3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile and Depressive-Disorder--Major

The serotonin transporter (5-HTT) plays a critical role in the regulation of serotonin neurotransmission and has been implicated in the pathophysiology of major depression. In a previous positron emission tomography study, we found no difference in brain 5-HTT binding between unmedicated recovered depressed patients and healthy controls.. This study aims to assess brain 5-HTT binding in a group of unmedicated acutely depressed patients in comparison to healthy controls.. We studied 5-HTT binding using [(11)C]DASB in conjunction with positron emission tomography in 12 medication-free depressed patients with a mean duration of illness of about 1 year and 24 healthy controls.. The depressed patients had lowered 5-HTT binding in several brain regions including brain stem, thalamus, caudate, putamen, anterior cingulate cortex and frontal cortex.. These results suggest that diminished availability of the 5-HTT in the brain may be a state marker of acute depression. Alternatively, low 5-HTT binding may delineate a group of depressed patients with a poor long-term prognosis.

Topics: Adult; Aniline Compounds; Brain; Case-Control Studies; Depressive Disorder, Major; Humans; Male; Middle Aged; Positron-Emission Tomography; Prognosis; Protein Binding; Serotonin Plasma Membrane Transport Proteins; Sulfides

Altered serotonergic function is thought to play a role in the pathophysiology of major depressive episodes based upon evidence from neuroimaging, pharmacological, postmortem and genetic studies. It remains unclear, however, whether depressed samples that differ with respect to having shown a unipolar versus a bipolar illness course also would show distinct patterns of abnormalities within the serotonergic system. The current study compared serotonin transporter (5-HTT) binding between unipolar-depressives (MDD), bipolar-depressives (BD) and healthy-controls (HC) to assess whether the abnormalities in 5-HTT binding recently found in depressed subjects with BD extend to depressed subjects with MDD.. The 5-HTT binding-potential (BP) measured using positron emission tomography (PET) and [(11)C]DASB was compared between unmedicated, depressed subjects with MDD (n = 18) or BD (n = 18) and HC (n = 34).. Relative to the healthy group both MDD and BD groups showed significantly increased 5-HTT BP in the thalamus (24%, 14%, respectively), insula (15%) and striatum (12%). The unipolar-depressives had elevated 5-HTT BP relative to both BD and HC groups in the vicinity of the periaqueductal gray (PAG, 20%, 22%, respectively). The bipolar-depressives had reduced 5-HTT BP relative to both HC and MDD groups in the vicinity of the pontine raphe nuclei. Depression-severity correlated negatively with 5-HTT BP in the thalamus in MDD-subjects.. The depressed phases of MDD and BD both were associated with elevated 5-HTT binding in the insula, thalamus and striatum, but showed distinct abnormalities in the brainstem. The latter findings conceivably could underlie differences in the patterns of illness symptoms and pharmacological sensitivity observed between MDD and BD.

Topics: Adolescent; Adult; Aniline Compounds; Bipolar Disorder; Brain Stem; Carbon Radioisotopes; Case-Control Studies; Cerebral Cortex; Depressive Disorder, Major; Female; Humans; Magnetic Resonance Imaging; Male; Matched-Pair Analysis; Middle Aged; Neostriatum; Positron-Emission Tomography; Radiopharmaceuticals; Reference Values; Serotonin Plasma Membrane Transport Proteins; Sulfides; Thalamus

The serotonin transporter (5-HTT) is a key target for selective serotonin reuptake inhibitors and may be involved in the pathophysiology of major depression. It is now possible to image 5-HTT directly in the human brain, but results from studies of acutely depressed patients have been inconsistent. The purpose of this study was to determine whether abnormalities in 5-HTT might be present in recovered depressed patients.. The authors measured the binding potential of 5-HTT using [11C]DASB in conjunction with positron emission tomography (PET) in 24 medication-free, recovered depressed male patients and 20 healthy male comparison subjects. The regional estimates of binding potential were obtained using a metabolite-corrected plasma input function method followed by Logan analysis, with the cerebellum as a reference region.. The authors found no significant difference in the binding potential of [11C]DASB between the recovered depressed patients and healthy comparison subjects in any of the brain regions (amygdala, anterior cingulate cortex, caudate nucleus, frontal cortex, hippocampus, insula, thalamus, and dorsal raphe) studied.. Men who recover from depression have normal availability of 5-HTT in brain regions thought to be involved in the pathophysiology of depression. The findings therefore do not support the proposal that recurrent depression is associated with long-standing deficits in 5-HTT.

Topics: Adult; Amygdala; Aniline Compounds; Brain; Brain Mapping; Cerebral Cortex; Depressive Disorder, Major; Frontal Lobe; Gyrus Cinguli; Humans; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; Serotonin; Serotonin Plasma Membrane Transport Proteins; Sulfides; Thalamus