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[[Image:Slot machine.jpg|right|thumb|A slot machine, commonly used for gambling.]]
[[Image:Martin Frobisher by Ketel.jpg|right|thumb|200px|Sir Martin Frobisher by [[Cornelis Ketel]], c. 1577]]

'''Dopamine dysregulation syndrome''' (DDS), sometimes also called '''hedonistic homeostatic dysregulation in Parkinson disease''', is a dysfunction of the [[reward system]] in subjects with [[Parkinson disease]] (PD) due to a long exposure to [[dopamine]] replacement therapy (DRT). It is characterized by self-control problems such as addiction to medication, [[Problem gambling|gambling]], or [[hypersexuality]].<ref name="pmid17988927">{{cite journal
|author=Merims D, Giladi N
|title=Dopamine dysregulation syndrome, addiction and behavioral changes in Parkinson's disease
|journal=Parkinsonism Relat. Disord.
|volume=14
|issue=4
|pages=273–80
|year=2008
|pmid=17988927
|doi=10.1016/j.parkreldis.2007.09.007
|url=
}}</ref>

==Causes==
[[File:Dopamine-3d-CPK.png|right|thumb|Three-dimensional model of the structure of a dopamine molecule. Dopamine is at the origin of DDS.]]

PD is a common [[neurology|neurological disorder]] characterized by a degeneration of dopamine [[neuron]]s in the [[substantia nigra]] and a loss of dopamine in the [[putamen]]. It is described as a motor disease, but it also produces cognitive and behavioral symptoms. The most common treatment is dopamine replacement therapy, which consists in the administration of levodopa ([[L-Dopa]]) to patients. L-Dopa is well known to improve motor symptoms but its effects in cognitive and behavioral symptoms are more complex.<ref name="pmid15935475">{{cite journal
|author=Cools R
|title=Dopaminergic modulation of cognitive function-implications for L-DOPA treatment in Parkinson's disease
|journal=Neurosci Biobehav Rev
|volume=30
|issue=1
|pages=1–23
|year=2006
|pmid=15935475
|doi=10.1016/j.neubiorev.2005.03.024
|url=
}}</ref> Dopamine has been related to the normal learning of stimuli with behavioral and motivational significance, [[attention]], and most importantly the [[reward system]].<ref name="pmid15247533">{{cite journal
|author=Evans AH, Lees AJ
|title=Dopamine dysregulation syndrome in Parkinson's disease
|journal=Curr. Opin. Neurol.
|volume=17
|issue=4
|pages=393–8
|year=2004
|month=August
|pmid=15247533
|doi=
|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1350-7540&volume=17&issue=4&spage=393
}}</ref> In accordance with the role of dopamine in reward processing, [[addiction|addictive]] [[drug]]s stimulate dopamine release.<ref name="pmid15247533"/>
Although the exact mechanism has yet to be elucidated; the role of dopamine in the reward system and addiction has been proposed as the origin of DDS.<ref name="pmid15247533"/> Models of addiction have been used to explain how dopamine replacement therapy produces DDS.<ref name="pmid14505581">{{cite journal
|author=Lawrence AD, Evans AH, Lees AJ
|title=Compulsive use of dopamine replacement therapy in Parkinson's disease: reward systems gone awry?
|journal=Lancet Neurol
|volume=2
|issue=10
|pages=595–604
|year=2003
|month=October
|pmid=14505581
|doi=
|url=http://linkinghub.elsevier.com/retrieve/pii/S1474442203005295
}}</ref>
One of this models of addiction proposes that over the usage course of a drug there is an [[habituation]] to the rewarding that it produces at the initial stages. This habituation is thought to be dopamine mediated. With a long-time administration of L-dopa the reward system gets used to it and needs higher quantities. As the user increases its drug intake there is a destruction of dopaminergic receptors in the [[striatum]] which acts in addition to an impairment in [[Executive functions|goal-direction mental functions]] to produce an enhancement of [[sensitization]] to dopamine therapy. The behavioral and mood symptoms of the syndrome are produced by the dopamine [[Drug overdose|overdose]].<ref name="pmid15247533"/>

