Serotonin transporter availability in the amygdala and bed nucleus of the stria terminalis predicts anxious temperament and brain glucose metabolic activity.
The serotonin transporter (5-HTT) plays a critical role in regulating serotonergic neurotransmission and is implicated in the pathophysiology of anxiety and affective disorders. Positron emission tomography scans using [(11)C]DASB [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile] to measure 5-HTT availability (an index of receptor density and binding) were performed in 34 rhesus monkeys in which the relationship between regional brain glucose metabolism and anxious temperament was previously established. 5-HTT availability in the amygdalohippocampal area and bed nucleus of the stria terminalis correlated positively with individual differences in a behavioral and neuroendocrine composite of anxious temperament. 5-HTT availability also correlated positively with stress-induced metabolic activity within these regions. Collectively, these findings suggest that serotonergic modulation of neuronal excitability in the neural circuitry associated with anxiety mediates the developmental risk for affect-related psychopathology.
Oler
Jonathan A
JA
Departments of Psychiatry, HealthEmotions Research Institute, University of Wisconsin-Madison, 53719, USA.
Fox
Andrew S
AS
Shelton
Steven E
SE
Christian
Bradley T
BT
Murali
Dhanabalan
D
Oakes
Terrence R
TR
Davidson
Richard J
RJ
Kalin
Ned H
NH
D000679:Amygdala / Q000000981:diagnostic imaging / Q000502:physiology*; D000814:Aniline Compounds; D000818:Animals; D001007:Anxiety / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001522:Behavior, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D016014:Linear Models; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography; D012686:Septal Nuclei / Q000000981:diagnostic imaging / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013440:Sulfides; D013694:Temperament / Q000502:physiology*
C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; D019788:Fluorodeoxyglucose F18; D005947:Glucose
Arch Gen Psychiatry. 2007 Feb;64(2):201-8
17283287
Neuroimage. 2003 Apr;18(4):975-89
12725772
Psychopharmacology (Berl). 2008 Mar;196(4):661-72
18058090
J Psychiatry Neurosci. 2007 Mar;32(2):86-102
17353938
Biol Psychiatry. 2007 Oct 15;62(8):870-7
17678634
Am J Psychiatry. 2006 Jan;163(1):52-8
16390889
Biol Psychiatry. 1998 Nov 1;44(9):812-24
9807637
Neuroscience. 2004;128(3):583-96
15381287
Neurosci Biobehav Rev. 2008 Sep;32(7):1293-314
18439676
Arch Gen Psychiatry. 2005 Feb;62(2):146-52
15699291
Neuroscience. 1990;36(2):431-47
1977101
J Cereb Blood Flow Metab. 2007 Sep;27(9):1533-9
17519979
Mol Psychiatry. 2008 Nov;13(11):1021-7
18414408
Neuropsychopharmacology. 2007 Jan;32(1):216-24
17019406
Neurosci Biobehav Rev. 2001 Dec;25(7-8):637-45
11801289
Neuropharmacology. 2008 Nov;55(6):1029-37
18621068
Science. 1989 Mar 31;243(4899):1718-21
2564702
J Neurosci. 1999 Jun 1;19(11):RC8
10341269
Neuroimage. 2009 Oct 1;47(4):1230-6
19505582
Biol Psychiatry. 2006 Sep 1;60(5):479-90
16414028
Am J Psychiatry. 1998 Aug;155(8):1023-8
9699688
Nat Neurosci. 2006 Nov;9(11):1362-3
17013380
Mol Psychiatry. 2008 Jun;13(6):606-13, 557
18268503
Biol Psychiatry. 2001 Nov 1;50(9):651-8
11704071
Neuropsychopharmacology. 2008 Dec;33(13):3221-5
18463627
Neurosci Biobehav Rev. 2006;30(2):126-47
16183121
Science. 2002 Jul 19;297(5580):400-3
12130784
IEEE Trans Med Imaging. 2001 Jan;20(1):45-57
11293691
Neurosci Biobehav Rev. 2005;29(8):1335-46
16095695
Phys Med Biol. 2001 Jul;46(7):1845-62
11474929
J Comput Assist Tomogr. 1998 Jan-Feb;22(1):139-52
9448779
Ann N Y Acad Sci. 2003 Dec;1008:189-200
14998885
Arch Gen Psychiatry. 2009 Jan;66(1):33-40
19124686
Science. 2003 Jul 18;301(5631):386-9
12869766
Biol Psychiatry. 2004 Jun 15;55(12):1171-8
15184036
J Neurosci. 2007 Aug 22;27(34):9233-7
17715358
Neuroscience. 2007 Sep 21;148(4):937-48
17766046
J Cereb Blood Flow Metab. 2003 Sep;23(9):1096-112
12973026
Psychopharmacology (Berl). 2005 Aug;180(4):670-9
15772862
Biol Psychiatry. 2006 May 1;59(9):816-20
16460693
Neuroimage. 1997 Nov;6(4):305-19
9417973
Neuroimage. 2002 Oct;17(2):825-41
12377157
Brain Res. 1977 Jan 14;120(1):85-102
137766
Synapse. 2003 Jun 15;48(4):184-8
12687637
Trends Cogn Sci. 2006 Apr;10(4):182-91
16530463
Ann N Y Acad Sci. 1999 Jun 29;877:700-2
10415687
Science. 2003 Jun 20;300(5627):1952-3
12817151
Neuroimage. 2007 Jan 15;34(2):500-8
17113790
Biol Psychiatry. 2007 Aug 15;62(4):327-31
17210141
Brain Struct Funct. 2008 Sep;213(1-2):73-91
18283492
Am J Psychiatry. 2001 Oct;158(10):1673-9
11579001
Science. 2004 Oct 29;306(5697):879-81
15514160
Neuroscience. 2005;136(1):193-203
16182456
PLoS One. 2008 Jul 02;3(7):e2570
18596957
Neuroimage. 1995 Mar;2(1):45-53
9343589
Neuroscience. 2001;104(4):1067-84
11457591