Sumber : NIH Public access

Beberapa perilaku, selain konsumsi zat psikoaktif, dapat menghasilkan “rewards” jangka pendek

yang menimbulkan perilaku persisten, seperti kurangnya kontrol terhadap perilaku. Kurangnya

kontrol terhadap perilaku adalah konsep inti mendefinisikan ketergantungan zat psikoaktif atau

kecanduan. Kesamaan ini telah melahirkan konsep non-zat atau "perilaku" kecanduan, yaitu,

suatu sindrom yang analog dengan kecanduan substansi, tetapi dengan fokus perilaku selain

konsumsi zat psikoaktif. Konsep kecanduan perilaku memiliki beberapa nilai heuristik ilmiah

dan klinis, tetapi masih kontroversial. Isu-isu seputar kecanduan perilaku saat ini sedang

diperdebatkan dalam konteks pengembangan DSM-V.

Beberapa kecanduan perilaku telah dihipotesiskan memiliki kemiripan dengan kecanduan

substansi atau zat. Diagnostik dan Statistik Manual, Edisi 4 (DSM-IV-TR) dipakai untuk kriteria

diagnosis beberapa kelainan seperti judi patologis (pathological gambling) yang termasuk dalam

ganguan kontrol impuls. Perilaku lain (atau gangguan kontrol impuls) telah dipertimbangkan

untuk dimasukkan dalam DSM yang akan datang seperti kompulsif membeli (compulsive

buying), memetik kulit patologis (pathologic skin Picking), kecanduan seksual (nonparaphilic

hypersexuality), kecanduan komputer / video game dan kecanduan internet.

Kecanduan perilaku dan kecanduan substansi memiliki banyak kesamaan dalam riwayat atau

perjalanan penyakit, fenomenologi, dan konsekuensi yang merugikan. Keduanya memiliki onset

lebih tinggi pada masa remaja dan dewasa muda dibandingkan dengan orang dewasa yang lebih

tua .

Kecanduan perilaku sering didahului oleh perasaan "ketegangan atau gairah sebelum melakukan

tindakan "dan" kesenangan, kepuasan atau bantuan pada saat melakukan tindakan ". Sifat ego-

syntonic dari perilaku ini adalah berdasarkan pengalaman serupa dengan pengalaman perilaku

penggunaan narkoba. Hal ini bertentangan dengan sifat ego-distonik gangguan obsesif

kompulsif. Namun, baik kecanduan perilaku dan substansi mungkin menjadi kurang ego-

syntonic dan lebih ego-dystonic dari waktu ke waktu, sebagai perilaku (termasuk mengambil

substansi) itu sendiri menjadi kurang menyenangkan dan lebih dari kebiasaan atau paksaan (2,7),

atau menjadi termotivasi kurang oleh penguatan positif dan penguatan negatif lainnya (misalnya,

relief disforia atau penarikan).

NEUROBIOLOGI

Substances of abuse directly activate via pharmacological mechanisms the brain reward

signaling, thus mimicking (and exceeding in magnitude) the signals of natural rewards. Hence,

the brain reward system falsely interprets the signals of the drugs as highly beneficial for the

survival/reproduction of the individual. Therefore, human predilection to the substances of abuse

might be caused by misfiring of the brain reward circuitry. Moreover, the predilection does not

only concern humans, but also animals, indicating that the brain reward system has developed

early in the course of evolution (Nesse & Berridge, 1997; Berridge & Kringelbach, 2008).

penyalahgunaan zat secara langsung mengaktifkan melalui mekanisme signaling reward otak,

melalui proses farmakologi, meniru (dan melebihi besarnya) sinyal dari imbalan alami. Oleh

karena itu, sistem reward otak palsu menafsirkan sinyal dari obat sebagai sangat bermanfaat bagi

kelangsungan hidup / reproduksi individu. Oleh karena itu, kecenderungan manusia untuk bahan

pelecehan mungkin disebabkan oleh tembak dari sirkuit reward otak. Selain itu, kecenderungan

tidak hanya menyangkut manusia, tetapi juga hewan, yang menunjukkan bahwa sistem reward

otak telah dikembangkan di awal evolusi (Nesse dan Berridge, 1997; Berridge dan Kringelbach,

2008)

Like substance use, gambling has also been very widespread, both timely and culturally, in the

history of the humankind (Arnold, 1977). Clearly, there is something in gambling that abuses the

brain systems developed in the needs for survival and reproduction. Life is full of choices in the

environment of limited resources, and each choice includes a risk. Risky choices could be

considered as gambling – weighing the different options according to their probability. With

limited resources and challenged long-term survival (which drives the evolution), more risk

prone behavior aiming for short-term benefits might provide the niche for survival (Petry, 2005;

Durrant et al., 2009).

Seperti penggunaan narkoba, perjudian juga telah sangat luas, baik tepat waktu dan budaya,

dalam sejarah umat manusia (Arnold, 1977). Jelas, ada sesuatu dalam perjudian yang

pelanggaran sistem otak dikembangkan dalam kebutuhan untuk bertahan hidup dan reproduksi.

Hidup ini penuh pilihan di lingkungan sumber daya yang terbatas, dan setiap pilihan termasuk

risiko. Pilihan berisiko dapat dianggap sebagai perjudian - menimbang pilihan yang berbeda

sesuai dengan probabilitas mereka. Dengan sumber daya terbatas dan menantang kelangsungan

hidup jangka panjang (yang mendorong evolusi), lebih berisiko perilaku rentan bertujuan untuk

keuntungan jangka pendek mungkin memberikan ceruk untuk bertahan hidup (Petry, 2005;

Durrant et al, 2009.)

The non-drug addictions, however, share many characteristics of drug addictions. Like substance

addictions, non-drug addictions manifest in similar psychological and behavioral patterns

including cravings, impaired control over the behavior, tolerance, withdrawal, and high rates of

relapse (Olsen, 2011). Non-drug addictions have thus been termed “behavioral addictions”. The

concept of non-drug addictions or behavioral addictions is relatively new, and is included for the

first time in the proposed revision of the Diagnostic and Statistical Manual of Mental Disorders

(DSM-5) (Holden, 2010). There are several compulsive activities that could be considered as

non-drug addictions (Olsen, 2011).

Kecanduan non-obat, bagaimanapun, berbagi banyak karakteristik dari kecanduan narkoba.

Seperti kecanduan zat, kecanduan non-obat terwujud dalam pola psikologis dan perilaku yang

sama termasuk ngidam, kontrol gangguan atas perilaku, toleransi, penarikan, dan tingginya

tingkat kekambuhan (Olsen, 2011). Kecanduan non-obat ini dengan demikian telah disebut

"kecanduan perilaku". Konsep kecanduan non-obat atau kecanduan perilaku relatif baru, dan

termasuk untuk pertama kalinya dalam usulan revisi Manual Diagnostik dan Statistik Gangguan

Mental (DSM-5) (Holden, 2010). Ada beberapa kegiatan yang kompulsif dapat dianggap sebagai

kecanduan non-obat (Olsen, 2011).

2.2 Neurobiology of judi patologis

Sistem rewards otak dan neurotransmitter dopamine

Sistem dopaminergik manusia terdiri dari beberapa jalur (Gambar 1). Jalur mesolimbic, berasal

dari daerah tegmental ventral (VTA) ke ganglia basal [nucleus accumbens (NACC), yang

terletak di striatum ventral], dianggap bagian penting dari sistem reward otak, meskipun juga

jalur mesocortical dan sistem neurotransmitter lainnya berpartisipasi dalam proses pengolahan

rangsangan terkait sistem reward (Koob & Nestler, 1997). Secara anatomis, striatum terdiri dari

NACC, kaudatus, dan putamen. Secara fungsional, striatum dapat dibagi ke bagian ventral,

asosiatif, dan sensorimotor (Haber & McFarland, 1999; Kegeles et al, 2010.). Striatum ventral

yang tidak hanya mencakup NACC, tetapi juga bagian ventral dari kaudatus dan putamen, yang

juga terhubung ke sistem limbik. Oleh karena itu, striatum ventral tidak memiliki batas anatomis

yang pasti, dan dengan demikian, penggambaran anatomi struktur agak menantang. Pembagian

fungsional dan koneksi dari striatum disajikan dalam Gambar 2.

Saat ini, terdapat beberapa teori yang menjelaskan mekanisme neurobiologis dari gangguan

adiksi: hipotesis sindrom defisiensi reward (RDS) hipotesis impulsif dan teori sensitisasi insentif

Hipotesis RDS te;lah dikembangkan atasa dasar studi genetic yang menghubungkan alel tertentu

dalam dopamine yang terkait gen berhubungan dengan gangguan adiksi. Hipotesis RDS

memprediksi bahwa individu dengan RDS memiliki tanggapan reward otak yang kurang untuk

untuk menghasilkan rangsangan.

Partly in parallel with the latter assuming more of a hyper- than hypodopaminergic state, the

incentive sensitization theory postulates that addiction results from the hypersensitized brain

reward system resulting from repeated drug exposure causing incentive salience for drug use

(Robinson & Berridge, 1993; 2008). Positron emission tomography (PET) imaging results have

mainly supported the principle of the RDS hypothesis, whereas fMRI studies have provided

inconclusive results [for a review, see (Hommer et al., 2011)].

