Anatomical MRI study of basal ganglia in major depressive disorder

The basal ganglia form a part of the brain neuroanatomic circuits that may be involved in mood regulation. Decreases in basal ganglia volumes have been previously reported in major depressive disorder patients in comparison to healthy controls. In this study, we measured caudate, putamen, and globus pallidus volumes in 25 patients with major depressive disorder (4 M; age+/-S.D.=41+/-11 years) and 48 healthy controls (29 M; age+/-S.D.=35+/-10 years), using high-resolution magnetic resonance imaging (MRI), in an attempt to replicate prior findings. Unlike most previous studies, we did not find significant differences between patient and control groups in basal ganglia volumetric measures. Nonetheless, there was a significant interaction between diagnosis and cerebral hemisphere, with MDD patients showing decreased asymmetry in globus pallidus volumes in comparison with healthy controls. Furthermore, in the patient group, left putamen volumes correlated inversely with length of illness, and left globus pallidus volume correlated directly with number of prior depressive episodes. These findings suggest that abnormalities in lateralization and possibly neurodegenerative changes in basal ganglia structures participate in the pathophysiology of major depressive disorder.     

Normal sexual dimorphism in the human basal ganglia

Male and female brains differ in both structure and function. Investigating this sexual dimorphism in healthy subjects is an important first step to ultimately gain insight into sex-specific differences in behavior and risk for neuropsychiatric disorders. The basal ganglia are among the main regions containing sex steroid receptors in the brain and play a central role in cognitive (dys)functioning. However, little is known about sexual dimorphism of different basal ganglia nuclei. The aim of the present study was to investigate sex-specific differences in basal ganglia morphology using MRI. We applied automatic volumetry on anatomical MRI data of two large cohorts of healthy young adults (n = 463 and n = 541) and assessed the volume of four major nuclei of the basal ganglia: caudate nucleus, globus pallidus, nucleus accumbens, and putamen, while controlling for total gray matter volume, total white matter volume, and age of the participant. No significant sex differences were found for caudate nucleus and nucleus accumbens, but males showed significantly larger volumes for globus pallidus and putamen, as confirmed in both cohorts. These results show that sexual dimorphism is neither a general effect in the basal ganglia nor confined to just one specific nucleus, and will aid the interpretation of differences in basal ganglia (dys)function between males and females.     

An MRI study of basal ganglia volumes in first-episode schizophrenia patients treated with risperidone

OBJECTIVE: The basal ganglia may contribute to extrapyramidal movement disorders, affective disturbances, and cognitive deficits in schizophrenia. Basal ganglia volumes are putatively affected by antipsychotic medications. The purpose of this study was to determine the long-term effects of risperidone treatment in a cohort of first-episode patients with schizophrenia. METHOD: The subjects were 30 patients with first-episode schizophrenia, 12 patients chronically treated with typical antipsychotics, and 23 healthy comparison subjects. They were scanned by magnetic resonance imaging at baseline. The first-episode patients received 1 year of continuous risperidone treatment, after which they and the comparison subjects were rescanned. Caudate, putamen, and globus pallidus volumes were determined from coronal images. RESULTS: The baseline caudate, putamen, and globus pallidus volumes were significantly larger in the chronically treated patients than in the untreated first-episode subjects and comparison subjects. These volumes did not differ between the first-episode patients and healthy comparison subjects. Basal ganglia volumes were unchanged after 1 year of exposure to risperidone in the first-episode subjects. Extrapyramidal movement disorders were present in the majority of chronically treated patients and more than one-third of the never-medicated first-episode patients at baseline. CONCLUSIONS: This group of first-episode patients did not exhibit abnormalities of basal ganglia volumes, nor were basal ganglia volumes affected by exposure to risperidone. Movement disorders were observed in both first-episode and chronically treated patients, suggesting effects of both illness and medications.     

Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug

The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound. Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients and 19 matched controls participated. Patients were randomly assigned to treatment with either low doses of the typical antipsychotic drug, zuclopenthixol, or the atypical compound, risperidone. High-resolution magnetic resonance imaging (MRI) scans were obtained in patients before and after 12 weeks of exposure to medication and in controls at baseline. Caudate nucleus, nucleus accumbens, and putamen volumes were measured. Compared with controls, absolute volumes of interest (VOIs) were smaller in patients at baseline and increased after treatment. However, with controls for age, gender and whole brain or intracranial volume, the only significant difference between patients and controls was a Hemisphere x Group interaction for the caudate nucleus at baseline, with controls having larger left than right caudate nuclei and patients having marginally larger right than left caudate volumes. Within patients, the two medication groups did not differ significantly with respect to volume changes after 3 months of low dose treatment in any of the VOIs. Nevertheless, when medication groups were examined separately, a significant volume increase in the putamen was evidenced in the risperidone group. The altered asymmetry in caudate volume in patients suggests intrinsic basal ganglia pathology in schizophrenia, most likely of neurodevelopmental origin.     

Localization of Basal Ganglia and Thalamic Damage in Dyskinetic Cerebral Palsy

BackgroundDyskinetic cerebral palsy affects 15%-20% of patients with cerebral palsy. Basal ganglia injury is associated with dyskinetic cerebral palsy, but the patterns of injury within the basal ganglia predisposing to dyskinetic cerebral palsy are unknown, making treatment difficult. For example, deep brain stimulation of the globus pallidus interna improves dystonia in only 40% of patients with dyskinetic cerebral palsy. Basal ganglia injury heterogeneity may explain this variability.MethodsTo investigate this, we conducted a qualitative systematic review of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Reviews and articles primarily addressing genetic or toxic causes of cerebral palsy were excluded yielding 22 studies (304 subjects).ResultsThirteen studies specified the involved basal ganglia nuclei (subthalamic nucleus, caudate, putamen, globus pallidus, or lentiform nuclei, comprised by the putamen and globus pallidus). Studies investigating the lentiform nuclei (without distinguishing between the putamen and globus pallidus) showed that all subjects (19 of 19) had lentiform nuclei damage. Studies simultaneously but independently investigating the putamen and globus pallidus also showed that all subjects (35 of 35) had lentiform nuclei damage (i.e., putamen or globus pallidus damage); this was followed in frequency by damage to the putamen alone (70 of 101, 69%), the subthalamic nucleus (17 of 25, 68%), the thalamus (88 of 142, 62%), the globus pallidus (7/35, 20%), and the caudate (6 of 47, 13%). Globus pallidus damage was almost always coincident with putaminal damage.ConclusionsNoting consistent involvement of the lentiform nuclei in dyskinetic cerebral palsy, these results could suggest two groups of patients with dyskinetic cerebral palsy: those with putamen-predominant damage and those with panlenticular damage involving both the putamen and the globus pallidus. Differentiating between these groups could help predict response to therapies such as deep brain stimulation.     

No effect of obstetric complications on basal ganglia volumes in schizophrenia

Background

Heterogeneous findings have been reported in studies of basal ganglia volumes in schizophrenia patients as compared to healthy controls. The basal ganglia contain dopamine receptors that are known to be involved in schizophrenia pathology and to be vulnerable to pre- and perinatal hypoxic insults. Altered volumes of other brain structures (e.g. hippocampus and lateral ventricles) have been reported in schizophrenia patients with a history of obstetric complications (OCs). This is the first study to explore if there is a relationship between OCs and basal ganglia volume in schizophrenia.

Methods

Thorough clinical investigation (including information on medication) of 54 schizophrenia patients and 54 healthy control subjects was undertaken. MR images were obtained on a 1.5 T scanner, and volumes of nucleus caudatus, globus pallidum, putamen, and nucleus accumbens were quantified automatically. Information on OCs was blindly collected from original birth records.

Results

Unadjusted estimates demonstrated a relationship between increasing number of OCs and larger volume of nucleus accumbens in schizophrenia patients and healthy controls. No statistically significant relationships were found between OCs and the basal ganglia volumes when controlled for intracranial volume, age, and multiple comparisons. There were no effects of typical versus atypical medication on the basal ganglia volumes. The patients with schizophrenia had larger globus pallidum volumes as compared to healthy controls, but there were no case–control differences for accumbens, putamen, or caudate volumes.

Conclusion

The present results do not support the hypothesis that OCs are related to alterations in basal ganglia volume in chronic schizophrenia.     

