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172 Laboratory Medicine in Psychiatry and Behavioral Science
Lithium level
Type of test Blood
Background and explanation
of test
Lithium is an alkali metal salt used to treat bipolar disorder
and mood instability in the context of dementia and other
neuropsychiatric conditions. Mounting evidence has
demonstrated that lithium has neuroprotective effects by
virtue of molecular actions that include the inhibition of gly
-
cogen synthase kinase-3β (GSK-3β) and inositol monophos-
phatase (IMP) as well as increased secretion of brain-derived
neurotrophic factor (BDNF). When used chronically for bi
-
polar disorder, lithium appears to counteract the cortical
thinning and reduced hippocampal volumes seen in the
normal course of the disease. There is now interest in the
potential of lithium to prevent or slow degenerative pro-
cesses in mild cognitive impairment, Alzheimer’s disease,
Parkinson’s disease, and amyotrophic lateral sclerosis.
These beneficial effects of lithium are contingent on maintain-
ing the lithium level within a narrow therapeutic range and
monitoring potential adverse effects on the kidneys, heart,
and thyroid gland. Over the years, the suggested upper limit
of the therapeutic range has been progressively lowered, par
-
ticularly for elderly patients. Once-daily dosing is recom-
mended, with the target
level kept as
low as possible to
minimize effects on
the kidney.
When the lithium level is checked, blood should be drawn
12 hours after the last dose (a trough level) for proper inter
-
pretation of results. When lithium is initiated or a change is
made in the dosage, levels should be checked in 1 week and
then every 2–3 months for the first 6 months of treatment.
After 6 months, levels should be checked every 6–12 months.
Other lab tests needed for screening and monitoring of lith
-
ium therapy are noted in the Psychotropic Medications
chapter.
Relevance to psychiatry and
behavioral science
Lithium toxicity can be acute, chronic, or
acute-on-chronic. In
patients on high-dosage maintenance treatment, lithium can
accumulate i
n the CNS to toxic
levels. If the patient then stops
lithium because of symptoms, the measured serum level
may
be normal even though the CNS level remains toxic, so
the
level must be interpreted in relation to the time since the last
dose.
With acute toxicity, GI symptoms are prominent, the correla-
tion of lithium level with signs and symptoms is poor, and
rapid recovery on holding the drug is the rule. With chronic
toxicity, CNS symptoms are more evident, and renal, cardiac,
and thyroid effects may be seen. Also with chronic toxicity,
the correlation of lithium level with signs and symptoms is
relatively good.
Preparation of patient Patients should be instructed to hold lithium until after
blood is drawn, and the phlebotomy appointment should be
scheduled as closely as possible to the 12-hour mark de-
scribed in the Background section above.
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173 Laboratory Tests
Lithium level (continued)
Indications • Routine monitoring of lithium therapy
• Signs/symptoms of lithium toxicity
Reference range Adults: standard range 0.60–0.80 mEq/L
• If poorly tolerated, but with good response, range could
be lowered to 0.40–0.60 mEq/L.
• If well tolerated, but with inadequate response, range
could be raised to 0.80–1.00 mEq/L.
Elderly patients: standard range 0.40–0.60 mEq/L
• If tolerated but response is inadequate, range could be
raised to a maximum of 0.70 or 0.80 mEq/L in patients
ages 65–79 years or a maximum of 0.70 mEq/L in those
≥80 years.
Critical value(s) ≥ 1.5 mEq/L indicates toxicity.
Increased levels • Overdose
• Sodium restriction
• Coadministration of NSAIDs, ACE inhibitors, angioten-
sin receptor blockers, thiazide diuretics, spironolactone,
diltiazem, verapamil, or fluoxetine
Decreased levels Coadministration of sodium chloride, sodium bicarbonate,
psyllium, fleawort or fleabane (herbals), acetazolamide, ami
-
nophylline, or theophylline
Interfering factors Collection of blood into a lithium heparin tube will cause a
spurious elevation in level.