Bertentangan dengan hipotesis RDS, hipotesis impulsif mengasumsikan kecanduan atau adiksi

disebabkan oleh ketidakseimbangan antara dua sistem saraf yang mengendalikan pengambilan

keputusan: Peningkatan sinyal reward dan gangguan sistem reflektif untuk mengendalikan

impuls. Sebagian secara parallel berasumsi hiperdopaminergik maupun hipodopaminergik, teori

sensitisasi insentif mendalilkan bahwa adiksi berasal dari hipersensitasi sistem reward otak yang

dihasilkan dari paparan obat berulang menyebabkan arti-penting insentif bagi penggunaan

narkoba. Hasil pencitraan oleh Tomografi emisi positron (PET), mendukung prinsip hipotesis

RDS, sedangkan penelitian fMRI tidak meyakinkan (Hommer et al., 2011)].

2.2.3 Neuroimaging studies in pathological gambling

2.2.3.1 Neuroimaging in pathological gambling

PET dan SPECT. Hanya ada sejumlah kecil studi neuroimaging diterbitkan pada PG. Dengan

menggunakan PET, penjudi patologis (tanpa PD) telah diselidiki oleh dua kelompok terpisah,

dengan fluorodeoxyglucose atau dengan raclopride. Studi awal menunjukkan tingkat

metabolisme fluorodeoxyglucose yang lebih tinggi di bagian dorsal striatum dan thalamus,

orbitofrontal, serta medial korteks frontal; dan penurunan tingkat metabolisme yang ditemukan

di bagian ventral striatum dan thalamus (Hollander et al, 2008;. Pallanti et al, 2010.).

Potensi pengikatan reseptor pada dopamine striatal D2 (D3) yang diukur dengan raclopride, tidak

menunjukan perbedaan yang signifikan antara penjudi patologis dan relawan sehat (Linnet et al.,

2010). Hollander dkk. Menyelidiki tujuh penjudi patologis tanpa menggunakan kelompok

kontrol fluorodeoxyglucose, dengan dan tanpa imbalan uang, dan menemukan bahwa hadiah

uang dikaitkan dengan peningkatan metabolisme di korteks primer visual, gyrus cingulate,

utamen, dan daerah prefrontal.

fMRI. studi fMRI pada penjudi patologis telah menunjukkan respon berkurang untuk menang

dan kalah judi di striatum ventral dan ventral prefrontal daerah korteks; meskipun data tersebut

tidak sepenuhnya seragam (Reuter et al, 2005;. de Ruiter et al, 2009;. Miedl et al, 2010.). Isyarat

perjudian bukan telah mengakibatkan peningkatan aktivasi dari beberapa daerah otak termasuk

korteks prefrontal, parahippocampal dan daerah kortikal oksipital pada penjudi patologis

dibandingkan dengan relawan yang sehat (Crockford et al, 2005;. Goudriaan et al, 2010;.. Miedl

et al, 2010) , meskipun ada juga hasil yang bertentangan (Potenza, 2008).

Ada juga data yang menunjukkan penurunan sensitivitas ditambah dengan aktivasi yang lebih

rendah pada bagian ventrolateral prefrontal akibat kekalahan judi pada penjudi patologis (de

Ruiter et al., 2009). Selain itu, juga ada bukti menunjuk ke peningkatan respon risiko frontal di

penjudi patologis selama perjudian (Miel et al., 2010). Selanjutnya, penjudi patologis telah

menunjukan ekspersi aktivitas ventromedial prefrontal kortikal yang berkurang selama proses

inhibisi,

Struktural. Sampai saat ini, hanya ada satu studi yang menyelidiki struktur otak pada PG (Yip et

al., 2011). Studi ini difokuskan hanya pada integritas substansi putih (whitw matter) pada tiga

subbagian corpus callosum, dan ditemukan penurunan secara bilateral fraksi anisotrofi pada genu

corpus callosum. Tidak ada studi menyelidiki morfometri subtansi putih atau abu-abu otak pada

penjudi patologis.m

2.3.1 Positron emission tomography (PET)

Positron emission tomography (PET) adalah pencitraan dengan metode non-invasif yang

memungkinkan dalam pencitraan molekuler vivo. Dalam PET, ligan radiolabeled digunakan

untuk menyelidiki bagian dan fungsi dari molekul ligan dalam organ, seperti otak

Raclopride adalah dopamin D2 (D3) antagonis reseptor yang bersaing untuk mengikat dengan

dopamin endogen. Sejak raclopride bersaing dengan dopamin endogen dengan cara yang

konsisten dengan model hunian (yaitu peningkatan hasil konsentrasi dopamin sinaptik

peningkatan hunian reseptor oleh dopamin, sehingga, mengurangi situs pengikatan tersedia untuk

radiotracer), digunakan dalam paradigma perpindahan untuk memperkirakan pelepasan dopamin

endogen setelah rangsangan farmakologis atau non-farmakologis

Uptake Fluorodopa melibatkan dekarboksilasi presinaptik levodopa dalam sel-sel saraf. Setelah

dekarboksilasi, fluorodopamine menjadi terperangkap di dalam sel. Penyerapan fluorodopa

tergantung pada aktivitas aromatik dekarboksilase asam amino (AADC) di otak. AADC

berpartisipasi untuk pengolahan L-DOPA, yang merupakan prekursor untuk semua monoamina

(dopamin, serotonin, dan noradrenalin)

2.3.2 Structural MRI and voxel-based morphometry (VBM)

Structural MRI. The nuclei of atoms behave like microscopic magnets. MRI scanner applies a

powerful magnetic field making the magnetic moments of the nuclei of atoms align in a parallel

or anti-parallel direction. This alignment induces a net magnetization, which is termed as the

magnetic moment. The nucleus of the hydrogen atom (H1) has the highest energy and is

abundant in the human body [mainly located in water molecules (H2O)], and thus is the nucleus

used in almost all clinical MR imaging. The time to return (relaxation time) to the original state

differs according to the proton density and the molecular structures of the tissue. Differences in

the relaxation times (for example T1- and T2-relaxation times) form the basis of tissue contrast

in the MR images. T1-weighted images are the most used ones in clinical settings, with excellent

discrimination of fat and water, shown bright and dark, respectively. T2 weighted images are

also widely used in clinical settings, similarly differentiating fat from water, but with opposite

tissue intensity coding as in T1-weighed images (fat is shown dark and water bright) [For a

review, see (Hendee & Morgan, 1984a; b)].

2.3.2 MRI struktural dan voxel berbasis morfometri (VBM)

Voxel-based morphometry (VBM). VBM is a method developed for analyzing local brain

volumes or densities in a voxel-based manner across the entire brain using the information of T1-

weighted images. The shape and size of human brain are variable, and thus the T1-weighted

images are first spatially normalized to the same stereotactic space using mutual information

algorithm to enable the voxel-wise analysis between different subjects. The gray and white

matter are segmented to different images, and analyzed separately. For the statistical voxel-wise

analysis, the images are smoothed to improve the signal-to-noise ratio, and general linear model

(GLM) is applied to identify regions with statistically significant effects of interest (Ashburner &

Friston, 2000).

Morfometri voxel berbasis (VBM). VBM adalah metode yang dikembangkan untuk

menganalisis volume otak lokal atau kepadatan dengan cara berbasis voxel di seluruh otak

menggunakan informasi dari gambar T1-tertimbang. Bentuk dan ukuran otak manusia adalah

variabel, dan dengan demikian gambar T1-tertimbang yang pertama spasial dinormalisasi ke

ruang stereotactic sama menggunakan algoritma informasi mutual untuk memungkinkan analisis

voxel-bijaksana antara subjek yang berbeda.

2.3.3 Diffusion tensor imaging (DTI)

Diffusion. Diffusion describes the random motion, or Brownian motion, of particles resulting

from the thermal energy carried by the molecules. DTI focuses on how free or isotropic the

diffusion (i.e. is the diffusion mechanically restricted in some way) is in a given location. In the

example of the brain, diffusion of the white matter is generally more restricted (axons allow

diffusion mainly along with longitudinal axis of the axon) than in the gray matter, and

cerebrospinal fluid has almost isotropic diffusion [for reviews, see (Le Bihan, 2003; Mukherjee

et al., 2008)].

2.3.3 Difusi tensor imaging (DTI) Difusi. Difusi menggambarkan gerak acak, atau gerak Brown,

partikel yang dihasilkan dari energi panas yang dibawa oleh molekul. DTI berfokus pada

bagaimana gratis atau isotropik difusi (yaitu adalah difusi mekanis dibatasi dalam beberapa cara)

di lokasi tertentu. Dalam contoh otak, difusi materi putih umumnya lebih terbatas (akson

memungkinkan difusi terutama bersama dengan sumbu longitudinal dari akson) daripada di

materi abu-abu, dan cairan serebrospinal memiliki difusi hampir isotropik [diulas, lihat (Le

Bihan 2003;. Mukherjee et al, 2008)].

