et al: The diagnostic accuracy of carbohydrate-deficient transfer-
rin, sialic acid and commonly used markers of alcohol abuse during abstinence. Clin Chim Acta
364:167–171, 2006
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55 Laboratory Tests
Carbohydrate-deficient transferrin (CDT) (continued)
National Institute on Alcohol Abuse and Alcoholism: Biomarkers of heavy drinking, in Assessing Alco-
hol Problems: A Guide for Clinicians and Researchers. Edited by Allen JP, Wilson VB. Available at:
https://pubs.niaaa.nih.gov/publications/assessingalcohol/allen.pdf. Accessed June 2021.
Niemelä O: Biomarker-based approaches for assessing alcohol use disorders.Int J Environ Res Public
Health 13(2):166, 2016
Rinck D, Frieling H, Freitag A, et al: Combinations of carbohydrate-deficient transferrin, mean corpus-
cular erythrocyte volume, gamma-glutamyltransferase, homocysteine and folate increase the signifi-
cance of biological markers in alcohol dependent patients. Drug Alcohol Depend 89:60–65, 2007
https://t.me/med1917
56 Laboratory Medicine in Psychiatry and Behavioral Science
Carbon dioxide (CO
2
)
Type of test Blood
Background and explanation
of test
This test is also known as bicarbonate, CO
2
content, and to-
tal CO
2
. Although CO
2
exists in the body as a dissolved gas
and as an ion, >95% of the total CO
2
content in normal
plasma comes from bicarbonate, which is regulated by the
kidneys. Only a small fraction of total CO
2
content is con-
tributed by dissolved CO
2
gas, which is regulated by the
lungs. Total CO
2
provides a measure of the buffering capac-
ity of the blood.
Relevance to psychiatry and
behavioral science
This lab result may provide a clue to the presence of purging
behaviors in patients with eating disorders. In addition, it
may be increased in alcoholism and decreased in alcoholic
ketosis, dehydration, head injury, or liver disease.
Preparation of patient None needed
Indications •
Component of blood panel used for routine screening
purposes
•
Used with blood gas values to determine whether an
acid-base imbalance is primarily respiratory or meta
-
bolic in origin
•
Signs/symptoms of fluid/electrolyte imbalance
•
Monitoring chronic kidney disease
Reference range Adults ≤60 years: 23–29 mEq/L
Adults >60 years: 23–31 mEq/L
Adults >90 years: 20–29 mEq/L
Critical value(s) <6.0 mEq/L
Increased levels •
Recurrent vomiting
•
Chronic obstructive pulmonary disease (emphysema)
• Aldosteronism
• Cushing’s syndrome
Decreased levels •
Recurrent diarrhea
• Acute renal failure
• Ethylene glycol or methanol poisoning
• Starvation
• Metabolic acidosis
• Diabetic ketoacidosis
• Addison’s disease
• Salicylate overdose
•
Use of chlorothiazide diuretics
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57 Laboratory Tests
Carbon dioxide (CO
2
) (continued)
Interfering factors Drugs that increase bicarbonate levels include fludrocorti-
sone, barbiturates, bicarbonates, hydrocortisone, loop di-
uretics, and steroids.
Drugs that decrease bicarbonate levels include methicillin,
nitrofurantoin, tetracycline, thiazide diuretics, and triam
-
terene.
Cross-references Blood Gases
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed June 2021.
Chernecky CC, Berger BJ: Laboratory Tests and Diagnostic Procedures, 5th Edition. St. Louis, MO, WB
Saunders, 2008
Fischbach F, Dunning MB: A Manual of Laboratory and Diagnostic Tests, 8th Edition. Philadelphia, PA,
Wolters Kluwer Health/Lippincott Williams and Wilkins, 2009
U.S. National Library of Medicine: CO2 blood test. MedlinePlus, 2021. Available at: https://
medlineplus.gov/ency/article/003469.htm. Accessed June
2021.
