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Biomedical subjects

L R Baxter

Publications and source records attributed to L R Baxter.

At least 19 recordsLinked to original sources
PubMed2001

Brain metabolic changes associated with symptom factor improvement in major depressive disorder.

BACKGROUND: Symptoms of major depressive disorder (MDD) have been linked to regional brain function through imaging studies of symptom provocation in normal control subjects and baseline studies of subjects with MDD. We examined associations between change in depressive symptom factors and change in regional brain metabolism from before to after treatment of MDD. METHODS: Thirty-nine outpatients with MDD underwent 18F-fluorodeoxyglucose positron emission tomography scanning before and after treatment with either paroxetine or interpersonal psychotherapy. Associations were determined between changes in regional brain metabolism and changes in four Hamilton Depression Rating Scale factors (anxiety/somatization [ANX], psychomotor retardation [PR], cognitive disturbance [COGN], and sleep disturbance) and two corresponding Profile of Mood States subscales (tension [TENS] and fatigue [FATIG]). RESULTS: Improvement in ANX, PR, TENS, and FATIG factors was associated with decreasing ventral frontal lobe metabolism. Improvement in ANX and TENS was also associated with decreasing ventral anterior cingulate gyrus (AC) and anterior insula activity, whereas improvement in PR was associated with increasing dorsal AC activity. COGN improvement was associated with increasing dorsolateral prefrontal cortex metabolism. CONCLUSIONS: Brain regions that show significant relationships with symptom provocation in normal control subjects have similar relationships with MDD symptoms as they improve with treatment.

Major Depressive Disorder↗
PubMed2001

Cerebral metabolism in major depression and obsessive-compulsive disorder occurring separately and concurrently.

BACKGROUND: The frequent comorbidity of major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) suggests a fundamental relationship between them. We sought to determine whether MDD and OCD have unique cerebral metabolic patterns that remain the same when they coexist as when they occur independently. METHODS: [18F]-fluorodeoxyglucose positron emission tomography (PET) brain scans were obtained on 27 subjects with OCD alone, 27 with MDD alone, 17 with concurrent OCD+MDD, and 17 normal control subjects, all in the untreated state. Regional cerebral glucose metabolism was compared between groups. RESULTS: Left hippocampal metabolism was significantly lower in subjects with MDD alone and in subjects with concurrent OCD+MDD than in control subjects or subjects with OCD alone. Hippocampal metabolism was negatively correlated with depression severity across all subjects. Thalamic metabolism was significantly elevated in OCD alone and in MDD alone. Subjects with concurrent OCD+MDD had significantly lower metabolism in thalamus, caudate, and hippocampus than subjects with OCD alone. CONCLUSIONS: Left hippocampal dysfunction was associated with major depressive episodes, regardless of primary diagnosis. Other cerebral metabolic abnormalities found in OCD and MDD occurring separately were not seen when the disorders coexisted. Depressive episodes occurring in OCD patients may be mediated by different basal ganglia-thalamic abnormalities than in primary MDD patients.

Adult↗
PubMed2001

Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings.

BACKGROUND: In functional brain imaging studies of major depressive disorder (MDD), regional abnormalities have been most commonly found in prefrontal cortex, anterior cingulate gyrus, and temporal lobe. We examined baseline regional metabolic abnormalities and metabolic changes from pretreatment to posttreatment in subjects with MDD. We also performed a preliminary comparison of regional changes with 2 distinct forms of treatment (paroxetine and interpersonal psychotherapy). METHODS: Twenty-four subjects with unipolar MDD and 16 normal control subjects underwent resting F 18 ((18)F) fluorodeoxyglucose positron emission tomography scanning before and after 12 weeks. Between scans, subjects with MDD were treated with either paroxetine or interpersonal psychotherapy (based on patient preference), while controls underwent no treatment. RESULTS: At baseline, subjects with MDD had higher normalized metabolism than controls in the prefrontal cortex (and caudate and thalamus), and lower metabolism in the temporal lobe. With treatment, subjects with MDD had metabolic changes in the direction of normalization in these regions. After treatment, paroxetine-treated subjects had a greater mean decrease in Hamilton Depression Rating Scale score (61.4%) than did subjects treated with interpersonal psychotherapy (38.0%), but both subgroups showed decreases in normalized prefrontal cortex (paroxetine-treated bilaterally and interpersonal psychotherapy-treated on the right) and left anterior cingulate gyrus metabolism, and increases in normalized left temporal lobe metabolism. CONCLUSIONS: Subjects with MDD had regional brain metabolic abnormalities at baseline that tended to normalize with treatment. Regional metabolic changes appeared similar with the 2 forms of treatment. These results should be interpreted with caution because of study limitations (small sample size, lack of random assignment to treatment groups, and differential treatment response between treatment subgroups).