Prinsip DTI. Seperti dijelaskan di atas (2.3.2), T1- konvensional atau tindakan MRI T2-

tertimbang sinyal intensitas, yang didominasi oleh konsentrasi air dari jaringan diberikan. Dalam

DTI, gradien medan yang diterapkan untuk mencapai lokasi frekuensi tergantung menggunakan

molekul air sebagai probe mikroskopis (atau intuitif dijelaskan, sebagai penandaan informasi

lokasi ke proton dari molekul air). Untuk mengukur difusi, magnet gradien medan berdenyut

digunakan, yang berarti menerapkan medan magnet homogen linear (gradien), yang dapat

dinyalakan dan dimatikan (maka disebut berdenyut).

5.2.3 Dopamin neurotransmisi

Rilis dopamine selama perjudian. SPM analisis mengungkapkan bahwa perjudian menginduksi

pelepasan dopamin. Dopamin dirilis di bagian asosiatif pada nucleus caudatus selama

pemindaian reward yang rendah, dan meluas ke striatum ventral selama pemindaian reward

tinggi (Gambar 10). Ada korelasi terhadap besarnya pelepasan dopamin antara pemindaian

dengan reward yang tinggi maupun dengan reward yang rendah (Gambar 11A). Besarnya

pelepasan dopamin tidak berbeda antara kelompok dan tidak ada daerah dengan peningkatan

yang signifikan terhadap pengikatan raclopride .

6.1.1.1 Behavioral responses to gambling

Pathological gamblers experienced a higher “urge to gamble” in study I, which is in concordance

with the increased incentive salience towards gambling actions in pathological gamblers as has

been described in the literature (Grant et al., 2010; Sodano & Wulfert, 2010). In addition, during

the monotonous hour-long non-rewarding gambling pathological gamblers experienced an

increasing “urge to gamble” while control subjects expressed less of an “urge to gamble” in the

course of the low-reward task possibly reflecting the impaired stimulus-outcome based learning

in PG (van Holst et al., 2010). However, there were no signs of attenuated (nor enhanced)

gambling induced euphoria in addicted individuals as could be expected based on the RDS

hypothesis (Blum et al., 2000).

6.1.1.1 tanggapan Perilaku judi Penjudi patologis mengalami lebih tinggi "mendesak untuk

berjudi" dalam penelitian saya, yang dalam konkordansi dengan arti-penting insentif peningkatan

terhadap tindakan perjudian di penjudi patologis seperti yang telah dijelaskan dalam literatur

(Grant et al, 2010;. Sodano & Wulfert, 2010) . Selain itu, selama jam-panjang judi penjudi-

penghargaan non patologis monoton mengalami peningkatan "mendesak untuk berjudi"

sementara subjek kontrol menyatakan kurang dari "mendesak untuk berjudi" dalam perjalanan

tugas rendah-hadiah mungkin mencerminkan perangsang terganggu pembelajaran hasil berbasis

di PG (van Holst et al., 2010). Namun, tidak ada tanda-tanda dilemahkan (atau ditingkatkan)

perjudian diinduksi euforia pada individu kecanduan seperti yang bisa diharapkan didasarkan

pada hipotesis RDS (Blum et al., 2000).

6.1.1.2 Gambling releases striatal dopamine

Several pharmacological [reviewed in (Volkow et al., 2009)] and non-pharmacological

[reviewed in (Egerton et al., 2009)] rewards have been shown to activate the mesolimbic

dopamine neurotransmission in humans. Furthermore, it has been shown that the magnitude of

the dopamine release by pharmacological rewarding agents, such as stimulants, relates to the

experienced euphoria induced by the drug (Volkow et al., 1999). The evidence of human in vivo

mesolimbic dopamine release associated with pharmacological rewards, however, is somewhat

less clear (Egerton et al., 2009).

6.1.1.2 rilis Perjudian dopamin striatal Beberapa farmakologi [Ulasan di (Volkow et al., 2009)]

dan non-farmakologis [Ulasan di (Egerton et al., 2009)] imbalan telah ditunjukkan untuk

mengaktifkan neurotransmisi dopamin mesolimbic pada manusia. Selain itu, telah ditunjukkan

bahwa besarnya pelepasan dopamin oleh agen farmakologis yang bermanfaat, seperti stimulan,

berkaitan dengan euforia berpengalaman yang disebabkan oleh obat (Volkow et al., 1999). Bukti

dari manusia in vivo rilis dopamin mesolimbic berhubungan dengan imbalan farmakologi,

bagaimanapun, agak kurang jelas (Egerton et al., 2009).

When applying similar methods (namely [11C]raclopride PET with displacement method) with

the non-pharmacological rewards as has been done with pharmacological agents, monetary

reward during a video game (although without sensorimotor control task or movement

correction) (Koepp et al., 1998), a gambling task (in PD patients) (Steeves et al., 2009), a

delayed monetary incentive task (Schott et al., 2008), or an active card selection task (Zald et al.,

2004); food (after fasting) (Small et al., 2003); and music (in individuals with exceptionally

strong emotional responses to the particular music) (Salimpoor et al., 2011) have shown a

statistically significant reduction in [11C]raclopride non-displaceable binding potential (BPND)

indicating endogenous dopamine release.

Ketika menerapkan metode yang serupa (yaitu [11 C] raclopride PET dengan metode

perpindahan) dengan imbalan non-farmakologis seperti yang telah dilakukan dengan agen

farmakologis, hadiah uang selama video game (meskipun tanpa tugas kontrol sensorimotor atau

koreksi gerakan) (Koepp et al. 1998), tugas perjudian (pada pasien PD) (Steeves et al, 2009),

tugas insentif moneter tertunda (Schott et al, 2008), atau tugas pilihan kartu aktif (Zald et al,

2004)...; makanan (setelah puasa) (Kecil et al, 2003.); dan musik (pada individu dengan respon

emosional yang sangat kuat untuk musik tertentu) (Salimpoor et al., 2011) telah menunjukkan

penurunan yang signifikan secara statistik pada [11 C] raclopride nondisplaceable mengikat

potensial (BOND) menunjukkan pelepasan dopamin endogen.

Interestingly, several studies with acute non-pharmacological rewards have produced only trend-

line effects, or significant effects only in subpopulations of the study’s sample in respect to

dopamine release (Egerton et al., 2009). This was also the case in the only previous study

investigating the dopamine release in gamblers and healthy volunteers using the Iowa Gambling

Task (Linnet et al., 2010; Linnet et al., 2011b).

Menariknya, beberapa penelitian dengan imbalan non-farmakologis akut telah menghasilkan

hanya efek trend-line, atau efek signifikan hanya pada sub-populasi dari sampel penelitian

sehubungan dengan rilis dopamin (Egerton et al., 2009). Ini juga terjadi di satu-satunya

penelitian sebelumnya menyelidiki pelepasan dopamin di penjudi dan sukarelawan sehat

menggunakan Perjudian Tugas Iowa (Linnet et al, 2010;. Linnet et al, 2011b.)

The previous findings together with the results of study I suggest that non-pharmacological

rewarding stimuli do release mesolimbic dopamine, but the effect sizes are of lesser magnitude

compared to pharmacological rewarding stimuli. Mesolimbic dopamine neurons originating from

the VTA to the basal ganglia have been shown to encode not only reward value, but also reward

risk, in non-human primates (Schultz et al., 1997; Fiorillo et al., 2003), and comparable

hemodynamical responses in humans have been seen as well (Preuschoff et al., 2006).

Temuan sebelumnya bersama-sama dengan hasil penelitian saya menunjukkan bahwa

rangsangan bermanfaat non-farmakologis lakukan melepaskan dopamin mesolimbic, tetapi efek

ukuran yang besarnya lebih rendah dibandingkan dengan rangsangan bermanfaat farmakologis.

Neuron dopamin mesolimbic yang berasal dari VTA ke ganglia basal telah ditunjukkan untuk

mengkodekan tidak hanya nilai pahala, tetapi juga memberikan penghargaan risiko, pada primata

non-manusia (Schultz et al, 1997;. Fiorillo et al, 2003.), Dan hemodinamik sebanding tanggapan

pada manusia telah dilihat juga (Preuschoff et al., 2006).

Furthermore, non-human primate studies have demonstrated the selective role of dopamine in the

form of stimulus-reward learning in which incentive salience is assigned to cues predicting the

reward (Flagel et al., 2011). Human neuroimaging studies with substance addictions have

confirmed existing conditioned striatal dopamine release in response to reward predicting cues

(Volkow et al., 2006). Study I replicates the previously reported mesolimbic dopamine release in

response to monetary rewards (Zald et al., 2004; Schott et al., 2008; Steeves et al., 2009), but

also shows that mere slot machine gambling without winning money is sufficient to induce

mesolimbic dopamine transmission. Moreover, the dopamine release during nonrewarding

gambling runs parallel with the dopamine release during rewarding gambling, although the

dopamine release was associated with hedonia (as captured by the terms ‘positive mood’ and

‘high’) only during winning gambling.

