Functional Abnormalities

The 60 Second Panic Solution

Anxiety and Panic Disorders Holistic Cure

Get Instant Access

Functional imaging further complements structural imaging findings in that the consequences of lesions for global and regional brain function in putative functional neurocircuits can also be assessed. In addition, one can test how similar mood symptoms occur with anatomically or neurochemically distinct disease states as well as why comparable lesions do not always result in comparable behavioral phenomena. Specific cohorts such as healthy family members or sib-pairs, presence or absence of specific risk factors (high and low neuroticism, presence and absence of specific genetic polymorphisms, family history, early abuse, etc.) can be systematically targeted. Parallel studies of primary affective disorder and patients with neurological depressions similarly provide complementary perspectives.

Brain Imaging. Positron emission tomography (PET) and single-photon emission tomography (SPECT) studies of both primary depression (unipolar, bipolar) and depression associated with specific neurological conditions (focal lesions, degenerative diseases, epilepsy, multiple sclerosis) identify many common regional abnormalities (reviewed in Mayberg, 1994; Ketter et al., 1996). For example, in depressed patients with one of three prototypical basal ganglia disorders—Parkinson's disease, Huntington's disease, and left caudate stroke—resting-state paralimbic hypometabolism (ventral prefrontal cortex, anterior cingulate, anterior temporal cortex) was found to differentiate depressed from nondepressed patients within each group, as well as depressed from nondepressed patients, independent of disease etiology (Mayberg, 1994). These regional findings, replicated in other neurological disorders (Bromfield et al., 1992; Hirono et al., 1998; Starkstein et al., 1990c), suggests involvement of critical common pathways for the expression of depression in distinct neurological populations, findings of potential relevance to studies of primary mood disorders (Fig. 7.3).

Cortical (common)

Paralimbic striatal (different)

Parkinson's Unipolar Bipolar

Figure 7.3. Metabolic profiles in depression of varying etiologies. Metabolic abnormalities identified with fluorodeoxyglucose (FDG) PET scanning in patients with unipolar depression (UP), bipolar depression (BP), and depression with Parkinson's disease (PD) are illustrated. The top row demonstrates a common pattern of symmetric dorsal and ventral prefrontal (F9), inferior parietal (P40), and anterior cingulate (Cg) hypometabolism across the three patient groups. The bottom row demonstrates disease-specific abnormalities, most notably in subcortical and limbic structures such as the anterior insula and striatum. Striatal hypermetabolism, common to BP and PD may contribute to mood lability, characteristic of BP but also seen in many PD patients including acute changes in mood state with deep-brain stimulation in this region. Abbreviations. F = frontal, cd = caudate, gp = globus pallidus, th = thalamus, ins = anterior insula, T = temporal, P = parietal, Cg = anterior cingulate; numbers are Brodmann designations metabolic increases decreases. (Data from Mayberg et al., 1997, and Stefurak et al., 2001b). See ftp site for color image.

Studies of blood flow and glucose metabolism in patients with primary depression also report frontal abnormalities, in general agreement with the pattern seen in neurological depressions (Baxter et al., 1989; others reviewed in Ketter et al., 1996). The most robust and consistent finding is decreased frontal lobe function, although normal frontal as well as hyperfrontal activity has also been reported (Drevets et al., 1992). Localization within the frontal lobe includes dorsolateral and ventral lateral pre-frontal cortex (Brodmann areas 9, 46, 10, 47), as well as orbital frontal cortices (BA 10, 11). Findings are generally bilateral, although asymmetries are described. Cingulate changes are also commonly seen and consistently involve anterior dorsal sectors (Ebert and Ebmeier 1996; Mayberg et al., 1997). Other limbic-paralimbic (amygdala, anterior temporal, insula) and subcortical (basal ganglia, thalamus) abnormalities have also been identified, but the findings are more variable (reviewed in Mayberg, 1997). Use of different analytic strategies (voxel-wise versus regions of interest) has been considered an important factor in explaining these apparent inconsistencies. Differences

Cortical (common)

