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Donald C Goff

Publications and source records attributed to Donald C Goff.

52 records · Page 3Linked to original sources
PubMed2004

Attitudes of schizophrenia outpatients toward psychiatric medications: relationship to clinical variables and insight.

BACKGROUND: Attitude toward medications is important for medication adherence. A patient's drug attitude probably reflects a weighing of benefits against experienced or anticipated side effects or risks associated with the medication. We predicted (1) that drug attitudes would be more positive among schizophrenia patients taking second-generation compared to first-generation antipsychotics because of their greater tolerability and efficacy; and (2) that greater insight into illness, fewer extrapyramidal symptoms, and better social functioning would be associated with better attitudes toward psychiatric medication. METHOD: In a cross-sectional study of 81 DSM-IV-diagnosed schizophrenia outpatients, we used multivariate analysis to determine clinical and demographic predictors of drug attitude. Drug attitude was assessed with the 10-item Drug Attitude Inventory (DAI). The relationship between the DAI and psychopathology, insight, extrapyramidal symptoms, level of functioning, and type of antipsychotic (first-generation versus second-generation versus clozapine) was examined. RESULTS: Less awareness of current symptoms, presence of deficit symptoms, and employment predicted a negative attitude toward psychiatric medications. Extrapyramidal symptoms did not predict drug attitude. Drug attitudes were no different between patients taking first- or second-generation antipsychotics or clozapine. CONCLUSION: Patients may not favor second-generation over first-generation antipsychotics, and extrapyramidal symptoms may not be a primary factor determining attitudes. While attitudes may be more positive in patients who recognize therapeutic drug effects, patients who work may view medications particularly negatively, possibly due to a sense of stigma. Because drug attitudes may reflect compliance and are difficult to predict, clinicians should inquire directly.

Adult↗
PubMed2003

Impaired hippocampal recruitment during normal modulation of memory performance in schizophrenia.

BACKGROUND: Patients with schizophrenia demonstrate poor verbal memory, ascribed to impaired prefrontal and hippocampal function. Healthy adults can increase recall accuracy following encoding interventions, such as item repetition and the formation of semantic associations. We examined the effects of these interventions on both memory performance and retrieval-related hippocampal activity in healthy adults and patients with schizophrenia. METHODS: Twelve patients with schizophrenia and twelve healthy control subjects participated. During study, subjects counted either the number of meanings or T-junctions in words seen only once or repeated four times. At test, O15-positron emission tomography scans were acquired while subjects completed word-stems with previously studied items. RESULTS: Control subjects recalled more words overall, but both groups demonstrated similar performance benefits following deeper encoding. Both item repetition and the use of a semantic encoding task were associated with memory retrieval-related hippocampal recruitment in control but not schizophrenic participants. Patients with schizophrenia demonstrated greater activation of prefrontal cortical areas during word retrieval. CONCLUSIONS: Despite a lack of hippocampal recruitment, patients with schizophrenia showed intact modulation of memory performance following both encoding interventions. Impaired hippocampal recruitment, in concert with greater prefrontal activation, may reflect a specific deficit in conscious recollection in schizophrenia.

Hippocampus↗
PubMed2003

Clinical characteristics, cognitive functioning, and criminal histories of outpatients with schizophrenia.

OBJECTIVE: The authors examined the relationships between clinical characteristics, cognitive functioning, and history of violent behavior and substance use among outpatients with schizophrenia. METHODS: Ninety-six patients with a diagnosis of schizophrenia or schizoaffective disorder completed a clinical and neuropsychiatric battery that included tests of general intelligence, executive and frontal lobe function, visual-motor processing, and motor function. Violent behavior was defined on the basis of arrest records. Self-reported violent behavior and substance use were recorded. The study participants were separated into three groups: history of violent arrest (N=34), nonviolent arrest (N=23), and no arrest (N=39). The three groups were compared for differences in demographic characteristics, clinical symptoms, and scores on neuropsychological tests. RESULTS: Fifty-seven (59 percent) of the 96 participants had a history of arrest. Persons who were arrested for nonviolent crimes had a significantly lower mean+/-SD number of arrests (3.39+/-3.7) than those arrested for violent crimes (9.24+/-8.9). No significant differences in neuropsychological test scores or clinical ratings were found between the three groups. The prevalence of substance use disorders was 65 percent, 57 percent, and 36 percent among patients with a history of violent, nonviolent, and no arrest, respectively. Only 47 percent of participants with a criminal history accurately reported this history, and 11 percent of participants with a history of drug-related arrests acknowledged previous substance use. CONCLUSIONS: Performance on neuropsychiatric tests does not distinguish stable outpatients with schizophrenia who have a history of violent behavior from those who do not have such a history. Two established predictors of violence, a history of arrests and substance abuse, are unreliable when assessed by self-report.