Selanjutnya, studi primata non-manusia telah menunjukkan peran selektif dopamin dalam bentuk

pembelajaran stimulus-reward yang arti-penting insentif ditugaskan untuk isyarat memprediksi

pahala (flagel et al., 2011). Studi neuroimaging manusia dengan kecanduan zat telah

dikonfirmasi ada pelepasan dopamin striatal dikondisikan dalam menanggapi penghargaan

isyarat memprediksi (Volkow et al., 2006). Penelitian saya meniru pelepasan dopamin

mesolimbic dilaporkan sebelumnya dalam menanggapi hadiah uang (Zald et al, 2004;. Schott et

al, 2008;. Steeves et al, 2009.), Tetapi juga menunjukkan bahwa hanya mesin slot judi tanpa

memenangkan uang cukup untuk menginduksi transmisi dopamin mesolimbic. Selain itu,

pelepasan dopamin selama perjudian non menguntungkan berjalan paralel dengan merilis

dopamin selama perjudian bermanfaat, meskipun pelepasan dopamin berhubungan dengan

hedonia (seperti yang ditangkap oleh istilah 'mood positif' dan 'tinggi') hanya selama menang

judi.

The slot machine gambling session of this study involved over 400 repetitions of unrelated

events, which had the elements of reward prediction, risk and high-reward (win) or low-reward

(no win). The difference in dopamine release between the two tasks could be explained by the

lowreward task represented as a powerful conditioned stimulus (spinning the wheels), and the

high-reward task as quite similar conditioned stimulus accompanied with greater unconditioned

stimulus (wins). This view is supported by the fact that the dopamine release during high-

reward, but not during low-reward, correlated with hedonia. Moreover, also consistent with this

idea, during non-rewarding gambling, the dopamine release occurred in the associative striatum,

known to participate in cue-reactivity, also during the rewarding gambling [see Figures 2 and 10,

(Kegeles et al., 2010)].

Sesi judi mesin slot penelitian ini melibatkan lebih dari 400 pengulangan peristiwa yang tidak

terkait, yang memiliki unsur-unsur prediksi reward, risiko dan imbalan tinggi (menang) atau

rendah-hadiah (tidak menang). Perbedaan dopamin rilis antara dua tugas dapat dijelaskan oleh

tugas reward rendah direpresentasikan sebagai stimulus kuat terkondisi (berputar roda), dan

tugas tinggi reward sebagai sangat mirip stimulus dikondisikan disertai dengan stimulus

berkondisi lebih besar (menang). Pandangan ini didukung oleh fakta bahwa pelepasan dopamin

selama tinggi-hadiah, tapi tidak rendah selama-reward, berkorelasi dengan hedonia. Selain itu,

juga konsisten dengan ide ini, selama non-menguntungkan perjudian, pelepasan dopamin terjadi

di striatum asosiatif, yang dikenal untuk berpartisipasi dalam isyarat-reaktivitas, juga selama

perjudian menguntungkan [lihat Gambar 2 dan 10, (Kegeles et al., 2010 )].

However, dopamine release capacity seems to also show a marked inter-individual variability,

irrespective of the challenge (Scott et al., 2007; Buckholtz et al., 2010b), which could also

explain the strong correlation between high-reward and low-reward dopamine release. There are

some studies supporting this view as the ventral striatal fMRI response to reward cues correlates,

not only with the magnitude of dopamine release in the corresponding task (Schott et al., 2008),

but also with pharmacologically or placeboinduced dopamine release (Scott et al., 2007;

Buckholtz et al., 2010a).

Namun, kapasitas pelepasan dopamin tampaknya juga menunjukkan variabilitas antar-individu

ditandai, terlepas dari tantangan (Scott et al, 2007;. Buckholtz et al, 2010b.), Yang juga dapat

menjelaskan korelasi kuat antara tinggi-rendah dan reward pahala pelepasan dopamin. Ada

beberapa penelitian yang mendukung pandangan ini sebagai fMRI respon striatal ventral untuk

menghargai isyarat berkorelasi, tidak hanya dengan besarnya pelepasan dopamin dalam tugas

yang sesuai (Schott et al., 2008), tetapi juga dengan farmakologi atau plasebo rilis diinduksi

dopamin (Schott et al, 2007;. Buckholtz et al, 2010a)

Interestingly, dopamine was released only on the right side of the striatum, which could relate to

hemispheric differences in dopaminergic reward processing as has been suggested in the case of

incentive motivation (Tomer et al., 2008). It is also possible that the captured effect is only the

peak of broader dopamine release, but this explanation seems unlikely, since there was not even

near-significant effect on the left striatum. Moreover, a recent [11C]raclopride PET study has

suggested that dopaminergic reward processing during gambling may indeed be lateralized to the

right ventral striatum (Martin-Soelch et al., 2011).

Menariknya, dopamin dirilis hanya di sisi kanan dari striatum, yang bisa berhubungan dengan

perbedaan belahan otak dalam pengolahan reward dopaminergik seperti yang telah disarankan

dalam kasus motivasi insentif (Tomer et al., 2008). Hal ini juga mungkin bahwa efek ditangkap

hanya puncak pelepasan dopamin yang lebih luas, tetapi penjelasan ini tampaknya tidak

mungkin, karena tidak ada bahkan efek dekat-signifikan pada striatum kiri. Selain itu, [11 C]

raclopride PET penelitian terbaru telah menyarankan bahwa pengolahan dopaminergik reward

selama perjudian mungkin memang akan lateralized ke striatum ventral kanan (Martin-Soelch et

al., 2011).

6.1.1.3 Is there blunted dopamine reward signaling in pathological gambling?

The RDS hypothesis predicts that most addicted individuals would express the lowest

dopaminergic and hedonic responses to rewarding gambling (Blum et al., 2000). There is a

substantial body of evidence from human neuroimaging studies supporting the blunted responses

to drugs in substance addictions (Volkow et al., 2011). However, the studies have been

conducted with substances and individuals addicted to substances that are known to

pharmacologically directly increase synaptic brain dopamine levels. Importantly, [11C]

raclopride PET studies in humans addicted to heroin did not reveal corresponding blunting of the

dopaminergic neurotransmission, although the drugs were capable of inducing euphoria, thus

questioning the role of dopamine in substance addictions, at least with substances whose effects

are not mediated primarily by dopamine (Daglish et al., 2008).

6.1.1.3 Apakah ada tumpul dopamin reward sinyal dalam judi patologis? RDS hipotesis

memprediksi bahwa kebanyakan orang kecanduan akan mengekspresikan dopaminergik

termurah dan tanggapan hedonis judi menguntungkan (Blum et al., 2000). Ada tubuh besar bukti

dari studi neuroimaging manusia yang mendukung tanggapan tumpul terhadap obat di kecanduan

substansi (Volkow et al., 2011). Namun, penelitian telah dilakukan dengan zat dan individu

kecanduan zat yang diketahui farmakologi langsung meningkatkan kadar dopamin otak sinaptik.

Yang penting, [11 C] raclopride studi PET pada manusia kecanduan heroin tidak

mengungkapkan sesuai menumpulkan dari neurotransmisi dopaminergik, meskipun obat yang

mampu merangsang euforia, sehingga mempertanyakan peran dopamin dalam kecanduan

substansi, setidaknya dengan zat yang efeknya tidak dimediasi terutama oleh dopamin (Daglish

et al., 2008)

There are also several other lines of evidence contradicting the RDS theory. For instance,

personality traits commonly associated with PG, such as impulsivity and antisociality (Steel &

Blaszczynski, 1998), are associated with increased mesolimbic dopamine responses to various

stimuli (Forbes et al., 2009; Buckholtz et al., 2010a; Buckholtz et al., 2010b). Moreover,

pathological gamblers have been shown to have increased midbrain reactions to near-misses

during slot machine gambling (Chase & Clark, 2010).

Ada juga beberapa jalur bukti lain yang bertentangan dengan teori RDS. Misalnya, ciri-ciri

kepribadian umumnya terkait dengan PG, seperti impulsif dan antisociality (Steel &

Blaszczynski, 1998), yang berhubungan dengan peningkatan respon dopamin mesolimbic

terhadap berbagai rangsangan (Forbes et al, 2009;.. Buckholtz et al, 2010a; Buckholtz et al.,

2010b). Selain itu, penjudi patologis telah terbukti telah meningkatkan reaksi otak tengah

mendekati-misses selama mesin slot judi (Chase & Clark, 2010)

As stated above, the results of this study confirm the previous reports that gambling with

monetary rewards releases dopamine in the mesolimbic system. However, despite the induced

hedonia and striatal dopamine release, there were no differences between pathological gamblers

and healthy volunteers in subjective feelings or dopamine release, and no difference in baseline

dopamine D2(D3) receptor binding either.

Sebagaimana dinyatakan di atas, hasil penelitian ini mengkonfirmasi laporan sebelumnya bahwa

perjudian dengan hadiah uang melepaskan dopamin dalam sistem mesolimbic. Namun, meskipun

hedonia diinduksi dan pelepasan dopamin striatal, tidak ada perbedaan antara penjudi patologis

dan relawan yang sehat dalam perasaan subjektif atau pelepasan dopamin, dan tidak ada

perbedaan dalam dopamin dasar D2 (D3) reseptor yang mengikat baik.