Adult↗
PubMed2000

Mammal-like striatal functions in Anolis. I. Distribution of serotonin receptor subtypes, and absence of striosome and matrix organization.

Serotonin (5-HT) 5-HT(2A) and 5-HT(2C) receptors are thought to play important roles in the mammalian striatum. As basal ganglia functions in general are thought highly conserved among amniotes, we decided to use in situ autoradiographic methods to determine the occurrence and distribution of pharmacologically mammal-like 5-HT(2A) and 5-HT(2C) receptors in the lizard, Anolis carolinensis, with particular attention to the striatum. We also determined the distributions of 5-HT(1A), 5-HT(1B/D), 5 HT(3), and 5-HT(uptake) receptors for comparison. All 5-HT receptors examined showed pharmacological binding specificity, and forebrain binding density distributions that resembled those reported for mammals. Anolis 5 HT(2A/C) and 5-HT(1A) site distributions were similar in both in vivo and ex vivo binding experiments. 5-HT(2A & C) receptors occur in both high and low affinity states, the former having preferential affinity for (125)I-(+/-)-2,5-dimethoxy-4-iodo-amphetamine hydrochloride ((125)I-DOI). In mammals (125)I-DOI binding shows a patchy density distribution in the striatum, being more dense in striosomes than in surrounding matrix. There was no evidence of any such patchy density of (125)I-DOI binding in the anole striatum, however. As a further indication that anoles do not possess a striosome and matrix striatal organization, neither (3)H-naloxone binding nor histochemical staining for acetylcholinesterase activity (AChE) were patchy. AChE did show a band-like striatal distribution, however, similar to that seen in birds.

Animals↗
PubMed2000

Mammal-like striatal functions in Anolis. II. Distribution of dopamine D(1) and D(2) receptors, and a laminar pattern of basal ganglia sub-systems.

We used in situ autoradiographic ligand binding methods to determine the occurrence and distribution of dopamine D(1) and D(2) receptor sub-types in the anole lizard, Anolis carolinensis. Both were present and exhibited pharmacological specificity characteristics similar to those described for mammals. However, unlike in mammals where in the neostriatum [outside the nucleus accumbens/olfactory tubercle complex (NA/OT)] these receptors exhibit only slight dorsolateral (D(2) high, D(1) low) to ventromedial (D(1 )high, D(2) low) gradients that co mingle extensively, in the anole striatum outside the NA/OT there was a striking laminar pattern, with little if any overlap between D(2) (high in a dorsal band) and D(1) (high ventral to the D(2) band) distributions. As D(1) receptors are related to the direct and D(2) to the indirect basal ganglia (BG) subsystems in mammals, we also determined anole striatal distributions of pre-proenkephalin mRNA, a marker for striatal efferents to the indirect BG subsystem in mammals. Here, too, there was a striking laminar pattern, with pre-proenkephalin mRNA in a band similar to that seen for D(2) receptors. The crisp neuroanatomical separation between these classic BG subsystem markers in Anolis striatum make this species attractive for the study of such systems' functions during behavior.

Animals↗
PubMed2000

Personality changes in adult subjects with major depressive disorder or obsessive-compulsive disorder treated with paroxetine.

