Serotonin e eketsehileng le Dopamine Transporter Ho iketsetsa meriana ea Psychotropic Meriana ea Naïve e nang le Generalized Social Anxiety Disorder e bontsitsoeng ke 123I-β- (4-Iodophenyl) -Tropane SPECT (2008)

J Nucl Med E se eka 2008 sefofane. 49 Che. 5 757-763

Nic J. van der Wee1, J. Frederieke van Veen1, Henk Stevens2, Irene M. van Vliet1, Peter P. van Rijk2 le Herman G. Westenberg1

+ Lingoliloeng tsa Sengoli

1Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands; le 2Department of Nuclear Medicine, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands

Bakeng sa mangolo kapa puisano le mangolo: Nic J. van der Wee, Lefapha la Psychiatry, Rudolf Magnus Setsi sa Neuroscience, HP B01.206, Setsi sa Bongaka sa Medical Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands. Lengolo-tsoibila: [imeile e sirelelitsoe]

inahaneloang

Phuputsong ea hona joale, re sebelisa monahano oa SPECT re hlahlobisitse 123I-β- (4-iodophenyl) -tropane e tlamang bokhoni ba ho tsamaisa serotonin le baeti ba dopamine ho bakuli ba nang le bothata ba ho tšoenyeha ka kakaretso sechabeng le taolong e ntle ea lilemo le thobalano.

Mekhoa: Makhopo a leshome le metso e 'meli a psychotropic - bakuli ba naïve ba nang le bothata ba ho tšoenyeha ka sechaba, mofuta oa kakaretso (basali ba 5 le banna ba 7) le 12 ka thobalano le lilemo tse lekanang tsa bophelo bo botle li ile tsa ithutoa. Palo ea mekhahlelo e ne e hahiloe ka har'a li-Scene tsa MRI-coreg usajili. Litefiso tsa ho tlama li ne li bapisoa ho sebelisoa tlhahlobo ea Mann-Whitney U. Likahare tse ka bang teng lipakeng tsa sebopeho se tlamang le Symbomatology li ile tsa hlahlojoa ho sebelisoa tšebelisano ea boemo ba maiketsetso ea Spearman.

Liphetho: Mekhoa e tlamang e phahameng haholo e fumanoe ka serotonin ka thalmus ea ka letsohong le letšehali la bakuli. Bakuli ba ne ba boetse ba na le monyetla o matla oa ho tlama transporter ea dopamine ho striatum.

Qeto: Phuputso e teng hona joale e fane ka bopaki bo tobileng ba tlhekefetso ho dopaminergic le li-system tsa serotonergic ho bakuli ba nang le khatello ea maikutlo ea kakaretso ea sechaba.

Selelekela

Boloetse ba ho tšoenyeha ka sechaba (bo boetse bo tsejoa e le phobia ea sechaba) ke boemo bo nyahamisang bo sithabetsang karolo e kholo ea baahi ka kakaretso. Hangata ho tsamaisana le maemo a sa feleng ebile ho sa tsamaee mme hangata ho lebisa ho nts'etsopele ea joala le khatello ea maikutlo. Karolo ea bohlokoa ea bokuli ba matšoenyeho sechabeng ke tšabo ea ho hlahlojoa ke ba bang ka tebello ea hore tlhahlobo e joalo e ka ba e mpe le e tlhabisang lihlong. Mathata a ho tšoenyeha ka sechaba a arotsoe ka li-subtypes tsa 2. Subtype ea pele, e boletsoeng ho DSM-IV (1) joalo ka kakaretso phobia ea sechaba ka kakaretso, e kenyelletsa ho tšaba maemo a mangata a boiketlo ba sechaba. Subtype ea bobeli, e bitsoang discrete kapa ho ba le mathata a itseng a ho tšoenyeha sechabeng, hangata e fella feela maemong a ts'ebetso a 1 kapa 2, eo ho bua ka phatlalatsa ho atileng ka ho fetisisa (2). Kaha ho na le bohlokoa ba tleliniki ba bokuli ba matšoenyeho a sechaba, neurobiology ea boemo bona e amohetse tlhokomelo e nyane ho fihlela joale.

