In Vivo D2 Dopamine Receptor Density in Psychotic and Nonpsychotic Patients With Bipolar Disorder
Department of Psychiatry, Johns Hopkins University, Baltimore, Md, USA. Archives of General Psychiatry
(Impact Factor: 14.48).
06/1995; 52(6):471-7. DOI: 10.1001/archpsyc.1995.03950180057008
A prior positron emission tomographic study from The Johns Hopkins University, Baltimore, Md, using N-methylspiperone labeled with carbon 11 reported elevated basal ganglia D2 dopamine receptor density (Bmax) values in neuroleptic-naive schizophrenic patients compared with controls. We have now extended these studies to include patients with bipolar disorder.
Patients with bipolar disorder (n = 14) either had never received neuroleptic medication or had been neuroleptic-free for more than 6 months, and they met DSM-III criteria for currently symptomatic affective disorder. Patients with bipolar disorder were compared with matched schizophrenic patients and normal controls. All received two positron emission tomographic scans, the second of which was preceded by oral administration of haloperidol lactate, to permit the calculation of D2 dopamine receptor Bmax.
Diagnostic groups differed in Bmax by analysis of variance (P < .0001); post hoc tests showed higher Bmax values for psychotic patients with bipolar disorder and schizophrenic patients compared with normal controls and for schizophrenic patients and psychotic patients with bipolar disorder compared with nonpsychotic patients with bipolar disorder. Among patients with bipolar disorder, Bmax values correlated significantly with the severity of psychotic symptoms (r = .63) on the Present State Examination but not with the severity of nonpsychotic mood symptoms.
We conclude that, like schizophrenic patients, patients with psychotic bipolar disorder have elevations of D2 dopamine receptor Bmax values and that such elevations in affective disorder are more closely associated with the presence of psychosis than with mood abnormality. Elevations in dopamine receptor values thus may occur in psychiatric states that are characterized by psychotic symptoms rather than being specific to schizophrenia.
Available from: Nicholas S Thaler
- "These findings suggest that individuals with BD I exhibit abnormal functioning in both cortical and subcortical regions, and that although patients may perform comparably to controls on certain behavioral tasks, they also harness different regions of the brain to compensate for hypoactive activity in regions of the brain typically used to complete such tasks. PET studies on dopamine have found that dopamine D1 receptor binding potentials are reduced in the frontal cortex but not in the caudate nucleus (Suhara et al., 1992; Wong et al., 1985), whereas D2 receptor density was found to be higher in patients with psychosis (Pearlson et al., 1995). Another study by Zubieta and colleagues (2000) found increased thalamic and brain stem concentrations of central vesicular monoamine transporter protein (VMAT2), which is a marker of monoaminergic activity. "
Available from: David W Morris
- "In this sample, SZP and BDP showed similar neuropsychological scores which challenges previous reports of more severe cognitive disturbance in SZP, compared to BDP (Seidman et al., 2002; Altshuler et al., 2004; Dickerson et al., 2004; Burdick et al., 2006). Characteristics of our sample may contribute to this finding, namely, this sample included only BDP with lifetime psychotic symptoms; whereas, the majority of previous studies combined psychotic and non-psychotic BD individuals (Pearlson et al., 1995; Potash, 2006; Glahn et al., 2006). This is consistent with previous reports of the negative effect of lifetime psychosis on cognitive function in BD (Glahn et al., 2007; Martinez-Aran et al., 2008). "
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ABSTRACT: This study sought to characterize the psychosis phenotype, contrasting cognitive features within traditional diagnosis and psychosis dimension in a family sample containing both schizophrenia and psychotic bipolar I disorder. Seventy-six probands with psychosis [44 probands with schizophrenia, 32 probands with psychotic bipolar I disorder] and 55 first-degree relatives [30 relatives of schizophrenia probands, 25 relatives of bipolar probands] were recruited. Standardized clinical and neuropsychological measures were administered. No differences in cognitive performance emerged between probands with schizophrenia and probands with psychotic bipolar disorder, or between relatives of probands with schizophrenia and relatives of probands with bipolar disorder in the domains of working and declarative memory, executive function and attention. Relatives overall showed higher cognitive performance compared to probands, as expected. However, when we segmented the probands and relatives along a psychosis dimension, independent of diagnostic groups, results revealed lower cognitive performance in probands compared to relatives without psychosis spectrum disorders, whereas relatives with psychosis spectrum disorders showed an intermediate level of performance across all cognitive domains. In this study, cognitive performance did not distinguish either probands or their first-degree relatives within traditional diagnostic groups (schizophrenia and psychotic bipolar disorder), but distinguished probands and relatives with and without lifetime psychosis manifestations independent of diagnostic categories. These data support the notion that schizophrenia and psychotic bipolar disorder present a clinical continuum with overlapping cognitive features defining the psychosis phenotype.
Available from: Heinrich J G Matthies
- "R signaling has been linked to numerous brain disorders including schizophrenia, bipolar disorder, drug abuse and ADHD (Seeman and Niznik, 1990; Volkow et al., 1993; Pearlson et al., 1995; Wang et al., 1997; Volkow et al., 2007). In addition, D 2 R associates with DAT and regulates its function (Bolan et al., 2007; Lee et al., 2007). "
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ABSTRACT: The neurotransmitter dopamine (DA) modulates brain circuits involved in attention, reward, and motor activity. Synaptic DA homeostasis is primarily controlled via two presynaptic regulatory mechanisms, DA D(2) receptor (D(2)R)-mediated inhibition of DA synthesis and release, and DA transporter (DAT)-mediated DA clearance. D(2)Rs can physically associate with DAT and regulate DAT function, linking DA release and reuptake to a common mechanism. We have established that the attention-deficit hyperactivity disorder-associated human DAT coding variant Ala559Val (hDAT A559V) results in anomalous DA efflux (ADE) similar to that caused by amphetamine-like psychostimulants. Here, we show that tonic activation of D(2)R provides support for hDAT A559V-mediated ADE. We determine in hDAT A559V a pertussis toxin-sensitive, CaMKII-dependent phosphorylation mechanism that supports D(2)R-driven DA efflux. These studies identify a signaling network downstream of D(2)R activation, normally constraining DA action at synapses, that may be altered by DAT mutation to impact risk for DA-related disorders.
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