BACKGROUND: Human and animal studies point to 3 dimensions of personality that change during pharmacotherapy with a selective serotonin reuptake inhibitor (SSRI). Specifically, harm avoidance has been found to decrease, social dominance has been found to increase, and hostility in social situations has been found to decrease with SSRI treatment. We sought to determine personality changes in subjects with either major depressive disorder (MDD) or obsessive-compulsive disorder (OCD) treated with paroxetine. We also sought to determine whether or not these personality changes were associated with disease state (MDD vs. OCD) or treatment response (responders vs. nonresponders). METHOD: Thirty-seven subjects diagnosed with either MDD or OCD (according to DSM-IV criteria) completed the Cattell 16 Personality Factor Inventory (16-PF) before and after treatment with paroxetine. Treatment response was defined as a Clinical Global Impressions-Improvement rating of "much" or "very much" improved and a drop in Hamilton Rating Scale for Depression score of at least 50% for MDD or Yale-Brown Obsessive Compulsive Scale score of at least 30% for OCD. RESULTS: No significant differences were found between subjects with MDD and OCD in personality change with treatment. In the whole group, treatment responders had a greater decrease than nonresponders in 16-PF factors relating to harm avoidance. An increase in social dominance factors and a decrease in factors relating to hostility in social situations were found, but these changes were not significantly different between responders and nonresponders. CONCLUSION: These findings indicate that certain personality dimensions change with SSRI treatment and that some of these changes are independent of clinical treatment response.

Adult↗
PubMed1999

Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine.

Functional brain imaging studies of subjects with Major Depressive Disorder (MDD) have suggested that decreased dorsolateral (DLPFC) and increased ventrolateral (VLPFC) prefrontal cortical activity mediate the depressed state. Pre- to post-treatment studies indicate that these abnormalities normalize with successful treatment. We performed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans on 16 outpatients with MDD before and after treatment with paroxetine (target dose = 40 mg/day). Regions of interest (ROIs) for this analysis were drawn by a rater blind to subject identity on the magnetic resonance image of each subject and transferred onto their coregistered PET scans. We hypothesized that DLPFC metabolism would increase, while ventral frontal metabolism [in the VLPFC, the orbitofrontal cortex (OFC), and the inferior frontal gyrus (IFG)] would decrease with successful treatment. Treatment response was defined as a decrease in the Hamilton Depression Rating Scale of > 50% and a Clinical Global Improvement Scale rating of 'much' or 'very much' improved. By these criteria, nine of the subjects were classified as treatment responders. These responders had significantly greater decreases in normalized VLPFC and OFC metabolism than did non-responders. There were no significant effects of treatment response on change in the DLPFC or IFG in this sample. However, there was a positive correlation between change in HAM-D scores and change in normalized IFG and VLPFC metabolism. There were no significant interactions with laterality. On pre-treatment scans, lower metabolism in the left ventral anterior cingulate gyrus was associated with better treatment response. These findings implicate ventral prefrontal-subcortical brain circuitry in the mediation of response to serotonin reuptake inhibitors in MDD.

Adult↗
PubMed1999

Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder.

Previous positron emission tomography (PET) studies of patients with obsessive-compulsive disorder (OCD) have found elevated glucose metabolic rates in the orbitofrontal cortex (OFC) and caudate nuclei that normalize with response to treatment. Furthermore, OCD symptom provocation differentially activates specific subregions of the OFC, which have distinct patterns of connectivity and serve different functions. Therefore, we sought to determine the role of specific subregions of the OFC and associated subcortical structures in mediating OCD symptoms, by determining how glucose metabolism in these structures changed with paroxetine treatment of OCD patients. We also sought to determine whether pretreatment OFC metabolism would predict response to paroxetine, as it has for other OCD treatments. Twenty subjects with OCD received [18F]-fluorodeoxyglucose (FDG)-PET scans before and after 8 to 12 weeks of treatment with paroxetine, 40 mg/day. In patients who responded to paroxetine, glucose metabolism decreased significantly in right anterolateral OFC and right caudate nucleus. Lower pretreatment metabolism in both left and right OFC predicted greater improvement in OCD severity with treatment. These results add to evidence indicating that orbitofrontal-subcortical circuit function mediates the symptomatic expression of OCD. Specific subregions of the OFC may be differentially involved in the pathophysiology of OCD and/or its response to pharmacotherapy.

Cerebral Cortex↗
PubMed1998

FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder.

In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [18F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F = 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group (tau = 0.35, P = 0.04), but worse outcome (tau = -0.57, P = 0.03) in the fluoxetine-treated group. These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication.

Adult↗
PubMed1998

Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder.