Adult↗
PubMed2002

Motor cortical excitability in schizophrenia.

BACKGROUND: Transcranial magnetic stimulation (TMS) provides a method to examine cortico-cortical motor excitability and hemispheric asymmetry in unmedicated and medicated schizophrenia patients. METHODS: Fourteen right-handed schizophrenia patients (seven on conventional neuroleptics and seven medication-free) were compared with seven right-handed, age- and gender-matched normal control subjects. Motor threshold for induction of motor-evoked potentials (MEPs) and bihemispheric intracortical inhibition and facilitation were measured with single-pulse and paired-pulse TMS. RESULTS: Medicated patients showed an approximately 5% higher motor thresholds in both hemispheres than unmedicated patients and control subjects. Normal control subjects had a nearly 10% higher threshold for the left than the right hemisphere, whereas the opposite was true for the patient groups (5-10% higher threshold on the right than the left). Medicated patients showed significantly decreased intracortical inhibition relative to unmedicated patients and control subjects. This difference was more pronounced for the right than for the left hemisphere. CONCLUSIONS: Treatment with conventional neuroleptics is associated with increased motor threshold and decreased intracortical inhibition, whereas unmedicated patients did not differ from normal control subjects on these measures; however, schizophrenia may be characterized by a reversed pattern of interhemispheric corticospinal excitability.

Adult↗
PubMed2002

D-Cycloserine added to risperidone in patients with primary negative symptoms of schizophrenia.

BACKGROUND: D-Cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor has previously been shown to improve negative symptoms when added to conventional antipsychotics and to worsen negative symptoms when added to clozapine. The purpose of this study was to examine the effects of D-cycloserine when added to risperidone on negative symptoms of schizophrenia. METHOD: Ten patients with schizophrenia who were treated with risperidone completed consecutive two week trials of placebo and four doses of D-cycloserine. Clinical assessments were videotaped and were scored by a rater who was blind to temporal sequence. RESULTS: D-Cycloserine at a dose of 50mg/day was associated with significant reduction in negative symptoms (mean=10%). Ratings of depression, extrapyramidal side effects, and cognitive function were unchanged. Serum concentrations of glutamate and serine increased significantly on this dose of D-cycloserine. CONCLUSIONS: This preliminary study suggests that combination of D-cycloserine, 50mg/day, with risperidone may improve negative symptoms of schizophrenia over a narrow dose range. The degree of improvement appears to be intermediate between improvement of negative symptoms observed with combination of D-cycloserine with conventional antipsychotics and worsening of negative symptoms observed with combination of D-cycloserine with clozapine in previous trials of identical design.

Adult↗
PubMed2002

Schizophrenic subjects show deficient inhibition but intact task switching on saccadic tasks.

BACKGROUND: Schizophrenic patients have executive function deficits, presumably on the basis of prefrontal cortex dysfunction. Although they consistently show impaired inhibition, the evidence of a task switching deficit is less consistent and is often based on performance of neuropsychological tests that require several cognitive processes (e.g., the Wisconsin Card Sort Test [WCST]). We investigated inhibition and task switching using saccadic tasks to determine whether schizophrenic patients have selective impairments of these executive functions. METHODS: Sixteen normal and 21 schizophrenic subjects performed blocks of randomly mixed prosaccade and antisaccade trials. This gave rise to four trial types: prosaccades and antisaccades that were either repeated or switched. Response accuracy and latency were measured. Schizophrenic subjects also performed the WCST. RESULTS: Schizophrenic subjects showed abnormal antisaccade and WCST performance. In contrast, task switching was normal and unrelated to either antisaccade or WCST performance. CONCLUSIONS: The finding of intact task switching performance that is unrelated to other measures of executive function demonstrates selective rather than general impairments of executive functions in schizophrenia. The findings also suggest that abnormal WCST performance is unlikely to be a consequence of deficient task switching. We hypothesize that inhibition and task switching are mediated by distinct neural networks, only one of which is dysfunctional in schizophrenia.

Adult↗
PubMed2002

Modulation of brain and serum glutamatergic concentrations following a switch from conventional neuroleptics to olanzapine.