These results are in concordance with the previous study investigating pathological gamblers and

matched controls with [11C]raclopride displacement method during Iowa Gambling Task (IGT)

performance (Linnet et al., 2010; Linnet et al., 2011b). Furthermore, the addiction severity and

slot machine gambling preference in pathological gamblers were linked to a greater dopamine

release and experienced a “high” during rewarding gambling. Concordant findings have been

reported with Parkinson patients with PG (Steeves et al., 2009). These findings could be

interpreted to be in contradiction with RDS behind the neuropathology of PG.

However, fMRI studies have demonstrated contradictory results showing blunted ventral striatal

hemodynamic response to gambling in pathological gamblers (Reuter et al., 2005). The

difference in findings by Reuter et al. and this study might relate to the temporal scale difference

between fMRI (capable to separate individual events in gambling) and [11C]raclopride PET

displacement method (averaging the effects during the whole scanning time), or by the fact that,

in this study, an ecologically valid gambling stimulus was used, to which part of the gamblers

were specifically addicted to, instead of a task just mimicking gambling. It is intriguing to

speculate that if we had investigated only gamblers who prefer slot machines, would we have

also seen the enhanced dopaminergic responses to gambling as was seen in the study by Steeves

and colleagues investigating PD patients with PG (Steeves et al., 2009).

One possible explanation behind the contradicting results could be that conditioned stimulus

during gambling drives the overall dopaminergic response magnitude seen in PET imaging.

However, this doesn’t seem plausible since there were no differences between the groups in

gambling without wins either, despite differing responses in “urge to gamble”, but the dopamine

release was linked to slot machine preference in gamblers. It is important to acknowledge that

study I, like other previous studies, was done at a single time point, year(s) after the emergence

of gambling problems in pathological gamblers. Therefore, the results reflect only the present

state of dopamine signaling and causal relationships can only be speculated.

Hasil ini dalam konkordansi dengan penelitian sebelumnya menyelidiki penjudi patologis

dankontrol cocok dengan [11 C] metode raclopride perpindahan selama Iowa Perjudian Tugas

(IGT) kinerja (Linnet et al, 2010;.. Linnet et al, 2011b). Selanjutnya, preferensi perjudian

keparahan kecanduan dan mesin slot di penjudi patologis yang terkait dengan pelepasan dopamin

yang lebih besar dan mengalami "tinggi" selama perjudian bermanfaat. Temuan sesuai telah

dilaporkan dengan pasien Parkinson dengan PG (Steeves et al., 2009). Temuan ini bisa

ditafsirkan menjadi bertentangan dengan RDS balik neuropatologi dari PG.Namun, penelitian

fMRI telah menunjukkan hasil yang bertentangan menunjukkan respon ventral tumpul striatal

hemodinamik untuk perjudian di penjudi patologis (Reuter et al., 2005). Perbedaan temuan oleh

Reuter dkk. dan penelitian ini mungkin berhubungan dengan perbedaan skala temporal antara

fMRI (mampu peristiwa individu yang terpisah dalam perjudian) dan [11C] metode raclopride

PET perpindahan (rata-rata efek selama sepanjang waktu scanning), atau oleh fakta bahwa,

dalam penelitian ini, stimulus perjudian ekologis valid digunakan, yang bagian dari penjudi

secara khusus kecanduan, bukan tugas hanya meniru perjudian. Hal ini menarik untuk

berspekulasi bahwa jika kita telah menyelidiki hanya penjudi yang lebih memilih mesin slot,

akan kami juga telah melihat tanggapan dopaminergik ditingkatkan untuk perjudian seperti yang

terlihat dalam studi oleh Steevesdan rekan menyelidiki pasien PD dengan PG (Steeves et al.,

2009). Satu penjelasan yang mungkin di balik hasil BERTENTANGAN bisa jadi stimulus

terkondisi selama perjudian mendorong besarnya respon dopaminergik keseluruhan terlihat pada

pencitraan PET. Namun, ini tidak tampak masuk akal karena tidak ada perbedaan antara

kelompok dalam perjudian tanpa kemenangan baik, meskipun berbeda tanggapan dalam

"mendesak untuk berjudi", tetapi pelepasan dopamin dikaitkan dengan slot yang preferensi mesin

di penjudi. Hal ini penting untuk mengakui bahwa penelitian saya, seperti studi sebelumnya lain,

dilakukan pada titik waktu tunggal, tahun (s) setelah munculnya masalah perjudian di penjudi

patologis. Oleh karena itu, hasil hanya mencerminkan kondisi sekarang dopamin signaling dan

hubungan kausal hanya bisa berspekulasi.

6.1.1.4 Dopamine D2(D3) receptor availability in pathological gambling

Chronic substance abuse (e.g. cocaine, amphetamine, alcohol, heroine, nicotine) has been shown

to be associated with reduced striatal dopamine D2(D3) receptor (DRD2) binding (Volkow et al.,

1993; Hietala et al., 1994; Wang et al., 1997; Volkow et al., 2001; Fehr et al., 2008). It has been

speculated that the reduced D2 receptor availability would result from a reduced number of

receptors (Volkow et al., 2009).

It should be noted, that these studies have investigated individuals with addiction to substances

that via direct pharmacological mechanisms affect the brain dopamine neurotransmission and

therefore, it might be complicated to interpret these findings relate to addiction perse. If these

changes in neurotransmission were the main neurobiological mechanism of addiction disorders

in general, one would expect comparable findings in patients with behavioral addictions. Indeed,

there is some evidence of reduced striatal DRD2 binding in obesity (Haltia et al., 2007; Volkow

et al., 2008), but the previous study by Linnet et al. did not find altered DRD2 binding in

pathological gamblers, which is in line with the results of the present study (Linnet et al., 2011a).

However, obesity might not fulfill the criteria for behavioral addiction and thus might have

different background neurobiology than PG (Holden, 2010). Although the results of both of these

studies oppose the findings with substance addicted individuals, the number of subjects were

relatively low (study I included 12 and the study by Linnet and colleagues 16 to 18 pathological

gamblers), and thus the negative results are susceptible to type II errors. Therefore, larger studies

are still needed to verify whether there truly is no alteration of the baseline DRD2 availability in

PG and in other forms of behavioral addictions.

Ketersediaan reseptor dopamin D2 6.1.1.4 (D3) di judi patologisPenyalahgunaan zat kronis

(misalnya kokain, amfetamin, alkohol, pahlawan, nikotin) telah terbukti berhubungan dengan

penurunan dopamin striatal D2 (D3) reseptor (DRD2) mengikat (Volkow et al, 1993;. Hietala et

al, 1994;. Wang et al, 1997;.. Volkow et al, 2001; Fehr et al, 2008).. Telah berspekulasi bahwa

ketersediaan reseptor D2 berkurang akan dihasilkan dari berkurangnya jumlah reseptor (Volkow

et al., 2009).Perlu dicatat, bahwa studi ini telah diselidiki individu dengan kecanduan zat yang

melalui mekanisme farmakologi langsung mempengaruhi neurotransmisi dopamin otak dan oleh

karena itu, mungkin rumit untuk menafsirkan temuan ini berhubungan dengan kecanduan perse.

Jika perubahan ini di neurotransmisi adalah mekanisme neurobiologis utama gangguan

kecanduan pada umumnya, orang akan berharap temuan sebanding pada pasien dengan

kecanduan perilaku. Memang, ada beberapa bukti dari penurunan striatal DRD2 mengikat dalam

obesitas (Haltia et al, 2007;.. Volkow et al, 2008), tetapi penelitian sebelumnya oleh Linnet dkk.

tidak menemukan diubah DRD2 mengikat dalam penjudi patologis, yang sejalan dengan hasil

penelitian ini (Linnet et al., 2011a).Namun, obesitas mungkin tidak memenuhi kriteria untuk

kecanduan perilaku dan dengan demikian mungkin memiliki latar belakang neurobiologi yang

berbeda dari PG (Holden, 2010). Meskipun hasil dari kedua studi ini menentang temuan dengan

substansi individu kecanduan, jumlah mata pelajaran yang relatif rendah (studi saya termasuk 12

dan studi oleh Linnet dan rekan 16 sampai 18 penjudi patologis), dan dengan demikian hasil

negatif yang rentan terhadap ketik II kesalahan. Oleh karena itu, penelitian yang lebih besar

masih diperlukan untuk memverifikasi apakah ada yang benar-benar ada perubahan ketersediaan

DRD2 dasar diPG dan dalam bentuk lain dari kecanduan perilaku.

6.2 Brain structure in pathological gambling

6.2.1 Brain white matter abnormality in pathological gambling

The diffusion tensor imaging (DTI) analysis (Study II) revealed extensive lower brain white

matter integrity involving multiple tracts in pathological gamblers compared to healthy

volunteers. The results demonstrate widespread white matter abnormality in an addiction

disorder in the absence of toxic effects of substances of abuse, although the changes are

comparable to white matter abnormalities in substance-addicted individuals.

