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Biomedical subjects

James B Lohr

Publications and source records attributed to James B Lohr.

15 recordsLinked to original sources
PubMed2006

PhenoChipping of psychotic disorders: a novel approach for deconstructing and quantitating psychiatric phenotypes.

Psychiatric phenotypes as currently defined are primarily the result of clinical consensus criteria rather than empirical research. We propose, and present initial proof of principle for, a novel approach to characterizing psychiatric phenotypes. We have termed our approach PhenoChipping, by analogy with, and borrowing paradigms and tools from, gene expression microarray studies (GeneChipping). A massive parallel profiling of cognitive and affective state is done with a PhenoChip composed of a battery of existing and new quantitative psychiatric rating scales, as well as hand neuromotor measures. We present preliminary data from 104 subjects, 72 with psychotic disorders (bipolar disorder-41, schizophrenia-17, schizoaffective disorder-14), and 32 normal controls. Microarray data analysis software and visualization tools were used to investigate: 1. relationships between phenotypic items ("phenes"), including with objective motor measures, and 2. relationships between subjects. Our analyses revealed phenotypic overlap among, as well as phenotypic heterogeneity within, the three major psychotic disorders studied. This approach may be useful in helping us move beyond current diagnostic classifications, and suggests a combinatorial building-block (Lego-like) structure underlies psychiatric syndromes. The adaptation of microarray informatic tools for phenotypic analysis readily facilitates direct integration with gene expression profiling of lymphocytes in the same individuals, a strategy for molecular biomarker identification. Empirically derived clusterings of (endo)phenotypes and of patients will better serve genetic, pharmacological, and imaging research, as well as clinical practice.

Adult↗
PubMed2006

Impaired hemispheric communication in schizophrenia: a study using the consonant-vowel-consonant task.

The ability of the left and right hemispheres to interact and cooperate in the processing of information is important for normal brain functioning. Some investigators have suggested that this cooperation in functioning occurs through a process called "metacontrol." Because studies have suggested that patients with schizophrenia may have problems with interhemispheric interaction, we considered that it could be informative to study such patients from the viewpoint of interhemispheric cooperation, and more specifically that of metacontrol. To do this we utilized an assessment procedure called the consonant-vowel-consonant (CVC) task, in which nonsense three-letter combinations (trigrams) are presented vertically to the left, right and both visual fields. The pattern of errors can be used to determine the type of processing the hemispheres use under the different conditions of presentation. Previous studies have shown that when trigram information is presented to both hemispheres, the left hemisphere appears to switch into a mode that more resembles right hemisphere processing, and we wished to determine if evidence for this switch in the mode of processing also occurred in a sample of patients with schizophrenia. To determine the specificity of any findings to schizophrenia, we also studied a group of patients with bipolar disorder. For the control and bipolar groups, our results showed the typical finding of superior processing in the right visual field (left hemisphere) over the left visual field, with presentation to both visual fields demonstrating a qualitative error pattern resembling that of the left visual field (right hemisphere). Patients with schizophrenia, however, did not demonstrate this switching into a right hemisphere mode upon bilateral presentation of the trigrams and instead seemed to show no switching, or actually switching into more of a left hemisphere mode. Our results suggest that patients with schizophrenia (but not bipolar disorder) may have abnormalities in the cooperative processing of information when it is presented to both hemispheres, and that this disturbance may reflect problems with metacontrol of hemispheric processing.

Adult↗
PubMed2006

Quantitative measurement of handwriting in the assessment of drug-induced parkinsonism.

Monitoring drug-induced side effects is especially important for patients who undergo treatment with antipsychotic medications, as these drugs often produce extrapyramidal side effects (EPS) resulting in movement abnormalities similar to parkinsonism. Scientists have developed several objective laboratory tests to measure and research drug-induced movement disorders, but equipment and tests are complex and costly and have not become accepted in large-scale, multi-site clinical trials. The goals of this study were to test whether a simple handwriting measure can discriminate between individuals with psychotropic-induced parkinsonism, Parkinson's disease, and healthy individuals, and to examine some of the psychometric properties of the measure. We examined pen movement kinematics during cursive writing of a standard word in 13 patients with idiopathic Parkinson's disease (PD), 10 schizophrenia patients with drug-induced parkinsonism (SZ), and 12 normal healthy control participants (NC). Participants were instructed to write the word "hello" in cursive twice, at three vertical height scales. Software was used for data acquisition and analysis of vertical stroke velocities, velocity scaling, and smoothness. There were four important results from this study: (1) both SZ patients with drug-induced EPS and PD participants exhibited impaired movement velocities and velocity scaling; (2) performance on the velocity scaling measure distinguished drug-induced EPS from normal with 90% accuracy; (3) SZ, but not PD participants displayed abnormalities in movement smoothness; and (4) there was a positive correlation between age and magnitude of the velocity scaling deficit in PD participants. This study demonstrates that kinematic analyses of pen movements during handwriting may be useful in detecting and monitoring subtle changes in motor control related to the adverse effects of psychotropic medications.

