Biomedical subjects

A Radant

Publications and source records attributed to A Radant.

At least 19 recordsLinked to original sources

PubMed2001

Biological markers and diagnostic accuracy in the genetics of posttraumatic stress disorder.

Family and twin studies suggest a substantial genetic contribution to the etiology of posttraumatic stress disorder (PTSD). Identification of the nature of this genetic contribution should enhance understanding of the pathophysiology of PTSD and suggest improved therapeutic strategies for its treatment. However, a broadly defined phenotype, specific requirement for an environmental exposure and high frequency of comorbid psychiatric illness all complicate genetic studies of PTSD. It is likely that genetic heterogeneity, incomplete penetrance, pleiotropy and the involvement of more than one gene all constitute formidable obstacles to the genetic analysis of PTSD. One way to circumvent these problems is to perform genetic analysis of traits associated with PTSD, rather than PTSD itself, an approach that has been fruitful for other diseases with complex modes of inheritance. Hypothalamic-pituitary-adrenal axis hypofunction, physiologic markers of increased arousal, and increased acoustic startle response are all potential PTSD-associated traits that might be susceptible to genetic analysis. However, the capacity of these traits to distinguish PTSD from non-PTSD patients and their familial pattern must be better defined before they can be employed in genetic studies.

Arousal↗

PubMed2001

Which duration of postsaccadic slowing identifies anticipatory saccades during smooth pursuit eye movements?

Increased frequency of anticipatory saccades during smooth pursuit eye movements is a potential marker of genetic risk for schizophrenia. Postsaccadic slowing criteria are used to separate anticipatory from other types of saccades. However, the necessary duration of slowed pursuit required to identify an anticipatory saccade remains undetermined. We explored the effect of various postsaccadic slowing duration criteria on effect size in a comparison of younger and older schizophrenic and normal adults. For large anticipatory saccades, varying the duration of postsaccadic slowing criteria did not notably change effect size. For smaller leading saccades, a limited 50-ms duration postsaccadic slowing criterion produced the largest effect size (1.54), and maintained a similar effect size across a broad age range. Leading saccades with a limited duration postsaccadic slowing criteria are a possible marker of genetic risk for schizophrenia.

Aged↗

PubMed2000

Smooth pursuit eye movements in schizophrenia and attentional dysfunction: adults with schizophrenia, ADHD, and a normal comparison group.

BACKGROUND: Smooth pursuit eye movement (SPEM) abnormalities are found in schizophrenia. These deficits often are explained in the context of the attentional and inhibitory deficits central to schizophrenia psychopathology. It remains unclear, however, whether these attention-associated eye movement abnormalities are specific to schizophrenia or are a nonspecific expression of attentional deficits found in many psychiatric disorders. Adult attention-deficit/hyperactivity disorder (ADHD) is an alternative disorder with chronic attentional and inhibitory dysfunction. Thus, a comparison of SPEM in adult schizophrenia and adult ADHD will help assess the specificity question. METHODS: SPEM is recorded during a 16.7 degrees per second constant velocity task in 17 adults with ADHD, 49 adults with schizophrenia, and 37 normal adults; all groups included individuals between ages 25-50 years. RESULTS: Smooth pursuit gain and the frequency of anticipatory and leading saccades are worse in schizophrenic subjects, with normal and ADHD subjects showing no differences on these variables. CONCLUSIONS: Many attention-associated SPEM abnormalities are not present in most subjects with ADHD, supporting the specificity of these findings to the attentional deficits seen in schizophrenia.

Adult↗

PubMed2000

Eye movement task measures inhibition and spatial working memory in adults with schizophrenia, ADHD, and a normal comparison group.

Schizophrenia and attention deficit/hyperactivity disorder (ADHD) are both associated with deficits in inhibition and working memory, although in ADHD the working memory deficit is hypothesized to be secondary to the inhibitory deficit. This similarity in cognitive processes has been paralleled by similarities across the two groups in the performance of working memory and inhibition tasks. The delayed oculomotor response task is an alternative task, which may allow greater separation of working memory from inhibitory components, and thus its use may provide additional information on primary vs. secondary deficits in these disorders. Ten young adult ADHD sufferers, 10 schizophrenic subjects, and 10 normal subjects were matched on age, gender, and education. Eye movements were recorded during delayed oculomotor response tasks with 1- and 3-s delays. Both the ADHD and the schizophrenic subjects demonstrated dis-inhibition (an increased percentage of premature saccades); however only schizophrenic subjects demonstrated an impaired working memory (decreased spatial accuracy of the remembered saccade). The results are consistent with the hypothesis that working memory is a primary deficit in schizophrenia, but secondary to the inhibitory deficit in ADHD.

