Brain Imaging in Clinical Psychiatry
In their preface, the editors set forth the intent of this volume, which is to provide “clinicians and researchers with a background and comprehensive introduction for imaging neuropsychiatric disorders.” To accomplish this, the editors have organized the chapters into three groups. The first four chapters set forth the basic principles of magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and single photon emission computed tomography (SPECT). Two chapters on neuroanatomy follow, the first on the functional neuroanatomy of the limbic system and planum temporale and the second on the morphology of normal brain development for ages 4–18. The remaining chapters consider the major psychiatric disorders by diagnostic area.
Developmental neuropsychopathology is covered first. Structural and functional data are considered for attention deficit hyperactivity disorder, autism, dyslexia, fragile X syndrome, childhood-onset schizophrenia, Sydenham's chorea, and Tourette's syndrome. The authors conservatively conclude that “the abundance of reported neuroanatomical findings has been more notable than the consistency of the findings.” A useful table of psychiatric indications for pediatric cerebral MRI scans is included.
Next are four chapters on neuromorphometric, MRS, PET, and SPECT studies of mood disorders. The presence of deep white matter hyperintensities on MRI in greater frequency in patients with late-onset depression than in younger patients appears to be the most consistent morphological finding; underlying cerebral atherosclerosis is the most likely cause in older patients. Alterations in phosphomonoesters and phosphodiesters have been noted with 31P-MRS in bipolar disorder, but similar changes have been found in schizophrenia, which brings the specificity of the changes into question. The few studies with 1H-MRS suggest that there are increased choline-containing and other compounds in bipolar disorder. 19F-MRS and 7Li-MRS have been used to determine the brain concentrations of fluorinated drugs such as fluoxetine and lithium.
Some, but not all, [18F]fluorodeoxyglucose (FDG) PET studies of primary depression have shown reduced FDG uptake (interpreted as reduced glucose metabolism) in the prefrontal cortex and caudate nucleus, which increases toward control values with successful treatment. PET cerebral blood flow studies with 15O-water show decreased flow in similar cortical areas, an indication of the normal coupling of cerebral blood flow and metabolism. Activation studies tend to show less activation following demanding tasks in subjects with depression than in normal control subjects. Findings of SPECT studies measuring regional cerebral blood flow have been consistent with those of PET studies, indicating reduced blood flow in the prefrontal cortex and basal ganglia. Some neuroanatomical theories of depression have been derived from the functional imaging data; these theories center around reduced activity in frontal cortical, basal ganglia, and thalamic circuits.
Next is a comprehensive chapter on anorexia nervosa and bulimia nervosa. The authors first comment on etiology, pathophysiology, comorbid symptoms (depressive and obsessive-compulsive), and animal studies. Methodological problems are considered, including changes in brain size with starvation (pseudoatrophy), appropriate control subjects, and statistical analysis (“fishing or science?”). Morphological studies include findings of reduced cerebral and increased ventricular volumes and reduced pituitary size. The authors summarize the functional imaging studies by stating that there are no clearly replicated specific functional imaging abnormalities demonstrated thus far, except perhaps a greater right-sided than left-sided decrease in cortical FDG uptake in bulimic patients than in control subjects.
Four chapters on schizophrenia and late-life psychosis follow. The first, on MRI, is encyclopedic (the table of individual studies is 24 pages long), and at the end the authors indicate that the two robust findings are lateral ventricular enlargement and temporal and medial temporal lobe volume reduction. MRS studies in schizophrenia are reviewed next; there were only a dozen or so through 1995. These have shown reduced N-acetyl aspartate in the temporal lobes, evidence of membrane alterations (phosphomonoesters and phosphodiesters), and possible alterations in energy metabolism (nucleotide triphosphates). The third chapter reviews PET studies of cerebral metabolism and blood flow, of which there are many, like the MRI studies. The authors conclude that the PET results on anterior-posterior and laterality differences in FDG uptake and blood flow, including those with cognitive activation, are equivocal. In this chapter, as in most of the others, potential sources of variability are mentioned, including patient selection, sample size, demographic factors, image acquisition technique and anatomical coregistration, and cognitive activation paradigms. The chapter on late-life psychosis covers primarily morphologic studies and comes to conclusions similar to those for earlier-age schizophrenia, i.e., ventricular enlargement and temporal lobe volume reduction. Additionally, increased thalamic volume and a greater number of discrete gray and white matter lesions have been described in elderly psychotic patients.
The chapter on brain imaging in phobic disorders includes panic disorder, posttraumatic stress disorder, social phobia, generalized anxiety disorder, and simple phobia. As might be expected, studies of these different diagnostic categories with different imaging techniques have yielded a variety of findings. The chapter on obsessive-compulsive disorder (OCD) is of interest because the neuroanatomical theories of OCD derived from imaging data center around increased activity in components of the frontal cortical, basal ganglia, thalamic, frontal cortical loop—opposite to the changes in these circuits in major depression, mentioned above. The chapter on personality disorders underscores the heterogeneity of these disorders and provides an interesting perspective on potential links between stable personality traits and regional brain function in the normal population.
The final chapters are on MRI and MRS in dementia, PET in dementia, application of PET to age-related cognitive changes, neuroimaging of HIV infection, and brain imaging in chronic fatigue syndrome. Because of the greater definitiveness of brain pathology in these neuropsychiatric disorders compared with the psychiatric disorders considered earlier, the findings emerge much more consistently and indeed are being used clinically to confirm diagnoses, a utility that still lies far in the future for imaging studies of psychiatric disorders. For example, bilateral temporoparietal reductions in cerebral blood flow and FDG uptake add considerable weight to the diagnosis of Alzheimer's disease in patients with signs and symptoms of dementia.
As mentioned at the beginning of this review, the editors intended to provide a comprehensive introduction to the imaging of neuropsychiatric disorders. Given the constraints of a single, multiauthored volume, they have accomplished this very well. The authors, about a third of whom are from the editors' own institution, Duke University, are respected authorities in neuroimaging.
This volume can serve as a practical introduction to the basics of several standard neuroimaging techniques and as a comprehensive review of imaging studies on neuropsychiatric disorders up to the mid-1990s. Newer techniques such as functional MRI, in which advances have been rapidly occurring in the last several years, are of necessity covered only briefly and will require the interested reader to consult additional sources such as journal review articles. The same can be said for the imaging studies presented for the various psychiatric conditions; most psychiatric illnesses are being vigorously explored by both structural and functional neuroimaging in many research centers, and new data are reported as frequently as new journal issues appear. Given the current speed and intensity of progress in the neuroimaging of neuropsychiatric disorders, the editors may wish to consider an update to this volume for the twenty-first century.