Lithuto tsa kalafo tse bonts'ang hore li-inhibitors tse khethiloeng tsa serotonin reuptake inhibitors (SSRIs) le inhibitors ea monoamine oxidase li sebetsa hantle mokhoeng oa ho tšoenyeha ka mathata a sechaba a hore tsela ea serotonergic le catecholaminergic e na le karolo., empa lipatlisiso tsena e ka ba tataiso e thata ho khethollang lefu la neurobiology. Liteko tsa phephetso tse nang le fenfluramine le m-chlorophenylpiperazine li fane ka bopaki bo bong bo potileng bakeng sa karolo ea serotonin (5-hydroxytryptamine, kapa 5-HT) bothateng ba matšoenyeho sechabeng (3,4). Ho kenyelletsa letsoho la dopaminergic tsamaisong ea matšoenyeho a sechaba ho khothalelitsoe ke litheko tsa hore litekanyetso tsa homeovanillic acid ho mokelikeli oa "cerebrospinal" li tlase ho ts'abo ea bakuli ba nang le ts'oaetso ea matšoenyeho a sechaba ho feta ho ba se nang (5). Ho feta moo, ho ata ha lefu la ho tšoenyeha ha sechaba ho eketseha ho bakuli bao lefu la Parkinson le hlahisang (6). Haufinyane tjena, lithuto tsa neanoimaging tsa 2 li fane ka bopaki bo tobileng ba hore li-dopamine li ka bapala karolo ea methapo ea mafu a matšoenyeho a sechaba. E sebelisa 123I-labels 2-β-carbomethoxy-3-β- (4-iodophenyl) -tropane (123I-β-CIT) e le sets'oants'o le moriana, Tiihonen et al. e fumane hore letsoalo la dopamine transporter (DAT) ho striatum le fokotsehile ho bakuli ba nang le khatello ea maikutlo ea kakaretso ea sechaba (7). Schneier et al., O sebelisa 123I-iodobenzamide SPECT, e fumane dopamine D e fokotsitsoeng2 tlamang bokgoni maemong ana a kelello (8). Le ha lithuto tsa neuroimaging li ka boela tsa fana ka bopaki bo tobileng bakeng sa karolo ea litsamaiso tsa serotonergic bothateng ba matšoenyeho a sechaba, ho tsebo ea rona feela 1 thuto e joalo e phatlalalitsoe ho fihlela joale (9). Thutong ena, e entsoeng ke Lanzenberger et al., 5-HT receptor 1A e tlamang libakeng tse 'maloa tsa limbic le paralimbic e fumanoe e fokotsehile ho bakuli ba nang le khatello ea maikutlo ea sechaba.

123I-β-CIT SPECT e ka sebelisoa ho bona ka leihlo transporter ea bobeli ba UV le 5-HT (5-HTT) bokong ba motho kamora ts'ebetso e le 'ngoe ea ligand. Tlamahano ea 123I-β-CIT seterekeng sa striatal e bontšitsoe hore e bonts'a haholo-holo tlamo ho DAT; tlama ka har'a thalamus, midbrain, le pons li bonts'a haholo ho 5-HTT (10,11). Ho tlama ho DAT le 5-HTT ho ka khetholloa ka ho sebelisa phapang ea nako ea nako ea 123Ho nkuoa hoa I-β-CIT ho li-DAT- le 5-HTT-libaka tse ruileng tsa boko (10). Phuputsong e teng hona joale, re sebelisitse mokhoa ona ho etsa lipatlisiso tsa DAT le 5-HTT tse nang le bokhoni ba ho phekola ka ho le letona li-psychotropic - naïve bakuli ba nang le mathata a ho tšoenyeha ka kakaretso (ho latela litekanyetso tsa DSM-IV) mme ha ba na comorbidity le taolong e phetseng hantle e tsamaeang habeli ka lilemo, thobalano le ho fana ka letsoho. Re ne re lebelletse mokhoa o tlamang 123I-β-CIT ho bonts'a lits'oants'o tse maemong a bobeli ba 5-HTT le DAT.

LISEBELISOA LE MEKHOA

Lihlooho

Boithuto bona bo amohetsoe ke komiti ea boitšoaro ea Univesithi ea Bongaka ea Univesithi, Utrecht, Netherlands, mme e entsoe ho latela litekanyetso tsa boitšoaro tsa phatlalatso ea Helsinki. Kamora hore ho fuoe tlhaiso e felletseng ea thuto ho lithuto, ho fumanoe tumello e ngotsoeng e fumanoeng. Bakuli ba tsoa ho ngaka ka kotloloho ba isoa tliliniking ea rona e khethehileng ea matšoenyeho kapa ba arabetse lipapatso. Litaolo tse phetseng hantle li ile tsa ngolisoa lipapatsong tsa lifolakha le likoranteng kapa tsa fumaneha ho database e se e ntse e le teng. Ke lithuto feela tse se nang nalane ea bophelo bo botle ba kelello, ts'ebeliso e mpe ea lithethefatsi, khatello ea maikutlo e atisang ho hlaha, ho ferekana kelellong, mathata a ho ja, mathata a mang a ho tšoenyeha, lits'oants'o le ho hoeleketsa ho kenyelelitsoe. Barupeluoa bohle ba ne ba se na nalane ea bophelo ba maloetse a nang le methapo ea methapo ea methapo mme ba ne ba le bophelo bo botle ba 'mele, joalo ka ha ho netefalitsoe ke liteko tsa' mele le tsa laboratori. Litho tse noang haholo linoelo tsa kofi tse ka tlase ho 6 tsa kofi le likarolo tsa 3 tsa joala ka letsatsi 'me li tsuba lisakerete tse tlase ho 6 ka letsatsi. Ho hlahlojoa ha psychopathology ea batho ba baholo hona joale le pele ho entsoe ka ho tsamaisa Mini International Neuropsychiatric Interview Plus, mofuta 5.0.0 (13). Matšoao a tšoaetso a netefalitsoe ke ngaka e nang le boiphihlelo. Ntle le moo, Liebowitz Social Anxcare Scale (LSAS) e ne e sebelisoa ho lekola ho teba ha matšoao a matšoenyeho a sechaba ha a kenella (14). Handsness e ile ea khethoa ka ho tsamaisa Edinburgh Handedness Scale (15).

Lintho li ile tsa qheleloa ka thoko ha li ne li e-na le lintlha tse fetang 13 ho 17-into Hamilton Depression Rating Scale (16). Lintho tse sebelisitsoeng mona ka tlase ho 2 wk kamora ho kenyeletsoa. Phekolo efe kapa efe ea boits'oaro ea kelello e ne e felisitsoe bonyane 3 mo pele ho thuto.