BACKGROUND: Recent evidence suggests that effects upon glutamatergic transmission may contribute to the therapeutic action of certain atypical antipsychotic agents. METHODS: Glutamate concentrations were measured in serum and were estimated (Glx/Cr) in cingulate cortex by proton magnetic resonance spectroscopy (MRS) in schizophrenia patients while they were being treated with conventional neuroleptics and then 8 weeks after switching to olanzapine. Serum glutamate concentrations were obtained from 11 subjects, and MRS estimates of Glx/Cr were available from 10 subjects at both time points. RESULTS: Serum glutamate concentrations significantly increased after the switch from conventional agents to olanzapine; brain glutamate (Glx/Cr) did not change significantly; however, brain glutamate (Glx/Cr) concentrations increased significantly in patients who exhibited an improvement in negative symptoms with olanzapine compared with patients with no change or worsening of negative symptoms. CONCLUSIONS: Comparisons performed following the switch from conventional agents to olanzapine are consistent with previous studies of clozapine and provide additional preliminary evidence supporting the hypothesis that effects on excitatory amino acid activity may contribute to olanzapine's efficacy for treating negative symptoms.

Adult↗
PubMed2002

Antisaccades and task switching: studies of control processes in saccadic function in normal subjects and schizophrenic patients.

Executive functions allow us to respond flexibly rather than stereotypically to the environment. We examined two such functions, task switching and inhibition in the antisaccade paradigm, in two studies. One study involved 18 normal subjects; the other, 21 schizophrenic patients and 16 age-matched controls. Subjects performed blocks of randomly mixed prosaccades and antisaccades. Repeated trials were preceded by the same type of trial (i.e., an antisaccade following an antisaccade), and switched trials were preceded by a trial of the opposite type. We measured accuracy rate and latency as indices of processing costs. Whereas schizophrenic patients had a threefold increase in error rate for antisaccades compared to normals, the effect of task switching on their accuracy did not differ from that in normal subjects. Moreover, the accuracy rate of trials combining antisaccade and task switching was equivalent to a multiplication of the accuracy rates from trials in which each was done alone. Schizophrenic latencies were disproportionately increased for antisaccades, but again they were no different from normal subjects in the effect of task switching. In both groups the effect of task switching on antisaccades was a paradoxical latency reduction. We conclude that the executive dysfunction in schizophrenia is not generalized but selective, sparing task switching from exogenous cues, in which the switch is limited to a stimulus-response remapping. The accuracy data in both groups support independence of antisaccade and task-switching functions. The paradoxical task-switching benefit in antisaccadic latency effects challenges current models of task switching. It suggests either carryover inhibition by antisaccadic performance in the prior trial or facilitation of antisaccades by simultaneous performance of other cognitive operations.

Attention↗
PubMed2002

Intact suppression of increased false recognition in schizophrenia.

OBJECTIVE: Recognition memory is impaired in patients with schizophrenia, as they rely largely on item familiarity, rather than conscious recollection, to make mnemonic decisions. False recognition of novel items (foils) is increased in schizophrenia and may relate to this deficit in conscious recollection. By studying pictures of the target word during encoding, healthy adults can suppress false recognition. This study examined the effect of pictorial encoding on subsequent recognition of repeated foils in patients with schizophrenia. METHOD: The study included 40 patients with schizophrenia and 32 healthy comparison subjects. After incidental encoding of 60 words or pictures, subjects were tested for recognition of target items intermixed with 60 new foils. These new foils were subsequently repeated following either a two- or 24-word delay. Subjects were instructed to label these repeated foils as new and not to mistake them for old target words. RESULTS: Schizophrenic patients showed greater overall false recognition of repeated foils. The rate of false recognition of repeated foils was lower after picture encoding than after word encoding. Despite higher levels of false recognition of repeated new items, patients and comparison subjects demonstrated a similar degree of false recognition suppression after picture, as compared to word, encoding. CONCLUSIONS: Patients with schizophrenia displayed greater false recognition of repeated foils than comparison subjects, suggesting both a decrement of item- (or source-) specific recollection and a consequent reliance on familiarity in schizophrenia. Despite these deficits, presenting pictorial information at encoding allowed schizophrenic subjects to suppress false recognition to a similar degree as the comparison group, implying the intact use of a high-level cognitive strategy in this population.

Adult↗
PubMed2002

Ionotropic glutamate receptors as therapeutic targets in schizophrenia.

Evidence implicating dysfunction of glutamatergic neurotransmission rests largely on the finding that antagonists of the NMDA subtype of glutamate receptor, especially the dissociative anesthetics like ketamine, can reproduce the full range of symptoms as well as the physiologic manifestation of schizophrenia such as hypofrontality, impaired prepulse inhibition and enhanced subcortical dopamine release. To test the hypothesis that schizophrenia may result from NMDA receptor hypofunction a number of clinical trials have examined the effects of agents that act on the glycine modulatory site on the NMDA receptor. Glycine, D-serine, and the partial agonist, D-cycloserine, have been shown to improve cognition and decrease negative symptoms in schizophrenic subjects receiving typical antipsychotics. Results with D-cycloserine suggest that clozapine may enhance glycine modulatory site occupancy. Preliminary results with an allosteric modulator of the AMPA subtype of glutamate receptor suggest enhanced cognitive functions in subjects treated with clozapine.

