Changes in Cortical and Subcortical Activity

Consistent with a decrease in synaptic connectivity is a decrease in synaptic activity. PET studies of regional cerebral blood flow (rCBF) using fluorodeoxyglucose (FDG) and functional MRI (fMRI) studies have revealed that abnormalities in numerous mental functions in patients with schizophrenia are associated with alterations in the normal activation of various cortical and subcortical areas.

Most consistently, PET and fMRI studies have shown that working memory and attention deficits in schizophrenia subjects are associated with decreased activity in the prefrontal cortex, particularly the dorsal lateral prefrontal cortex (DLPFC) (Velakoulis and Pantelis, 1996). In addition, several studies (Heckers et al., 1999; Lahti et al., 2001) have shown that patients with deficit schizophrenia have greater "hypofrontality" than patients with nondeficit schizophrenia, further supporting the concept of schizophrenia as a heterogeneous disease. Holcomb and colleagues (2000) showed that the anterior cingulate cortex is less activated in patients with schizophrenia than in normal volunteers during performance of a difficult cognitive task (see Fig. 9.4). In PET studies, patients with schizophrenia also exhibited abnormal activation of cortical areas such as the frontal eye fields. This occurred during other functions that are known to be abnormal in this patient population, including smooth pursuit and saccadic eye movements (Ross et al., 1995; O'Driscoll et al., 1998).

Changes in brain activity have also been reported in subcortical areas including the hippocampus, thalamus, and basal ganglia. For instance, patients with schizophrenia have reduced hippocampal activation during episodic memory retrieval (Heckers et al., 1998). In PET/FDG studies, floridly psychotic schizophrenia patients show increased activation in the hippocampus and parahippocampal gyrus, which correlate significantly with the severity of their positive psychotic symptoms (Tamminga et al., 1992). PET

Figure 9.4. Subtraction analysis of PET scan showing lesser activation (yellow) of the anterior cingulate cortex in schizophrenic persons compared to normal volunteers during performance of a difficult cognitive task. [Adapted from: Am J Psychiatry, 2000 157(10):1634-1645. Copyright 2000, the American Psychiatric Association, http://ajp.psychiatryonline.org. Reprinted by permission.] See ftp site for color image.

Figure 9.4. Subtraction analysis of PET scan showing lesser activation (yellow) of the anterior cingulate cortex in schizophrenic persons compared to normal volunteers during performance of a difficult cognitive task. [Adapted from: Am J Psychiatry, 2000 157(10):1634-1645. Copyright 2000, the American Psychiatric Association, http://ajp.psychiatryonline.org. Reprinted by permission.] See ftp site for color image.

revealed a reduced glucose metabolism in the thalamus of schizophrenia patients during an olfactory identification test (Clark et al., 2001). fMRI reveals lower metabolism in the striatum of schizophrenia subjects, and this is normalized by antipsychotic medication in subjects that respond to medication (Velakoulis and Pantelis, 1996). In addition, electron microscopic studies of postmortem striatum from patients with schizophrenia show a 20 percent decrease in the number of mitochondria, subcellular organelles that generate energy (Kung and Roberts, 1999). Fewer mitochondrial profiles suggest decreased energy demands or diminished capacity to respond to energy requirements. These data are consistent with in vivo imaging that show decreased striatal metabolism in people with schizophrenia (Buchsbaum et al., 1992).

The decreased metabolism in cortical and subcortical areas observed in PET and FDG studies is consistent with perturbations in synaptic activity. While these abnormalities appear to be widespread, it is likely that specific symptoms of schizophrenia are related to the dysfunction of particular brain regions that act in concert. These groups of functionally related brain regions, or circuits, normally perform such functions such as movement and vision (Alexander et al., 1986). There is evidence that abnormalities in one such circuit (the anterior cingulate or limbic circuit), which includes the hippocampus, some neocortical regions, and associated subcortical areas, underlie psychotic symptoms such as hallucinations, delusions, and formal thought disorders. In contrast, blunted affect, poverty of speech, and other features typical of deficit schizophrenia appear to be due to abnormalities in another circuit that includes the dorsolateral prefrontal cortex, inferior parietal cortex, and associated subcortical regions (Carpenter et al., 1993).

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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