Cross-references Bipolar and Related Disorder Due to Another Medical
Condition
Lithium
Czarnywojtek A, Zgorzalewicz-Stachowiak M, Czarnocka B, et al: Effect of lithium carbonate on the
function of the thyroid gland: mechanism of action and clinical implications.J Physiol Pharmacol
71(2), 2020
Davis J, Desmond M, Berk M: Lithium and nephrotoxicity: a literature review of approaches to clinical
management and risk stratification. BMC Nephrol 19(1):305, 2018
Forlenza OV, De-Paula VJ, Diniz BS: Neuroprotective effects of lithium: implications for the treatment of
Alzheimer’s disease and related neurodegenerative disorders.ACS Chem Neurosci 5(6):443–450, 2014
Foulser P, Abbasi Y, Mathilakath A, Nilforooshan R: Do not treat the numbers: lithium toxicity.BMJ Case
Rep 2017:bcr-2017-220079, 2017
Giakoumatos CI, Nanda P, Mathew IT, et al: Effects of lithium on cortical thickness and hippocampal sub-
field volumes in psychotic bipolar disorder.J Psychiatr Res 61:180–187, 2015
Gong R, Wang P, Dworkin L: What we need to know about the effect of lithium on the kidney.Am J
Physiol Renal Physiol 311(6):F1168–F1171, 2016
Mehta N, Vannozzi R: Lithium-induced electrocardiographic changes: a complete review.Clin Cardiol
40(12):1363–1367, 2017
Nolen WA, Licht RW, Young AH, et al: What is the optimal serum level for lithium in the maintenance
treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task
Force on Treatment With Lithium. Bipolar Disord 21(5):394–409, 2019
https://t.me/med1917
174 Laboratory Medicine in Psychiatry and Behavioral Science
Lithium level (continued)
Schoot TS, Molmans THJ, Grootens KP, Kerckhoffs APM: Systematic review and practical guideline for
the prevention and management of the renal side effects of lithium therapy.Eur Neuropsychophar
-
macol 31:16–32, 2020
Wen J, Sawmiller D, Wheeldon B, Tan J: A review for lithium: pharmacokinetics, drug design, and toxic-
ity. CNS Neurol Disord Drug Targets 18(10):769–778, 2019
https://t.me/med1917
175 Laboratory Tests
Liver function tests (LFTs)
Type of test Blood
Background and explanation
of test
LFTs usually include ALT, AST, ALP, direct and total serum
bilirubin, albumin, and PT. The tests can be grouped concep
-
tually as follows:
• Tests of hepatocellular injury—ALT and AST
• Tests of cholestasis—ALP
• Tests of excretory function—bilirubin (direct and total)
• Tests of biosynthetic function—albumin and PT
The first two categories do not measure liver function per se,
but instead indicate whether the pattern of liver injury is pri
-
marily hepatocellular or cholestatic.
Disproportionate elevations of ALT and AST compared to
ALP are associated with acute or chronic injury to the liver
itself. A disproportionate elevation of ALP compared to
ALT and AST is associated with bile duct obstruction. Iso
-
lated bilirubin elevation may reflect a disorder of bilirubin
processing.
The inclusion of biosynthetic tests helps to minimize false-
negative results in patients with advanced hepatocellular
injury (e.g., alcoholic cirrhosis), in whom AST and ALT val
-
ues may be normal or low. It should be noted, however , that
albumin can be low and PT prolonged for reasons other
than liver disease.
Tests used to follow up on screening abnormalities include
GGT to determine whether ALP elevations are due to liver
disease or bone disease, hepatitis serology to detect viral
hepatitis, and autoimmune disease markers. If non-
alcoholic fatty liver disease is suspected, imaging studies
(ultrasound, CT, or MRI) are used to visualize the liver, and
transient elastography using ultrasound may be used to
measure liver stiffness.
Relevance to psychiatry and
behavioral science
LFTs may be abnormal in several conditions encountered in
psychiatry, including alcohol use disorder, hepatitis B and
C viral infections, the metabolic syndrome, Wilson’s dis-
ease, and during refeeding in severe anorexia nervosa.
Drugs of abuse that can cause abnormal LFTs include co-
caine, ecstasy, phencyclidine (PCP), toluene inhalants, and
anabolic steroids. Many herbal and alternative medical
remedies affect the liver, and these substances are often
overlooked as potential culprits. Especially problematic
from a liver function standpoint are the herbs chaparral,
gentian, skullcap, germander, alchemilla, and senna. A va-
riety of Chinese herbs are implicated as well, as is shark
cartilage. Numerous prescribed medications are known to
affect LFTs, including all classes of psychotropic drugs. An-
tipsychotic drugs have in rare cases been reported to cause
fatal hepatic injury, with chlorpromazine possibly the worst
offender.
