Advances in neuroimaging technologies have created both opportunities and challenges in the study of psychosis. Eager to obtain a “window to the mind,” neuroimaging has been embraced by investigators applying diverse methods to examine brain structure and function in psychiatric disorders. With progress in quantitative computational anatomy methodologies, we are at the threshold of an exciting era in psychiatric research that can capitalize on the ability to study the living brain with refined approaches both for hypothesis testing and for exploration. In vivo measurement is afforded by magnetic resonance imaging (MRI) examining neuroanatomy through structural MRI (sMRI), connectivity through diffusion tensor imaging (DTI), and neurochemistry through magnetic resonance spectroscopy (MRS). Magnetic resonance also enables examination of brain physiology using functional MRI (fMRI) methods. Other functional neuroimaging methods include positron emission tomography (PET), which enables measurement of local cerebral glucose metabolism, blood flow, and receptor function. Single-photon computed emission tomography (SPECT) can also be used to measure cerebral perfusion and receptor function.
The diversity and complementarity of neuroimaging methods can place them in a crucial position for integrative translational research. Neuroimaging can intersect basic and clinical efforts in elucidating the underlying processes of complex psychotic disorders. By supplying data obtained on patients, neuroimaging has a firm hold on the clinical phenotype, and by informing on brain systems, it can link to molecular substrates. Furthermore, combining neuroimaging with genetic strategies can yield a powerful methodology with unprecedented potential for novel treatments (). The challenge we face is making this happen by mobilizing the increasing array of procedures and measures relevant to clinically important questions such as diagnosis, course of illness, and outcome.
A Schematic Representation of the Central Role of Neuroimaging Intersecting Between Basic Science and Clinical Applications.
After 3 decades of neuroimaging research, is the technology informative to efforts to deconstruct psychosis? Based on brain-imaging studies can we examine a patient with first-episode psychosis and determine with some confidence whether schizophrenia or bipolar disorder are on the horizon? Might we even be able to use imaging as an early diagnostic aid in those at genetic or symptomatic high risk?
The research agenda in neuroimaging and psychosis has not been geared from the outset to be clinically relevant in differential diagnosis. Rather, most studies in psychosis have focused on 1 disorder with the explicit primary goal of understanding its specific pathophysiology. An implicit secondary goal has been to improve diagnosis and clinical management. When imaging, commonly structural, has been applied clinically as part of the workup of a psychotic patient, the purpose has been to rule out a space occupying lesion or developmental malformation that may potentially cause the psychosis. Although incidental findings have been reported in MRI studies of even healthy people1
and patients who present with psychosis,2
such findings are infrequent and commonly asymptomatic. This is not to say that obtaining a scan is of no value where an organic psychosis is suspected; a recent analysis of 253 adult psychiatric patients who underwent a clinical MRI, 38 (15%) had some form of treatment modification as a result of the neuroimaging findings, and in 6 patients a medical condition was identified as a result of the MRI.3
However, in the absence of quantitative analysis, routine brain imaging cannot aid in the differential diagnosis of psychosis without considering the clinical presentation.4
Thus far, studies using imaging techniques to determine prognosis or treatment response have not generated sufficiently replicated findings. There are, however, encouraging results from several studies evaluating these technologies as possible predictors of diagnosis.
Most neuroimaging studies have been conducted in schizophrenia. A PubMed search in October 2006 shows 490 citations for “schizophrenia and neuroimaging” and only 134 for “bipolar and neuroimaging.” Only 31 studies are cited for the conjunctive “schizophrenia and bipolar and neuroimaging” query. Few prospective studies contain the information that would permit comparison between patients with schizophrenia and those with bipolar illness. Inconsistent findings within disorders have often led to controversy and have been attributed to disease heterogeneity. Over the past decade, advances in quantitative techniques have established some firm findings about schizophrenia and related disorders. As importantly, these techniques have also highlighted areas where further study is required and where methodological practices need to be improved.
This article will briefly highlight the knowledge we have gained about psychosis using brain-imaging methods by emphasizing the results from consistently replicated studies, systematic reviews, and meta-analyses of the relevant literature. We shall consider structural imaging (sMRI, DTI), neurochemical imaging (MRS, receptor studies), and functional imaging techniques in patients with schizophrenia and the affective psychoses, including studies of at-risk populations. The latter enable integration of genetic and neuroimaging paradigms in our efforts to elucidate neurobiological mechanisms that underlie these disorders that may guide treatments.