Adult↗
PubMed2006

Striatopallidal regulation of affect in bipolar disorder.

BACKGROUND: Evidence from the neuroimaging literature suggests that the basal ganglia plays an important role in the regulation of affect. This conclusion stems almost exclusively from group comparisons and it remains unclear whether previous findings can be confirmed from a longitudinal study of mood change. The aim of this study was to increase our understanding of the functional role of the basal ganglia and thalamus in relation to change in affect in patients with bipolar disorder. METHODS: Ten bipolar disorder subjects participated in a functional MRI study. We used a simple motor reaction time task to probe subcortical regions bilaterally. Subjects were scanned twice, once when their self-reported mood ratings indicated hypomania or euthymia and then again when they were in depressed states. RESULTS: Subjects in their euthymic or hypomanic states exhibited increased caudate activity bilaterally and the globus pallidus of the left hemisphere. Longitudinal analyses revealed a significant association between an increase in severity of depression and a decrease in activity in the external segment of the right globus pallidus. CONCLUSIONS: Our findings suggest that the globus pallidus is less responsive during a simple motor task in the depressed compared to the normal or euthymic states in patients with bipolar disorder. These results are consistent with current physiologic models of basal ganglia circuitry in which an increase in caudate activity results in an increase in inhibitory GABAergic outflow to the external globus pallidus and subsequent decrease in thalamocortical excitation and may underlie the clinical manifestations of depression in bipolar disorder. LIMITATIONS: The findings of this study need to be interpreted with caution as correlation coefficients may be overestimated in this small study sample.

Adult↗
PubMed2006

Abnormalities in motor physiology in bipolar disorder.

The primary purpose of this study was to examine motor physiology disturbances in a group of patients with bipolar disorder by using sensitive instrumental procedures. The secondary aim of the study was to examine the effects of the affective state on motor functions. The authors studied 67 individuals meeting DSM-IV criteria for bipolar disorder and 47 healthy comparison subjects. Electromechanical measures of force steadiness and scaling of movement velocity to distance were performed. The authors found that performance on the force steadiness and velocity scaling measures was significantly poorer in the subjects with bipolar disorder, with 58% and 63% of the patients scoring outside the normal range on the force steadiness and velocity scaling measures, respectively. Eighty-four percent of subjects showed impairment on either measure, and 37% showed impairment on both measures. The force steadiness and velocity scaling abnormalities appeared to occur independently of one another and also were not associated with affective state or current medication status. This study demonstrates that motor abnormalities suggestive of basal ganglia dysfunction occur in many patients with bipolar disorder.

Adult↗
PubMed2006

Pharmacogenetics for off-patent antipsychotics: reframing the risk for tardive dyskinesia and access to essential medicines.

First-generation antipsychotics (FGAs) induce tardive dyskinesia, a debilitating involuntary hyperkinetic movement disorder, in 20-50% of individuals with a psychotic illness during chronic treatment. There is presently no curative treatment or definitive predictive test for tardive dyskinesia. The authors note that the three antipsychotic drugs enlisted in the most recent (14th) World Health Organization Model List of Essential Medicines--chlorpromazine, fluphenazine and haloperidol--belong to the FGA therapeutic class. In this regard, the need to choose between the competing objectives of ensuring global access to affordable and efficacious medicines, such as FGAs, and the formidable long-term risk for tardive dyskinesia, may create an ethical conundrum. Pharmacogenetics has thus far been conceptually framed as a tool to individualize therapy with new drugs under patent protection. However, the authors suggest that pharmacogenetics may also improve access to pharmacotherapy through the reintroduction of affordable second-line generic drugs or FGAs with suboptimal safety, as first-line therapy, in targeted subpopulations in whom they present a lower risk for tardive dyskinesia. To impact positively on global public health and distributive justice, a directory complementary to the essential medicines library--one that enlists the 'essential biomarkers' required for optimal pharmacotherapy--may benefit patients who do not have adequate access to new antipsychotic medications. This review discusses pharmacogenetic associations of tardive dyskinesia that are in part supported by meta-analyses and the oxidative stress-neuronal degeneration hypothesis.

Antipsychotic Agents↗
PubMed2005

Lateralized cognitive dysfunction and psychotic symptoms in schizophrenia.

