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Chapter 2. Laboratory Testing and Imaging Studies in Psychiatry

H. Florence Kim, M.D.; Paul E. Schulz, M.D.; Elisabeth A. Wilde, Ph.D.; Stuart C. Yudofsky, M.D.
DOI: 10.1176/appi.books.9781585623402.323687

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Laboratory and diagnostic testing traditionally have not held a central role in the diagnosis and treatment of patients with psychiatric disorders. This contrasts with the other specialties of modern medicine, which have come to rely heavily on laboratory and imaging modalities to provide the necessary information to diagnose and treat patients with disorders such as cancer, heart disease, and pulmonary problems.

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FIGURE 2–1. Computed tomography (CT) tissue attenuation values and appearance.Source. Adapted from J Levine lecture "Structural Neuroimaging in Psychiatry," given as part of the Neuroimaging in Psychiatry lecture series, Department of Psychiatry, Baylor College of Medicine, March 2006.

FIGURE 2–2. MRI comparison axial cuts, bipolar disorder patient versus matched control.MRI (T1-weighted) images of a 58-year-old healthy control patient (left) as compared with a patient of comparable age with bipolar disorder (right) but without any significant medical or substance abuse history. Although not diagnostic, common findings in neuroimaging research studies with bipolar disorder patients include diffuse gray matter loss, enlargement of the ventricles, and mild prefrontal volume loss.Source. Images courtesy of Elisabeth A. Wilde, PhD, Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, Texas.

FIGURE 2–3. Side-by-side comparison of structural imaging modalities: CT and MRI.The sensitivity of head CT versus MRI of the brain in the same patient is demonstrated here in a patient who presented with memory loss. A, Head CT scan shows a large area of decreased density consistent with edema. It is difficult to ascertain whether there is an underlying mass or what its shape might be. B, The image is from a brain MRI (T2 image) and also demonstrates an area of increased intensity of about the same shape as the CT abnormality. The patient was found to be HIV positive, and a subsequent brain biopsy demonstrated that the mass was a B-cell lymphoma.Images courtesy of Paul E. Schulz, MD, Department of Neurology, Baylor College of Medicine, Houston, Texas.

FIGURE 2–4. Diffusion tensor imaging (DTI).A, Fractional anisotropy color map derived from DTI in the sagittal plane. Red indicates white matter fibers coursing in a right-left direction, blue indicates fibers running in a superior-inferior direction, and green reflects fibers oriented in an anterior-posterior direction. B, Fiber tracking using DTI of the total corpus callosum overlaid on a T1-weighted inversion recovery image from the same brain.Source. Images courtesy of Elisabeth A. Wilde, PhD, Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, Texas.

FIGURE 2–5. Diffusion tensor imaging (DTI) in traumatic brain injury and bipolar disorder.Fiber tracking of the corpus callosum in A, a 16-year-old male patient who sustained severe traumatic brain injury and B, an uninjured young man of the same age. The arrow indicates the absence of fibers emanating from the posterior body of the corpus callosum. Note also the reduced length and number of fibers emanating from other aspects of the corpus callosum body, likely resulting from injury to the white matter in this area. The mean fractional anisotropy of the fibers in this system was significantly reduced. In addition to quantitative measures of anisotropy, DTI can be used to examine aberrant fiber patterns such as that demonstrated in a 55-year-old female bipolar patient (C) as compared with the expected pattern demonstrated in a woman of comparable age without history of illness (D). Interestingly, the patient had no significant abnormalities evident on conventional magnetic resonance imaging.Source. Images courtesy of Elisabeth A. Wilde, PhD, Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, Texas.

FIGURE 2–6. Side-by-side comparison of structural and functional neuroimaging: magnetic resonance imaging (MRI) and positron emission tomography (PET).Axial image of brain MRI (fluid attenuated inversion recovery images [FLAIR] sequence) and corresponding PET scan of a patient with Alzheimer's disease. The MRI image (A) shows prominent atrophic change in the posterior regions of the brain, consistent with striking reduction of metabolic activity in the posterior parietal lobes on PET imaging.Source. Image courtesy of Ziad Nahas, MD, MSCR, Department of Psychiatry, Medical College of South Carolina, Charleston, South Carolina.

