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The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels.
We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.
The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.
Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.
Previous studies suggested that a disturbance of the dopamine system underlies the pathophysiology of bipolar disorder (BD). In addition, the therapeutic action of medications for treating BD, such as valproate (VPA), might modulate dopamine system activity, but it remains unclear. Here, we aimed to investigate the role of the striatal dopamine transporter (DAT) in BD patients and in social defeat (SD) mice treated with VPA.
We enrolled community-dwelling controls (N = 18) and BD patients (N = 23) who were treated with VPA in a euthymic stage. The striatal DAT availabilities were approached by TRODAT-1 single photon emission computed tomography. We also established a chronic SD mouse model and treated mice with 350 mg/kg VPA for 3 weeks. Behavioral tests were administered, and striatal DAT expression levels were determined.
In humans, the level of striatal DAT availability was significantly higher in euthymic BD patients (1.52 ± 0.17 and 1.37 ± 0.23, p = 0.015). Moreover, the level of striatal DAT availability was also negatively correlated with the VPA concentration in BD patients (r = −0.653, p = 0.003). In SD mice, the expression of striatal DAT significantly increased (p < 0.001), and the SD effect on DAT expression was rescued by VPA treatment.
The striatal DAT might play a role in the pathophysiology of BD and in the therapeutic mechanism of VPA. The homeostasis of DAT might represent a new therapeutic strategy for BD patients.
It is well-known that attention deficit hyperactivity disorder (ADHD) is associated with changes in the dopaminergic system. However, the relationship between central dopaminergic tone and the blood oxygen level-dependent (BOLD) signal during receipt of rewards and penalties in the corticostriatal pathway in adults with ADHD is unclear.
Single-photon emission computed tomography with [99mTC]TRODAT-1 was used to assess striatal dopamine transporter (DAT) availability. Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa Gambling Test.
DAT availability was found to be associated with the BOLD response, which was a covariate of monetary loss, in the medial prefrontal cortex (r = 0.55, P = .03), right ventral striatum (r = 0.69, P = .003), and right orbital frontal cortex (r = 0.53, P = .03) in adults with ADHD. However, a similar correlation was not found in the controls.
The results confirmed that dopaminergic tone may play a different role in the penalty-elicited response of adults with ADHD. It is plausible that a lower neuro-threshold accompanied by insensitivity to punishment could be exacerbated by the hypodopaminergic tone in ADHD.
The present study examined the relationship between the Lie scale scores and striatal D2/D3 receptor availability with respect to the cerebellum in 42 healthy community volunteers in Taiwan using single photon emission computed tomography (SPECT) with [123I]iodo-benzoaminde (IBZM). Even after controlling of age and educational level, subjects' Lie scale scores of the Maudsley personality inventory correlate negatively with D2/D3 receptor availability. Individual with higher Lie scale scores may have higher impulsivity due to lower dopaminergic availability.
Previous studies have indicated that there is dopamine transporter (DAT) dysregulation and P300 abnormality in adults with attention-deficit hyperactivity disorder (ADHD); however, the correlations among the three have not been fully explored.
A total of 11 adults (9 males and 2 females) with ADHD and 11 age-, sex-, and education-level-matched controls were recruited. We explored differences in DAT availability using single-photon emission computed tomography and P300 wave of event-related potentials between the two groups. The correlation between DAT availability and P300 performance was also examined.
DAT availability in the basal ganglia, caudate nucleus, and putamen was significantly lower in the ADHD group. Adults with ADHD had lower auditory P300 amplitudes at the Pz and Cz sites, as well as longer Fz latency than controls. DAT availability was negatively correlated to P300 latency at Pz and Fz.
Adults with ADHD had both abnormal DAT availability and P300 amplitude, suggesting that ADHD is linked to dysfunction of the central dopaminergic system and poor cognitive processes related to response selection and execution.
El presente estudio examinoó la relación entre las puntuaciones de la Escala de Sinceridad y la disponibilidad del receptor D2/D3 estriatal con respecto al cerebelo en 42 voluntarios comunitarios sanos en Taiwán utilizando tomografía computarizada por emisión de fotón ύnico (SPECT) con yodobenzamida (,IBZM). Las puntuaciones en la Escala de Sinceridad del Inventario de Personalidad de Maudsley de los sujetos correlacionan negativamente con la disponibilidad del receptor D2/D3 incluso después de controlar la edad y el nivel educativo. Los individuos con puntuaciones más altas en la Escala de Sinceridad pueden tener impulsividad más alta debido a una disponibilidad dopaminérgica más baja.
Background. Although a correlation between the central dopaminergic system and intelligence may exist, the results from imaging studies remain inconclusive. The aim of this study was to explore the relationship between striatal dopamine D2/D3 receptor availability and verbal intelligence quotient (VIQ) using single photon emission computed tomography (SPECT).
Method. Striatal D2/D3 receptor availability of 64 healthy subjects was determined with the [123I]iodobenzamide ([123I]IBZM) ligand. Intelligence quotients (IQs) of the subjects were measured by the Wechsler Adult Intelligence Scale – Revised (WAIS-R).
Results. In addition to age, left striatal D2/D3 receptor availability correlated positively with VIQ. In females, left striatal D2/D3 receptor availability was the only variable that correlated significantly with the similarities subtest of VIQ.
Conclusions. There is a relationship between left striatal D2/D3 receptor availability and verbal intelligence, which varies, predominantly in males.
Objective. Although studies have indicated that the human basal ganglia have a specific role in different memory systems, the functional significance of the striatal dopamine activities for the basal ganglia remains less clear. This study assessed the relationship between measures of striatal dopamine activities and indices of different memory systems in healthy individuals.
Method. Single photon emission computed tomography and [123I]IBZM (iodobenzamide) were used to assess the striatal dopamine D2/D3 receptor density in 62 healthy volunteers aged between 19 and 61 years. All subjects underwent a Wechsler Memory Scale – Revised test.
Results. Dopamine D2/D3 receptor densities in the striatum decline with age. Stepwise regression analysis showed that verbal delayed recall and working memory account for most of the variance in dopamine D2/D3 measurements. These relationships remain significantly after controlling for age effects.
Conclusions. Brain striatal dopamine activities are also significantly associated with various memory systems, in addition to motor functions. This may explain why patients with neuropsychiatric disorders may have both memory and motor impairments.
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