BACKGROUND: Neuroimaging studies provide strong evidence that the pathophysiology of obsessive-compulsive disorder (OCD) involves abnormal functioning along specific frontal-subcortical brain circuits. METHOD: A literature search was carried out for all brain imaging studies of patients with OCD. We also reviewed the basic science literature on the functional neuroanatomy of cortico-basal ganglia circuits, and integrated this information with neuroimaging data in OCD to formulate a theoretical model of brain mediation of OCD symptoms and response to treatment. RESULTS: At least a subgroup of patients with OCD may have abnormal basal ganglia development. Functional neuroimaging studies indicate that OCD symptoms are associated with increased activity in orbitofrontal cortex, caudate nucleus, thalamus and anterior cingulate gyrus. CONCLUSIONS: OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, perhaps due to an imbalance of tone between direct and indirect striato-pallidal pathways. We present a model which describes how frontal-subcortical brain circuitry may mediate OCD symptomatology, and suggest a hypothesis for how successful treatments may ameliorate symptoms, via their effects on circuit activity.

Brain Diseases↗
PubMed1997

Electroconvulsive therapy increases circadian amplitude and lowers core body temperature in depressed subjects.

BACKGROUND: Reduced amplitude of the circadian temperature rhythm and elevated nocturnal body temperature normalize after successful pharmacotherapy of major depression. METHODS: Core body temperature was continually monitored in three groups: a) 6 depressed patients before an electroconvulsive therapy (ECT) course and b) after an ECT course; and c) 6 healthy, sex-matched controls of similar age. RESULTS: The 24-hour profile of temperature was significantly different in patients pre-ECT than in patients post-ECT or in controls. Post-ECT subjects and controls manifested 24-hour profiles similar to one another. Circadian temperature rhythm amplitude increased after ECT. The mean asleep and mean 24-hour temperatures were significantly higher in patients pre-ECT than post-ECT and controls. CONCLUSIONS: We find that ECT restores a disrupted circadian temperature rhythm in depressed patients.

Adult↗
PubMed1997

Oral 18F-fluoro-2-deoxyglucose for primate PET studies without behavioral restraint: demonstration of principle.

We describe a method of orally administering 18F-fluoro-2-deoxyglucose (FDG) for positron emission tomography (PET) scans to determine local cerebral metabolic rates for glucose (LCMRGlc), normalized to that of whole brain, in fully conscious, non-restrained primates. Oral FDG-PET studies were performed in both non-restrained and chaired monkeys, and in one human where results could be compared with traditional intravenous FDG administration. The oral route of FDG administration gave images and whole brain-normalized PET LCMRGlc results comparable to those obtained by the intravenous route. This oral FDG-PET method may provide a useful means by which to obtain measures of LCMRGlcs for brain structures, relative to each other, in non-restrained, non-drugged primates in field and laboratory studies. This method might also have clinical applications for PET studies of children.

Administration, Oral↗
PubMed1996

Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder.

BACKGROUND: We sought to determine in a new patient sample whether symptomatic improvement in obsessive-compulsive disorder treated with behavior modification is accompanied by significant changes in glucose metabolic rates in the caudate nucleus, measured with positron emission tomography, as seen in a previous study. Second, by combining samples from this and the previous study, we also examined whether there were pathologic correlational relationships among brain activity in the orbital cortex, caudate nucleus, and thalamus that obtained before behavioral treatment of obsessive-compulsive disorder, but that decreased significantly with symptom improvement. METHODS: Nine patients with obsessive-compulsive disorder were studied with positron emission tomography before and after 10 weeks of structured exposure and response prevention behavioral and cognitive treatment. Results were analyzed both alone and combined with those from nine similar subjects from the previous study. RESULTS: Behavior therapy responders had significant (P < .05) bilateral decreases in caudate glucose metabolic rates that were greater than those seen in poor responders to treatment. Before treatment, there were significant correlations of brain activity between the orbital gyri and the head of the caudate nucleus and the orbital gyri and the thalamus on the right. These correlations decreased significantly after effective treatment. CONCLUSIONS: These results replicate and extend previous findings of changes in caudate nucleus function with behavior therapy for obsessive-compulsive disorder. A prefrontal cortico-striato-thalamic brain system is implicated in mediation of symptoms of obsessive-compulsive disorder.

