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132 Laboratory Medicine in Psychiatry and Behavioral Science
Follicle-stimulating hormone (FSH) (continued)
Indications (continued) • Aiding in the diagnosis of pituitary disorders and dis-
eases of the ovaries or testes
• Used with other tests to determine cause of hypothy-
roidism in females and endocrine dysfunction in males
• In children, used with LH to diagnose precocious or de-
layed puberty
Reference range See ranges published by individual laboratories. Values dif-
fer by stage of puberty, sex, and phase of menstrual cycle.
FSH values increased in pregnancy, with degree of increase
dependent on trimester. Reference range units differ accord
-
ing to laboratory methods.
Critical value(s) None
Increased levels • Primary gonadal failure (ovarian or testicular)
• Ovarian or testicular agenesis
• Klinefelter’s syndrome
• Reifenstein syndrome
• Menopause
• Castration
• Alcohol use disorder
• Gonadotropin-secreting pituitary tumor
• Orchitis or other testicular injury (from radiation,
chemotherapy, tumor, autoimmune disease, trauma,
or viral infection such as mumps)
Decreased levels • Secondary ovarian failure due to pituitary or hypotha-
lamic lesion
• Pregnancy
• Anorexia nervosa
• Polycystic ovary syndrome
• Hemochromatosis
• Sickle cell anemia
• Severe illness
• Hyperprolactinemia
• Delayed puberty
Interfering factors FSH levels can be increased with use of low-dose estrogens,
cimetidine, clomiphene, digitalis, and levodopa.
FSH levels can be decreased with use of high-dose estrogens,
oral contraceptives, megestrol, phenothiazines, and GnRH
analogues.
Cross-references Alcohol Use Disorder
Anorexia Nervosa
Klinefelter’s Syndrome
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133 Laboratory Tests
Follicle-stimulating hormone (FSH) (continued)
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed July 2021.
ARUP Laboratories: Luteinizing hormone and follicle stimulating hormone, Lab Test Directory. Salt Lake
City, UT,
ARUP Laboratories, 2021. Available at: https://ltd.aruplab.com/Tests/Pub/0070193. Ac-
cessed July 2021.
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
https://t.me/med1917
134 Laboratory Medicine in Psychiatry and Behavioral Science
Fragile X DNA testing
Type of test Genetic
Background and explanation
of test
The expansion of a segment of DNA known as a CGG
(cytosine-guanine-guanine) trinucleotide repeat in the non-
coding region of the fragile X mental retardation 1 gene
(FMR1) underlies the development of several fragile X–
associated disorders.
FXS develops in those with >200 CGG repeats (a full muta-
tion). This is a neurodevelopmental disorder involving in-
tellectual disability and autism spectrum disorder (ASD) in
more than half of affected individuals.
A premutation involving 55–200 CGG repeats is associated
with fragile X tremor/ataxia syndrome (FXTAS), fragile X
primary ovarian insufficiency (FXPOI), and fragile X–
associated neuropsychiatric disorders (FXAND).
This test uses PCR methods for the analysis.
Relevance to psychiatry and
behavioral science
FXS involves a constellation of symptoms related to silenc-
ing of FMR1: intellectual disability, ASD, generalized anxi-
ety, social avoidance, and hyperactive behaviors. Other
associated childhood conditions include seizures, recurrent
otitis media, strabismus, and obesity. In adults with FXS,
there is increased risk of hypertension, obesity, GI disorders,
parkinsonism, mood disorders, and anxiety. Structural MRI
shows enlargement of the caudate nucleus and lateral ven-
tricles and reduction of the cerebellar vermis volume.
A subset of premutation carriers will go on to develop
FXTAS, a neurodegenerative disease with an incidence that
increases with age. Symptoms include kinetic tremor, cere
-
bellar ataxia, neuropathy, impaired executive function,
memory problems, and personality changes. MRI findings
that occur long before clinical symptoms include loss of cer
-
ebellar and brainstem volume and white matter changes.
FXAND that occur in premutation carriers are not as well
characterized but include anxiety disorders (generalized
anxiety disorder, specific phobia, social phobia) and OCD.
These conditions affect both adults and children.