Adult↗

PubMed1999

The effects of age on a smooth pursuit tracking task in adults with schizophrenia and normal subjects.

BACKGROUND: Performance during a smooth pursuit eye movement (SPEM) task has been proposed as a marker of genetic risk for schizophrenia, although the precise component of SPEM tracking most associated with genetic risk remains undetermined. Normal adult aging is associated with deterioration on SPEM tasks; it remains unclear whether investigations of SPEM abnormalities will allow inclusion of older subjects in genetic studies. This study examines 1) the effect of normal aging on several components of SPEM performance; and 2) whether schizophrenic-normal differences found in young adults continue over a broad adult age span. METHODS: SPEM was recorded during a 16.7 degrees per sec constant velocity task in 64 normal adults, ages 18 to 79 years, and 58 schizophrenic subjects, ages 18 to 70 years. RESULTS: Smooth pursuit gain, the percent of total eye movements due to catch-up saccades, the frequency of large anticipatory saccades, and the frequency of leading saccades all deteriorate with increasing age. After correction for age, schizophrenic to control differences persist on most eye movement variables with the largest effect sizes for leading saccades (1.56) and smooth pursuit gain (1.17). CONCLUSIONS: The tendency to use saccades to anticipate target motion, even in small steps (leading saccades), deserves further attention as a potential marker useful in genetic analyses.

Adolescent↗

PubMed1999

Evidence for bilineal inheritance of physiological indicators of risk in childhood-onset schizophrenia.

Childhood-onset schizophrenia is proposed to be associated with increased genetic loading compared with adult-onset schizophrenia because of its earlier age of onset and generally greater severity of symptoms. Diminished suppression of P50 auditory evoked responses to repeated stimuli and elevated anticipatory saccades during smooth pursuit eye movements are markers of genetic risk that are found in members of families with schizophrenia even in the absence of the full clinical disorder and appear to be transmitted in a single gene autosomal dominant fashion. Adult-onset schizophrenia is generally associated with one parent who demonstrates abnormal P50 sensory gating and elevated anticipatory saccades and one parent who is normal on the physiologic measures (i.e., unilineal inheritance). This study investigates whether childhood-onset schizophrenia is similarly unilineal or is associated with the inheritance of genetic risk factors from both parents (i.e., bilineal inheritance). Ten childhood-onset schizophrenic probands and their parents were studied. Their P50 sensory gating and anticipatory saccades were compared with adult-onset schizophrenic probands and their parents. Bilineality, measured as physiological impairment in both parents, occurred more frequently in childhood-onset probands than in adult-onset probands for both P50 sensory gating deficits (60% versus 13%) and elevated anticipatory saccades (60 versus 0%). Additionally, childhood-onset schizophrenic probands performed more poorly than adult-onset probands on the anticipatory saccade measure. This physiological evidence suggests that childhood-onset schizophrenia may be associated with increased genetic loading because of contributions of genetic risk from both parents.

Adolescent↗

PubMed1999

Amplitude criteria and anticipatory saccades during smooth pursuit eye movements in schizophrenia.

Increased frequency of anticipatory saccades during smooth pursuit eye movements is a potential marker of genetic risk for schizophrenia even in the absence of clinical symptomology. The operational definition of anticipatory saccades has often included an amplitude criterion; however, these amplitude criteria have often differed across studies. This study reports on the effect of varying amplitude criteria on the effect size in a comparison of 29 schizophrenic adults and 29 normal subjects during a 16.7 degrees/s constant velocity task. The inclusion of small amplitude anticipatory saccades, with amplitudes of 1-4 degrees, consistently increased effect size (largest effect size = 1.61). The inclusion of large anticipatory saccades, with amplitudes of 4 degrees or greater, had an inconsistent impact on effect size. The separation of anticipatory saccades into leading saccades (anticipatory saccades with amplitude 1-4 degrees) and large anticipatory saccades (amplitude > 4 degrees) deserves further exploration.

Adult↗

PubMed1998

Anticipatory saccades during smooth pursuit eye movements and familial transmission of schizophrenia.