Bakuli ba leshome le metso e 'meli le li-taolo tse phetseng hantle tsa 12 ba ngolisitsoe. Lithuto tsohle li phethile thuto. Bakuli le lits'ebetso li ne li ts'oantsoe hantle bakeng sa thobalano mme li ne li sa fapana haholo ka lilemo le ho beoa. Ho bonts'oa likarolo tsa batho le tsa bongaka ho Lethathamo 1.                                            

TABLE 1 Bophara ba batho le lithuto tsa bophelo bo botle ba bongaka

Ho Fumana litšoantšo le ho sekaseka setšoantšo

Litšoantšo li ile tsa fumanoa tsa ba tsa hlahlojoa ho sebelisoa mekhoa e ts'oanang le thutong ea rona ea pejana e tlalehiloeng mabapi le bakuli ba nang le bothata bo fetelletseng ba kelello (17). Letsatsing la pele la ho hlahlojoa, lihlooho li ile tsa fumana ente ea methapo ea 150 MBq ea 123I-β-CIT (MAP ea bongaka ea bongaka ea 'mele; bohloeki ba radionuclidic [125I/123I] bonyane 9.5 × 10-3 ka nako ea calibration le bohloeki ba radiochemical bonyane 95%). Re sebelisitse mohala oa "patm 3000" o katiloeng ka makhetlo a mararo (3) o nang le li-collimators tsa Ultra-high-resolution le bolelele bo felletseng bo bolelele ba 12 mm. Lihora tse 'ne ka mor'a ente, ho ile ha etsoa scan ninemani ea pele bakeng sa ho hlahloba 5-HTT. Pakeng tsa 22 le 24 h kamora ho ente, ho ile ha fumanoa scan ninete ea bobeli ho lekanya tlama ho DAT (18-20). Lithuto tse qotsitsoeng kofi le nicotine ho 6-10 h pele ho tlhaiso e ngoe le e ngoe ea SPECT. Hang ka mor'a ho hlahlojoa ha pele, lithuto li ile tsa amohela 20 mg ea paroxetine hore e lahle 123I-β-CIT e tsoang ho 5-HTT e le hore ho tlamaha ho DAT ho ka ikemisoa ka nepo (18). Boithuto bo 'maloa bo bontšitse hore litekanyetso tse itekanetseng (mohlala, 10 mg) ea paroxetine le tse ling tse matla tsa li-blockback tsa 5-HT tse khutlisetsang, ho lula 5-HTT e se e batla e le boholo bo phahameng (10,21,22). Ho laola liphapang tse ka bang teng tsa metabolism lipakeng tsa lihlooho, re khethile tekanyetso e phahameng ea molomo ea 20 mg. Tekanyo ea 20-mg ea paroxetine e ne e mamelletsoe hantle ke lithuto tsohle. Ha ho ntse ho hlahlojoa, lithuto li ne li phahamisoa, mahlo le litsebe li butsoe 'me hlooho e ts'oeroe ho se ts'oereng hlooho. Re ile ra netefatsa hore bakuli ba lula ba falimehile 'me ha ba sisinyehe. Bakeng sa qeto e nepahetseng ea boholo ba sehlooho ka seng (VOIs), lithuto tsohle li bile le sebopeho sa MRI (3-dimensional field field echo; nako ea echo / nako ea ho pheta-pheta, 4.6 / 30 ms; flip angle, 30 °; lebala la pono, 256 × 256 mm; matrix, 128 × 128 × 130 mm; botenya ba selae, 2 mm) 2 h pele ho entoa ea 123I-β-CIT. Likahare tsa MRI li ile tsa hlophisoa bocha tsamaisong ea boemo bo tšoanang ea bokong ba Montreal (23). Li-VOI li hlalositsoe ka letsoho litlhahlobong tsa MRI tse nchafalitsoeng ke mofuputsi ea neng a sa tsebe hore na taba eo ke mang le hore na o hlahlojoe eng, ka software ea pontšo e tsoang Setsing sa Litšoantšo sa Brain sa Setsi sa Montreal Neuroimaging Institute (24). Hobane sepheo sa thuto ea rona e ne e le tlhekefetso e mpe maemong a 5-HTT bothateng ba matšoenyeho a sechaba, VOIs ea 5-HTT e kenyelelitse thalamus e kaholimo le ho le letona le midbrain / pons, athe rona re ile ra beha VOI ea DAT ka letsohong le letšehali. le striatum e nepahetseng e nkuoe hammoho. Ho feta moo, khetho ena e ile ea lumella papiso e tobileng ea liphetho tsa DAT le thuto e fetileng ea Tiihonen et al. (7). Re hlophisitse tlhahlobo ea tlhahlobo ea litaba ea hoc ea hoc moo ho tla etsoa litlhaloso tse tlase ho le ho le letona maemong ao ho eona ROI striatum e bonts'ang phapang e kholo lipakeng tsa bakuli le taolo. Cerebellum e ne e sebelisoa e le sebaka sa litšupiso, se emelang tlamang 123Ke-β-CIT.