Preparation of patient Genetic counseling, both before and after testing
Indications •
Individuals with intellectual disability, developmental
delay, speech and language delay, ASD, or learning dis-
abilities of unknown cause
• Females with infertility, elevated FSH levels, premature
ovarian failure, primary ovarian insufficiency, or irregu-
lar menstrual periods
• Adults older than 50 years with features of FXTAS
• Females who are pregnant or considering pregnancy
who request fragile X carrier testing
https://t.me/med1917
135 Laboratory Tests
Fragile X DNA testing (continued)
Positive test • > 200–1,000 repeats—full mutation
• 55–200 repeats—premutation (risk of FXTAS, FXPOI,
and FXAND)
Negative test A normal result is 5–40 CGG repeats.
Interfering factors None known
Cross-references Fragile X Syndrome
Grigsby J, Brega AG, Bennett RE, et al: Clinically significant psychiatric symptoms among male carriers
of the fragile X premutation, with and without FXTAS, and the mediating influence of executive func
-
tioning. Clin Neuropsychol 30(6):944–959, 2016
Hagerman RJ, Hagerman P: Fragile X-associated tremor/ataxia syndrome: features, mechanisms and
management. Nat Rev Neurol 12(7):403–412, 2016
Hall DA, Berry-Kravis E: Fragile X syndrome and fragile X-associated tremor ataxia syndrome.Handb
Clin Neurol 147:377–391, 2018
Salcedo-Arellano MJ, Dufour B, McLennan Y, et al: Fragile X syndrome and associated disorders: clinical
aspects and pathology. Neurobiol Dis 136:104740, 2020
Santos E, Emeka-Nwonovo C, Wang JY, et al: Developmental aspects of FXAND in a man with the FMR1
premutation. Mol Genet Genomic Med 8(2):e1050, 2020
https://t.me/med1917
136 Laboratory Medicine in Psychiatry and Behavioral Science
Functional magnetic resonance imaging (fMRI)
Type of test Imaging
Background and explanation
of test
fMRI of the brain is an enhancement of MRI in which images
are taken in rapid succession while the patient performs a
task. Change in signal intensity and blood flow from image
to image facilitates understanding of brain function in the
context of neurological or psychiatric disease. The test does
not involve any radiation exposure. It is at present used only
for presurgical planning and in research.
Relevance to psychiatry and
behavioral science
In patients with schizophrenia, studies of prefrontal cortex
activation have yielded conflicting findings, some with hy
-
poactivation and others with hyperactivation. The discrep-
ancies may be explained by the differing baseline cognitive
efficiency of subjects and the memory load of the tasks pre-
sented, among other factors. In patients with mood disor-
ders, state-dependent (manic vs. depressed) alterations are
seen in frontolimbic activity. In addition, prefrontal cortex
hypoactivity may underlie observed cognitive deficits. Pa
-
tients with anxiety disorders (PTSD, social anxiety disorder,
and specific phobias) show hyperactivation of the amygdala
and insula on fMRI study.
Preparation of patient Patients must be carefully screened to ensure that no loose
metal objects enter the room where the scanner resides.
This test takes about 1 hour, depending on the experimental
protocol. During that time, the patient lies supine in the
scanner wearing headphones and viewing a screen reflected
in a mirror above their head. Patients must lie still during
testing.
Indications •
Presurgical planning
• Research protocols
Interfering factors Metal produces artifacts and may endanger the patient and
the magnet.
Image may be distorted by patient movement.
Cross-references Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Agarwal N, Port JD, Bazzocchi M, et al: Update on the use of MR for assessment and diagnosis of psy-
chiatric diseases. Radiology 255:23–41, 2010
O’Connor EE, Zeffiro TA: Why is clinical fMRI in a resting state? Front Neurol 10:420, 2019
https://t.me/med1917
137 Laboratory Tests
Gamma-glutamyltransferase (GGT)
Type of test Blood
Background and explanation
of test
The primary source of serum GGT is the liver, and elevated
GGT can be used as a marker of recent heavy drinking.
Mounting evidence suggests that GGT elevation is also
linked to fatty liver disease, atherosclerosis, diabetes, car
-
diovascular disease, heart failure, lung inflammation, met-
abolic syndrome, neuroinflammation, cognitive decline,
and vascular dementia. GGT is an independent risk factor
for all-cause mortality.