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176 Laboratory Medicine in Psychiatry and Behavioral Science
Liver function tests (LFTs) (continued)
Relevance to psychiatry and AST and ALT often increase when a drug is initiated or with
behavioral science (continued) a dosage increase, but this is not necessarily an indication for
drug discontinuation. If AST and ALT values are <3 times
the baseline value and the ALP and bilirubin are normal,
LFTs can simply be checked weekly. When values plateau,
testing intervals can be lengthened. If AST and/or ALT rises
>3 times the baseline or >2 times the upper limit of normal
(ULN), the drug should be stopped and/or GI consultation
obtained. Other indications for drug discontinuation in
-
clude elevation of ALP or bilirubin, PT prolongation, and
clinical signs or symptoms of hepatotoxicity.
Preparation of patient None needed
Indications • Routine health screening (part of CMP)
• Signs/symptoms of liver dysfunction
• History of alcohol overuse
• Exposure to hepatitis
• Exposure to hepatotoxic drug(s) or chemicals
• Monitoring liver dysfunction
Reference range See entries for individual LFTs.
Critical value(s) See entries for individual LFTs.
Abnormal test • Non-alcoholic fatty liver disease—now the most common
cause of chronic liver disease—is associated with mild
elevations of ALT and AST. Other common causes are
alcohol-related liver injury and chronic viral hepatitis.
• An AST-to-ALT ratio ≥ 3:1 suggests alcoholic liver disease.
• If ALP is elevated, GGT should be checked. If GGT is
elevated and ALP is ≥2 times the ULN or the symptoms
or elevations persist, a liver ultrasound should be ob
-
tained to evaluate possible biliary obstruction.
• Bilirubin levels are a reliable marker of severity of liver
disease.
• Low serum albumin indicates advanced disease in cir-
rhosis but is not a reliable marker of acute liver injury.
• Prolonged PT is a reliable marker of acute liver injury
affecting synthetic capacity and consistent with liver
failure.
• Abnormal LFTs are highly prevalent in patients with
COVID-19 infection, but the significance of this finding
is not yet clear.
Interfering factors See entries for individual LFTs.
Cross-references Alanine Transaminase
Albumin
Alcohol Use Disorder
Alkaline Phosphatase
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177 Laboratory Tests
Liver function tests (LFTs) (continued)
Cross-references (continued) Aspartate Transaminase
Bilirubin
Hepatitis, Viral
Metabolic Syndrome
Wilson’s Disease
Bertolini A, van de Peppel IP, Bodewes FAJA, et al: Abnormal liver function tests in patients with COVID-
19: relevance and potential pathogenesis.Hepatology 72(5):1864–1872, 2020
Fischbach FT, Fischbach MA:
A Manual
of Laboratory and Diagnostic Tests,
10th Edition. Philadelphia,
PA, Wolters
Kluwer Health/Lippincott Williams and Wilkins, 2018
Gopal DV, Rosen HR: Abnormal findings on liver function tests: interpreting results to narrow the diag-
nosis and establish a prognosis. Postgrad Med 107:100–114, 2000
Harris RH, Sasson G, Mehler PS: Elevation of liver function tests in severe anorexia nervosa.Int J Eat Dis-
ord 46(4):369–374, 2013
Johnston DE: Special considerations in
interpreting liver function tests.
Am
Fam Physician 59:2223–2230,
1999
Marwick KF, Taylor M, Walker SW: Antipsychotics and abnormal liver function tests: systematic re
-
view. Clin Neuropharmacol 35(5):244–253, 2012
Piano S, Dalbeni
A, Vettore E, et al: Abnormal liver
function tests predict transfer to
intensive care unit
and death in COVID-19.
Liver Int 40(10):2394–2406, 2020
Woreta TA, Alqahtani SA: Evaluation of abnormal liver tests.Med Clin North Am 98(1):1–16, 2014
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178 Laboratory Medicine in Psychiatry and Behavioral Science
Lorazepam level
Type of test Blood
Background and explanation
of test
Benzodiazepines are Schedule IV sedative-hypnotic drugs
used to treat anxiety and insomnia. Lorazepam is an inter
-
mediate-acting drug with a half-life of 9–16 hours with no
active metabolites. It is not extensively metabolized in the
liver. Levels are rarely checked except to confirm overdose,
noncompliance, or use without a prescription. In the latter
case, a urine drug screen is more likely to be used than a
blood level.
