Does regional brain perfusion correlate with eating disorder symptoms in anorexia and bulimia nervosa patients?

OBJECTIVE: Using single photon emission computed tomography (SPECT), we sought brain perfusion correlates of eating disorder symptoms in anorexia and bulimia nervosa patients. METHOD: We investigated 67 female eating disordered (ED) patients. Eating disorder symptoms were measured by the Eating Disorders Inventory (EDI). Determination of brain areas in which regional perfusion co-varied with drive for thinness, bulimia, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness and maturity fears was done by open explorative correlation analysis using Statistical Parametrical Mapping (SPM). RESULTS: A significant positive correlation between scores on body dissatisfaction and ineffectiveness, and brain perfusion in the prefrontal and parietal cortex was demonstrated. There were no correlations between other eating disorder symptoms and brain perfusion. CONCLUSION: Based on the finding of an association between regional brain flow and body dissatisfaction and ineffectiveness, we argue that neurobiological findings in ED patients may not only reflect emotional and behavioural factors but cognitive-evaluative features as well.

Differences of cortical 5-HT2A receptor binding index with SPECT in subtypes of anorexia nervosa: relationship with personality traits?

OBJECTIVE: Using single photon emission computed tomography and the 5-HT2A receptor antagonist, 123I-5-I-R91150, we explored differences in 5-HT2A binding index in anorexia nervosa patients with and without bulimic features. We also searched for associations between temperament dimensions and cortical 5-HT2) binding. METHOD: About 9 restrictive and 7 bulimic anorexia nervosa patients were examined and cortical 123I-5-I-R91150 binding index values were compared between the two subgroups. Open explorative correlation analysis was used to examine any relationships between binding index values and temperament scores, as assessed with the Temperament and Character Inventory. RESULTS: 5-HT2A binding index was significantly reduced in the parietal cortex in bulimic anorexia nervosa patients in comparison with restrictive anorectics. Further, a positive correlation was documented between reward dependence and parietal 5-HT2A binding index across patients in the two subgroups. DISCUSSION: Restrictive anorexia nervosa patients differ from binging/purging anorexia nervosa patients on the basis of a reduced parietal 5-HT2A binding index in the latter. We speculate that the finding of a positive correlation between parietal 5-HT2A binding and reward dependence might reflect an association between these two variables, at least in anorexia nervosa patients.

Serotonin transporter and dopamine transporter imaging in the canine brain.

The serotonergic and dopaminergic systems are involved in a wide range of emotional and behavioral aspects of animals and humans and are involved in many neuropsychiatric disorders. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are designed to block the 5-HT transporter (SERT), thereby increasing the available 5-HT in the brain. Functional imaging with specific SERT and dopamine transporter (DAT) ligands contributes to the study of the SSRI-transporter interaction. First, we evaluated the feasibility of a canine model in the study of the SERT and DAT with the radioligands [123I]-beta-CIT and [123I]-FP-CIT as well as single-photon emission computed tomography imaging. Second, we studied the effect of SSRIs (sertraline, citalopram and escitalopram) on the SERT and DAT in two dogs. The position of the canine model in the study of the SERT and DAT is discussed and compared with other animal models.

Sex steroid level, androgen receptor polymorphism, and depressive symptoms in healthy elderly men.

OBJECTIVES: To determine the prevalence of depression in a cohort of elderly men as assessed using a 30-item Geriatric Depression Scale (GDS) score and to describe the association between this score and sex steroids, androgen receptor (AR) polymorphism, and general health status. DESIGN: Observational study on the relationship between sex steroid status and health-related parameters. SETTING: Community-based. PARTICIPANTS: Ambulatory men (n=236 in 1997, n=192 in 2000) aged 70 and older at inclusion in 1996, interviewed in 1997 and 2000. MEASUREMENTS: Serum levels of testosterone, estradiol, sex hormone binding globulin (SHBG), dehydroepiandrosterone-sulfate (DHEAS), cortisol, and the AR gene cytosine, adenine, guanine (CAG)-repeat length polymorphism were determined. Free testosterone and free estradiol were calculated. Questionnaires included GDS, 36-item Short Form, and Rapid Disability Rating Scale-2. RESULTS: Median age was 75.3 years (interquartile range=73.5-78.5). A GDS score of 11 or greater was found in 30 (12.7%) men. Age and GDS score were significantly interrelated (P<.01), as were all health-assessment scores. GDS scores were not related to (free) testosterone or AR polymorphism in 1997 or 2000. In 1997 only (n=236), higher GDS scores were related to higher estradiol, free estradiol, and DHEAS levels. CONCLUSION: The data did not support a role for testosterone in depression in elderly community-based men as assessed using the GDS.

Brain perfusion SPECT in impulsivity-related personality disorders.

