Neuroreceptor imaging in depression (original) (raw)
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Pet imaging of serotonin 1A receptor binding in depression
Biological Psychiatry, 1999
The serotonin-1A (5HT1A) receptor system has been implicated in the pathophysiology of major depression by postmortem studies of suicide victims and depressed subjects dying of natural causes. This literature is in disagreement, however, regarding the brain regions where 5HT1A receptor binding differs between depressives and controls and the direction of such differences relative to the normal baseline, possibly reflecting the diagnostic heterogeneity inherent within suicide samples. PET imaging using the 5HT1A receptor radioligand, [ 11 C]WAY-100635, may clarify the clinical conditions under which 5HT1A receptor binding potential (BP) is abnormal in depression. Methods: Regional 5HT1A receptor BP values were compared between 12 unmedicated depressives with primary, recurrent, familial mood disorders and 8 healthy controls using PET and [carbonyl-11 C]WAY-100635. Regions-of-interest (ROI) assessed were the mesiotemporal cortex (hippocampus-amygdala) and midbrain raphe, where previous postmortem studies suggested 5HT1A receptor binding is abnormal in depression. Results: The mean 5HT1A receptor BP was reduced 41.5% in the raphe (p Ͻ .02) and 26.8% in the mesiotemporal cortex (p Ͻ .025) in the depressives relative to the controls.
Molecular Neurobiology of Depression: PET Findings on the Elusive Correlation with Symptom Severity
Frontiers in Psychiatry, 2013
Molecular mechanisms in the brain are assumed to cause the symptoms and severity of neuropsychiatric disorders. This review concerns the elusive nature of relationships between the severity of depressive disorders and neuromolecular processes studied by positron emission tomography (PET). Recent PET studies of human depression have focused on serotonergic, dopaminergic, muscarinic, nicotinic, and GABAergic receptors, as well as central processes dependent on monoamine oxidase, phosphodiesterase type 4, amyloid plaques, neurofibrillar tangles, and P-glycoprotein. We find that reliable causal links between neuromolecular mechanisms and relief from depressive disorders have yet to be convincingly demonstrated. This situation may contribute to the currently limited use of PET for exploring the neuropathways that are currently viewed as being responsible for beneficial effects of antidepressant treatment regimes.
Biological Psychiatry, 2009
ABSTRACT BACKGROUND: Several lines of evidence implicate abnormal serotonergic function in suicidal behavior and completed suicide, including low serotonin transporter binding in postmortem studies of completed suicide. We have also reported low in vivo serotonin transporter binding in major depressive disorder (MDD) during a major depressive episode using positron emission tomography (PET) with [11C]McN5652. We quantified regional brain serotonin transporter binding in vivo in depressed suicide attempters, depressed nonattempters, and healthy controls using PET and a superior radiotracer, [11C]DASB. METHODS: Fifty-one subjects with DSM-IV current MDD, 15 of whom were past suicide attempters, and 32 healthy control subjects underwent PET scanning with [11C]DASB to quantify in vivo regional brain serotonin transporter binding. Metabolite-corrected arterial input functions and plasma free-fraction were acquired to improve quantification. RESULTS: Depressed suicide attempters had lower serotonin transporter binding in midbrain compared with depressed nonattempters (p = .031) and control subjects (p = .0093). There was no difference in serotonin transporter binding comparing all depressed subjects with healthy control subjects considering six a priori regions of interest simultaneously (p = .41). CONCLUSIONS: Low midbrain serotonin transporter binding appears to be related to the pathophysiology of suicidal behavior rather than of major depressive disorder. This is consistent with postmortem work showing low midbrain serotonin transporter binding capacity in depressed suicides and may partially explain discrepant in vivo findings quantifying serotonin transporter in depression. Future studies should investigate midbrain serotonin transporter binding as a predictor of suicidal behavior in MDD and determine the cause of low binding.
PET brain imaging with 11CMcN5652 shows increased serotonin transporter availability in major depression
Journal of Affective Disorders, 2004
Background: Alterations in the brain serotonin (5-HT) system have been found in patients with depression. We used the selective 5-HT transporter site ligand [ 11 C](+)McN5652 and positron emission tomography (PET) to examine the hypothesis that alterations in 5-HT transporter levels may be present in selected regions of the brain in depressed patients. Methods: Four drug free depressed patients and four healthy control subjects were studied using [ 11 C](+)McN5652 and PET. The distribution volume (DV) ratio of the PET ligand in selected regions of interest (ROIs) compared to cerebellum were calculated for the ROIs. Results: Patients showed significantly larger DV ratios in the left frontal cortex ( P = 0.013) and right cingulate cortex ( P = 0.043) compared to control subjects. Limitation: The sample size was modest with gender differences between the subject groups. The PET agent, [ 11 C](+)McN5652, may have a lower binding affinity for the 5-HT transporter in the cortical regions compared to other brain regions. Conclusion: These findings suggest that 5-HT transporter sites may be increased in the frontal and cingulate cortices of depressed patients. These alterations in 5-HT transporter sites may be of pathophysiologic significance in the etiology of depression and its treatment. D
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2009
The dopamine type-1 receptor has been implicated in major depressive disorder (MDD) by clinical and preclinical evidence from neuroimaging, post mortem, and behavioral studies. To date, however, selective in vivo assessment of D(1) receptors has been limited to the striatum in MDD samples manifesting anger attacks. We employed the PET radioligand, [(11)C]NNC-112, to selectively assess D(1) receptor binding in extrastriatal and striatal regions in a more generalized sample of MDD subjects. The [(11)C]NNC-112 nondisplaceable binding potential (BP(ND)) was assessed using PET in 18 unmedicated, currently depressed subjects with MDD and 19 healthy controls, and compared between groups using MRI-based region-of-interest analysis. The mean D(1) receptor BP(ND) was reduced (14%) in the left middle caudate of the MDD group relative to control group (p<0.05). Among the MDD subjects D(1) receptor BP(ND) in this region correlated negatively with illness duration (r=-0.53; p=0.02), and the le...
Molecular tools for assessing human depression by positron emission tomography
European Neuropsychopharmacology, 2009
We review reports published over the past 5 years on positron emission tomography (PET) of neurotransmission in depressive disorders. The molecular tools of PET neuroimaging are compounds labeled with a positron-emitting nuclide. PET radioligands have been used in recent years to study several aspects of monoaminergic and cholinergic neurotransmission in the brain of depressed subjects and healthy controls. The value of kinetic parameters of certain PET radioligands has often been reported to be lower in depressed subjects than in healthy ones, but there is usually no reliable relationship between the binding potential of the neuroreceptor or transporter and the clinical condition of depressed subject. In addition, many recent PET studies have noted either higher binding potentials in depressed subjects or no difference between binding potentials of depressed and healthy subjects. In our view, recent research has neither proved nor refuted the idea that neuromolecular processes that can be assessed by the radioligands currently available for PET studies of humans are causally related to depressive disorders. The future success of PET research for understanding molecular mechanisms in depressive disorders may therefore require the invention and development of further molecular tools for studying a wider range of neuronal events in the living human brain.
Archives of General Psychiatry, 2007
Context: Depression in bipolar disorder is clinically indistinguishable from that observed in major depressive disorder. As in major depression, selective serotonin reuptake inhibitors targeting brain serotonin transporters are first-line treatments for bipolar depression. Associations of serotonin transporter promoter polymorphisms and bipolarity have been reported; however, research on alterations in serotonergic neurotransmission in bipolar depression remains scant.