Ho lumella tlhaiso-leseling e nepahetseng ea "scan" ea MRI le SPECT, re sebelisitse matšoao a fiducial. Matšoao a fiducial a ne a bopehile joaloka khoune, a maoto a bōpehileng joaloka sefapano, 'me a beoa borokhong ba nko le kaholimo ho manonyeletso a mandibular. Boemo ba lesupa le leng le le leng bo bontšitsoe ka matheba a mane letlalong la taba ho lumella ho beoa hoa matšoao hanghang pele ho tlhahlobo ea SPECT. Vithamine A le 57Li-co li ne li sebelisoa e le liemeli tse fapaneng bakeng sa sekala sa MRI le SPECT, ka ho latellana. Matla a ne a behiloe tlhōrōng ea 160 keV ka fensetere ea 20% bakeng sa 123I-β-CIT le tlhōrōng ea 120 keV e nang le fensetere ea 15% bakeng sa 57Co Ka mor'a ts'ebetso e tloaelehileng, litšoantšo tsa boko tsa SPECT li ile tsa qhekelloa ho li-voxels tsa isotropic tse nang le boholo ba 2 mm 'me tsa tšoaroa ka ho eketsehileng e le li-volumes tsa 3-elemental to coregister ka hare ho sebopeho sa 3-sebopeho sa litekanyetso tsa MRI. Coreg usajili e entsoe ka mokhoa o ikhethileng mme e ne e ipapisitse le boemo ba matšoao a fidu sechabeng, ho sebelisoa setsi sa software sa ngoliso ea multimodality le software e eketsehileng e ntlafalitsoeng Setsing sa Brain Imaging sa Montreal Neurologic Institute (25). Mofuputsi ea neng a etsa lipatlisiso tsa mantlha o ne a sa tsebe boitseko le tlhahlobo ea litaba.

Bakeng sa VOI e 'ngoe le e' ngoe e arohaneng, karo-karolelano ea tlamo e khethehileng ea 123I-β-CIT ho 5-HTT kapa DAT e ile ea baloa ho latela mokhoa o sebelisitsoeng khatisong e neng e phatlalalitsoe pejana 123Boithuto ba I-β-CIT: palo ea radioactivity ka kakaretso ka voxel ka e ngoe ka VOI ha e bapisoa le palo ea litaba tsa radioxishene ka motsotsoana o mong le o mong ka hara cerebellum, e arotsoe ke palo ea radioactivity ka kakaretso ka voxel e le ngoe ea "cerebellum".

Tlhahlobo ea Litekanyetso

Age e ne e bapisoa ho sebelisa Seithuti t tlhatlhobo. Ho tsepamisa maikutlo le ho kenella hare bakeng sa ngoliso ea VOI ho ile ha hlahlojoa ka ho lekanya li-coefficients tsa intraclass ho latela mokhoa o phatlalalitsoeng ke Bartko le Carpenter (26). Likarolo tse ikhethileng tsa 123I-β-CIT e ne e bapisoa le Mann-Whitney U tlhatlhobo. Bakeng sa tlama ea 5-HTT, likhakanyo seterekeng sa midbrain / pons le ho le thalmus ea ka letsohong le letona li ile tsa hlahlojoa; bakeng sa binding ea DAT, tekanyo ho striatum e ile ea hlahlojoa. Li-coarmffation tsa li-speaker tsa boemo ba puisano li ile tsa baloa ho lekola khokahano lipakeng tsa litekanyetso tse ikhethileng tsa sekhahla le lintlha tsa LSAS Bohlokoa ba mefuta e 'meli bo tlalehiloe ho pholletsa le eona. Khalemelo ea Bonferroni bakeng sa lipapiso tse ngata (libaka tsa 4 tsa phaello) e hlahisitse phetoho P boleng ba tlase ho 0.0125.

LIPOTSO

Li-corfflass tse kopanyang li-intraclass tsa interrater le ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea ho fumana li-VOIs e ne e le lipakeng tsa 0.86 le 0.99 (e bolelang ± SD, 0.95 ± 0.05) le 0.61 le 0.98 (ho bolela, 0.81 ± 0.14), ka ho latellana. Ho mokuli oa 1, ho ka fumanoa lipalo feela tsa 5-HTT; scan ninemina ea ho qetela e ne e sa khone ho ts'oaroa ka botsitso ho skena sa MRI ka lebaka la litsebi tsa maiketsetso tse tsamaeang.

Li-VOIs tsa "cerebellum" e ne e le 104,208 ± 16,211 mm3 bakeng sa bakuli le 93,943 ± 11,445 mm3 bakeng sa taolo. Li-VOIs tsa libaka tsa midbrain / pons e ne e le 6,441 ± 1,370 mm3 bakeng sa bakuli le 6,127 ± 1,455 mm3 bakeng sa taolo. Li-VOIs tsa thalamus e nepahetseng e ne e le 3,962 ± 855 mm3 bakeng sa bakuli le 4,544 ± 1,678 mm3 bakeng sa taolo, 'me VOIs ea thalamus ea leqeleng e ne e le 4,051 ± 914 bakeng sa bakuli le 4,610 ± 686 mm3 bakeng sa taolo. Li-VOIs tsa caudate e nepahetseng e ne e le 3,142 ± 519 mm3 bakeng sa bakuli le 2,933 ± 608 mm3 bakeng sa li-control, mme li-VOIs bakeng sa putamen e nepahetseng e ne e le 2,064 ± 407 mm3 bakeng sa bakuli le 1,990 ± 497 mm3 bakeng sa taolo. Li-VOIs tsa caudate ea leqeleng e ne e le 2,899 ± 598 mm3 bakeng sa bakuli le 3,181 ± 573 mm3 bakeng sa li-control, mme li-VOIs bakeng sa putamen e setseng e ne e le 2,022 ± 478 mm3 bakeng sa bakuli le 2,064 ± 407 mm3 bakeng sa taolo. Ho ne ho se na phapang e kholo ka boholo ba li-VOIs tse ntlafalitsoeng lipakeng tsa bakuli le taolo.

