Laboratory Diagnosis in Neurology, 1 Ed.

Psychiatric Disorders

M. Uhr

No specific laboratory tests are available for psychiatric disorders. Nevertheless, laboratory diagnosis is important in psychiatry, since psychiatric symptoms are often signs of systemic or neurological diseases. On the other hand, psychiatric disorders show a high comorbidity with physical diseases.

Basic and Specific Laboratory Diagnosis

Basic laboratory tests should be performed at the first encounter with a psychiatric patient (Table 11.8). If specific diseases are suspected, more specific laboratory diagnosis should follow, depending on the psychopathology and the patient's history (Table 11.9). Screening of psychiatric patients for syphilis and thyroid disease should be considered, and vitamin levels (especially vitamin B12 and folic acid) should be determined (Chap. 6, “Determination of Vitamins”).

Table 11.8 Basic laboratory diagnostic tests in psychiatric disease

Routine laboratory tests

• N+, K+, Ca2+, creatinine, urea

• GOT, GPT, AP, GGT, LDH, CK

• Total protein, bilirubin, lipase, uric acid

• Triglycerides, cholesterol, fasting blood sugar

• TPHA, basal cortisol, basal TSH

• ESR, blood count (including erythrocytes and hemoglobin), MCV, leukocytes, granulocytes, thrombocytes, INR, PTT

• Urine status and pregnancy test

• Pharmaceutical drug levels, if applicable

• Vitamin B12 and folic acid

* AP, alkaline phosphatase

Drug Screening

Drug screening for the diagnosis of drug-induced mental disorders and to monitor replacement therapy is of special importance. In the past, radioimmunoassays were used relatively often for drug screening; results are now obtained quite quickly by means of modern automated analysis based on enzyme immunoassays (EIA, ELISA) or fluorescence polarization immunoassays (FPIA). Rapid tests are also available which are easy to carry out for detecting drugs in urine. Tests for determining amphetamine, cannabis, cocaine, opiates, methadone, alcohol, and pharmaceuticals (e. g., barbiturates and benzodiazepines) in both urine and blood predominate, along with tests for determining the alcohol content of breath.

Pitfalls of Drug Screening

Drug addiction tests may yield false-positive results. A positive test result should therefore be confirmed by a more sophisticated analytical procedure.

Alcohol Markers

Tests are available for GGT, GOT, GPT, MCV, and CDT as alcohol markers. CDT (carbohydrate-deficient transferrin) is an iron transport protein that has partly or completely lost its sialic acid residues. The half-life of an elevated CDT level is about 2 weeks. For this reason, CDT is a good marker for showing alcohol abuse during the days before blood collection. The CDT test is very sensitive and will show the consumption of more than 60 g of pure alcohol per day over a longer period.

Drug Therapy Monitoring

Other specialties of psychiatric laboratory diagnosis include the detection of undesired drug side effects by means of laboratory tests, drug therapy monitoring of psychopharmaceuticals (Chap. 6, “Intoxication”), and pharmacogenetic characterization:

• Pharmacogenetic characterization: This concerns the genotyping of drug-metabolizing variants of cytochrome P450. Drugs are metabolized slowly or rapidly depending on the individual patients (“poor” metabolizers vs. “extensive” metabolizers). In addition, numerous drug interactions require individual adjustment. For further details, the reader must be referred to the specialist literature.

Table 11.9 Specific laboratory diagnosis of psychiatric diseases

Diagnosis

Psychopathological syndromes

Differential laboratory diagnosis

Multiple sclerosis

Multiple sclerosis

Dementia syndrome, depressive or manic syndrome

CSF analysis (Chap. 10, “Multiple Sclerosis”)

Inflammatory brain diseases

Inflammatory brain diseases

Delirium syndrome, unresponsiveness

• Blood: inflammatory signs, blood culture

• CSF: pleocytosis, possibly barrier dysfunction, increase in lactate, pathogen detection

Lyme disease (Borrelia burgdorferi), stages 2–3

Delirium syndrome, unresponsiveness

• IgM/IgG detection in the blood, depending on the stage

Borrelia PCR from skin biopsy and CSF

• Intrathecal immunoglobulin production (Chap. 10, “Neuroborreliosis”)

HIV encephalopathy

Dementia syndrome, apathetic syndrome

• HIV ELISA

• Western blot (confirmation test)

• Detection of HIV RNA

• T helper cells, CSF analysis

Neurosyphilis

Dementia syndrome, manic or depressive syndrome, organic personality change

• Screening test: TPHA test

• Confirmation test: FTA-ABS test

• Follow-up parameters: VDRL test, CSF analysis (Chap. 10, “Neurosyphilis”)

Degenerative processes

Creutzfeldt-Jacob disease

Dementia syndrome

• Neuron-specific enolase

• CSF: 14–3-3 protein (Chap. 11, “Creutzfeldt-Jakob Disease”)

Alzheimer's disease

Dementia syndrome

• No specific laboratory diagnosis

• Amyloid β, tau protein (Chap. 11, “Alzheimer's Disease”)

Huntington's chorea

Personality change, dementia syndrome

• Sydenham's chorea: ESR, CRP, and possibly ASL titers; leukocytosis

• Molecular genetic diagnosis (Chap. 8)

Alcohol diseases

Wernicke's encephalopathy

Confusion syndrome, delirium syndrome

• Vitamin B1 deficiency (possibly also vitamin B12/B6 deficiency)