抽动秽语综合征患者基底节结构特点分析

目的探讨抽动秽语综合征(Tourette syndrome,TS)患者可能存在的基底节结构改变.方法对10例右利手男性TS患者和10例匹配正常健康人进行头颅MRI检查,应用三维重建技术分别对尾状核、壳核、苍白球和全脑体积进行测量,比较两组之间的基底节体积差异,分析左右侧结构体积的对称性.结果对照组左侧基底节体积大于右侧(P＜0.05);TS组双侧基底节各结构体积均明显减小,左侧更显著,左右侧体积比较无显著差异(P＞0.05);基底节各结构体积与症状严重程度不相关.结论正常右利手人群中存在着基底节结构体积不对称性,左侧偏大;双侧基底节体积减小、丧失正常的不对称性,是TS患者的特征性结构改变.     

Anatomical MRI study of basal ganglia in bipolar disorder patients

This study examined possible anatomical abnormalities in basal ganglia structures in bipolar disorder patients. Caudate and putamen gray matter volumes, and globus pallidus total volume were measured with magnetic resonance imaging (MRI) in 22 DSM-IV bipolar patients (age+/-S.D.=36+/-10 years; eight drug-free and 14 lithium monotherapy patients) and 22 matched healthy control subjects (age+/-S.D.=38+/-10 years). No significant differences were found between bipolar patients and healthy control subjects for any of the basal ganglia measures (t-tests, P>0.05). Age was inversely correlated with left putamen volumes in patients (R=-0.44, P=0.04), but not in healthy control subjects (R=-0.33, P=0.14). Older patients (>36 years old) had a significantly larger left globus pallidus than younger ones (< or =36 years old) (ANOVA, P=0.01). In a multiple regression analysis, after entering age as independent variable, the length of illness predicted smaller left putamen volumes, explaining 10.4% of the variance (F=4.07, d.f.=2, P=0.03). No significant effects of episode type, number of prior episodes, or gender were found in any basal ganglia measurements (ANOVA, P>0.05). In conclusion, our findings indicate that the basal ganglia may be anatomically preserved in bipolar patients. This is in contrast to available findings for unipolar disorder. However, our findings also suggest that age and length of illness may have significant effects on basal ganglia structures in bipolar patients, which may be more pronounced among bipolar I patients, and of relevance for the pathophysiology of the disorder.     

The basal ganglia: a neural network with more than motor function

The basal ganglia is a group of subcortical nuclei involved in motor control, cognition, and emotion. Basal ganglia disorders are manifested by abnormal movement and a number of neuropsychiatric disorders. Basal ganglia nuclei are organized into sensorimotor, associative, and limbic territories based on their connectivity and function. The caudate nucleus, putamen, and subthalamic nucleus comprise the input nuclei of the basal ganglia. The internal segment of globus pallidus and substantia nigra reticulata are the output nuclei. The input and output nuclei are interconnected by direct and indirect pathways. The cerebral cortex, basal ganglia, and thalamus communicate with each other via closed (segregated) parallel as well as open (split) loops. Recent anatomic, functional, and clinical data have necessitated modifications in the classical models of local connectivity between input and output nuclei of the basal ganglia as well as in the corticobasal ganglia-thalamus-cortical loops.     

Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity disorders

BACKGROUND: Previous studies have provided preliminary serological evidence supporting the theory that symptoms of tic disorders or obsessive-compulsive disorder (OCD) may be sequelae of prior streptococcal infection. It is unclear, however, whether previously reported associations with streptococcal infection were obscured by the presence of diagnostic comorbidities. It is also unknown whether streptococcal infection is associated in vivo with anatomical alterations of the brain structures that have been implicated in the pathophysiology of these disorders. METHODS: Antistreptococcal antibody titers were measured in 105 people diagnosed as having CTD, OCD, or attention-deficit/hyperactivity disorder (ADHD) and in 37 community controls without a disorder. Subjects were unselected with regard to their history of streptococcal exposure. Basal ganglia volumes were measured in 113 of these subjects (79 patients and 34 controls). RESULTS: A DSM-IV diagnosis of ADHD was associated significantly with titers of 2 distinct antistreptococcal antibodies, antistreptolysin O and anti-deoxyribonuclease B. These associations remained significant after controlling for the effects of CTD and OCD comorbidity. No significant association was seen between antibody titers and a diagnosis of either CTD or OCD. When basal ganglia volumes were included in these analyses, the relationships between antibody titers and basal ganglia volumes were significantly different in OCD and ADHD subjects compared with other diagnostic groups. Higher antibody titers in these subjects were associated with larger volumes of the putamen and globus pallidus nuclei. CONCLUSIONS: These findings suggest that the prior reports of an association between antistreptococcal antibodies and either CTD or OCD may have been confounded by the presence of ADHD. They also support the hypothesis that in susceptible persons who have ADHD or OCD, chronic or recurrent streptococcal infections are associated with structural alterations in basal ganglia nuclei.     