However, there were no differences in brain regional gray or white matter volumes between the

groups. The discrepancy in the results of the two methods could reflect differences in sensitivity

of the methods and/or differences in underlying biological aspects these methods are able to

detect (microscopic axonal diffusion with DTI and brain tissue volume changes with VBM). It is

also possible that the abnormalities in axonal diffusion precede volumetric changes, and thus,

would have been seen in more severe cases or longer durations of PG. The more severe

disordered gambling is associated with more comorbid psychiatric disorders (Crockford & el-

Guebaly, 1998), and would have led to exclusion from this study, and subsequently to the

underestimation of the volumetric changes. In addition, the relatively small sample size for a

volumetric study may have led to false negative findings in brain regional volumetry.

In parallel with the negative VBM results of this study, a previous study investigating PD

patients with (n=33) and without (n=24) ICDs did not find group differences in focal gray matter

volumes (Biundo et al., 2011). However, Biundo et al. did not investigate brain white matter

integrity in their patients. It should also be noted that PD ICDs might constitute a distinct entity

and have a different neurobiological background compared to the behavioral addictions in the

general population. Also, alterations in the brain structure might be more difficult to detect in

older individuals suffering from a neurological disorder, because of the variation in focal brain

structures due to age- or disease-related confounding effects to the possible structural changes

associated with the addiction disorder.

Based on the results of this study, several white matter tracts were affected in PG, including

tracts with limbic connections (the cingulum, the anterior thalamic radiation, the

uncinate/inferior longitudinal fascicle), the superior longitudinal fascicle, the inferior fronto-

occipital fascicle, and the anterior limb of internal capsule; which have all been shown to be

affected also by substance abuse at least in one study (Lim et al., 2008; Liu et al., 2008; Ashtari

et al., 2009; Jacobus et al., 2009; Pfefferbaum et al., 2009; Yeh are convincing number of studies

demonstrating altered diffusion in corpus callosum in substance addictions (Moeller et al.,

2007a; Lim et al., 2008; Yeh et al., 2009; Lane et al., 2010; Xu et al., 2010) and in PG (Yip et

al., 2011).

Yip et al. limited their investigations to only the subsections of the corpus callosum finding low

white matter integrity in the genu, whereas the present study demonstrated extensive low white

matter integrity also including the genu, the body and the splenium of corpus callosum.

Together, these results suggest that the white matter disruption might be related to addiction and

not to direct toxic effects of the pharmacological substances. In addition, the integrity of the

uncinate/inferior longitudinal fascicle has been shown to modify the ventral striatal

hemodynamical response of loss versus gain in a gambling task in healthy volunteers (Camara et

al., 2010), and further, altered hemodynamical reward processing has been demonstrated in PG

(Reuter et al., 2005).

The results of study II combined with the results by earlier studies suggest a role for

dysfunctional white matter with limbic connections in the neurobiology of PG. It is not clear if

the white matter changes predispose individuals for developing addiction disorders or whether

the changes are a consequence of the disorder. This was a crosssectional study in a single time-

point, and thus, it is impossible to determine when the white matter abnormality has developed.

Only part of the previous studies have found correlations (but mostly rather modest) with white

matter integrity abnormality and addiction severity or duration (Chung et al., 2007; Lim et al.,

2008; Liu et al., 2008; Alicata et al., 2009; Pfefferbaum et al., 2009; Yeh et al., 2009; Xu et al.,

2010) and there are several negative results (Moeller et al., 2007a; Moeller et al., 2007b; de Win

et al., 2008; Salo et al., 2009; Lane et al., 2010; Martín-Santos et al., 2010).

In study II, there was no correlation between gambling-related parameters and white matter

integrity impairment, which could be interpreted to suggest premorbid white matter abnormality.

However, the lack of correlations in this, or previous studies could also be false negatives due to

small sample sizes, heterogeneity of the studied samples, and/or insensitivity of the methods.

Sumber Annals

Episodes of gambling are linked to activation of the sympathetic nervous system and cortisol

release, with associated (nongenomic) changes, and gambling disorder is also reasonably

comorbidwith substance use disorders. Nevertheless, it seems reasonable to suppose that the

actively damaging effects of addictive drugs should be absent or at least minimal in individuals

with gambling disorder without such comorbidities. In the most extreme version of this

argument, gambling disorder may constitute a prototypical addiction and offer a means of

studying the addictive process in brains that are not disrupted by exogenous drug effects.

Episode perjudian terkait dengan aktivasi sistem saraf simpatik dan kortisol rilis, dengan terkait

(nongenomic) perubahan, dan gangguan perjudian juga cukup komorbiditas dengan gangguan

penggunaan zat. Namun demikian, tampaknya masuk akal untuk menduga bahwa efek aktif

merusak obat adiktif harus absen atau setidaknya minimal pada individu dengan gangguan

perjudian tanpa komorbiditas seperti. Dalam versi paling ekstrim dari argumen ini, gangguan

perjudian mungkin merupakan kecanduan prototipikal dan menawarkan cara mempelajari proses

adiktif dalam otak yang tidak terganggu oleh efek obat eksogen.

Using functional neuroimaging, other work has examined the comparison with nicotine

dependence, a drug addiction where overt neurotoxicity might be expected to be negligible.

Individuals with gambling disorder and nicotine dependence showed reduced recruitment of the

ventrolateral PFC by choice feedback (both gains and losses) on a reversal learning task and

reduced activation of the dorsomedial PFC during a response inhibition task. Executive planning

tasks dependent on the dorsolateral PFC were spared in both groups.

Menggunakan neuroimaging fungsional, pekerjaan lain telah meneliti perbandingan dengan

ketergantungan nikotin, kecanduan obat di mana neurotoksisitas yang jelas mungkin diharapkan

akan diabaikan. Individu dengan gangguan perjudian dan ketergantungan nikotin menunjukkan

penurunan rekrutmen ventrolateral PFC dengan umpan balik pilihan (baik keuntungan dan

kerugian) pada pembalikan tugas dan aktivasi berkurang dari dorsomedial PFC belajar selama

tugas penghambatan respon. Tugas perencanaan eksekutif tergantung pada dorsolateral PFC

selamat pada kedua kelompok.

The pattern that emerges from these studies is one of impulsivity as a shared marker that is

therefore proposed to reflect the predisposition to develop a range of addictive disorders,

including gambling disorder but also conceivably other non-drug-related risky behaviors, such as

risky sexual behaviors. This conclusion is substantiated by several other lines of evidence.

Taking an endophenotype approach, Ersche et al. have compared cognitive and imaging markers

in stimulant users and their unaffected first-degree relatives, showing a shared elevation of

impulsivity underpinned by white matter integrity of the lateral PFC; notably, the related trait of

sensation seeking was only present in the affected probands and may thus be a determinant of

initial recreational engagement with drugs.

Pola yang muncul dari studi ini adalah salah satu dari impulsivitas sebagai penanda bersama

yang oleh karena itu diusulkan untuk mencerminkan kecenderungan untuk mengembangkan

berbagai gangguan adiktif, termasuk gangguan perjudian tetapi juga perilaku non-obat terkait

dibayangkan lainnya berisiko, seperti berisiko seksual perilaku. Kesimpulan ini diperkuat oleh

beberapa jalur lain bukti. Mengambil pendekatan endophenotype, Ersche dkk. telah

membandingkan penanda kognitif dan pencitraan pada pengguna stimulan dan tidak terpengaruh

kerabat tingkat pertama mereka, menunjukkan elevasi bersama impulsif didukung oleh integritas

materi putih dari lateral PFC; terutama, sifat terkait mencari sensasi hanya hadir dalam probands

terkena dan dengan demikian dapat menjadi penentu keterlibatan rekreasi awal dengan obat.

Two initial studies usingwhole-brain voxel-based morphometry in patients with gambling

disorder failed to identify any regions showing significant gray matter change. By contrast,

widespread reductions were observed in a matched group of heavy drinkers. However, with an a

priori focus on the striatum and the PFC, a later study in gambling disorder detected increased

gray matter volumes in both regions, and similar hypertrophy has been described as a marker of

regular video game play in adolescents. Changes in white matter tracts and resting-state

connectivity have also been reported in gambling disorder.

Dua penelitian awal menggunakan seluruh otak morfometri berbasis voxel pada pasien dengan

gangguan perjudian gagal untuk mengidentifikasi daerah yang menunjukkan perubahan

signifikan materi abu-abu. Sebaliknya, pengurangan luas diamati dalam kelompok cocok

peminum berat. Namun, dengan apriori fokus pada striatum dan PFC, sebuah penelitian di

kemudian gangguan perjudian terdeteksi meningkat volume materi abu-abu di kedua wilayah,

dan hipertrofi serupa telah digambarkan sebagai penanda bermain video game biasa pada remaja.

Perubahan dalam saluran materi putih dan konektivitas istirahat-negara juga telah dilaporkan di

judi gangguan

A reasonable conclusion at the current time is that signs of structural brain changes can be

detected in gambling disorder, but these changes appear minor in comparison to most substance

addictions. What is needed next are longitudinal studies that chart the changes within a group of

gamblers over time, particularly around the time of their transition into disordered and

compulsive use.