FIGURE 2–7. Side-by-side comparison of single photon emission computed tomography (SPECT) versus positron emission tomography (PET).SPECT (top row) and PET images from two patients with clinically similar degrees of mild cognitive impairment. The PET scan demonstrates parietal changes, suggesting that this patient is at greater risk of developing Alzheimer's disease. The PET scan also demonstrates much better resolution than the SPECT scan.Source. Images courtesy of Paul E. Schulz, MD, Department of Neurology, Baylor College of Medicine, Houston, Texas.

FIGURE 2–8. Structural magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging of a healthy control subject and a patient with traumatic brain injury.Coronal slices (MRI) and three-dimensional reconstruction of the cortical surface (pink) and hippocampi (yellow) of a typically developing adolescent male (left) and an adolescent male with traumatic brain injury (right). Note the significant cortical and hippocampal atrophy in the patient as compared with the age-matched control. The top right image portrays PET findings overlaid on the MRI. PET reveals significant bilateral metabolic defects in the patient's mesial temporal areas as indicated by the absence of "warm" colors. Red represents areas of the greatest metabolic activity, followed by orange, yellow, green, blue, and violet.Source. Images courtesy of Erin Bigler, PhD, University of Utah, Salt Lake City, Utah.

FIGURE 2–9. Structural magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging of a patient with hypoxic brain injury.Despite the absence of significant findings on structural imaging, PET reveals areas of significant hypometabolism in the left temporal area as indicated by the arrow. Red represents areas of the greatest metabolic activity, followed by orange, yellow, green, blue, and violet. The center image is a fusion of the MRI and PET images.Source. Images courtesy of Erin Bigler, PhD, University of Utah, Salt Lake City, Utah.

FIGURE 2–10. Single photon emission computed tomography (SPECT), structural magnetic resonance imaging (MRI), and magnetoencephalography (MEG) imaging of a patient with traumatic brain injury.Findings from multiple neuroimaging modalities in a patient with traumatic brain injury reveal structural and functional deficits in the inferior frontal and temporal regions, common sites of focal injury in head trauma. Functional imaging reveals even more extensive defects in perfusion (SPECT, left) and dipole abnormality (MEG, right) than the areas of focal injury evident on structural MRI (center). The fused image (bottom) displays the results of the SPECT and MEG overlaid on the MRI.Source. Images courtesy of Erin Bigler, PhD, University of Utah, Salt Lake City, Utah.

FIGURE 2–11. Neuroreceptor imaging.Magnetic resonance imaging (A, C, E, G, I) and co-registered positron emission tomography images (B, D, F, H, J) acquired from 40 to 100 minutes following injection of 14.9 mCi [11C]DASB in a 40-year-old healthy male volunteer. A, B: Sagittal plane close to the midline, showing accumulation of activity in the midbrain, thalamus, and caudate. This picture also illustrates the low level of activity in the cerebellum. Activity concentration is also seen in the cortical gray matter (cingulate cortex). C, D: Transaxial plane, illustrating activity concentration in thalamus and striatum. E, F: Transaxial plane at the level of the midbrain. The very high activity concentration is seen at the level of the dorsal raphe. The amygdala is also seen on this plane. G, H: Coronal plane at the level of the anterior striatum, illustrating the ventrodorsal gradient of SERT in the striatum. This view also shows activity concentration in cingulate and temporal cortices. I, J: Coronal plane at the level of the postcommissural striatum, illustrating activity concentrations in the caudate and putamen, in the thalamus, and in the amygdala.Source. Images courtesy of Gordon Frankle, MD, Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.