==Signs and symptoms==
[[File:Punding.jpg|right|thumb|Punding, a possible symptom of DDS, is the repetition of complex motor behaviors such as collecting or arranging objects.]]
The most common symptom is craving for dopaminergic medication. However other behavioral symptoms can appear independently of craving or co-occur with it.<ref name="pmid14505581"/> Craving is an intense impulse of the subject to obtain medication even in the absence of symptoms that indicate its intake.<ref name="pmid14505581"/> To fulfill this need the person will self-administer extra doses. When self administration is not possible aggressive outbursts or the use of strategies such as symptom simulation or bribery to access additional medication can also appear.<ref name="pmid14505581"/>

[[Hypomania]], manifesting with feelings of [[Euphoria (emotion)|euphoria]], omnipotence, or grandiosity, are prone to appear in those moments when medication effects are maximum; while [[dysphoria]], characterized by sadness, psychomotor slowing, [[fatigue (medical)|fatigue]] or [[apathy]]; are typical with DRT withdrawal.<ref name="pmid14505581"/> Different [[impulse control disorder]]s have been described including [[Problem gambling|gambling]], [[Oniomania|compulsive shopping]], [[eating disorder]]s and [[hypersexuality]].<ref name="pmid14505581"/> Behavioral disturbances; most commonly [[aggression|aggressive]] tendencies are the norm. [[Psychosis]] is also common.<ref name="pmid14505581"/> Other possible symptom is [[punding]], repetition of complex motor behaviors such as collecting or arranging objects.<ref name="pmid14505581"/>

==Diagnosis==
Diagnosis of the syndrome is clinical since there are no laboratory tests to confirm it. For diagnosis a person with documented responsiveness to medication has to increase medication intake beyond dosage needed to relieve his parkinsonian symptoms in a pathological addiction-like pattern. A current mood disorder ([[Major depressive disorder|depression]], [[anxiety]], hypomanic state or euphoria), behavioral disorder (excessive gambling, shopping or sexual tendency, aggression, or social isolation) or an altered perception about the effect of medication also have to be present.<ref name="pmid15390130">{{cite journal
|author=Pezzella FR, Colosimo C, Vanacore N, ''et al''
|title=Prevalence and clinical features of hedonistic homeostatic dysregulation in Parkinson's disease
|journal=Mov. Disord.
|volume=20
|issue=1
|pages=77–81
|year=2005
|month=January
|pmid=15390130
|doi=10.1002/mds.20288
|url=
}}</ref> A [[questionnaire]] on the typical simptomatology of DDS has also been developed and can help in the diagnosis proccess.<ref name="pmid14598089">{{cite journal
|author=Pezzella FR, Di Rezze S, Chianese M, ''et al''
|title=Hedonistic homeostatic dysregulation in Parkinson's disease: a short screening questionnaire
|journal=Neurol. Sci.
|volume=24
|issue=3
|pages=205–6
|year=2003
|month=October
|pmid=14598089
|doi=10.1007/s10072-003-0132-0
|url=
}}</ref>

==Prevention==
The main prevention measure proposed is the prescription of the minimum effective dopamine dose for individuals at risk.<ref name="pmid15247533"/> The minimization of the use of short duration formulations of L-Dopa can also prevent the syndrome.<ref name="pmid15247533"/>

==Management==
First choice management measure consists in the enforcement of a L-Dopa dosage reduction; usually responding many of the syndrome features to this action.<ref name="pmid15247533"/> Cessation of [[dopamine agonist]]s therapy may also be of use.<ref name="pmid18068992">{{cite journal
|author=Kimber TE, Thompson PD, Kiley MA
|title=Resolution of dopamine dysregulation syndrome following cessation of dopamine agonist therapy in Parkinson's disease
|journal=J Clin Neurosci
|volume=15
|issue=2
|pages=205–8
|year=2008
|month=February
|pmid=18068992
|doi=10.1016/j.jocn.2006.04.019
|url=
}}</ref> Some behavioral characteristics may respond to [[psychotherapy]]; and [[social support]] is important to control [[risk factor]]s. In some cases [[Antipsychotic|antipsychotic drugs]] may also be of use in the presence of psychosis, aggression, gambling or hypersexuality.<ref name="pmid15247533"/>