BACKGROUND: Smooth pursuit eye movement (SPEM) abnormalities are a putative marker of genetic risk for schizophrenia. Accurate SPEM performance requires the subject to activate neural systems responsible for smooth pursuit tracking, while simultaneously suppressing activity of neurons responsible for saccadic movements that would move the eye ahead of the target. This study examined whether specific aspects of SPEM dysfunction cosegregate with genetic risk in parents of schizophrenic probands. METHODS: Eighteen probands and their parents had SPEM recorded. Parents with an ancestral history of schizophrenia were hypothesized to be more likely than their spouses without such a history to carry a genetic risk for schizophrenia. RESULTS: Ten families had a single parent with a positive ancestral history for schizophrenia. The frequency of anticipatory saccades, which were mostly small, and the fraction of total eye movement that they represented were the only measures that differentiated the more likely genetic carrier parents in these families from their spouses and age-matched normals. CONCLUSIONS: Failure to suppress saccadic anticipation of target motion during smooth pursuit appears an aspect of SPEM dysfunction related to presumed genetic risk for schizophrenia.

Adult↗

PubMed1998

Familial transmission of two independent saccadic abnormalities in schizophrenia.

Difficulties with inhibiting inappropriate responses, i.e. disinhibition, and problems with spatial memory are both presumed to be a part of the phenotypic expression of the genetic risk for schizophrenia. Schizophrenic probands are impaired on saccadic eye movement tasks which require (a) response inhibition to prepotent stimuli and (b) generation of an accurate response to a remembered or calculated spatial location, but it is unknown how these deficits are inherited. Sixteen schizophrenic probands, their 32 parents, and two normal control groups completed a delayed oculomotor response and an antisaccade task. The parents with a positive ancestral family history for chronic psychosis (n = 8) were presumed to be more likely than their family history-negative spouses to be genetic carriers for schizophrenia. Probands and their positive family history parents had more failures of response inhibition than did normal control groups. However, it was the probands and their negative family history spouses who demonstrated impaired accuracy of the remembered- or antisaccades. Disinhibition may be closely tied to a specific genetic risk for schizophrenia. However, a second familial factor related to the maintenance or manipulation of spatial information may also contribute to the genetic risk of the full clinical disorder.

Adult↗

PubMed1996

Early expression of smooth-pursuit eye movement abnormalities in children of schizophrenic parents.

OBJECTIVE: Disordered smooth-pursuit eye movements (SPEM) and, specifically, small anticipatory saccades that disrupt SPEM have been hypothesized to be a marker of genetic vulnerability to schizophrenia. This study compares SPEM in children of schizophrenic parents with normally developing control children to assess whether SPEM abnormalities are also present in a subset of at-risk children. METHOD: With infrared oculography, SPEM was examined in 13 children of schizophrenic parents and 19 normally developing controls (aged 6 to 15 years). Measures of smooth-pursuit gain and root mean square error were used in addition to more specific measures of catch-up saccades and anticipatory saccades. RESULTS: Children of schizophrenic parents differed from normally developing controls on gain and root mean square error, but not on catch-up saccades. Small anticipatory saccades were significantly more frequent in the at-risk group. The percentage of total eye movements due to anticipatory saccades identified 54% of the at-risk group (compared with none of the control group) as performing more than two standard deviations above (worse than) the control mean. CONCLUSIONS: The presence of increased anticipatory saccades is evidence for an oculomotor dysfunction that may be a phenotype of the genetic risk for schizophrenia, expressed years prior to the possible development of clinical illness.

Adolescent↗

PubMed1996

Reduced benzodiazepine sensitivity in patients with panic disorder: comparison with patients with obsessive-compulsive disorder and normal subjects.

OBJECTIVE: The authors sought to replicate their previous finding of reduced response to diazepam in patients with panic disorder, to test whether this effect was specific for panic disorder, and to determine whether this reduced response was merely an artifact of resistance to sedation from anxiety-related overarousal. METHOD: The effects of four increasing intravenous doses of diazepam on saccadic eye movement velocity and accuracy (the latter being a saccadic variable that is unaffected by sedation), short-term memory, and self- and observer-rated sedation were assessed in 18 patients with panic disorder, 15 patients with obsessive-compulsive disorder, and 14 normal comparison subjects. The ratios of effect to blood level areas under the curve for both ascending and descending limbs of the effect/blood level curves were compared for each variable. RESULTS: Patients with panic disorder showed significantly less diazepam effect on saccadic velocity and accuracy for the ascending limb of the blood level curve than comparison subjects. Patients with obsessive-compulsive disorder showed similar differences from comparison subjects but only for saccadic velocity. There were no group differences in diazepam effects on memory and sedation. CONCLUSIONS: Patients with panic disorder are less sensitive than comparison subjects to diazepam. Although this difference is not an artifact of resistance to sedation, it may not be specific for panic disorder but rather may reflect a more nonspecific aspect of anxiety disorders.

Adult↗

PubMed1995

Human oculomotor function: reliability and diurnal variation.