Animals↗
PubMedDate not supplied

Dietary intake profile of patients with schizophrenia.

BACKGROUND: The increasing prevalence of overweight and obesity has become a priority public health issue in the United States. Forty to 62% of people with schizophrenia are obese or overweight (1, 2). High morbidity and mortality in schizophrenia may be attributed to an unhealthy lifestyle such as poor diet, lack of exercise, smoking, and substance abuse (3). Obesity is associated with greater risk of developing hypertension, type 2 diabetes, coronary heart disease, stroke, death, and reduced quality of life compared with that found in the general population (4, 5). We performed a cross-sectional study evaluating the dietary intake of patients with schizophrenia or schizoaffective disorder treated with atypical antipsychotic agents. METHODS: Dietary intake of 88 patients from an urban community mental health clinic was measured using a four-day dietary record. Nutritional variables included total energy intake, fat, protein, carbohydrate, cholesterol, fiber, sucrose, folate, calcium, sodium, zinc, alcohol and caffeine. Data were compared to the general population using data matched for age, gender, and ethnicity from the National Health and Nutrition Examination Survey (NHANES), 1999-2000. RESULTS: The Body Mass Index (BMI) of the schizophrenia group (M = 31.3, SD = 12.67) was significantly greater than the NHANES group (M = 28.3, SD = 6.62) (p = .001). The schizophrenia group consumed significantly fewer calories, carbohydrate, protein, total fat, saturated fat, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), fiber, folate, sodium and alcohol and significantly more caffeine than the NHANES group. CONCLUSIONS: The findings may suggest that obesity in schizophrenia patients is not solely related to food consumption, but perhaps other effects including medication side effects and reduced physical activity. Education and interventions for the schizophrenia population should focus more on overall lifestyle factors such as physical activity and healthy food choices.

Adult↗
PubMedDate not supplied

Pharmacologic implications of neurobiological models of schizophrenia.

The dopamine model of schizophrenia has been supplanted by several additional models in order to account for genetic findings, risk factors, course of illness, and the diversity of symptom domains. The increasing number and complexity of potential models for this heterogeneous disorder offer new targets for pharmacologic treatment that differ in their appropriate time points for intervention and in their potential effects on the course of illness. This article reviews relevant neurodevelopmental, biochemical, and neurodegenerative models with respect to potential pharmacologic opportunities.

Antioxidants↗
PubMedDate not supplied

Neuroimaging-genetic paradigms: a new approach to investigate the pathophysiology and treatment of cognitive deficits in schizophrenia.

Cognitive impairment is a prominent and debilitating feature of schizophrenia. Genetic predisposition likely accounts for a large proportion of these cognitive deficits. Direct associations between candidate genes and cognitive dysfunction have been difficult to establish, however, largely due to the subtle effects of these genes on observable behavior. Neuroimaging techniques can provide a sensitive means to bridge the neurobiology of genes and behavior. Here we illustrate the use of neuroimaging-genetics paradigms to elaborate the relationship between genes and cognitive dysfunction in schizophrenia. After reviewing principles important for the selection of genes, neuroimaging techniques, and subjects, we describe how imaging-genetics investigations have helped clarify the contribution of five candidate genes (COMT, GRM3, G72, DISC1, and BDNF) to cognitive deficits in schizophrenia. The potential of this approach for improving patient care will depend on its ability to predict outcomes with greater accuracy and sensitivity than current clinical measures.

Brain↗
PubMedDate not supplied

Catatonic coma with profound bradycardia.

Catatonia may be monosymptomatic at presentation, with stupor or coma as the cardinal and only manifestation. A case of catatonic coma with profound bradycardia is presented to help clinicians recognize this entity and include catatonia in the differential diagnosis of coma as a rare etiology after other more common causes of coma have been excluded. Cases of catatonic coma are nevertheless important to identify because treatment with intravenous benzodiazepines is simple and highly effective. The authors argue that the descriptive term "catatonic coma" is preferable over terms implying psychogenesis, such as "psychogenic" or "hysterical" coma; for catatonia, the authors have a specific treatment, in the form of benzodiazepines; for "psychogenesis," there is none.

Adult↗