• Possibly increased transaminase levels, CDT

Korsakow's syndrome

Confusion syndrome, delirium syndrome, dementia syndrome

• Possibly vitamin B1 deficiency (possibly also vitamin B12/B6 deficiency)

• Possibly increased transaminase levels

Endocrine diseases

Hypothyroidism

Depressive and anxiety syndromes, dementia syndrome

• FT4, basal TSH (screening test)

• Thyroid antibodies (TgAb and anti-TPOAb)

Hyperthyroidism

Manic and anxiety syndromes

• FT3, FT4, basal TSH, TRH test

• TSH receptor antibodies (TRAb and anti-TPOAb)

Hypoparathyroidism

Schizophrenic syndrome

• Serum: calcium, magnesium, phosphate, and parathyroid hormone

• Urine: calcium and phosphate

Hyperparathyroidism (primary)

Depressive and anxiety syndromes

• Serum: calcium, parathyroid hormone, phosphate

• Urine: calcium and phosphate

Hypocortisolism

Anorexia, neurasthenic and depressive syndromes

• Serum: cortisol, sodium, potassium

• Plasma ACTH, ACTH stimulation test

• Adrenal cortex autoantibody

Hypercortisolism

Depressive, anxiety, and schizophrenic syndromes

• Circadian rhythm of serum cortisol, cortisol in 24-h urine

• ACTH in the plasma, ACTH after administration of CRH plus dexamethasone suppression test

Pheochromocytoma

Anxiety syndrome

• Plasma catecholamines

• Catecholamines in 24-h urine

Hypophyseal insufficiency

Depressive and neurasthenic syndromes

Basal hypophyseal hormones

Hyperprolactinemia

Depressive and anxiety syndrome

Prolactin level

Systemic lupus erythematosus

Schizophrenic syndrome

• ESR, CRP, α2-globulins

• Anti-dsDNA, ANA, anti-Sm, antiphospholipid antibody, complement (C 3, C 4) (Chap. 10, “Systemic Vasculitis and Connective Tissue Diseases”)

Vasculitis

Mood disorders

ESR, CRP, p-ANCA, c-ANCA, ANA (Chap. 10, “Systemic Vasculitis and Connective Tissue Diseases”)

Metabolic and toxic processes

Hyperglycemia

Hypoglycemia

Hyponatremia

Hypernatremia

Hypokalemia

Confusion syndrome, delirium syndrome, unresponsiveness

Blood sugar, sodium, osmolarity of serum, potassium in serum

Wilson's disease

Personality change, dementia syndrome, depressive and schizophrenic syndromes

Copper and ceruloplasmin in serum, copper in the urine, molecular genetic diagnosis

Uremia

Confusion syndrome, delirium syndrome, semi-consciousness, schizophrenic syndrome

Urea and creatinine, osmolarity of urine

Hepatic encephalopathy

Confusion syndrome, delirium syndrome, semi-consciousness

Ammonia

Deficiency diseases

(Chap. 6, “Determination of Vitamins”)

• Recognition of side effects: In the context of psychopharmacological treatment, laboratory follow-up tests should be performed to recognize side effects as soon as possible and to optimize the therapeutic dosage. Blood count, GOT, GPT, GGT, urea, and creatinine should therefore be regularly checked during therapy with tricyclic antidepressants, neuroleptics, and other antidepressants, as well as clozapine and atypical neuroleptics (for details, see the specialist literature). This holds true particularly for clozapine therapy, where weekly blood counts and monthly determinations of transaminases, urea, and creatinine are required during the first 4 months.

For details on intoxication after a suicide attempt or during lithium therapy, see Chap. 6, “Intoxication.”

CSF Analysis

CSF analysis follows the normal standards (Chap. 5). There are no specific CSF findings for psychiatric disorders, although it should be remembered that 20–30% of all patients with depression or schizophrenia show a barrier dysfunction. It should also be remembered that in about 10% of patients with schizophrenia, the CSF shows signs of inflammation (Bechter et al., 2010; Reiber et al., 2010).

References

Bechter K, Reiber H, Herzog S, Fuchs D, Tumani H, Maxeiner HG. Cerebrospinal fluid analysis in affective and schizophrenic spectrum disorders: Identification of subgroups with immune responses and blood–CSF barrier dysfunction. Journal of Psychiatric Research 2010, in press

Reiber H, Uhr M. Liquordiagnostik. In: Berlit P (ed). Klinische Neurologie. 3rd ed. Heidelberg: Springer Verlag; 2010

Table 11.7 Diagnostic criteria for variant Creutzfeldt-Jakob disease (vCJD)

I

A

Progressive neuropsychiatric disease

B

Duration of disease > 6 months

C

Routine examinations do not yield an alternative diagnosis

D

No evidence of iatrogenic CJD

E

No evidence of familial CJD

II

A

Early psychiatric symptoms

B

Persistent painful sensory symptoms

C

Ataxia

D

Myoclonia or choreatic symptoms or dystonia

E

Dementia

III

A

EEG does not show pattern typical of sporadic CJD (or EEG is not possible)

B

MRI shows bilateral symmetric signal intensity in the pulvinar

IV

A

PrPCJD-positive tonsil biopsy

Definite vCJD

IA and neuropathologic confirmation of vCJD

Probably vCJD

I and 4 out of 5 symptoms from II, III A, III B

and IV A; or

I and IV A

Possible vCJD

I and 4 out of 5 symptoms of II and III A



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