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58 Laboratory Medicine in Psychiatry and Behavioral Science
Carotid ultrasound
Type of test Imaging/Ultrasound
Background and explanation
of test
Ultrasound technology utilizes the reflections from high-
frequency sound waves to create images of the internal
anatomy and structural pathology. Doppler analysis pro
-
vides information about blood flow velocity and distur-
bance. These technologies are combined in the carotid
duplex study, which evaluates the carotid vessels and, to a
lesser extent, the vertebral vessels.
In color duplex ultrasound, vascular lesions (e.g., plaque,
stenosis, occlusion) are visualized in grayscale simultane
-
ous with color-encoded images of flow patterns. When
pathological findings are demonstrated, quantification can
be achieved by analysis of Doppler spectral waveforms. The
carotid arteries are examined in transverse and longitudinal
section, with particular attention paid to the carotid bifurca
-
tion where pathology is most likely to occur. The vertebral
arteries, because of their smaller size and partial inaccessi
-
bility, are examined only in longitudinal section.
Relevance to psychiatry and
behavioral science
Patients with carotid or vertebral artery stenosis may pre-
sent with intermittent or nonspecific symptoms that appear
to be psychiatric in nature. For example, patients with TIAs
are sometimes diagnosed as having panic attacks, and those
with vertebrobasilar insufficiency may present with “dizzi
-
ness” and be referred for evaluation of suspected somatic
symptom disorder or illness-related anxiety.
Preparation of patient A certain degree of patient cooperation required. Patients
will be supine for test, asked to breathe quietly and evenly,
and requested to remain silent and minimize swallowing so
artifact can be minimized. Exam takes ~30 minutes.
Indications •
Suspected vascular disease in carotid or vertebral distri-
bution
• Cervical bruit
•
Risk factors for cerebrovascular disease (e.g., diabetes)
•
History of stroke or TIA
•
Light-headedness, dizziness, or blackouts
• Headaches
• Memory impairment
•
Follow-up after carotid vascular surgery or stenting
•
Follow-up for known asymptomatic carotid disease
Normal test •
Normal vascular anatomy and course of arteries
•
No evidence of stenosis or occlusion
•
No kinking or coiling of the carotid artery
•
Normal flow patterns
•
Normal thickness of arterial walls
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59 Laboratory Tests
Carotid ultrasound (continued)
Critical value(s) ≥ 60% occlusion of a carotid artery may be an indication for
surgery or stenting, even in patients who are asymptomatic.
Abnormal test • Stenosis
• Occlusion
• Dissection
• Aneurysm
• Carotid body tumor
• Arteritis
• Subclavian steal syndrome
Interfering factors Extreme obesity, patient movement, and cardiac dysrhyth-
mias may all affect test results.
Cross-references Stroke
Fauci AS, Braunwald E, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, 17th Edition.
New York, McGraw-Hill, 2008
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Saxena A, Ng EYK, Lim ST: Imaging modalities to diagnose carotid artery stenosis: progress and pros-
pect.Biomed Eng Online 18(1):66, 2019
https://t.me/med1917
60 Laboratory Medicine in Psychiatry and Behavioral Science
Cerebrospinal fluid amyloid-β
1–42
(CSF Aβ
1–42
)
Type of test CSF
Background and explanation
of test
The processes of accumulation, aggregation, and deposition
of the amyloid-β peptide Aβ
1–42
are believed to be central to
the pathogenesis of Alzheimer’s disease (AD). CSF Aβ
1–42
levels are lower in AD patients compared with age-matched
cognitively healthy patients, although a considerable over
-
lap in values is noted between AD, mild cognitive impair-
ment, and control groups. In addition, the correlation of
Aβ
1–42
level and severity of dementia is not strong. For these
reasons, CSF Aβ
1–42
is of limited value in the individual clin-
ical patient. The ratio of Aβ
1–42
to Aβ
1–40
in CSF is a better
measure, with significant differences found between AD
and control groups. Even better is the combination of this
ratio with other measures, such as CSF phosphorylated tau
and neuroimaging (amyloid PET, tau PET).