Basal ganglia volumes in first-episode schizophrenia and healthy comparison subjects.

BACKGROUND: Previous studies suggest that dysfunction of cortico-striato-pallido-thalamic (CSPT) circuitry may be involved in the pathophysiology of schizophrenia but also show that basal ganglia structure is highly plastic and may be influenced by antipsychotic treatments. Controversy remains about whether basal ganglia pathology can be detected in vivo among treatment-na?ve patients. We conducted a magnetic resonance imaging (MRI) study to examine basal ganglia structures and the limbic forebrain in first episode schizophrenia and healthy comparison subjects. METHODS: Fifty-one patients with first-episode schizophrenia and 28 healthy comparison subjects participated in the study. A high-resolution, special contrast (white matter nulling) MRI sequence was used to measure the caudate nucleus, nucleus accumbens, putamen, and subcommissural limbic forebrain. RESULTS: Volumes of the basal ganglia regions of interest (adjusted for total brain volume and age) did not differ significantly between the groups. Age correlated significantly with caudate and putamen volumes bilaterally in the healthy comparison group, but not among patients. CONCLUSIONS: The findings suggest that there are no volumetric abnormalities in basal ganglia before treatment in first-episode schizophrenia. The lack of a negative correlation between age and striatal volume among patients may implicate illness-associated factors that alter normal age-related changes in basal ganglia size.     

Reduced basal ganglia volumes after switching to olanzapine in chronically treated patients with schizophrenia

OBJECTIVE: A follow-up study of patients with schizophrenia was conducted to examine change in striatal volumes and extrapyramidal symptoms after a change in medication. METHOD: Thirty-seven patients with schizophrenia and 23 healthy volunteers were examined. Patients at baseline receiving typical antipsychotics (N=10) or risperidone but exhibiting limited response (N=13) were switched to treatment with olanzapine. Patients receiving risperidone and exhibiting a good response (N=14) continued treatment with risperidone. Caudate, putamen, and pallidal volumes were assessed with magnetic resonance imaging. The Extrapyramidal Symptoms Rating Scale was used to assess clinical signs and symptoms. RESULTS: At baseline, basal ganglia volumes in patients treated with typical antipsychotics were greater than in healthy subjects (putamen: 7.0% larger; globus pallidus: 20.7% larger). After the switch to olanzapine, putamen and globus pallidus volumes decreased (9.8% and 10.7%, respectively) and did not differ from those of healthy subjects at the follow-up evaluation. Akathisia was also reduced. In the patients receiving risperidone at baseline, basal ganglia volumes did not differ between those exhibiting good and poor response, and no significant volume changes were observed in subjects with poor risperidone response after the switch to olanzapine treatment. CONCLUSIONS: Olanzapine reversed putamen and globus pallidus enlargement induced by typical antipsychotics but did not alter volumes in patients previously treated with risperidone. Changes in striatal volumes related to typical and atypical antipsychotics may represent an interactive effect between individual medications and unique patient characteristics.     

Putamen hypertrophy in nondemented patients with human immunodeficiency virus infection and cognitive compromise

BACKGROUND: Documented death and dysfunction of basal ganglia cells in patients seropositive for human immunodeficiency virus (HIV) suggest that the virus may cause structural compromise to these regions. OBJECTIVES: To examine subcortical volumes in nondemented patients seropositive for HIV (HIV+) by means of a novel automated neuroanatomic morphometric analysis tool, and to investigate relationships among cognitive function, immune health, and subcortical volumes. DESIGN AND SETTING: Cross-sectional study of subcortical morphometry and cognitive function conducted at the Boston University Center for Memory and Brain and the Massachusetts General Hospital Athinoula A. Martinos Center for Biomedical Imaging. PATIENTS: Twenty-two nondemented HIV+ patients and 22 age- and education-matched healthy control participants. MAIN OUTCOME MEASURES: Subcortical segmentation volumes, neuropsychological performance, and immunological variables. RESULTS: Nondemented HIV+ patients demonstrated relative and isolated putamen hypertrophy compared with control participants. Putamen volume enlargement in HIV+ patients was related to motor slowing and immune status, such that higher CD4 lymphocyte levels were associated with larger putamen volumes. There were no other subcortical volume differences between the groups. CONCLUSIONS: This study suggests that basal ganglia hypertrophy accompanies HIV-related mild cognitive compromise. These findings may represent a structural imaging parallel to functional imaging studies demonstrating basal ganglia hypermetabolism in HIV+ patients with mild cognitive compromise and early HIV-associated brain disease.     