Paralimbic striatal (different)

Figure 7.3. Metabolic profiles in depression of varying etiologies. Metabolic abnormalities identified with fluorodeoxyglucose (FDG) PET scanning in patients with unipolar depression (UP), bipolar depression (BP), and depression with Parkinson's disease (PD) are illustrated. The top row demonstrates a common pattern of symmetric dorsal and ventral prefrontal (F9), inferior parietal (P40), and anterior cingulate (Cg) hypometabolism across the three patient groups. The bottom row demonstrates disease-specific abnormalities, most notably in subcortical and limbic structures such as the anterior insula and striatum. Striatal hypermetabolism, common to BP and PD may contribute to mood lability, characteristic of BP but also seen in many PD patients including acute changes in mood state with deep-brain stimulation in this region. Abbreviations. F = frontal, cd = caudate, gp = globus pallidus, th = thalamus, ins = anterior insula, T = temporal, P = parietal, Cg = anterior cingulate; numbers are Brodmann designations metabolic increases decreases. (Data from Mayberg et al., 1997, and Stefurak et al., 2001b). See ftp site for color image.

among patient subgroups (familial versus sporatic; bipolar versus unipolar, primary versus neurological), as well as heterogeneous expression of clinical symptoms is also thought to significantly contribute to this variance, but there is not yet a consensus.

Biochemical Imaging. Several neurochemical markers have also been examined in depressed patients using imaging, but findings are quite variable. Decreases in serotonin transporter 5-HTT binding has been reported in brainstem (Malison et al., 1998) but not in any of the other regions identified in post-mortem studies of depressed suicides, such as ventral prefrontal cortex or anterior cingulate. 5-HT1A and 5-HT2A receptor densities have also been examined but with inconsistent findings in the drug-free state (Sargent et al., 2000; Meyer et al., 1999). Relationships between receptor and transporter markers or between neurochemical and regional metabolic changes have not yet been systematically explored, as has been a growing trend in postmortem examinations. Studies of other markers of interest are limited by the lack of suitable radioligands.

Clinical Correlates. The best replicated behavioral correlate of a resting-state abnormality in depression is that of an inverse relationship between prefrontal activity and depression severity (reviewed by Ketter et al., 1996). Prefrontal activity has also been linked to psychomotor speed and executive functions (Bench et al., 1993), parietal and parahippocampal activity with anxiety (Osuch et al., 2000), medial frontal and cin-gulate activity with cognitive performance (Bench et al., 1993), and that of amygdala with cortisol status (Drevets et al., 2002). A more complex ventral-dorsal segregation of frontal lobe functions has also been described with anxiety/tension positively correlated with ventral prefrontal activity and psychomotor and cognitive slowing negatively correlated with dorsolateral activity (Brody et al., 2001a). The prefrontal cortex overac-tivity seen in patients with a more ruminative/anxious clinical presentation is consistent with findings described in primary anxiety and obsessional disorders, memory-evoked anxiety and fear in healthy subjects, and even normal variations in individual response to the testing environment due to novelty or state anxiety (Liotti et al., 2000).

Correlative Mapping Studies. Direct mapping of specific behavioral features is an alternative approach, allowing head-to-head comparisons of patients and healthy controls (Dolan et al., 1993). With this type of design, one can both quantify the neural correlates of the performance decrement as well as identify potential disease-specific sites of task reorganization. These types of studies can be performed with any of the available functional methods, including PET, functional MRI (fMRI), and event related potentials (ERP). Using this strategy, for example, George et al. (1997) demonstrated blunting of an expected left anterior cingulate blood flow increase during performance of a Stroop task. A shift to the left dorsolateral prefrontal cortex, a region not normally recruited for this task in healthy subjects, was also observed. Elliot et al. (1997a), using the Tower of London test, described similar attenuation of an expected blood flow increase in dorsolateral prefrontal cortex and failure to activate anterior cingulate and caudate regions recruited in controls.

Was this article helpful?

0 0
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.

Get My Free Ebook


Post a comment