Kesimpulan yang wajar pada saat ini adalah bahwa tanda-tanda perubahan struktural otak dapat

dideteksi dalam gangguan perjudian, tetapi perubahan ini muncul kecil dibandingkan dengan

kebanyakan kecanduan substansi. Apa yang dibutuhkan selanjutnya adalah studi longitudinal

yang memetakan perubahan dalam kelompok penjudi dari waktu ke waktu, terutama di sekitar

waktu transisi mereka ke gangguan dan penggunaan kompulsif.

Functional magnetic resonance imaging (fMRI) studies using reward processing and decision-

making tasks describe consistent abnormalities across the key nodes in this circuit in gambling

disorder—the striatum, medial PFC, amygdala, and insula. However, some experiments point to

hypoactivity within this system, while others indicate hyperactivity of the same regions. These

two sets of data support contrasting theoretical positions (reward deficiency versus sensitization/

incentive salience accounts, respectively).

Fungsional magnetic resonance imaging (fMRI) studi menggunakan pengolahan reward dan

tugas pengambilan keputusan menggambarkan kelainan konsisten di node kunci dalam sirkuit ini

dalam gangguan-perjudian striatum, medial PFC, amigdala, dan insula. Namun, beberapa

percobaan menunjukkan hiperaktif dalam sistem ini, sementara yang lain menunjukkan

hiperaktivitas daerah yang sama. Kedua set dukungan data yang kontras posisi teoritis (defisiensi

reward terhadap rekening arti-penting sensitisasi / insentif, masing-masing).

Although some of these discrepancies may be dueto technical issues in resolving certain brain

regions and the design challenges in temporally segregating selection, anticipation, and outcome

periods within a trial, two exemplary recent studies provide a different perspective. Sescousse et

al. modified the classic monetary incentive delay task to compare brain activity during both the

anticipation and receipt of monetary rewards and sexual rewards (i.e., erotic images). Behavioral

data (response latencies) indicated an interaction effect such that males with gambling disorder

(n = 18) were more motivated by financial reward but less motivated by the erotic rewards. The

same interaction was also expressed in the ventral striatum, which showed hypoactivity to the

erotic cues.

Meskipun beberapa perbedaan ini mungkin dueto masalah teknis dalam menyelesaikan daerah

otak tertentu dan tantangan desain di temporal memisahkan seleksi, antisipasi, dan periode hasil

dalam sidang, dua studi terbaru teladan memberikan perspektif yang berbeda. Sescousse dkk.

dimodifikasi klasik tugas delay insentif moneter untuk membandingkan aktivitas otak selama

kedua antisipasi dan penerimaan hadiah uang dan imbalan seksual (yaitu, gambar erotis). Data

perilaku (latency respon) menunjukkan efek interaksi tersebut bahwa laki-laki dengan gangguan

perjudian (n = 18) yang lebih termotivasi oleh imbalan keuangan tetapi kurang termotivasi oleh

imbalan erotis. Interaksi yang sama juga dinyatakan dalam striatum ventral, yang menunjukkan

hypoactivity ke isyarat erotis.

The orbitofrontal cortex in the patients with gambling disorder showed a stronger response to

the monetary outcomes, and also appeared to process these financial rewards as if they were

primary rewards (money is a highly ingrained conditioned reinforcer). The important message

from this paper is that addictionsmay be associated with an imbalance between different reward

types,41 and that the compatibility of the task rewardwith the abused commoditywill critically

determine changes in the brain reward system

Korteks orbitofrontal pada pasien dengan gangguan perjudian menunjukkan respon yang lebih

kuat dengan hasil moneter, dan juga muncul untuk mengolah imbalan keuangan seolah-olah

mereka imbalan primer (uang adalah sangat mendarah daging penguat AC). Pesan penting dari

tulisan ini adalah bahwa kecanduan mungkin terkait dengan ketidakseimbangan antara jenis

hadiah yang berbeda, 41 dan kompatibilitas pahala tugas dengan komoditas disalahgunakan kritis

akan menentukan perubahan sistem reward ota

Of course, fMRI provides only an indirect measure of dopamine transmission, and other work

has used positron emission tomography (PET) with dopamine radioligands like raclopride.

Reduced striatal dopamine D2 receptor binding is a robust effect in individuals with drug

addictions; this has been observed across stimulant, heroin, alcohol, and nicotine dependence, as

well as in preclinical models of high impulsivity.

Tentu saja, fMRI hanya menyediakan ukuran tidak langsung dari transmisi dopamin, dan

pekerjaan lain telah menggunakan positron emission tomography (PET) dengan radioligands

dopamin seperti raclopride. Mengurangi dopamin striatal reseptor D2 mengikat adalah efek yang

kuat pada individu dengan kecanduan narkoba; ini telah diamati di seluruh stimulan, heroin,

alkohol, dan ketergantungan nikotin, serta dalam model praklinis impulsif tinggi.

Thus, there was a strong prediction that individuals with gambling disorder should display the

same effect. Surprisingly, four independent PET studies to date have failed to detect any group

differences in baseline (i.e., resting) dopamine D2 receptor availability in gambling disorder,

although individual differences were seen as functions of impulsivity markers and symptom

severity (Fig. 1)

Dengan demikian, ada prediksi yang kuat bahwa individu dengan gangguan perjudian harus

menampilkan efek yang sama. Anehnya, empat studi PET independen untuk saat ini telah gagal

untuk mendeteksi perbedaan kelompok di awal (yaitu, istirahat) ketersediaan reseptor D2

dopamin dalam gangguan perjudian, meskipun perbedaan individu dilihat sebagai fungsi

penanda impulsif dan keparahan gejala (Gambar 1)

Salah satu wilayah yang sangat sensitif terhadap efek rewards adalah insula anterior. Wilayah ini

menunjukkan aktivitas yang tumpang tindih untuk menang dan nyaris kalah: respon insula untuk

kalah berkorelasi dengan kerentanan sifat distorsi perjudian, dan dalam studi

magnetoencephalography, sinyal membentang dari korteks orbitofrontal menuju insula dikaitkan

dengan keparahan gangguan perjudian. Data pada gambar dibawah ini memberikan bukti untuk

keterlibatan penyebab insula dalam dua efek kognitif klasik dalam perjudian, dan menghasilkan

prediksi bahwa pasien dengan gangguan perjudian akan menunjukkan keterlibatan wilayah

insula, sehingga membuat mereka lebih rentan terhadap kognisi ini.

The classic neuropsychological model of addictions by Jentsch and Taylor highlights the balance

between a subcortical accelerator system (comprising the nucleus accumbens and amygdala) and

a prefrontal cortical braking system. This has much in common with classic dual-process

accounts of decision making.115 In the transition into drug addiction, the reflexive system

becomes sensitized through learning processes, while the prefrontal brake is concurrently eroded

by the damaging effects of the drugs. Later extensions of this model usefully separate the

substrates for initial intoxication and subsequent craving, and point out the involvement of the

hippocampus in holding drugrelatedmemories.

Model neuropsikologi klasik adiksi oleh Jentsch dan Taylor menyoroti keseimbangan antara

sistem akselerator subkortikal (terdiri dari nucleus accumbens dan amigdala) dan sistem kortikal

prefrontal. Ini memiliki banyak kesamaan dengan proses pengambilan keputusan.

insula merupakan pintu gerbang antara sistem reward subkortikal dan sistem prefrontal yang

bertanggung jawab untuk pengambilan keputusan dan kontrol penghambatan (inhibisi)

Research into the syndrome has been somewhat hampered by a lack of consensus on its

assessment, with different groups modifying drug-use or problem-gambling screens, focusing on

general internet use or video game play specifically, and employing different thresholds for a

diagnosis.

Adiksi game internet

Kandidat yang paling mungkin untuk bergabung dengan gangguan judi sebagai kecanduan atau

adiksi perilaku saat ini adalah gangguan game internet. Individu yang terkena menghabiskan

beberapa jam setiap hari bermain video game, tipikal mereka biasanya bermain multiplayer

online role-playing games (MMORPG) seperti World of Warcraft-dengan konsekuensi negatif

yang didirikan dalam hal kinerja akademik dan fungsi social.

Perkiraan prevalensi bervariasi, namun sebuah laporan baru-baru ini telah membentuk konsensus

instrumen internasional sembilan item yang diharapkan akan memperbaiki masalah ini. Data

kognitif dan neurobiologis pada game internet tumbuh pada tingkat yang cepat. Sebuah studi

raclopride-PET klasik terdeteksi pelepasan dopamin striatal, dan pengurangan pengikatan striatal

D2 yang telah dijelaskan dalam sebuah penelitian kecil pada laki-laki sedang dirawat karena

kecanduan internet

Studi kognitif dan MRI fungsional telah menemukan bukti isyarat reaktivitas, dengan gambaran

perubahan sinyal di medial PFC. Sindrom ini jelas terkait dengan impulsif sifat, dan gangguan

kognitif, tindakan impulsif, mirip dengan gangguan perjudian. Bermain video game juga

berhubungan dengan gairah fisiologis substansial, mirip dengan perjudian.