To provide information on test-retest reliability for seven oculomotor paradigms currently used in studies of schizophrenia and other neuropsychiatric conditions, we tested eight controls at four weekly intervals, twice in the morning (8-10 AM) and twice in the afternoon (3-5 PM). Intraclass correlation coefficients were significant (p < .05) for both AM and PM pairs of measures as well as for mean AM and PM pairs for closed-loop pursuit gain, open-loop pursuit gain (using velocity as the measure), saccadic frequency during pursuit and fixation, visually and nonvisually guided saccadic latency and velocity, antisaccadic latency, and premature reflexive saccades during the memory-guided saccade task. Acceleration as a measure of open-loop gain (for slower targets) and accuracy of saccades to a moving target were only reliable at PM testing time. Nonvisually guided saccadic accuracy and inappropriate reflexive saccades during the antisaccade task were not reliable, possibly due to the narrow range of values for these measures. Except for approximately 10% fewer saccades during pursuit and fixation in the morning, there were no consistent diurnal differences. These findings suggest that, in a small sample of subjects, most measures of oculomotor function are stable across time and may reflect underlying neurophysiologic traits.

Adolescent↗

PubMed1995

Effects of diphenhydramine on human eye movements.

Peak saccadic eye movement velocity (SEV) and average smooth pursuit gain (SP) are reduced in a dose-dependent manner by diazepam and provide reliable, quantitative measures of benzodiazepine agonist effects. To evaluate the specificity of these eye movement effects for agents acting at the central GABA-benzodiazepine receptor complex and the role of sedation in benzodiazepine effects, we studied eye movement effects of diphenhydramine, a sedating drug which does not act at the GABA-benzodiazepine receptor complex. Ten healthy males, aged 19-28 years, with no history of axis I psychiatric disorders or substance abuse, received 50 mg/70 kg intravenous diphenhydramine or a similar volume of saline on separate days 1 week apart. SEV, saccade latency and accuracy, SP, self-rated sedation, and short-term memory were assessed at baseline and at 5, 15, 30, 45, 60, 90 and 120 min after drug administration. Compared with placebo, diphenhydramine produced significant SEV slowing, and increases in saccade latency and self-rated sedation. There was no significant effect of diphenhydramine on smooth pursuit gain, saccade accuracy, or short-term memory. These results suggest that, like diazepam, diphenhydramine causes sedation, SEV slowing, and an increase in saccade latency. Since the degree of diphenhydramine-induced sedation was not correlated with changes in SEV or saccade latency, slowing of saccadic eye movements is unlikely to be attributable to sedation alone. Unlike diazepam, diphenhydramine does not impair smooth pursuit gain, saccadic accuracy, or memory. Different neurotransmitter systems may influence the neural pathways involved in SEV and smooth pursuit again.

Adult↗

PubMed1995

Benzodiazepine sensitivity in panic disorder: effects of chronic alprazolam treatment.

The aim of the current study was to determine the degree to which patients with panic disorder develop tolerance to subjective and physiological effects of benzodiazepine after chronic treatment with alprazolam. Response to acute administration of diazepam was assessed in 19 panic disorder patients receiving chronic treatment with alprazolam and 23 untreated panic disorder patients. At baseline in the laboratory, the two groups did not differ in peak saccadic eye movement velocity, saccade latency, short-term memory, plasma cortisol and growth hormone concentrations, heart rate, and self-rated levels of sedation and anxiety. Compared with untreated patients, alprazolam-treated patients displayed significantly less diazepam-induced change in peak saccadic velocity, saccade latency, growth hormone secretion, memory, and self-rated levels of sedation. There was no difference between groups in diazepam effects on plasma cortisol concentrations or self-rated anxiety. Within alprazolam-treated patients, diazepam-induced slowing of peak saccade velocity was significantly inversely correlated with illness severity, as measured by reported panic attacks per week and severity of phobic avoidance, but not with alprazolam dose, blood level, or duration of treatment. Because the alprazolam-treated group reported more panic attacks per week than the untreated panic patients, treated patients were divided into those who were asymptomatic versus those with continuing panic attacks. The subgroup of nine alprazolam-treated subjects who were asymptomatic also showed significantly less diazepam effects than the group of untreated panic disorder patients, suggesting that overall group differences were at least partially attributable to the development of tolerance to selected benzodiazepine effects with chronic alprazolam treatment.

Adult↗

PubMed1994

Quantitative effects of typical and atypical neuroleptics on smooth pursuit eye tracking in schizophrenia.