GGT elevation due to excessive alcohol use usually normal-
izes with abstinence within 2–3 weeks. If GGT remains ele-
vated, further diagnostic evaluation may be warranted to
exclude conditions such as fatty liver, biliary obstruction,
cholangitis, or cholecystitis. Other laboratory measures can
inform this workup; for example, elevation of GGT in com
-
bination with elevation of ALP suggests hepatobiliary dis-
ease.
Relevance to psychiatry and
behavioral science
Elevation of GGT has high sensitivity for liver disease but
low specificity in the evaluation of etiology. Specificity im
-
proves through patient selection; although the GGT assay
would have little use in screening for alcoholic liver disease,
it would be highly useful in confirming recent drinking in a
chronic drinker in treatment who is supposedly abstinent.
In males, GGT is used alone for this indication. In females,
it is best used in tandem with CDT. Specificity also improves
when elevated GGT is found in combination with an AST
-
to-ALT ratio >2, which is consistent with alcoholic liver dis-
ease. As noted above, elevated GGT may have a role in the
pathogenesis of several other neuropsychiatric conditions.
Preparation of patient Patients should fast for 8 hours and should abstain from al-
cohol for 24 hours before testing.
Indications •
Detecting covert alcohol ingestion (recent drinking)
•
Detecting hepatobiliary disease
•
Monitoring progression of liver disease or liver metas-
tases
Reference range Adult males: 7–47 U/L
Adult females: 5–25 U/L
Elderly individuals may have
slightly higher levels.
Values may vary with method used; consult lab reference
values.
Critical value(s) None
Increased levels •
Recent heavy drinking
• Hepatic necrosis
• Pancreatitis
•
Hepatic tumor or metastasis
https://t.me/med1917
138 Laboratory Medicine in Psychiatry and Behavioral Science
Gamma-glutamyltransferase (GGT) (continued)
Increased levels (continued) • Diabetes, metabolic syndrome
• Pancreatic cancer
• Hepatotoxic drugs
• Epstein-Barr virus
• Cholestasis
• Cytomegalovirus
• Renal failure
• Reye’s syndrome
Decreased levels Late pregnancy
Interfering factors Increased levels may be seen with phenytoin, phenobarbi-
tal, and anticoagulants because of enzyme induction, and
with excessive meat consumption.
Decreased levels seen with oral contraceptives or clofibrate.
Cross-references Alanine Transaminase
Alcohol Use Disorder
Aspartate Transaminase
Carbohydrate-Deficient Transferrin
Cirrhosis
Liver Function Tests
Bradley R, Fitzpatrick AL, Jenny NS, et al: Associations between total serum GGT activity and metabolic
risk: MESA. Biomark Med 7(5):709–721, 2013
Corti A, Belcastro E, Dominici S, et al: The dark side of gamma-glutamyltransferase (GGT): pathogenic
effects of an “antioxidant” enzyme.Free Radic Biol Med 160:807–819, 2020
Fujii H, Doi H, Ko T, et al: Frequently abnormal serum gamma-glutamyl transferase activity is associated
with future development of fatty liver: a retrospective cohort study.BMC Gastroenterol 20(1):217,
2020
Hong SH, Lee JS, Kim JA, et al: Gamma-glutamyl transferase variability and the risk of hospitalisation
for heart failure.Heart 106(14):1080–1086, 2020
Koenig G, Seneff S: Gamma-glutamyltransferase: a predictive biomarker of cellular antioxidant inade-
quacy and disease risk. Dis Markers 818570, 2015
Lee YB, Han K, Park S, et al: Gamma-glutamyl transferase variability and risk of dementia: a nationwide
study. Int J Geriatr Psychiatry 35(10):1105–1114, 2020
Praetorius Björk M, Johansson B: Gamma-glutamyltransferase (GGT) as a biomarker of cognitive decline
at the end of life: contrasting age and time to death trajectories. Int Psychogeriatr 30(7):981–990, 2018
https://t.me/med1917
139 Laboratory Tests
Glucose
Type of test Blood
Background and explanation
of test
Glucose is the body’s primary source of cellular energy,
obtained from carbohydrates in the diet and conversion of
glycogen stored in the liver and muscles. A constant supply
of glucose is required for normal brain function. A variety of
hormones r egulate glucose levels, the most important of
which are insulin and glucagon. Glucagon is secreted when
glucose levels are low, and this results in a cascade of events
that drive glucose levels up. Insulin is secreted when glucose
levels are high, driving glucose into cells and lowering serum
glucose levels.