Relevance to psychiatry and
behavioral science
Lorazepam is often a drug of choice among sedatives for a
variety of psychiatric indications. Toxicity with chronic ben
-
zodiazepine ingestion may manifest as confusion, disorien-
tation, memory impairment, ataxia, decreased reflexes, and
dysarthria. Past practice using prolonged dosing of IV lora
-
zepam to control agitation in the ICU resulted in numerous
cases of propylene glycol toxicity associated with the dilu-
ent, so that practice has been discontinued. 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. 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
• Suspected overdose
• Signs of toxicity in a treated patient
• Suspected noncompliance with prescribed therapy
Reference range 50–240 ng/mL (with dosage of 1–10 mg/day)
Critical value(s) Toxicity >300 ng/mL
Note: Administration of flumazenil does not affect drug
level.
Increased levels • Overdose
• Overuse
Decreased levels Noncompliance
Interfering factors None
Cross-references Urine Drug Screen
ARUP Laboratories: Lorazepam, in Lab Test Directory. Salt Lake City, UT, ARUP Laboratories, 2021.
Available at: https://ltd.aruplab.com/Tests/Pub/0090181. Accessed August 2021.
Chernecky CC, Berger BJ: Laboratory Tests and Diagnostic Procedures, 5th Edition. St. Louis, MO,
WB Saunders, 2008
Wu AHB: Tietz Clinical Guide to Laboratory Tests, 4th Edition. St. Louis, MO, WB Saunders, 2006
https://t.me/med1917
179 Laboratory Tests
Lyme antibodies
Type of test
Background and explanation
of test
Blood
CSF in suspected Lyme meningitis
Synovial fluid in suspected Lyme arthritis
Lyme disease, caused by the spirochete Borrelia burgdorferi, is
the most common tick-borne illness in the United States and
Europe. It often begins with the characteristic skin lesion
known as erythema migrans at the site of the tick bite. Within
days to weeks, the spirochete may disseminate so that pa
-
tients develop cardiac, neurological, and/or rheumatological
symptoms. Treatment with an antibiotic accelerates resolu
-
tion of the disease. If no treatment is given, the disease may
resolve spontaneously but can then recur.
In the United States, laboratory testing for Lyme disease has
been greatly overused. Guidelines for testing are as follows:
• The tick should be saved for species identification, but
the tick itself should not be tested.
• Asymptomatic patients with a tick-bite history do not
require testing.
• Patients presenting with an erythema migrans rash
should be treated immediately; confirmatory testing is
not needed.
• Testing methods for the diagnosis of Lyme disease are of
two types: antigen testing for B. burgdorferi and antibody
testing to detect the immune response. Antigen testing
is not recommended at this time, in part because of the
low sensitivity of existing assays.
• Antibody testing uses a two-tiered approach, with an
initial enzyme immunoassay (EIA) followed by either a
second EIA or Western blots if the first EIA test is posi
-
tive or borderline. This approach works well for later
stages of infection but has low sensitivity for early infec
-
tion. These assays do not distinguish active from inac-
tive infection, and seropositivity may persist for years,
even after treatment and resolution of the clinical dis-
ease.
•Aculture of
B. burgdorferi has low sensitivity,
requires a
lengthy incubation, and dictates special media and ex-
pertise. It is not routinely used.
• PCR assay for B. burgdorferi is used for evaluation of sy-
novial fluid samples in patients with suspected Lyme ar-
thritis and in cases of reinfection in which persistent
antibodies make the usual serological tests unreliable.
• To test for Lyme neuroborreliosis, simultaneous sam-
pling of serum and CSF for antibodies is recommended,
because sampling only CSF could yield spurious results
due to passive transfer of antibodies from blood to CSF.
The two-tiered approach is used.
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180 Laboratory Medicine in Psychiatry and Behavioral Science
Lyme antibodies (continued)
Background and explanation • ECG should be performed in patients evaluated for
of test (continued) Lyme disease who have signs or symptoms of carditis:
dyspnea, edema, palpitations, lightheadedness, chest
pain, and/or syncope.
Relevance to psychiatry and Lyme disease affects the nervous system in 10%–15% of cases,
behavioral science with manifestations including lymphocytic meningitis, cra-
nial neuritis, painful radiculoneuritis, and mononeuropathy
multiplex. During ac tive systemic infection, encephalopathy
can be seen.