Pallidal gap junctions‐triggers of synchrony in Parkinson's disease?

Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin‐36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in an existing computational model of the basal ganglia. We detected connexin‐36 in the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that the number of connexin‐36 spots in PD tissues increased by 50% in the putamen, 43% in the GPe, and 109% in the GPi compared with controls. In the computational model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal ganglia became especially susceptible to synchronize with input from the cortex when gap junctions were numerous and high in conductance. In conclusion, connexin‐36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei. In PD, neural injury and dopamine depletion could increase this coupling. Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia. © 2014 International Parkinson and Movement Disorder Society     

MRI abnormalities in tardive dyskinesia

Most investigators studying tardive dyskinesia (TD) hypothesize that the condition is due to a neurochemical abnormality of the striatum. Recently, numerous CT studies have been done to verify brain abnormalities in patients with TD; the findings have, however, been conflicting. The present study was designed to detect possible neuropathological abnormalities in the basal ganglia in a young sample of schizophrenic patients with TD as compared with schizophrenic patients without TD and normal controls. Magnetic resonance imaging (MRI) was used to measure the volumes of the caudate, putamen, globus pallidus, lateral ventricle, and intracranium. The volumes of the caudate nuclei of the patients with TD were significantly smaller than the volumes of the caudate nuclei of the patients without TD and normal controls. This abnormality in the caudate may be related to some previous condition, which may prove a substrate that is necessary for TD to establish itself in association with neuroleptic use. Further studies are necessary to confirm our findings and to determine the pathophysiologic nature of these structural alterations and the role played by neuroleptics, whether primary or secondary.     

Structural analysis of the basal ganglia in schizophrenia

Increases in the total volume of basal ganglia structures have been reported in schizophrenia. However, patterns of basal ganglia shape change, which can reveal localized changes in substructure volumes, have not been investigated. In this study, the total volume and shape of several basal ganglia structures were compared in subjects with and without schizophrenia. T(1)-weighted magnetic resonance scans were collected in 54 schizophrenia and 70 comparison subjects. High-dimensional (large-deformation) brain mapping was used to assess the shape and volume of several basal ganglia structures. The relationships of shape and volume measures with psychopathology, cognition and motor function were also assessed. Left and right volumes of the caudate and putamen, as well as the right globus pallidus volume, were significantly increased in subjects with schizophrenia as compared to comparison subjects after total brain volume was included as a covariate. Significant differences in shape accompanied these volume changes in the caudate, putamen and globus pallidus, after their total volumes were included as covariates. There were few significant correlations between volume or shape measures and either cognitive function or clinical symptoms, other than a positive correlation between an attention/vigilance cognitive dimension and the volume of the caudate and putamen, and a negative correlation between nucleus accumbens volume and delusions. In conclusion, basal ganglia volumes relative to total brain volume were larger in schizophrenia subjects than healthy comparison subjects. Specific patterns of shape change accompanied these volume differences.     

Fronto-thalamo-striatal gray and white matter volumes and anisotropy of their connections in bipolar spectrum illnesses.

