Striatal dopamine transporter availability in unmedicated bipolar disorder

Anand, Amit; Barkay, Gavriel; Džemidžić, Mario; Albrecht, Daniel; Karne, Harish; Zheng, Qi; Hutchins, Gary D.; Normandin, Marc D.; Yoder, Karmen K.

doi:10.1111/j.1399-5618.2011.00936.x

Cited by 121 publications

(78 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The importance of our findings is highlighted from studies indicating that polymorphisms in the DAT gene may induce lower DAT levels in patients with BD (Anand et al, 2011;Pinsonneault et al, 2011). Lower striatal DAT levels have also been observed in people with ADHD (Fusar-Poli et al, 2012) and seasonal affective disorder (Neumeister et al, 2001).…”

Section: Discussionmentioning

confidence: 63%

“…Hence, chronic reductions of DAT expression in mice may model more aspects of BD than acute DAT inhibition alone. The etiological validity of the chronic DAT KD model is likely limited, however, by the fact that these animals express only 10% of the transporter (Zhuang et al, 2001), whereas only a B20% reduction of DAT availability is observed in euthymic BD patients (Anand et al, 2011). As yet, DAT levels in BD patients in the manic phase have yet to be established.…”

Section: Discussionmentioning

confidence: 99%

“…Supporting this assumption, polymorphisms in the DAT gene have been linked with BD (Greenwood et al, 2006;Pinsonneault et al, 2011), likely lowering functional DAT levels (Horschitz et al, 2005). Reduced striatal DAT levels are seen in unmedicated BD patients (Anand et al, 2011) and postmortem tissue (Rao et al, 2012). Thus, the relationship between reduced DAT functioning and its contribution to impaired risk-based decision-making in BD patients may be important, but remains undetermined.…”

Section: Introductionmentioning

confidence: 92%

“…Hence, although we predicted increased risk-taking in mice with reduced DAT expression because of the reduced expression observed in unmedicated patients, it will be important for future studies to combine these behavioral assessments with physiological measurements, eg, via PET (Anand et al, 2011) or measurement in peripheral lymphocytes (Buttarelli et al, 2011). Another limitation is that experimental animals are kept in stable and controlled environments (ie, circadian rhythms/light exposure), whereas evidence suggests that environmental factors such as long day-lengths contribute to BD symptoms (Blumberg, 2012).…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Reduced Dopamine Transporter Functioning Induces High-Reward Risk-Preference Consistent with Bipolar Disorder

Enkhuizen

Henry

Minassian

et al. 2014

Neuropsychopharmacol

View full text Add to dashboard Cite

Individuals with bipolar disorder (BD) exhibit deleterious decision making, negatively impacting their lives. Such aberrant decision making can be quantified using the Iowa Gambling Task (IGT), which requires choosing between advantageous and disadvantageous options based on different reward/punishment schedules. The mechanisms underlying this behavioral deficit are unknown, but may include the reduced dopamine transporter (DAT) functioning reported in BD patients. Using both human and mouse IGTs, we tested whether reduced DAT functioning would recreate patterns of deficient decision making of BD patients. We assessed the IGT performance of 16 BD subjects (7 female) and 17 healthy control (HC) subjects (12 female). We recorded standard IGT performance measures and novel post-reward and post-punishment decision-making strategies. We characterized a novel single-session mouse IGT using C57BL/6J mice (n ¼ 44). The BD and HC IGT performances were compared with the effects of chronic (genetic knockdown (KD; n ¼ 31) and wild-type (n ¼ 28) mice) and acute (C57BL/6J mice (n ¼ 89) treated with the DAT inhibitor GBR12909) reductions of DAT functioning in mice performing this novel IGT. BD patients exhibited impaired decision making compared with HC subjects. Both the good-performing DAT KD and GBR12909-treated mice exhibited poor decision making in the mouse IGT. The deficit of each population was driven by highreward sensitivity. The single-session mouse IGT measures dynamic risk-based decision making similar to humans. Chronic and acute reductions of DAT functioning in mice impaired decision-making consistent with poor IGT performance of BD patients. Hyperdopaminergia caused by reduced DAT may impact poor decision making in BD patients, which should be confirmed in future studies.

show abstract

Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Reduced Dopamine Transporter Functioning Induces High-Reward Risk-Preference Consistent with Bipolar Disorder

Enkhuizen

Henry

Minassian

et al. 2014

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…reported an exception [282]). Amsterdam and Newberg [283] reported higher striatal DAT binding in the right posterior putamen and left caudate in a small number of patients with bipolar disorder; Chang and colleagues [284] reported that unmedicated euthymic subjects with bipolar disorder had significantly relatively higher whole striatal DAT binding; and Anand and colleagues [285] reported relatively lower DAT availability in the dorsal caudate nucleus (DCN) bilaterally. There is also evidence that the presence of psychosis may moderate patterns of DA receptor binding.…”

Section: Reviewmentioning

confidence: 99%

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Dichter

Damiano

Allen

2012

J Neurodevelop Disord

253

207

View full text Add to dashboard Cite

This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

show abstract

Intracellular Signaling Cascades in Bipolar Disorder

Jones

Rong

Shariq

et al. 2020

Bipolar Disorder: From Neuroscience to Treatment

View full text Add to dashboard Cite

Bipolar spectrum disorders carry a significant public health burden. Disproportionately high rates of suicide, incarceration, and comorbid medical conditions necessitate an extraordinary focus on understanding the intricacies of this disease. Elucidating granular, intracellular details seems to be a necessary preamble to advancing promising therapeutic opportunities. In this chapter, we review a wide range of intracellular mechanisms including mitochondrial energetics, calcium

show abstract

Striatal dopamine transporter availability in unmedicated bipolar disorder

Abstract: The results of this study support the hypothesis that there are abnormalities in the dopaminergic system in BPD, and suggest that DAT availability may be related to the neuropathology of BPD. Future studies are needed to determine if DAT availability cycles with disease phase.

Cited by 121 publications

References 60 publications

Reduced Dopamine Transporter Functioning Induces High-Reward Risk-Preference Consistent with Bipolar Disorder

Reduced Dopamine Transporter Functioning Induces High-Reward Risk-Preference Consistent with Bipolar Disorder

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Intracellular Signaling Cascades in Bipolar Disorder

Contact Info

Product

Resources

About