Ho ne ho se na phapano ea bohlokoa ea ho tlama ho tloaelehileng sebakeng sa pontšo pakeng tsa bakuli le taolo; lipalo tse tloaelehileng tsa "cerebellar" ho 4 h e ne e le 20.38 ± 3.70 maemong a taolo le 20.90 ± 4.12 ho bakuli, mme ho 22-24 h lipalo li ne li le 3.75 ± 1.15 ho li-control le 3.37 ± 1.02 ho bakuli.

Mann-Whitney U Teko e bontšitse hore karolelano e tlamang ea 5-HTT ka thalamus ea leqeleng le ka ho le letona e ne e phahame haholo ho bakuli ho feta litulong tse phetseng hantle tsa mmuso (P = 0.001) (Feie. 1). Ha ho phapang e kholo e fumanoeng sebakeng sa midbrain / pons. Karolelano e tlamang ea DAT ho striatum e ne e phahame haholo ho bakuli ho feta litulong tse tšoanang (P = 0.011) (Feie. 2). Litekanyetso tse tlamang tsa 5-HTT le DAT libakeng tse khahlisang bakuli le taolo li khutsufatsoe ho Lethathamo 2. Ha ho lintlha tsa bohlokoa tse fumanoeng pakeng tsa lintlha tsa LSAS le DAT kapa 5-HTT e tlamang ho bakuli.

TLHAHLISO 1. Tekanyo ea ho tlama ha 5-HTT ka ho le letšehali le ka ho le letona thalamus ea psychotropic kalafo-naïve bakuli ba nang le mathata a kakaretso a khatello ea maikutlo (n = 12) le lilemo- le taolo e amanang le thobalano (n = 12) e lekantsoeng 123KHOTSO I-β-CIT. * P = 0.001; Tlhahlobo ea 2-tailed Mann-Whitney U.

 
TLHAHLISO 2. Blitekanyetso tsa inding bakeng sa DAT ho latela kalafo ea psychotropic - naïve bakuli ba nang le khatello ea maikutlo ea ho tšoenyeha sechabeng (n = 12) le lilemo- le taolo e amanang le thobalano (n = 12) e lekantsoeng le 123KHOTSO I-β-CIT. * P = 0.011; Tlhahlobo ea 2-tailed Mann-Whitney U.
 
TABLE 2  Karolelano ea Boitlamo ba ho Kopanya bakeng sa DAT le 5-HTT ho Thuto ea Baahi  

 
Re sebelisitse tlhaiso-leseling e hatisitsoeng ea hoc ho hoc le ho lekola li-striatum tse ka ho le letšehali le bakeng sa setamen sa ka ho le letona le setle. Tlhahlobo ena e senoletse hore ho kopanya letsatsi ho "putamen" e nepahetseng ho ne ho le bohlokoa haholo ho bakuli ho feta ho litekanyetso tsa bophelo bo botle, boemong ba bohlokoa bo sa hlophisitsoeng bakeng sa lipapiso tse ngata.P = 0.012).

TŠOHLOA

Re fumane e phahame haholo 123Litekanyetso tse tlamang tsa I-β-CIT ka thalmus ea leqeleng le ho le letona (tse qaqileng bakeng sa 5-HTT) le ho striatum (e khethehileng bakeng sa DAT) ea lingaka tsa psychotropic-naïve bakuli ba nang le bothata ba ho tšoenyeha ka kakaretso sechabeng ba sa fumaneng tlhahlobo ea maikutlo kalafo. taolo e phetseng hantle e tsamaisana le lilemo, thobalano le ho beleha. Ha ho lits'oants'o tse bobebe tsa ho tlama likarolo tsa 5-HTT-rich midbrain / pons sebakeng ha li fumanoe. Ha ho lintlha tsa bohlokoa tse fumanoeng pakeng tsa 5-HTT le tekanyo ea litekanyetso le lintlha ka sekhahla sa tekanyo ea matšoao (LSAS).

Ho tsebo ea rona, sena e bile tlhahlobo ea pele ea thuto 123Litekanyetso tse tlamang tsa I-β-CIT ka bobeli ba libaka tsa 5-HTT-tse nang le libaka tse ruileng tsa DAT ho bakuli ba nang le bothata ba ho tšoenyeha ka kakaretso sechabeng.. Ho fumana ha rona bokhoni bo kopanyang ba 5-HTT ho thalamus ho fana ka pontšo e tobileng ea hore 5-HT e na le karolo ho pathophysiology ea kakaretso ea matšoenyeho a sechaba a tšoenyehileng. Lintlha tse fetolang li kentse letsoho marang-rang a libaka tsa boko, ho kenyeletsa le cortex ea pele, striatum, thalamus, le amygdala, ho pathophysiology ea kakaretso ea matšoenyeho a sechaba a tšoenyehileng (27,28).

