Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania

Perry, William; Minassian, Arpi; Feifel, David; Braff, David L.

doi:10.1016/s0006-3223(01)01184-2

Cited by 245 publications

(204 citation statements)

References 31 publications

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“…Considering that reinforcement learning signals are conveyed to the cingulate cortex by the mesencephalic dopamine system (Holroyd and Coles, 2002), we suggest that dysfunctional NAcc activation during prediction error processing (as found in this study) leads to cortical and subcortical hyperactivity in mania (Caligiuri et al, 2003). Our findings add to the hypothesis that deficits in gating functions as measured by prepulse inhibition in manic patients may be due to impairments in the corticostriatial circuitry (Perry et al, 2001). Accordingly, unsuccessful motor inhibition was associated with decreased striatal fMRI activation in pediatric bipolar disorder.…”

Section: Outcomesupporting

confidence: 78%

Abnormal Reward System Activation in Mania

Abler

Greenhouse

Öngür

et al. 2007

Neuropsychopharmacol

195

137

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Transmission of reward signals is a function of dopamine, a neurotransmitter known to be involved in the mechanism of psychosis. Using functional magnetic resonance imaging (fMRI), we investigated how expectation and receipt of monetary rewards modulate brain activation in patients with bipolar mania and schizophrenia. We studied 12 acutely manic patients with a history of bipolar disorder, 12 patients with a current episode of schizoaffective disorder or schizophrenia and 12 healthy subjects. All patients were treated with dopamine antagonists at the time of the study. Subjects performed a delayed incentive paradigm with monetary reward in the scanner that allowed for investigating effects of expectation, receipt, and omission of rewards. Patients with schizophrenia and healthy control subjects showed the expected activation of dopaminergic brain areas, that is, ventral tegmentum activation upon expectation of monetary rewards and nucleus accumbens activation during receipt vs omission of rewards. In manic patients, however, we did not find a similar pattern of brain activation and the differential signal in the nucleus accumbens upon receipt vs omission of rewards was significantly lower compared to the healthy control subjects. Our findings provide evidence for abnormal function of the dopamine system during receipt or omission of expected rewards in bipolar disorder. These deficits in prediction error processing in acute mania may help to explain symptoms of disinhibition and abnormal goal pursuit regulation.

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Section: Outcomesupporting

confidence: 78%

Abnormal Reward System Activation in Mania

Abler

Greenhouse

Öngür

et al. 2007

Neuropsychopharmacol

195

137

View full text Add to dashboard Cite

show abstract

“…Intriguingly, association of the 5-HT 2A receptor gene polymorphism with ADHD has been recently reported (Levitan et al, 2002). Furthermore, the behavioral phenotype of DAT KO mice also closely resembles that of bipolar depressive disorder in humans, as both exhibit general hyperactivity and deficits in PPI (Perry et al, 2001). The capacity of standard treatments for bipolar disorder, such as lithium, carbamazepine, and valproate, to reverse behavioral deficits in DAT KO mice remains to be determined in the further validation of these mice as a model of human disease.…”

Section: Discussionmentioning

confidence: 92%

The Selective Serotonin-2A Receptor Antagonist M100907 Reverses Behavioral Deficits in Dopamine Transporter Knockout Mice

Barr

Lehmann-Masten

Paulus

et al. 2003

Neuropsychopharmacol

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A hyperdopaminergic state in humans has been hypothesized to contribute to the pathology of a number of psychiatric illnesses, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Mice that display elevated synaptic levels of dopamine due to a genetically engineered deletion of the dopamine transporter (DAT) model behavioral deficits that simulate the above conditions. As novel treatment strategies for these disorders have focused on the serotonin (5-HT) 2A receptor, we determined the capacity of the highly selective 5-HT 2A receptor antagonist M100907 to reverse behavioral deficits in DAT knockout (KO) mice. Prior to drug treatment, DAT KO mice exhibited increased levels of locomotor activity and highly linearized movement in a novel environment, as well as reduced prepulse inhibition (PPI) of acoustic startle, compared to wild-type littermates. Treatment with M100907 (0.3-1.0 mg/ kg, but not 0.1 mg/kg) reversed locomotor deficits in DAT KO mice. Similarly, treatment with 1.0 mg/kg M100907 reversed the PPI deficits in DAT KO mice. These data indicate that selective 5-HT 2A receptor antagonists, such as M100907, may represent a class of drugs that can be used to treat conditions in which a chronic, elevated dopaminergic tone is present and contributes to abnormal behavior and sensorimotor gating deficits.

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“…This group of disorders has been suggested to reflect a family of disorders which can be characterized as having deficits in the gating of motor (Huntington's, Tourette's), sensory (schizophrenia), and/or cognitive information (OCD) Hoenig et al, 2005). In addition, more recent studies have revealed similar deficits in PPI in another psychotic disorder, namely bipolar disorder patients, at least in the manic phase of the illness (Perry et al, 2001). Bipolar disorder has long been conceptualized as including failure of motor inhibition.…”

Section: Sensorimotor Gating Deficits In Psychiatric Disordersmentioning

confidence: 99%

The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

2006

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Prepulse inhibition (PPI) of startle is an operational measure of the pre-attentive filtering process known as sensorimotor gating. Originally identified in patients with schizophrenia, PPI deficits have been observed in multiple but not all psychiatric disorders. Thus, as with most signs and symptoms of psychiatric disorders, deficits in PPI cut across diagnostic categories. It remains unclear whether the diversity of disorders exhibiting deficient PPI bespeaks diagnostic overlaps or comorbidities. Given the recent focus on treatments for cognitive deficits of schizophrenia independently of treating psychosis, the relationship of PPI deficits to cognitive deficits becomes of interest. Although PPI cannot be considered to be a cognitive process per se, abnormalities in pre-attentive information processing may be predictive of or lead to complex cognitive deficits. Animal models of PPI deficits produced by dopamine agonists reliably predict existing antipsychotics. Nevertheless, since neither PPI nor cognitive deficits in schizophrenia are ameliorated by standard antipsychotics, current research is exploring the predictive value of non-dopaminergic PPI models in identifying treatments for gating disturbances independently of their relevance to specific disorders. Both PPI and cognitive deficits in schizophrenia patients are not reversed by first generation antipsychotics but may be attenuated by clozapine. Similarly, effects of glutamate antagonists on symptoms in patients and PPI in animals appear to be reduced by clozapine. Hence, treatment-induced reversals of deficits in PPI produced by glutamate antagonists may provide animal, and human, models to aid in the discovery of treatments of cognitive deficits in patients already treated with existing antipsychotics.

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Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania

Cited by 245 publications

References 31 publications

Abnormal Reward System Activation in Mania

Abnormal Reward System Activation in Mania

The Selective Serotonin-2A Receptor Antagonist M100907 Reverses Behavioral Deficits in Dopamine Transporter Knockout Mice

The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

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