==Epidemiology==
DDS is not common among PD patients. Prevalence may be around 4%.<ref name="pmid17988927"/><ref name="pmid15390130"/> Its prevalence is higher among males with an early onset of the disease.<ref name="pmid14505581"/> Previous [[substance abuse]] such as [[alcoholism|heavy drinking]] or drugs intake seems the main risk factor along a history of [[affective disorder]].<ref name="pmid14505581"/>

==History==
PD was first formally described in 1817;<ref name="pmid11983801">{{cite journal
|author=Parkinson J
|title=An essay on the shaking palsy. 1817
|journal=J Neuropsychiatry Clin Neurosci
|volume=14
|issue=2
|pages=223–36; discussion 222
|year=2002
|pmid=11983801
|doi=
|url=
}}</ref> however L-dopa did not enter clinical practice until almost 1970.<ref name="pmid5637779">{{cite journal
|author=Cotzias GC
|title=L-Dopa for Parkinsonism
|journal=N. Engl. J. Med.
|volume=278
|issue=11
|pages=630
|year=1968
|month=March
|pmid=5637779
|doi=
|url=
}}</ref><ref name="pmid5820999">{{cite journal
|author=Yahr MD, Duvoisin RC, Schear MJ, Barrett RE, Hoehn MM
|title=Treatment of parkinsonism with levodopa
|journal=Arch. Neurol.
|volume=21
|issue=4
|pages=343–54
|year=1969
|month=October
|pmid=5820999
|doi=
|url=
}}</ref> In these initial works there were already reports of neuropsychiatric complications.<ref name="pmid5820999"/> During the following decades cases featuring DDS symptoms in relation to dopamine therapy such as hypersexuality, gambling or punding, appeared.<ref name="pmid10495047">{{cite journal
|author=Fernandez HH, Friedman JH
|title=Punding on L-dopa
|journal=Mov. Disord.
|volume=14
|issue=5
|pages=836–8
|year=1999
|month=September
|pmid=10495047
|doi=
|url=
}}</ref><ref name="pmid6685318">{{cite journal
|author=Vogel HP, Schiffter R
|title=Hypersexuality--a complication of dopaminergic therapy in Parkinson's disease
|journal=Pharmacopsychiatria
|volume=16
|issue=4
|pages=107–10
|year=1983
|month=July
|pmid=6685318
|doi=
|url=
}}</ref><ref name="pmid10945141">{{cite journal
|author=Seedat S, Kesler S, Niehaus DJ, Stein DJ
|title=Pathological gambling behaviour: emergence secondary to treatment of Parkinson's disease with dopaminergic agents
|journal=Depress Anxiety
|volume=11
|issue=4
|pages=185–6
|year=2000
|pmid=10945141
|doi=10.1002/1520-6394(2000)11:4<185::AID-DA8>3.0.CO;2-H
|url=
}}</ref> DDS was first described as a syndrome in the year 2000;<ref name="pmid10727476">{{cite journal
|author=Giovannoni G, O'Sullivan JD, Turner K, Manson AJ, Lees AJ
|title=Hedonistic homeostatic dysregulation in patients with Parkinson's disease on dopamine replacement therapies
|journal=J. Neurol. Neurosurg. Psychiatr.
|volume=68
|issue=4
|pages=423–8
|year=2000
|month=April
|pmid=10727476
|pmc=1736875
|doi=
|url=http://jnnp.bmj.com/cgi/pmidlookup?view=long&pmid=10727476
}}</ref> and between three and seven years later the first review articles on the syndrome were written; showing an increasing awareness of the DDS importance.<ref name="pmid17988927"/><ref name="pmid14505581"/><ref name="pmid15247533"/> Diagnostic criteria were proposed in 2005.<ref name="pmid15390130"/>
==References==
{{reflist|2}}

[[Category:Parkinson's disease]]
[[Category:Aging-associated diseases]]
[[Category:Psychiatry]]
[[Category:Neurology]]

Revision as of 08:26, 24 December 2008

Sir Martin Frobisher by Cornelis Ketel, c. 1577
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