Likarolo tse ngata tsa marang-rang a nang le mathata a ho tšoenyeha ka tikoloho a batho ba bangata ba kenella kahare ho serotonergic kapa dopaminergic neurons. Ho se sebetse hantle ha litšupa-nako tsa thothokiso ea litaba tse amanang le litekanyetso tsa sechaba le boemo bo fetelletseng ba lipotoloho tse nang le mathata a bophelo li ka bapala karolo ea mantlha ho pathophysiology ea bokuli ba matšoenyeho sechabeng (29).

Ho fumana ha rona bokaholimo bo tlamang ba 123I-β-CIT ea 5-HTT ka har'a thalamus ea bakuli ba nang le khatello ea maikutlo ea sechaba e ka hlalosoa e le lebaka le fokotsehileng la mahloriso a 5-HT a fokotsehileng haufi le morekisi (a lumella 123I-β-CIT ho tlama ka letsoele le phahameng haholo), ho tloha bophahamong bo phahameng ba 5-HTT, kapa ho tsoa ho kopanyo ea bobeli.

Maemo a fokotsehileng a mofuta oa 5-HT a fokotsehileng bokong ba bakuli ba nang le bothata ba ho tšoenyeha ka maemo a sechaba a ka bonahala a lumellana le 'nete ea hore li-SSRIs li sebetsa hantle bothateng ba matšoenyeho a sechaba (30). Tumellanong le mohopolo ona, ho tlalehiloe hore taolo e pheta-phetoang ea li-SSRI ho baithaopi ba phetseng hantle ba ka eketsa kamano ea sechaba (31). Haufinyane tjena, Argyropoulos et al. e bonts'itse hore ho fokotsa ho fumaneha hoa 5-HT bokong ka ho putlama ha tryptophan ho bakile keketseho e kholo ea matšoenyeho a amanang le phephetso ho bakuli ba nang le bothata ba ho tšoenyeha ba sechaba ka katleho (32). Khopolo-taba ea phetisetso ea serotonergic e fokotsehileng e lula e fapane le litlaleho tse ling tse fanang ka maikutlo a hore ho eketseha ha 5-HT neurotransication ke ho ts'oenyeha hoa moea. Harmer et al. Haufinyane tjena ho tlalehiloe tsebiso e sa hlokeng tšabo ea sefahleho se tšosang ho baithaopi ba basali kamora ho putlama ha tryptophan, athe tsamaiso e matla ea SSRI citalopram ho baithaopi ba phetseng hantle e ile ea eketsa ho amoheloa ke lifahleho tse tšabang (33,34). Ka mokhoa o makatsang, li-SSRIs hangata li bonts'a phello e matla ea ho ba le letsoalo le fetohang le feto-fetoha le "anxiolysis" ho tsamaiso e phetoang. Mochine o ikarabellang bakeng sa phetoho ena ha o tsejoe empa o ka 'na oa hlalosoa ka liphetoho tse feto-fetohang (dampening) tsamaisong ea serotonergic kapa marangrang a mang a amanang le neuronal.

Matla a tlamang a 5-HTT a tlamang e kanna ea ba sesosa sa mathata a eketsehileng a 5-HTT ho bakuli ba nang le khatello ea maikutlo ea sechaba., e bonts'ang molumo o phahameng oa homeostatic oa sistimi ea serotonergic (e nang le methapo e tlase ea 5-HT receptors). Monyetla ona o ne o tla tsamaellana le liphetho tse tsoang ho Lanzenberger et al., Ea fumaneng maemo a 5-HT receptor 1A a fokotsehile mathateng a matšoenyeho a sechaba (9). Kamora nako, matla a kopanyang a 5-HTT le 'ona a ka ikemisetsa ka liphatsa tsa lefutso. Arbelle et al. Haufinyane tjena ho tlaleha kopano e lipakeng tsa 5-HTT promoter sebakeng sa 44-base-joene le kenyelletso / ho tlosoa le lihlong molemong oa bana bao e seng karolo ea bobeli (35). Bafuputsi ba tlalehile kamano e kholo lipakeng tsa 5-HTT XTUMX-base-pair ea nako e telele ea ho kenya / ho tlosa polymorphism le lihlong mohlaleng oa bona. Bana ba neng ba homozygote bakeng sa bolelele bo bolelele, bo bonts'itsoeng ho hlahisa mongolo o phahameng oa liphatsa tsa lefutso mme ho ka etsahala hore bongata ba 44-HTT e phahameng, ba ne ba e-na le lintlha tse phahameng haholo sekaleng sa lihlong (36). Ha motho a hlajoa ke lihlong ke mofuta oa mofuta oa pherekano ea ho tšoenyeha ka sechaba, 'moko oa 5-HTT o ka fetoloang e le sesosa sa kotsi ea ho holisa mofets'e, oo ka nako e' ngoe o ka hlalosang ho fumana ha rona matla a tlamang a 5-HTT. Ka bomalimabe, liphatsa tsa lefutso la matšoenyeho a sechaba ha li e-so ithutoe ka nepo. Ho khahlisang, phuputso e entsoeng ke van Dyck et al. Ha ea ka ea supa kamanong e tobileng ea maemo a phahameng a 5-HTT le 5-HTT polymorphism empa e khothalelitse kamano e rarahaneng haholoanyane (37).