FIGURE 2–12. Functional magnetic resonance imaging of working memory.Increased regional blood flow evident in prefrontal cortex while a subject is performing the Sternberg Task (left image). Corresponding images in Brainsight™ Frameless used for stereotactic targeting with transcranial magnetic stimulation (right images).Source. Images courtesy of Ziad Nahas, MD, MSCR, Department of Psychiatry, Medical College of South Carolina, Charleston, South Carolina.

FIGURE 2–13. Functional magnetic resonance (fMRI) and transcranial magnetic stimulation (TMS) as a neuroscience tool.fMRI interleaved with TMS over left prefrontal cortex in healthy volunteers illustrating both local and transsynaptic functional connectivity of cortical-subcortical networks.Source. Images courtesy of Ziad Nahas, MD, MSCR, Department of Psychiatry, Medical College of South Carolina, Charleston, South Carolina.
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TABLE 2–1. Selected medical conditions with psychiatric manifestations
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TABLE 2–2. Useful screening labs in the workup of the neuropsychiatric patient
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TABLE 2–3. Recommended diagnostic workup for a patient with new-onset psychosis
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TABLE 2–4. Recommended diagnostic workup for a patient with new-onset depressive or manic symptoms
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TABLE 2–5. Recommended diagnostic workup for a patient with new-onset anxiety symptoms
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TABLE 2–6. Recommended diagnostic workup for a patient with altered mental status
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TABLE 2–7. Recommended diagnostic workup for a patient with cognitive decline
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TABLE 2–8. Substances of abuse
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TABLE 2–9. Medication monitoring
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TABLE 2–10. Psychiatric drug metabolism by specific P450 enzymes
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TABLE 2–11. Drug metabolizer phenotype classification
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TABLE 2–12. Selected investigational biological and genetic markers
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TABLE 2–13. Tissue signal on T1 versus T2 weighting
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TABLE 2–14. Comparison of computed tomography (CT) and magnetic resonance imaging (MRI)
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TABLE 2–15. Indications for computed tomography (CT), prior to or instead of magnetic resonance imaging (MRI)
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TABLE 2–16. Comparison of SPECT, PET, and fMRI
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TABLE 2–17. Summary of neuroimaging findings in selected psychiatric disorders
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Laboratory testing of the psychiatric patient in the past has been utilized mainly to uncover medical or neurological causes of psychiatric symptoms.

The consensus of studies evaluating the role and value of laboratory testing is that patients who have psychiatric signs and symptoms but who do not exhibit other physical complaints or symptoms will benefit from a small screening battery that includes serum glucose concentration, BUN concentration, creatinine clearance, and urinalysis. Female patients older than 50 years will also benefit from a screening TSH test regardless of the presence or absence of mood symptoms.

More extensive laboratory screening may be necessary for psychiatric patients who do have concomitant physical complaints or findings on physical examination or for patients who are of higher risk, such as elderly or institutionalized patients or those with low socioeconomic status, self-neglect, alcohol or drug dependence, or cognitive impairment.

Newer laboratory testing methods such as pharmacogenetic testing and testing for investigational genetic and biological markers have the potential to transform and dramatically increase the importance of laboratory testing in the workup of the psychiatric patient.

Imaging may also be helpful when atypical features are present, such as an older age at onset of psychiatric illness, or when cognitive impairment is present.

Neuroimaging does not yet play a diagnostic role for any of the primary psychiatric disorders, but it is still an integral part of the clinical workup for psychiatric patients to rule out underlying medical causes of psychiatric symptoms.

Current neuroimaging methods provide both structural and functional data about the brain. Structural imaging techniques such as CT and MRI provide a fixed image of the brain's anatomy and spatial distribution. Newer functional neuroimaging techniques such as PET and SPECT provide information about brain metabolism, blood flow, the presynaptic uptake of transmitter precursors, neurotransmitter transporter activity, and postsynaptic receptor activity.

Functional scans should always be interpreted in the context of the underlying structural images.

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Based on a variety of studies, it appears that patients with psychiatric complaints alone, without other medical problems or symptoms, would benefit from which of the following screening tests?
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