Our understanding of hemispheric asymmetries in schizophrenia can be attributed to extensive neuropsychological and neuroimaging research on this topic; however, it has yet to be determined whether lateralized cognitive dysfunction represents a single core trait in schizophrenia or whether the lateralized impairments are domain specific. To test whether lateralized deficits are core features in schizophrenia we examined performance across a wide range of lateralized cognitive domains including attention, fluency, recognition memory, perception, and arousal. We also examined the relationship between lateralized impairments and psychotic and affective symptoms to determine whether abnormal hemispheric asymmetries were possibly state-related. The sample consisted of 43 subjects with schizophrenia and 66 normal healthy comparison subjects without psychiatric illness. Schizophrenia subjects exhibited abnormal right hemisphere performance on a test of recognition memory and abnormal left hemisphere performance on a measure of arousal. These findings suggest that lateralized cognitive disturbances in schizophrenia do not represent a single core lateralized deficit. Regarding the symptom analyses, severity of positive symptoms was related to right hemisphere cognitive impairment (including fluency and recognition memory), whereas severity of negative symptoms was related to left hemisphere cognitive impairment (including fluency). Overall, our findings suggest that lateralized dysfunction can occur in both hemispheres in schizophrenia, and that the positive psychotic symptoms may relate more to right hemisphere impairment, whereas negative psychotic symptoms may related more to left hemisphere impairment.

Adult↗
PubMed2005

A randomized trial of short-term acute residential treatment for veterans.

OBJECTIVE: A variety of alternatives to acute psychiatric hospital care have been developed over the past several decades. including San Diego's short-term acute residential treatment (START) program, now comprising a certified and accredited network of six facilities with a total of 75 beds. This study compared outcomes, patient satisfaction, and episode costs for a sample of 99 veterans who received acute care either at an inpatient unit at a Department of Veterans Affairs (VA) hospital or at a START facility. METHODS: Consenting participants were randomly assigned to one of the two treatment settings. Follow-up was conducted at two months. During the follow-up period, participants received treatment as usual. Multiple standardized measures were used to maximize validity in assessing symptoms, functioning, and quality of life. RESULTS: Participants who were treated in either a hospital or the START program showed significant improvement between admission, discharge, and two-month follow-up, with few statistically significant differences between the groups in symptoms and functioning. There was some evidence that START participants had greater satisfaction with services. Mean costs for the index episode were significantly lower for START participants (65 percent lower) than for those who were treated in the hospital. CONCLUSIONS: The results of this study suggest that the START model provides effective voluntary acute psychiatric care in a non-hospital-based setting at considerably lower cost. Efforts to replicate and evaluate the model at additional locations merit attention.

Acute Disease↗
PubMed2004

Functional brain asymmetries during visuomotor tracking.

This study examined brain asymmetries elicited during visuomotor tracking. Thirty-two healthy participants performed a fixed gaze, dynamic, pinch force, visuomotor tracking task during a functional magnetic resonance imaging study. The dynamic task required the subject to press a rubber bulb with the thumb to trace a cosine square wave varying in force amplitude from 0-500 cN and having a frequency of 1.5 Hz. Response hand order and direction of the stimulus presentation (right-to-left or left-to-right) were permuted across participants. Two forms of functional cerebral asymmetry were observed, hemispheric specialization and homologous lateralized response. The superior portion of the right middle frontal gyrus and the left supplementary motor area appeared specialized for VM tracking regardless of response hand used or stimulus movement direction. Lateralized effects appeared in the primary sensorimotor hand area, putamen, parietal operculum/posterior insula, dentate nucleus of the cerebellum, precuneus, and middle occipital gyrus. These lateralized areas of activation surfaced when either response hand or direction of stimulus movement was manipulated. The VM task used in this study activated asymmetrical neural activity in the vertically organized skelotomotor system and in sensory systems involving visual attention or proprioception.

Adult↗
PubMed2004

A functional magnetic resonance imaging study of cortical asymmetry in bipolar disorder.

OBJECTIVES: Individuals with bipolar disorder (BPD) exhibit motor, perceptual, and cognitive disturbances involving predominantly right hemisphere dysfunction. This asymmetry has been used to advance the hypothesis that the pathogenesis of bipolar disorder may be related to disturbances of the right cerebral hemisphere. We employed functional magnetic resonance imaging to examine hemispheric asymmetries in manic and depressed BPD. A secondary goal of the study was to examine effects of psychotropic medications on blood volume changes in the motor cortices. METHODS: We studied 18 right-handed BPD and 13 right-handed normal healthy comparison subjects. Blood oxygen level dependent (BOLD) responses in the primary motor area (M1) and supplementary motor area (SMA) of both hemispheres were elicited during reaction time (RT) tasks. RESULTS: Healthy subjects activated the SMA in a reciprocal fashion with significantly greater activity in the left SMA for right hand trials and the right SMA for left hand trials. Depressed BPD subjects failed to show this normal reciprocity indicating a failure to suppress unwanted activity in the ipsilateral right SMA, whereas manic BPD subjects failed to suppress unwanted ipsilateral SMA activity in both hemispheres. Manic and depressed BPD subjects exhibited greater activity in the left primary motor area suggesting increased cortical excitability. BPD subjects treated with antipsychotics or mood-stabilizing medications exhibited longer RTs, lower BOLD responses in M1 and SMA, and a loss of normal hemispheric asymmetry in the SMA than untreated subjects. CONCLUSIONS: The presence of a right hemisphere disturbance in BPD is consistent with the hypothesis that the right hemisphere may be dominant in mood regulation. The presence of both left and right hemisphere disturbances in mania may explain the coexisting psychotic and affective symptoms observed in this condition.