Monyetla o matla oa ho tlama oa ho etsa lintho ka mokhoa o ikhethileng oa li-striatum tse fumanoeng thutong ena o fapana le dintlha tse tlalehiloeng pejana ke Tiihonen et al., Ea fumaneng monyetla o fokotsang litheko tsa dopamine tse tlamang tlokotsing ea matšoenyeho a sechaba ka ho sebelisa tracer e tšoanang.7). Phapang pakeng tsa liphetho pakeng tsa lithuto tsa 2 e ke ke ea hlalosoa habonolo. Phapang e totobetseng haholo lipakeng tsa lithuto tsa 2 ke tlhahlobo ea rona e nepahetseng haholoanyane ea li-VOIs ka ho sebelisa MRI scan coreg usajili le ho kenyelletsoa ha bakuli ba psychotropic-naïve ntle le comorbidity thutong ea hona joale. Leha ho le joalo, lithuto tsena ka bobeli li ne li e-na le lithuto tse fokolang — e leng moeli o lulang o beha kotsing ea litholoana tse ntle. Joalokaha ho tšohliloe kaholimo, ha motho a toloka data ea boithuto ba hae, o lokela ho nahana hore tšebelisano lipakeng tsa radiotracer le transporter e lekantsoe ke palo ea radiotracer, palo ea transporter le kamano ea eona, le bongata ba ligands tse hlolisang, ke hore, dopamine ea nako e telele. . Kahoo, se fumanoang hajoale se ka hlalosoa e le boemo bo tlase ba dopamine kapa mofuta o phahameng oa letsatsi ho bakuli ba nang le bothata ba ho tšoenyeha ka sechaba kapa ho kopana ka bobeli.

Boholo, lithuto tsa pejana tse hlahlobang tsamaiso ea dopaminergic bothateng ba matšoenyeho a sechaba li bonahala li supa ketsahalo e fokotsehileng ea dopaminergic. Schneier et al. ho tlaleha tse tlase 123I-iodobenzamide e tlamang bokhoni ba dopamine D2 li-receptors ho bakuli ba nang le khatello ea maikutlo ea sechaba. Bangoli ba re ho fumana hona ho etsa mosebetsi o tlase oa dopamine (8). Monyetla o tlamang o tlase, leha ho le joalo, o ka boela oa lumellanngoa le ts'ebetso e ntlafalitsoeng ea dopaminergic kapa (transitory) dopamine e haufi le li-receptor kapa kamano e fetotsoeng ea receptor, joalo ka ha ho ile ha buisanoa ke Mathew et al. (28). O boleletsoe mosebetsi oa dopaminergic o ka fokotsa letsoalo kapa botsitso ba D2 Li-receptors 'me ka nako e ts'oanang hlohlelletsa letsoalo la DAT, athe maemo a phahameng a dopamine a ka qothisana lehlokoa le bona 123I-iodobenzamide ea li-receptor e tlamang.

Lintlha tse tsoang mehlaleng ea liphoofolo li bontšitse hore ts'ebetso ea dopaminergic e phahameng ka nako ea striatum nakong ea khatello ea maikutlo e ka fokotseha D2 letsoalo la receptor (38). Tumellanong le mohopolo oa tšebetso e ntlafalitsoeng ea dopaminergic, Barnett et al. sa tsoa tlaleha litlamorao tse molemo bakeng sa atypical antipsychotic olanzapine ho bakuli ba nang le khatello ea kelello ea kelello (39). Ha li kopantsoe hammoho, liphumano tsena li fana ka maikutlo a hore ho hlokomela ha rona boemo bo phahameng ba letsatsi la DAT ka hara striatum mohlomong ho hlalositsoe hantle ke phetiso e phahameng ea dopaminergic. Ho khahlisang, phuputso ea morao-rao e sebetsang ea MRI e sebelisa mosebetsi o sa ts'oaneng oa ho ithuta e le mokhoa oa ho sebetsa ka ts'ebetso e bonts'itse ts'ebetso e fokotsehileng e amanang le ts'ebetso ea striatum ho bakuli ba nang le khatello ea maikutlo ea sechaba (40). Leha lithuto tse 'maloa li kentse letsoho pherekanong e bakoang ke ho hloka botsitso ka linako tse itseng, ho nka karolo ha litheko tse khethehileng ha ho a hlahlojoe ka botlalo. Ka tlhahlobo ea rona ea tlhahlobo ea tlhaelo-leseling ea post hoc, re fumane ho tlatsana le ho feta hoa letsatsi la tsoalo ho "putamen" e nepahetseng ka nako ea nako ea bophelo bo botle. Leha ho le joalo, keketseho ena e ne e le bohlokoa ka tekanyo e sa hlophisitsoeng bakeng sa lipapiso tse ngata, mme ho kenya letsoho ha putamen lithutong tse amanang le nako ea selemo ho lokela ho kopanngoa lithutong tse ling ho sebelisoa mekhoa e meng.

Ho hlakile hore karolo e ka etsahalang ea tlhekefetso ho dopaminergic le serotonergic system e hloka ho hlakisoa haholoanyane.. Ka bobeli dopamine (ka D1 le D2 li-receptors) le 5-HT (ka 5-HT receptor 2) li tsejoa ho fetola tšebetso ea thabo (ke hore, glutamate) le inhibitory (ke hore, γ-aminobutyric acid) li-neurotransmitters ka har'a li-striatum le li-corticothalamolimbic circry. Lintlha tse mabapi le litšebelisano tsena hantle li ntse li sa hlaka.