Adult↗
PubMed1996

Risperidone augmentation of SRI treatment for refractory obsessive-compulsive disorder.

BACKGROUND: Although serotonin reuptake inhibitors (SRIs) are the mainstay of pharmacologic treatment for obsessive-compulsive disorder (OCD), many patients do not have an adequate response to these medications. One approach to treating SRI-refractory OCD patients has been to add other classes of medications to the SRI. We predicted that augmentation with risperidone would alleviate symptoms in SRI-refractory OCD patients. METHOD: 21 patients were treated openly with the combination of an SRI and adjunctive risperidone (mean dose = 2.75 mg/day). All met DSM-IV criteria for obsessive-compulsive disorder and had a variety of comorbid disorders. Prior to addition of risperidone, all patients had failed to respond to at least one adequate trial of an SRI. Response was determined by clinical judgment and standardized rating scales. RESULTS: 5 (24%) of the 21 patients experienced side effects (most commonly, akathisia), which forced discontinuation of risperidone. Of the 16 patients who tolerated combined treatment, 14 (87%) had substantial reductions in obsessive-compulsive symptoms within 3 weeks. Patients with horrific mental imagery had the strongest and fastest response, often within a few days. Patients with comorbid psychotic disorders improved gradually over 2 to 3 weeks. Patients with comorbid tic disorders had the poorest rate of response and highest rate of akathisia. CONCLUSION: These results suggest that risperidone augmentation is effective and well tolerated in patients with SRI-refractory obsessive-compulsive disorder. Response to risperidone augmentation appears to be influenced by symptom subtypes and comorbid conditions. Controlled trials are required to confirm the efficacy of risperidone augmentation for refractory OCD.

Adult↗
PubMed1994

Lithium sustains the acute antidepressant effects of sleep deprivation: preliminary findings from a controlled study.

Early morning sleep deprivation (patient awake from 0200 to 2200 hours) produces a same-day antidepressant effect in approximately one-half of patients with major depression. Unfortunately, these antidepressant effects are short-lived and patients usually relapse to baseline depression levels within 48 hours. Recent work suggests, however, that the use of lithium with early morning sleep deprivation sustains this rapid antidepressant effect and makes it clinically useful. In a 30-day study, we compared the abilities of four different treatments (lithium plus early morning sleep deprivation, lithium plus a control sleep deprivation procedure, and desipramine with either of the two sleep manipulations) to induce a rapid (next-day) and sustained antidepressant response in 16 depressed patients. Lithium plus early morning sleep deprivation produced a quicker response than lithium with the control sleep deprivation, and the response was sustained for at least 30 days. In this design, however, lithium/early morning sleep deprivation was no faster than either of the two desipramine/sleep deprivation conditions in inducing remission. These results support the results of previous studies and suggest further investigation of this novel sleep/pharmacologic intervention is warranted.

Adult↗
PubMed1994

Positron emission tomography studies of cerebral glucose metabolism in obsessive compulsive disorder.

In the last 7 years, positron emission tomography (PET) scanning studies of obsessive compulsive disorder have given us new insights into misfunctionings of brain systems that may mediate the symptomatic expression of this classical "neurosis." Work by several PET groups indicates that a prefrontal cortex-basal ganglia-thalamic circuit may be the brain pathway leading to the broken record patterns of obsessions and compulsions.

Brain↗
PubMed1993

Results of a clinical receiver operating characteristic study comparing filtered backprojection and maximum likelihood estimator images in FDG PET studies.

The results of a receiver operator characteristic (ROC) study comparing maximum likelihood estimator (MLE) reconstructions of human FDG PET brain scan data to filtered backprojection reconstructions of the same data are reported. The purpose of the study was to determine whether MLE reconstructions would result in higher detectability of small focal lesions introduced artificially into otherwise normal scan data. One physician assisted in defining the location and intensity of the lesions and five physicians read the final images. Data from 90 datasets were used for the study. Of those, 42 were left in their original "normal" condition and 48 were modified by added lesions. All datasets were reconstructed by the two methods and submitted to the five physicians for evaluation. The results show an increase in the area under the ROC curve from approximately 0.65 for filtered backprojection to approximately 0.71 for the maximum likelihood reconstructions for four of the five observers with good statistical significance.

Brain↗