It is important to interpret serum levels with respect to the
time of the last meal. Hyperglycemia in the fasting state sug-
gests a diagnosis of diabetes mellitus. This can be confirmed
with a glycosylated hemoglobin test or a glucose tolerance
test. Hypoglycemia is most common in patients with “brit
-
tle” diabetes who have taken too much insulin. Very low
blood sugar values as shown in the Critical Values section
below may be injurious to the brain.
Relevance to psychiatry and
behavioral science
High blood glucose levels can be associated with delirium,
the metabolic syndrome, acute stress response, and acute
pancreatitis and found in patients treated with atypical anti-
psychotics, phenothiazines, TCAs, lithium, or β-blockers
(other than propranolol). Low blood glucose levels can be
associated with alcohol use disorder, anorexia nervosa, panic
attacks or other anxiety syndromes, depression, and agitation
and may be seen in patients treated with propranolol or
MAOIs.
Preparation of patient Patients should fast for 8 hours before testing, with water
allowed. They should not fast for >16 hours, because feed
-
back processes can raise glucose levels. Insulin and oral hy-
poglycemic medications should be held until blood is drawn.
Indications •
Routine health screening
•
Suspicion of diabetes based on clinical signs and
symptoms
•
Suspicion of hypoglycemia based on clinical signs and
symptoms
• Acute change in mental status
•
Workup for patients with panic attacks or unexplained
anxiety
• Monitoring patients taking atypical antipsychotics
Reference range Fasting plasma glucose in adults
• <60 years: 74–106 mg/dL
• 60–90 years: 82–115 mg/dL
• >90 years: 75–121 mg/dL
Whole-blood glucose levels are 90% of plasma glucose
levels.
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140 Laboratory Medicine in Psychiatry and Behavioral Science
Glucose (continued)
Critical value(s) Diagnosis of diabetes mellitus (World Health Organization/Amer-
ican Diabetes Association criteria)
•Fasting glucose ≥ 126 mg/dL, or
• 2-hour level after 75-g oral glucose load ≥200 mg/dL, or
•HbA1C ≥ 6.5% or
•Random glucose ≥ 200 mg/dL plus symptoms of hyper-
glycemia
Panic values
• Males: <50 mg/dL or >400 mg/dL
• Females: <40 mg/dL or >400 mg/dL
Increased levels • Diabetes mellitus
• Acute stress response
• Cushing’s syndrome
• Pheochromocytoma
• Chronic renal failure
• Glucagonoma
• Acute pancreatitis
• Diuretic therapy
• Acromegaly
• Pregnancy
• Drugs: TCAs, β-blockers, corticosteroids, dextrothyrox-
ine, diazoxide, diuretics, epinephrine, estrogens, gluca-
gon, isoniazid, lithium, phenothiazines, phenytoin,
salicylate toxicity, triamterene
Decreased levels • Insulinoma
• Hypothyroidism
• Hypopituitarism
• Addison’s disease
• Severe liver disease
• Insulin overdose
• Starvation, anorexia nervosa
• Drugs: acetaminophen, alcohol, anabolic steroids, clofi-
brate, disopyramide, gemfibrozil, insulin, MAOIs, pent-
amidine, propranolol, thiazolidinediones, sulfonylureas,
biguanides, meglitinides, α-glucosidase inhibitors, incre-
tin mimetics
Interfering factors Dextrose-containing IV fluids
Cross-references Diabetes Mellitus
Hyperglycemia
Hypoglycemia
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141 Laboratory Tests
Glucose (continued)
Chernecky CC, Berger BJ: Laboratory Tests and Diagnostic Procedures, 5th Edition. St. Louis, MO, WB
Saunders, 2008
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
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