Qetellong, ho latela sephetho sa thuto e teng hona joale, ho ke ke ha khonahala ho qolla hore na litlolo tse fumanoang dopaminergic le serotonergic ke mabaka a ho ferekana kapa ho hlonephaha ha mmele. Thutong ea rona, ha re fumane kamano e kholo lipakeng tsa lintlha ka tekanyo ea litekanyetso tsa bongaka le tlhekefetso ho serotonergic le dopaminergic system. Ka kakaretso, lithuto tsa neuroimaging litabeng tsa mafu a kelello li batla li sa fumane kamano e fokolang kapa e fokolang feela lipakeng tsa methapo ea methapo ea methapo le liphetoho tsa methapo. E fetileng 123Phuputso ea I-β-CIT mabapi le mathata a ho tšoenyeha ka sechaba le eona ha ea ka ea fumana kamano lipakeng tsa litekanyetso tse tlamang le Symbomatology (7). Ho ba sieo ha khokahano efe kapa efe ho rona le thutong e fetileng ho ka bakoa ke thepa ea psychometric ea tekanyo e sebelisitsoeng ea bongaka le heterogeneity ea mathata a ho tšoenyeha sechabeng joalo ka ha ho hlalositsoe ke DSM-IV empa hape e ka hlalosoa e supa taba ea hore ketsahalo ea lefu la ho tšoenyeha ka sechaba ha le amane ka ho toba le litlolo tse fumanoeng. Ho bohlokoa hape ho hlokomela phapano lipakeng tsa lipehelo tse tlamang ho bakuli le taolo, ho fana ka maikutlo a hore tlhekefetso e fumanoeng e kanna ea amana le ho ba kotsing kapa litšobotsi tsa botho. Tlhaloso e 'ngoe e ka ba hore litlolo tse fumanoeng ke litholoana tsa ho ba le khatello ea maikutlo ho batho ba bang (ke hore, "leqeba" la kelello).

Boithuto ba rona bo ne bo na le lintlha tse 'maloa tse matla. Bakuli le lits'oants'o li ne li tšoana ka bobeli. Bakuli e ne e le li-psychotropic meriana-naïve mme ba ne ba sena tlhahlobo ea kelello ea mokokotlo ka axis I, 'me boholo ba bona ba ne ba sa fumana kalafo ea kelello ea pele ho nako. Ntle le moo, tlhaiso-leseling ea SPECT e ile ea hlahlojoa ho sebelisoa scans ea MRI e ngolisitsoeng hantle, ho lumella boikemisetso bo nepahetseng ba li-VOIs. Ho bile le mefokolo e ka bang teng thutong ea joale. Boholo ba mehlala e ne e le nyane 'me re sebelisa li-VOIs tse fokolang.

Re bone ka leihlo la 5-HTT feela ho 4 h kamora ho tsamaisoa ha ligand. Nako ena ea pono, leha ho le joalo e kanna ea fokotsa monyetla oa ho fumana litlolo tse eketsehileng maemong a 5-HTT, joalo ka ha ho bonts'itsoe ke thuto ea Willeit et al. ka bokuli bo amanang le nako e tlang (20). Thutong eo, 5-HTT e ile ea bonoa ho 4 h ka mor'a ho entoa 123I-β-CIT hape le 24 h, ha boemo ba pseudoequilibrium bo fihlelloa. Phapang e fumanoe feela ho lintho tse fumanoeng ka SPECT ho 24 h ka mora ente. Re ile ra latela mokhoa o hlalositsoeng ke Kuikka et al. mme re sebelisitse paroxetine, 20 mg, ho lahla thepa ka botlalo 123I-β-CIT e tsoang 5-HTT (18). Tsamaiso ea paroxetine e kanna ea lebisa ho eketseho ea matšoao a (sechabeng) matšoenyeho, empa keketseho e joalo (bonolo) e tlalehiloe ke mokuli oa 1 feela.

Khabareng, le ha ho le bonolo ho e sebelisa ka BOPHELO, ha e theko e tlase, ebile e na le index ea polokeho e phahameng ho feta PET, e boetse e sebelisa mekhoa e ikhethileng ebile e na le sephetho se futsanehileng sa li-anatomic.

QETELLO

Lintlha tsa rona li fana ka bopaki bo tobileng ba ho kenya letsoho lits'ebetsong tsa dopaminergic le serotonergic ho pathophysiology ea likhathatso tsa matšoenyeho a sechaba.. Liphetho tsena li hloka ho phetoa le ho hlahlojoa ho eketsehileng lithutong tse lekolang phello ea pharmacotherapy le psychotherapy ka bobeli ho serotonergic le dopaminergic transporter le bokhoni ba receptor-binding litlamong tse akaretsang tsa khatello ea kelello ea sechaba.

lumela hore baa fokola

Re leboha Alice van Dongen, mothusi oa lipatlisiso tsa bongaka Lefapheng la Bongaka ba Nyutlelie ka thuso ea hae le mehopolo mabapi le thuto.

Karolo e fetilengKarolo e latelang

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  • E amohetse khatiso July 24, 2007.
  • E amohetse khatiso January 16, 2008.