Adult↗
PubMed2003

An fMRI study of affective state and medication on cortical and subcortical brain regions during motor performance in bipolar disorder.

Structural neuroimaging studies have identified abnormalities in the basal ganglia in patients with bipolar disorder. Findings have been mixed with regard to affective state and have not elaborated on the role of medication on functional brain activity. The aims of the present study were to use functional magnetic resonance imaging (fMRI) to test whether depressed and manic bipolar disorder patients differ in terms of activity in cortical and subcortical brain areas and to examine the effects of psychotropic medication. Twenty-four bipolar disorder subjects and 13 healthy comparison subjects participated in an fMRI study of manual reaction time. Both manic and depressed subjects exhibited abnormally elevated blood oxygen level dependent BOLD responses in cortical and subcortical areas. Manic bipolar subjects had significantly higher BOLD responses in the left globus pallidus and significantly lower BOLD responses in the right globus pallidus compared with depressed bipolar patients. Correlational analyses revealed significant relationships between the severity of mania and activity within the globus pallidus and caudate. Patients off antipsychotic or mood-stabilizing medication exhibited significantly higher BOLD responses throughout the motor cortex, basal ganglia and thalamus compared with patients on these medications. These results suggest that affective state in bipolar disorder may be related to a disturbance of inhibitory regulation within the basal ganglia and that antipsychotics and/or mood stabilizers normalize cortical and subcortical hyperactivity.

Affect↗
PubMed2003

Oxidative mechanisms and tardive dyskinesia.

Tardive dyskinesia has been and continues to be a significant problem associated with long-term antipsychotic use, but its pathophysiology remains unclear. In the last 10 years, preclinical studies of the administration of antipsychotics to animals, as well as clinical studies of oxidative processes in patients given antipsychotic medications, with and without tardive dyskinesia, have continued to support the possibility that neurotoxic free radical production may be an important consequence of antipsychotic treatment, and that such production may relate to the development of dyskinetic phenomena. In line with this hypothesis, evidence has accumulated for the efficacy of antioxidants, primarily vitamin E (alpha-tocopherol), in the treatment and prevention of tardive dyskinesia. Early studies suggested a modest effect of vitamin E treatment on existing tardive dyskinesia, but later studies did not demonstrate a significant effect. Because evidence has continued to accumulate for increased oxidative damage from antipsychotic medications, but less so for the effectiveness of vitamin E, especially in cases of long-standing tardive dyskinesia, alternative antioxidant approaches to the condition may be warranted. These approaches may include the use of antioxidants as a preventive measure for tardive dyskinesia or the use of other antioxidants or neuroprotective drugs, such as melatonin, for established tardive dyskinesia.

Antioxidants↗
PubMed2002

Treatment predictors of extrapyramidal side effects in patients with tardive dyskinesia: results from Veterans Affairs Cooperative Study 394.

Predictors for the development of tardive dyskinesia (TD) have been studied extensively over the years, yet there are few studies of predictors of the course of TD after it has developed. Moreover, few studies have examined predictors of the course of other extrapyramidal side effects (EPS) in patients maintained on neuroleptics. The purpose of this study was to determine which modifiable variables are important in the prediction of EPS in patients with persistent TD over a period of as long as 2 years. One hundred fifty-eight patients enrolled in the Veterans Affairs Cooperative Study 394 were included in this study. A linear mixed-effects (LME) analysis to estimate the Abnormal Involuntary Movement Scale score (for TD severity), Simpson-Angus Scale (for parkinsonism severity), and Barnes Akathisia Scale at any given time after intake assessment was performed. The severity of each of the TD and EPS outcomes at any given visit was predicted by their respective baseline severity scores. Additional predictors of a favorable course of TD included lower doses of antipsychotic medications and use of anticholinergic medications. Other predictors of a favorable course of EPS included younger age and the use of atypical antipsychotic medication (for rigidity) and the use of anticholinergic medication (for tremor). These findings indicate that clinician-modifiable factors related to medication usage can influence the outcome of TD and EPS in patients with persistent TD.

Adult↗