BACKGROUND: Neurons in the basal ganglia are connected to areas of prefrontal cerebral cortex involved in higher cognitive functions, and these connections occur primarily via the thalamus. In patients with bipolar disorder, regardless of age, neuroimaging studies have consistently reported an increased number of white matter hyperintensities, indicating possible alterations in striatum-thalamus and thalamus-prefrontal cortex connections. METHODS: In the current study, we acquired high-resolution magnetic resonance imaging (MRI) and diffusion tensor (DT) scans of 40 patients with bipolar spectrum (BPS) illnesses (bipolar type I = 17, bipolar type II = 7, cyclothymia = 16) and 36 sex- and age-matched control subjects. Two researchers, without knowledge of diagnosis, outlined the caudate, putamen, and thalamus on contiguous axial MRI slices. We measured the volumes of the basal ganglia, thalamus, and gray/white matter of the frontal cortex. RESULTS: Bipolar spectrum patients as a single group did not differ from control subjects in thalamus and the basal ganglia volumes, but the cyclothymia patients had reductions in the volumes of putamen and the thalamus compared with control subjects. The BPS patients had significantly reduced volume of the white and the gray matter of the frontal cortex. Furthermore, compared with control subjects, BPS patients as a group showed alterations in anisotropy of the internal capsule adjacent to the striatum and thalamus and the frontal white matter. CONCLUSIONS: Our findings indicate that BPS patients may have distinct anatomical alterations in brain structures involved in the regulation of mood and cognition, as well as alterations in these structures' connection to related brain areas.     

Automatic striatal volumetry allows for identification of patients with chorea-acanthocytosis at single subject level

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disease with erythrocyte membrane dysfunction, progressive hyperkinesia, and neuropsychological abnormalities. Neuropathologic and neuroimaging investigations demonstrate damage to the basal ganglia. Here, a novel automated technique of voxel-based magnetic resonance imaging (MRI) analysis was applied to determine the volumes of caudate nucleus and putamen in nine patients with proven ChAc in comparison with 257 healthy controls. At individual subject level, ChAc patients and controls could be reliably discriminated by the volume of the caudate, using a cut-off of 5 ml, or by a value of −3 in terms of z scores. Putaminal volumes were also significantly reduced in ChAc patients, but showed some overlap with controls. The results indicate that this new automated volumetric MRI analysis offers an objective imaging tool for identification of ChAc patients by quantification of basal ganglia atrophy and lends itself to extension to other basal ganglia diseases.     

Psychiatric symptoms associated with cortical-subcortical dysfunction in Alzheimer's disease

Positron emission tomography was used to evaluate 3 Alzheimer's disease (AD) patients: 1 with major depression, 1 with emotional lability, and 1 with apathy. Compared with 5 non-mood-disordered AD patients, the patient with depression had diminished relative regional cerebral blood flow (rel-CBF) in the anterior cingulate and superior temporal cortices, bilaterally. This patient also showed diminished rel-CBF in the left dorsolateral prefrontal and right medial temporal and parietal cortices. The patient with emotional lability had diminished rel-CBF in the anterior cingulate and dorsolateral prefrontal cortices, bilaterally, and left basal ganglia. The patient with apathy had diminished rel-CBF in the basal ganglia and dorsolateral prefrontal cortex, bilaterally. Results are consistent with the hypothesis of a common frontal-temporal-subcortical substrate (e.g., involving aminergic nuclei) in the etiology of depression in AD. Frontal-subcortical dysfunction may also be associated with emotional lability and apathy in AD, although these may be related to a greater involvement of frontal-basal ganglia circuits.     

Greater availability of brain dopamine transporters in major depression shown by [99m Tc]TRODAT-1 SPECT imaging

OBJECTIVE: Studies of laboratory animals have shown that administration of antidepressants of all pharmacological classes produces changes in dopamine transporter binding affinity. These observations suggest that dopamine transporter function may play a critical role in the pathophysiology of depression. The present study was an examination of the availability of brain dopamine transporter sites in patients with major depression and in healthy comparison subjects. METHOD: Single photon emission computed tomographic (SPECT) brain scans were acquired for 15 drug-free depressed patients and 46 age- and gender-matched healthy comparison subjects by using [(99m)Tc]TRODAT-1, a selective dopamine transporter imaging agent. Specific regions of interest in the basal ganglia and supratentorial areas of the brain were examined. Specific uptake values of dopamine transporter [(99m)Tc]TRODAT-1 binding affinity were calculated from the SPECT scan data, and the values for the patients and healthy subjects were compared. RESULTS: The specific uptake values of [(99m)Tc]TRODAT-1 binding were significantly higher in the right anterior putamen (23%), right posterior putamen (36%), left posterior putamen (18%), and left caudate nucleus (12%) of the patients than in the comparison subjects. These differences persisted when the data were further analyzed according to gender and age. CONCLUSIONS: Dopamine transporter affinity may be higher than normal in the basal ganglia of depressed patients. These findings suggest that dopamine function may be altered in depression and may also be a mechanism of antidepressant activity.