Smooth pursuit eye movement (SPEM) gain, total saccades, and subtypes of saccades were quantified from the visual pursuit tracking of 26 fluphenazine-treated patients with schizophrenia and 42 normal controls. Tracking was repeated in 16 patients who underwent a placebo-controlled, double-blind crossover comparison of fluphenazine and clozapine. Fluphenazine-treated patients showed significant reduction in SPEM gain and significant increases in both total, intrusive, and anticipatory saccades and in saccadic amplitude, when compared to controls. Clozapine significantly reduced SPEM gain and significantly increased total and catch-up saccades, when compared to placebo or fluphenazine. High amplitude of intrusive saccades in drug-free patients predicted poor response to clozapine, suggesting that intact frontal cortical function may enable optimal clozapine response.

Adult↗

PubMed1994

Eye movement effects of diazepam in sons of alcoholic fathers and male control subjects.

Both animal and human studies suggest that the GABA-benzodiazepine receptor complex may be involved in the acute effects of ethanol, as well as the development of tolerance and dependence with chronic ethanol use. The current study was performed to assess sensitivity to benzodiazepines, and thus the functional sensitivity of the GABA-benzodiazepine receptor system, in subjects at high risk for alcoholism. Sons of alcoholic fathers (SOAs; n = 27) were compared with male controls without a family history of alcoholism (n = 23) in response to diazepam versus placebo. SOAs and controls received four logarithmically increasing doses of intravenous diazepam or placebo in randomized order on 2 days at least 1 week apart. Effects of diazepam were assessed using two eye movement tasks, peak saccadic eye movement velocity, and average smooth pursuit eye movement gain, which provide reliable, quantitative measures of benzodiazepine effects. In addition, memory, self-rated sedation, and pleasurable drug effects were measured. In comparison with control subjects, SOAs displayed significantly less diazepam effects on peak saccade velocity, average smooth pursuit gain, memory, and self-rated sedation, but significantly greater pleasurable drug effects. Differences in response to diazepam between SOAs and male controls may reflect altered functional sensitivity of the central GABA-benzodiazepine receptor system or a more general difference between groups in the effects of CNS active or sedating drugs.

Adult↗

PubMed1993

Benzodiazepine pharmacodynamics: utility of eye movement measures.

The utility of several measures of saccadic and smooth pursuit eye movements as benzodiazepine pharmacodynamic measures was explored in 24 psychiatrically and medically health control subjects. Measures of sedation and memory impairment were also included. Subjects received four logarithmically increasing doses of intravenous diazepam at 15-min intervals on 1 day resulting in monotonically increasing plasma diazepam levels, and placebo on another day in random order 1 week apart. Measures were collected twice at baseline, once after each dose of diazepam/placebo and twice more, 15 and 30 min after the last dose. Peak saccadic velocity and smooth pursuit gain showed the greatest overall and dose-dependent drug effect among eye movement measures. Although effect sizes at the highest dose for memory impairment and self-rated sedation were comparable to these two measures, reliability (i.e., placebo-day fluctuation) with these measures was considerably poorer. Log-linear pharmacodynamic modeling was used to calculate the effective dose (ED30) or concentration (EC30) required to reduce saccadic velocity or pursuit gain by 30%. Almost all (23/24) subjects had linear and easily interpretable plots for saccadic velocity, while a majority (19/24) of subjects had interpretable plots for smooth pursuit gain. The distribution of ED30 and EC30 values showed a wide range of sensitivities to diazepam. These findings suggest that saccadic velocity and smooth pursuit gain are sensitive, reliable, quantitative benzodiazepine pharmacodynamic measures.

Adolescent↗

PubMed1993

Hypertonic saline infusion increases plasma norepinephrine concentrations in normal men.

We recently demonstrated in patients with panic disorder that hypertonic saline infusion induces acute panic with the same frequency and intensity as the standard hypertonic sodium lactate infusion. We now report the effects in normal men of hypertonic saline infusion on neuroendocrine systems possibly relevant to panic and anxiety. We administered a 150-min infusion of hypertonic saline (5% sodium chloride) which increased plasma osmolality from 288 +/- 1 to 303 +/- 2 mOsm/kg and produced the appropriate increase of plasma arginine vasopressin (AVP). Plasma norepinephrine (NE) increased substantially during hypertonic saline infusion compared to a normal saline infusion of equal volume and duration. Mean arterial pressure (MAP) also increased and there were significant positive correlations between MAP and NE, but not between MAP and AVP during hypertonic saline infusion. Plasma epinephrine and cortisol did not differ between conditions. Although the pattern of plasma adrenocorticotrophic hormone (ACTH) response differed between hypertonic saline and normal saline conditions, ACTH concentrations did not increase compared to baseline in either condition. These data suggest that hypertonic saline infusion increases sympathetic nervous system activity in normal men.

Adrenocorticotropic Hormone↗