BACKGROUND: Impulsive behaviours in patients with cluster B personality disorders are associated with low glucose metabolism and regional cerebral blood flow in the frontal cortex and subcortical structures. The aim of this study is to confirm the presence of a particular pattern of brain perfusion in a sample of borderline (BPD) and anti-social personality disorder (ASPD) patients using brain perfusion single photon emission computed tomography (SPECT). METHODS: A brain perfusion SPECT study was performed in 37 patients with BPD or ASPD (and no Axis I diagnosis) and 34 healthy control participants. Data were acquired on a triple head Toshiba gamma camera. Scatter and attenuation correction was done. Reconstructed SPECT images were analyzed by Statistical Parametrical Mapping (SPM99). RESULTS: There were no significant differences in age and gender distributions between the patients and the healthy controls. With regard to the functional imaging results, patients were characterized by a reduced regional cerebral blood flow (rCBF) in right temporal and prefrontal brain areas, including the right lateral temporal cortex (BA 21), the right frontopolar cortex (BA 10) and the right ventrolateral prefontal cortex (BA 47). CONCLUSIONS: Patients with BPD and ASPD who showed impulsive behaviour have diminished rCBF in areas of the right prefrontal and temporal cortex.

Blunted prefrontal perfusion in depressed patients performing the Tower of London task.

Impairment of cognition is common in depression, and many tasks on which depressed patients are impaired are sensitive to frontal lobe dysfunction. Performance on the Tower of London (TOL) task, which includes setting up and maintaining multiple subgoals at the same time, has been shown to depend on intact prefrontal cortices. Single photon emission computed tomography (SPECT) with 99mTc-ethyl cysteinate dimer was used to compare cognitive activation in nine depressed patients and nine normal controls during performance of the TOL task. Planning times and accuracy were measured as performance parameters, and functional imaging data were analysed with statistical parametric mapping (SPM99) to determine significant voxel-wise differences in activation between the two groups. During activation, depressed patients were as accurate as controls but differed in that they spent more thinking time. These findings agree with the results of neuropsychological studies. Compared with the normal controls, depressed patients were characterized by a blunted perfusion response in the right middle frontal cortex [Brodmann area (BA) 6] and the left superior frontal gyrus (BA 9), and by increased perfusion in the right superior temporal gyrus (BA 21) and the insular cortex (BA 13). This study shows that a SPECT activation procedure using the TOL task under classical test conditions is feasible in depressed patients.

Comparison of cortical 5-HT2A receptor binding in bulimia nervosa patients and healthy volunteers.

OBJECTIVE: Bulimia nervosa has been associated with alterations in central serotonergic (5-HT) function. This study investigated iodine-labeled 4-amino-N-[1-[3-(4-fluorophenoxy) propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide ((123)I-5-I-R91150) binding to the 5-HT(2A) receptor in the brain by using single photon emission computed tomography in acutely ill bulimia nervosa patients. METHOD: Cortical (123)I-5-I-R91150 binding in 10 normal-weight patients with bulimia nervosa, purging type, was compared with that of 11 healthy volunteers. RESULTS: The 5-HT(2A) binding index of the bulimia nervosa patients, with and without correction for age, was not significantly different from that of the comparison group. CONCLUSIONS: As a group, acutely ill bulimia nervosa patients cannot be discriminated from healthy subjects on the basis of cortical (123)I-5-I-R91150 binding to the 5-HT(2A) receptor.

Toward clinical application of neuropsychological activation probes with SPECT: a spatial working memory task.

UNLABELLED: The concept of working memory is central to theories of human cognition, because it is essential to human skills such as decision making and deductive reasoning. Although PET and functional MRI have provided robust data on the recruitment of specific pathways in working memory tasks, the experimental settings of these studies may not be transferable to a clinical situation. Hence, to develop neuropsychological SPECT activation probes that are suitable for daily clinical practice, this study reports on a neuropsychological activation task of spatial working memory under classical neuropsychological test conditions in healthy subjects. METHODS: Reaction times and accuracy were measured as behavioral parameters and functional imaging data were analyzed with statistical parametric mapping to determine significant voxel-wise changes between the perception task and the memory task. RESULTS: Subjects reacted more slowly and performed less accurately during the memory task compared with the perception task, findings that are in keeping with other neuropsychological studies. Also, the overall pattern of brain activations revealed in our experiment is consistent with the data of the literature, thereby validating our test probe. CONCLUSION: From a practical viewpoint, the close resemblance of the test conditions of the SPECT procedure with those of the investigation room and the relative simplicity of the task under study probably constitute major advantages for future clinical application of the SPECT procedure in patients with cognitive impairments.

Decreased 5-HT2a receptor binding in patients with anorexia nervosa.

UNLABELLED: Indirect estimations of brain neurotransmitters in patients with anorexia nervosa (AN) and low weight have demonstrated a reduction in brain serotonin (5-HT) turnover in general and led to hypotheses about dysfunction in the 5-HT(2a) receptor system. It was our aim to investigate the central 5-HT(2a) receptor binding index using SPECT brain imaging. METHODS: The 5-HT(2a) receptors of low-weight patients with AN were studied by means of the highly specific radioiodinated 5-HT(2a) receptor antagonist 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide or (123)I-5-I-R91150. Fifteen patients with clinical diagnoses of AN and 11 age-matched healthy volunteers received intravenous injections of 185 MBq (123)I-5-I-R91150 and were scanned with high-resolution brain SPECT. RESULTS: Compared with healthy volunteers, patients with AN had a significantly reduced 5-HT(2a) binding index in the left frontal cortex, the left and right parietal cortex, and the left and right occipital cortex. A significant left-right asymmetry was noted in the frontal cortex (left < right). CONCLUSION: These results are in accordance with diminished metabolic and perfusion of frontal and parietal cortices reported in recent neuroimaging studies and imply localized disturbed serotonergic function. The data are discussed in the light of possible confounding factors related to the low-weight AN status. A regional cortical reduction in 5-HT(2a) binding index is not likely to be caused by a general reduction in serotonergic function due to the possible confounding factors. Suggestions for further research are given.