The Redish et al. model for gambling addiction can be extended in a straight forward manner

to video game play. Actions within a video game generate bivalent outcomes, and it is self-

evident that humans will work to achieve symbolic gains and avoid symbolic losses, in much the

same way as for monetary outcomes. The game environment is uncertain, with rewards delivered

on an unpredictable variable-ratio schedule of reinforcement, which is identical to gambling. In

fact, the structural characteristics of video games lend themselves to a very similar analysis to

gambling games.

Menurut Redish, dkk adiksi judi memiliki kesamaan dengan adiksi game internet. Tindakan

dalam game internet menghasilkan hasil bivalen yakni keuntungan simbolis dan menghindari

kerugian simbolis, dalam akan melakukan banyak cara untuk mendapatkan keuntungan hasil.

One is the avatar: players play as a consistent character who gradually develops within the game

environment across many sessions. The second is the multiplayer component, which means that

the game continues while any individual player is offline, which could foster checking behaviors

or counterfactual thoughts.As such, internet gaming is a behavior that lends itself to evaluation in

terms of discrete psychological properties and comparisons with the cognitive effects of

gambling. While the field is too premature to allow any strong conclusions, this is set to be a

fruitful line of inquiry.

Naltrexone

Naltrexone, a μ-opioid receptor antagonist, is effective in the treatment of a range of impulsive

behaviours/disorders such as kleptomania, self injurious behaviours and borderline personality

disorder. It is also useful in reducing high-urge and craving states in people dependent on alcohol

and heroin. Naltrexone’s predominant mechanism of action is via the modulation of the

mesolimbic dopamine pathway involved in reward and reinforcement. Hence, it is postulated that

naltrexone could be used to reduce the rewarding and reinforcing properties of gambling

behaviours and thus decrease the urge to gamble.

Kim & Grant (2001a) treated 17 individuals with DSM–IV diagnosis of pathological gambling

for 6 weeks with naltrexone and found significant decreases in gambling thoughts, urges and

behaviour. The average dose of naltrexone in this study was 157 mg/day. In a much larger study

(83 participants) they noted that 75% of gamblers treated with naltrexone improved significantly

on a range of outcome measures (Kim & Grant, 2001b).

The mean dose of naltrexone was again high (188 mg/day) and only half the sample completed

the study. Many participants reported significant adverse effects and many had elevated liver

function tests, a particular concern with high-dose naltrexone treatment.

Mood stabilisers

Some researchers have conceptualised pathological gambling as a bipolar-spectrum disorder,

because of shared characteristics such as impulsivity. As the impulsive behaviours in mania are

treated effectively with mood stabilisers, it has been suggested that these may also be effective in

the treatment of pathological gambling.

Case reports have shown lithium and carbamazepine to be effective in the treatment of the

disorder. Pallanti et al (2002) evaluated the efficacy of lithium and valproate in a randomised

singleblind study. In all, 15 people on lithium and 16 on valproate completed the 14-week trial.

Both groups improved significantly over the trial period (61% of those taking lithium and 68%

of those taking valproate, with no significant differences in improvement between groups). A

more recent study of sustained-release lithium carbonate treatment of a sample of 40

pathological gamblers with bipolar affective disorder found significant improvements in

gambling and affective instability in the treatment group compared with placebo

(Hollander et al, 2005)

Psychological interventions

Behavioural treatments

Behavioural theorists view gambling as a learned maladaptive behaviour that can be unlearned

through behavioural treatments derived from both classical and operant learning theories. Much

of the early work (in the 1960s) on evaluating behavioural treatments for pathological gambling

focused on aversion therapy, which is no longer used. Barker & Miller (1966) were the first to

report the successful use of electrical aversion therapy in a pathological gambler. Seager (1970)

found that 5 out of 14 gamblers were abstinent for 1–3 years after aversion treatment. Koller

(1972) reported significant improvement in gambling behaviour in 8 out of 12 individuals given

aversion treatment. However, some participants in the study also received other interventions,

such as attending

Gamblers Anonymous.

Other behavioural treatments that have been used successfully include imaginal desensitisation,

imaginal relaxation, behavioural monitoring, covert sensitisation and spousal contingency

contracting. McConaghy et al (1983) compared aversion therapy and imaginal desensitisation in

20 pathological gamblers and demonstrated both treatments to be effective. They also noted that

the imaginal desensitisation group had significantly lower levels of state and trait anxiety, and

fewer gambling behaviours and urges at 1-year follow-up, compared with the aversion therapy

group. In a much larger study (n = 120), McConaghy et al (1991) compared four behavioural

treatments – aversion therapy, imaginal desensitisation, imaginal relaxation and in vivo

desensitisation – and found patients receiving imaginal desensitisation to have the best outcome.

This study had a relatively longterm follow-up (5.5 years), but the drop-out rate was

very high (nearly 50%). Although a range of behavioural treatments have been found to be

effective in the treatment of pathological gambling, these days behavioural therapy is more often

administered in conjunction with cognitive treatment, as a cognitive–behavioural treatment

package.

Cognitive treatments

Cognitive errors such as gamblers’ beliefs about randomness and chance, and the false notion

that they can control and predict outcome, play a key role in the development and maintenance

of gambling. Cognitive therapy attempts to correct these cognitive errors, which reduces the

motivation to gamble.

Ladouceur et al (2001) randomly allocated pathological gamblers to either a cognitive therapy

group or a waiting-list control group and demonstrated that 86% of treatment completers no

longer fulfilled the criteria for pathological gambling. They also found that after treatment,

gamblers had increased perception of control over the problem and better self-efficacy. These

positive effects were maintained at 1-year follow-up. Cognitive therapy has also been found to

be effective when delivered in a group format to pathological gamblers.

As already mentioned, in clinical practice cognitive therapy is often administered as part of a

cognitive– behavioural package.

Cognitive–behavioural treatments

These treatments combine cognitive and behavioural aspects and attempt to alter gamblers’

cognitions and behaviours. Sharpe & Tarrier (1993) developed a cognitive–behavioural approach

that involves identifying high-risk situations (through functional analysis) or internal and

external triggers that lead to urges to gamble and then working on effective coping strategies.

Other treatments often incorporated in cognitive–behavioural packages include training in

assertiveness, problem-solving, social skills, relapse prevention and relaxation. Specific

cognitive–behavioural treatment models have been developed and evaluated by Petry (2002) and

Ladouceur et al (2002). Sylvain et al (1997) evaluated the efficacy of cognitive–behavioural

treatment in a sample of 29 male pathological gamblers. The treatment incorporated cognitive

restructuring, problem-solving training, social skills training and relapse prevention.

Perawatan kognitif-perilaku

Perawatan ini menggabungkan kognitif dan aspek perilaku dan upaya untuk mengubah kognisi

dan perilaku penjudi '. Sharpe & Tarrier (1993) mengembangkan pendekatan kognitif-perilaku

yang melibatkan identifikasi situasi berisiko tinggi (melalui analisis fungsional) atau pemicu

internal dan eksternal yang menyebabkan dorongan untuk berjudi dan kemudian bekerja pada

strategi yang efektif. Pengobatan lain sering dimasukkan dalam paket kognitif-perilaku meliputi

pelatihan di ketegasan, pemecahan masalah, keterampilan sosial, pencegahan kambuh dan

relaksasi. Model pengobatan khusus kognitif-perilaku telah dikembangkan dan dievaluasi oleh

Petry (2002) dan Ladouceur et al (2002). Sylvain et al (1997) mengevaluasi efektivitas

pengobatan kognitif-perilaku dalam sampel dari 29 penjudi patologis laki-laki. Pengobatan

dimasukkan restrukturisasi kognitif, pelatihan pemecahan masalah, pelatihan keterampilan sosial

dan pencegahan kambu

Results indicated statistically and clinically significant improvement on many outcome measures

and the gains were maintained at 1-year follow-up. In a randomised study, Echeburura et al

(1996) compared four treatments: individual stimulus control and in vivo exposure; group

cognitive restructuring; a combination of the two; and a waiting-list control. At 12-month follow-

up, the rates

Gamblers Anonymous

Gamblers Anonymous is a self-help group modeled on Alcoholics Anonymous. It was founded

in 1957 in California and is currently one of the most popular and extensively accessed treatment

models for pathological gambling. Gamblers Anonymous uses a medical model of pathological

gambling and views total abstinence as the treatment goal. The ‘12-step recovery program’ forms

the cornerstone of this treatment and gamblers are assisted in working through steps 1 to 12 by

regular attendance at and active participation in group meetings.

It is surprising that despite its popularity, very little research evidence exists to support the

efficacy of Gamblers Anonymous. In a study of 232 attendees of Gamblers Anonymous groups,

Stewart & Brown (1988) found abstinence rates of 7.5% at 1-year follow-up. They also found

that nearly a quarter of new members did not attend a second meeting and nearly three-quarters

attended fewer than 10 meetings.

Generally, despite its high rate of attrition, those who regularly attend Gamblers Anonymous

groups benefit from this intervention. From a clinical perspective it is more pragmatic to offer

Gamblers Anonymous in conjunction with other treatments.