Relevance to psychiatry and
behavioral science
This test is used for selected cases in the workup of cognitive
impairment to provide evidence for or against a diagnosis
of AD.
Preparation of patient See Cerebrospinal Fluid Analysis
Indications Aiding in the differential diagnosis of AD
Reference range See laboratory reference range.
Critical value(s) See laboratory reference.
Increased levels Not applicable
Decreased levels A decreased Aβ
1–42
-to-Aβ
1–40
ratio is a biomarker of a patho-
logical state in AD and other diseases involving cognitive
impairment, such as Parkinson’s disease.
Interfering factors CSF specimen requires special handling.
Cross-references Alzheimer’s Disease
Cerebrospinal Fluid Analysis
Cerebrospinal Fluid Tau Protein
Blennow K, Zetterberg H: Biomarkers for Alzheimer’s disease: current status and prospects for the fu-
ture. J Intern Med 284(6):643–663, 2018
Hansson O, Lehmann S, Otto M, et al: Advantages and disadvantages of the use of the CSF amyloid β
(Aβ) 42/40 ratio in the diagnosis of Alzheimer’s disease. Alzheimers Res Ther 11(1):34, 2019
Jack CR Jr, Bennett DA, Blennow K, et al: NIA-AA research framework: toward a biological definition of
Alzheimer’s disease. Alzheimers Dement 14(4):535–562, 2018
Lim EW, Aarsland D, Ffytche D, et al: Amyloid-β and Parkinson’s disease. J Neurol 266(11):2605–2619,
2019
Selkoe DJ, Hardy J: The amyloid hypothesis of Alzheimer’s disease at 25years.EMBO Mol Med 8(6):595–
608, 2016
https://t.me/med1917
61 Laboratory Tests
Cerebrospinal fluid analysis
Type of test CSF sampling by lumbar puncture (LP)
Background and explanation
of test
In psychiatric settings, an LP is usually performed for diag-
nostic indications. Information is obtained regarding CSF
protein, glucose, cellular elements (RBCs and WBCs), anti
-
gens, immunoglobulin, and other disease biomarkers.
Opening pressure may or may not be measured. The report
returned from the lab includes cell counts (with differential
for WBCs if count is >5), total protein, albumin, glucose,
IgG, IgA, IgM, oligoclonal bands if present, specific antibod
-
ies if present (e.g., measles or rubella), lactate if requested,
and the appearance of a yellow color of CSF by visual in
-
spection.
Relevance to psychiatry and
behavioral science
As noted in the Indications section below, certain psychiatric
and neuropsychiatric presentations may necessitate LP
with CSF analysis.
Preparation of patient Anticoagulant therapy should be held, or the effects re-
versed, before the procedure is started so INR is <1.2. Pa-
tients should be questioned regarding any history of lumbar
spinal surgery, stenosis, or deformity such as scoliosis that
might limit direct access to the subarachnoid space. Brain
CT or MRI must be performed before LP in patients present
-
ing with focal neurological deficits, new-onset seizures, al-
tered level of consciousness, or papilledema. MRI may also
be indicated for immunocompromised patients, to look for
occult masses. Patients should be informed about possible
adverse effects of LP, which include headache, back pain,
infection, bleeding, and radicular symptoms. Rare adverse
effects include cranial neuropathies (diplopia, facial numb-
ness, hearing loss) and, potentially, brain herniation.
Indications •
Delirium or mental status change of unknown etiology
• Seizures of unknown etiology
•
Acute, severe, or persistent headache or stiff neck
•
Suspected CNS infection
•
Unexplained fever in an immunocompromised patient
•
Suspected subarachnoid hemorrhage with negative CT
scan
• Multiple sclerosis
• Transverse myelitis
• Neurosarcoidosis
• Guillain-Barré syndrome
• Pseudotumor cerebri
• Carcinomatous meningitis
• CNS lymphoma
Contraindications to LP • Mass lesion in the posterior fossa
•
Intracranial lesion with mass effect (seen on CT or MRI)
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