Application of a neuropsychological activation probe with SPECT: the 'Tower of London' task in healthy volunteers.

BACKGROUND: Human planning is a complex mental process that may be evaluated by the 'Tower of London' (TOL) task, which includes setting up and maintaining multiple subgoals at the same time. Although positron emission tomography and functional magnetic resonance imaging have provided reliable data on the recruitment of a neural network engaged in planning tasks, the experimental settings of these studies cannot be applied in clinical conditions. Hence, this study reports on the TOL task under classical neuropsychological test conditions using single photon emission computed tomography (SPECT) activation in 10 healthy subjects. METHODS: Participants first performed a control task and then an activation task, i.e., the TOL planning task In the planning task, subjects were required to change, in the minimum number of moves possible, an initial arrangement of beads to match a goal arrangement. Subjects solved a set of eight TOL problems of increasing difficulty. A control task was designed such that it eliminates planning abilities, which is the process of interest. Planning times and accuracy were measured as performance parameters and functional imaging data were analysed with statistical parametric mapping (SPM99) to determine significant voxel-wise activations between the planning task and the control task. RESULTS: Both overall and for each difficulty level, measures of accuracy were within the normal range. Similar results were found for the overall thinking time and thinking times of each difficulty level. That is, performance of the healthy subjects during the TOL task replicated the typical pattern of results found with appropriate control samples in the literature. Also, activation of the right prefrontal cortex was consistent with other functional imaging results, thereby validating the use of the TOL task in a SPECT activation paradigm. CONCLUSIONS: Based on the present study it may be concluded that the close resemblance of the test conditions of the SPECT activation procedure with those of the TOL task in the investigation room constitutes a major advantage for future application of the SPECT activation procedure in clinical conditions.

Mindfulness and reduced cognitive reactivity to sad mood: evidence from a correlational study and a non-randomized waiting list controlled study.

Cognitive Reactivity (CR) refers to the degree to which a mild dysphoric state reactivates negative thinking patterns, and it has been found to play a key causal role in depressive relapse. Although Mindfulness-Based Cognitive Therapy (MBCT) directly aims to address this mechanism of CR, the relationship between mindfulness and CR has not been tested to date. Using a cross-sectional design (Study 1; n = 164) and a non-randomized waiting list controlled design (Study 2; MBCT [n = 18] vs. waiting list [n = 21]), the authors examined the relationship between naturally occurring levels of mindfulness (Study 1) and MBCT (Study 2) on the one hand, and CR on the other hand. In line with predictions, it was found that (a) trait mindfulness is significantly negatively correlated with CR, even when controlled for current depressive symptoms and prior history of depression (Study 1), and that (b) MBCT, compared to a matched control group, significantly reduces CR, and that this effect of MBCT on reduction of CR is mediated by a positive change in mindfulness skills (Study 2). Results provide first evidence for the claim that mindfulness practices in MBCT are designed to address the process of CR.

Imaging of mild traumatic brain injury using 57Co and 99mTc HMPAO SPECT as compared to other diagnostic procedures.

BACKGROUND: Traumatic brain injury (TBI) is usually assessed with the Glasgow Coma Scale (GCS), CT and EEG. TBI can result from either the primary mechanical impact or secondary (ischemic) brain damage, in which calcium (Ca) plays a pivotal role. This study was undertaken to compare the applicability of SPECT using 57Co as a Ca-tracer in patients with mild traumatic brain injury. MATERIAL/METHODS: 8 patients with mild TBI (GCS 15) were clinically examined and studied with EEG, neuropsychological testing (NPT) and SPECT within 2 days post-TBI. After i.v.-administration of 37 MBq (1 mCi) 57Co (effective radiation dose 0.34 mSv x MBq(-1); 1.24 rem x mCi(-1); physical half-life 270 days, biological half-life 37.6 h), single-headed SPECT (12 h pi) was performed, consecutively followed by standard 925 MBq (25 mCi) Tc-99m HMPAO SPECT. RESULTS: In 6 of the 8 patients, baseline NPT and SPECT showed focal abnormalities in the affected frontal and temporal brain regions, which were in good topographical accordance. CT and EEG did not detect (structural) lesions in any of these cases. CONCLUSIONS: Single-headed 57Co-SPECT is able to show the site and extent of brain damage in patients with mild TBI, even in the absence of structural lesions. It may confirm and localize NPT findings. The predictive value of 57Co-SPECT should be assessed in larger patient series.