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Interpretation of brain-mapping studies in which group of depressed bipolar patients buy ciplox discount antibiotic and alcohol. The finding was again complex tasks are employed require careful use of specific seen when extended to a group of depressed bipolar using control tasks as opposed to simple 'rest' state images buy ciplox 500 mg fast delivery antibiotic resistance washington post. The CMRG measures and cheap generic ciplox uk antibiotic quinine, then again, when extended to a group best control tasks will differ from the task of interest in only of unipolar depressed patients with familial pattern. Important work has been brainstem serotonergic systems; all systems implicated in done, however. For example, induction of different emo- mood and behavior regulation. Mayberg and associates tions via different strategies has been accomplished and (121) also detected decreased CMRG in the rostral anterior demonstrates neuroanatomic systems independent of the cingulate of unipolar depressed patients compared to con- induction strategy (117,118). An alternative to inducing a con- gion found by Drevets and colleagues. However, in a highly sciously perceived emotion is to present affect-laden stimuli creative approach, Mayberg and associates (122) examined at an unconscious level (119). This work developed a tech- the regional changes in neural activity with multiple PET nique for presenting fearful faces with masking to prevent scans after improvement of symptoms in depressed patients conscious processing of the visual stimuli. Fearful faces, in and compared those to the regional changes in neural activ- contrast to neutral or happy faces, have been reported by ity induced by script-induced sadness in control subjects multiple investigators to invoke an increase in amygdala (see Fig. Affective symptom remission was associated activity. By masking the briefly presented ( 40 msec) fear- with an increased activity within dorsolateral prefrontal cor- ful faces with neutral faces, Whalen and colleagues (119) tex, inferior parietal, dorsal anterior cingulate, and posterior developed a task that isolates the subconscious processing cingulate and decreases in ventral limbic and paralimbic of affect laden stimuli without the confounding variable of sites, including the subgenual anterior cingulate and poste- individual cognitive processing. Such paradigm design may similar pattern of regional brain activity, but in the opposite prove useful in investigation of affective illnesses such as direction, in the normals during induced sadness. For disease is still in its infancy because of only recent develop- depressed patients, the increases in dorsal cortical regions ment of some appropriate task paradigms; however, the area may reflect increased cognitive function in the remitted has substantial promise. The decreases in the subgenual anterior cingulate as used to map changes in brain activity in depressed patients and normal controls while viewing a film segment chosen symptoms resolve appears more complicated. The depressed patients had signifi- possible to conclude from the data presented in Mayberg cantly more activation in areas of the prefrontal cortex. In- and associates (122) that the depressed state reflects an in- creased activation in the prefrontal cortex of the depressed creased and abnormal functioning of the subgenual cingulate cortex could be secondary to increased processing of the that returns to baseline during remission. For many tasks increased Drevets and colleagues (3) clearly showing decreased metab- prefrontal activation accompanies an increase in task diffi- olism in the subgenual cingulate during a depressive episode culty; however, several issues, including the potential for needs to be reconciled. One explanation is that the decreased differences in cognitive response or attention level to the activity is conceivably an actual increase in functional activ- film being shown, must temper the interpretation of this ity that only appears decreased on PET imaging owing to work. Further fMRI work on the processing of emotional partial volume effects. This region was also reported by stimuli in depressed patients is ongoing and will certainly Drevets and colleagues to have sizable decreases in volume shed more light on this fascinating area of research. Some consensus has begun to emerge pointing to abnor- Nevertheless, the subgenual cortex and adjacent anterior Chapter 74: Imaging of Affective Disorders 1073 cingulate appear to play an important role in emotional regulation and expression. Molecular Imaging of Neurotransmitter Systems in Affective Disorders Numerous hypotheses have been proposed relating mono- amine systems and depression. Serotonin, dopamine, and norepinephrine have all been implicated to various degrees in the behavioral changes and treatment of depression. Of these three, reports indicating a constellation of specific se- rotonergic dysfunctions in major depressive disorders have been the most convincing. For this reason, much effort in A the imaging community has been focused on developing tools for imaging different aspects of the serotonergic system in vivo. Generally, these tools have involved the develop- ment and validation of radioligands specific for serotonin receptor subtypes (with more than 14 serotonin receptors isolated to date); however, alternative approaches to image serotonergic function have been reported as well. A report by Mann and co-workers (123) demonstrated reduced sero- tonin responsivity in depressed patients. In that work, fenfl- uramine, an indirect serotonin agonist, was used as a phar- macologic challenge and FDG PET imaging was used to image the brain responses. Depressed patients showed much less FDG uptake changes in response to fenfluramine than normal controls. Such an approach is limited, however, by the uncertainty in the relationship of the FDG changes and B specific aspects of the serotonergic system. A: Left images show changes in regional cerebral Before reviewing the progress in this rapidly moving blood flow (CBF) (with [15O]water PET) associated with transient field, it is important to note that there is considerable diffi- sadness in eight healthy volunteers. Right images show changes in regional glucose metabolism (with FDG PET) after six weeks of culty in synthesizing the literature in both PET and SPECT treatment in eight unipolar depressedpatients. Coronal (top row) imaging of receptor function owing to a lack of common and sagittal (bottom row) views. Sadness is associated with in- data analysis procedures among various imaging groups. As creases in ventral paralimbic regions and decreases in dorsal fron- tal regions. With recovery from depression, the reverse is seen: the different data analysis techniques have specific inherent ventral decreases and dorsal cortical increases. Slice locations are assumptions and limitations, it is useful to briefly review in millimeters relative to the anterior commissure. For the sake of brevity, we will limit Brodmann area designations. R, right; L, left; A, anterior; P, poste- rior; F, prefrontal; ins, anterior insula; Cg24, dorsal anterior cingu- this review to receptor imaging; however, the issues are often late;Cg25,subgenualcingulate;pCg,posteriorcingulate;Cb,cere- identical for imaging of other systems. Color scale: red indicates increases Generally, the PET or SPECT imaging device records and green indicates decreases in flow or metabolism. B: Logical images showing anatomical overlap of significant changes com- the brain distribution of a radiotracer that binds selectively mon to both experiments. Top row: Concordant areas with in- at the receptor (or transporter). In many applications a brain creased flow during sadness and decreased metabolism during region is identified and a time–activity curve for that region remission. Bottom row: Areas with decreased flow during sadness and increased metabolism during remission. Multiple factors directly influ- mann area designations. Red indicates ence the amount of tracer that accumulates in any given changes unique to sadness; dark blue indicates changes unique brain region: concentration of receptors (Bmax), dissociation to remission of depression; lighter blue indicates changes com- constant between the receptor and ligand (Kd), and nonspe- mon to both. Arrows signify direction of change associated with each condition. In addition, the amount of uptake in the entire brain is dependent on the level of radiotracer in plasma and the degree to which the radiotracer nonspecifically binds to plasma proteins.