Individuals diagnosed with Lyme disease have a greatly in-
creased risk of psychiatric disorders, including mood disor-
ders, suicidality, and completed suicide, that is highest in the
first 1–3 years after diagnosis. Recurrence of Lyme disease
symptoms further elevates this risk. It should be noted that
the converse is not true; individuals diagnosed with psychi
-
atric disorders do not necessarily have an increased risk of
Lyme disease, and testing in the general psychiatric popula
-
tion has given rise to a great deal of controversy.
Symptoms that have been attributed to “chronic Lyme dis-
ease” may in some cases be due to “posttreatment Lyme dis-
ease,” a syndrome characterized by symptoms seen within
6 months of treatment that persist for 6 months or longer.
This posttreatment syndrome is thought to arise from per
-
sistent immune activation, a hypothesis bolstered by recent
[
11
C]DPA-713 PET studies of the TSPO in affected patients vs.
healthy control subjects.
Preparation of patient None needed
Indications Suspected Lyme disease in a symptomatic patient
Reference range Negative EIA test
Negative Western blot analysis
Critical value(s) None
Positive test •
Recent infection with B. burgdorferi
• Past exposure to B. burgdorferi
• Exposure to another spirochete
Negative test No exposure
Blood drawn too early for antibodies to have formed
Interfering factors False-positive results can be seen with other spirochetes, in-
cluding the organisms that cause syphilis and leptospirosis.
Other diseases can also cause false-positive results, includ-
ing HIV infection, malaria, Epstein-Barr virus, and autoim-
mune disorders such as SLE and rheumatoid arthritis.
IgG antibodies may be present from Lyme infection in the
distant past.
Antibiotics can change test results in some cases.
Cross-references Lyme Disease
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181 Laboratory Tests
Lyme antibodies (continued)
Chaconas G, Castellanos M, Verhey TB: Changing of the guard: how the Lyme disease spirochete sub-
verts the host immune response. J Biol Chem 295(2):301–313, 2020
Coughlin JM, Yang T, Rebman AW, et al: Imaging glial activation in patients with post-treatment Lyme
disease symptoms: a pilot study using [11C]DPA-713 PET. J Neuroinflammation 15(1):346, 2018
Dumes AA: Lyme disease and the epistemic tensions of “medically unexplained illnesses.”Med An-
thropol 39(6):441–456, 2020
Hinds K, Sutcliffe K: Heterodox and orthodox discourses in the case of Lyme disease: a synthesis of ar-
guments. Qual Health Res 29(11):1661–1673, 2019
John TM, Taege AJ: Appropriate laboratory testing in Lyme disease.Cleve Clin J Med 86(11):751–759,
2019
Lantos PM: Chronic Lyme disease.Infect Dis Clin North Am 29(2):325–340, 2015
Lantos PM, Rumbaugh J, Bockenstedt LK, et al: Clinical practice guidelines by the Infectious Diseases So-
ciety of America (IDSA), American Academy of Neurology (AAN), and American College of Rheuma-
tology (ACR): 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease.Arthritis
Care Res (Hoboken) 73(1):1–9, 2021
Marques AR: Laboratory diagnosis of Lyme disease: advances and challenges.Infect Dis Clin North Am
29(2):295–307, 2015
Mead P, Petersen J, Hinckley A: Updated CDC recommendation for serologic diagnosis of Lyme dis-
ease. MMWR Morb Mortal Wkly Rep 68(32):703, 2019
Moore A, Nelson C, Molins C, et al: Current guidelines, common clinical pitfalls, and future directions
for laboratory diagnosis of Lyme disease, United States. Emerg Infect Dis 22(7):1169–1177, 2016
Nigrovic LE, Lewander DP, Balamuth F, et al: The Lyme disease polymerase chain reaction test has low
sensitivity.Vector Borne Zoonotic Dis 20(4):310–313, 2020
Schriefer ME: Lyme disease diagnosis: serology. Clin Lab Med 35(4):797–814, 2015
Schutzer SE, Body BA, Boyle J, et al: Direct diagnostic tests for Lyme disease. Clin Infect Dis 68(6):1052–
1057, 2019
Shapiro ED. Clinical practice: Lyme disease. N Engl J Med 370(18):1724–1731, 2014
Waddell LA, Greig J, Mascarenhas M, et al: The accuracy of diagnostic tests for Lyme disease in humans,
a systematic review and meta-analysis of North American research. PLoS One 11(12):e0168613, 2016
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