Screening young adults for psychiatric vulnerability: a preliminary comparison of biological and clinical measures.
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Biomedical subjects
Publications and source records attributed to M S Buchsbaum.
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From an original sample of 375 college students and employees studied for platelet MAO activity, 66 subjects representing the lower and upper deciles of the sample were contacted for further study, including administration of the booklet form of the MMPI. We analyzed what psychological characteristics might be associated with differences in MAO activity and attempted to cross-validate these characteristics by using them to predict the separability of low vs. high MAO subjects. Each subject was randomly assigned to one of two groups in which the low and high MAO subjects were balanced for sex. For 16 women in group A, a MAO scale discriminated low and high subjects with 100% accuracy. For 18 men in group A, a separate MAO scale discriminated with 94% accuracy. To cross-validate these results, the two scales were applied to another population; both discriminated low and high MAO women and men with a combined 97% accuracy. The thematic content of the two scales is discussed in the light of other reports on the psychological characteristics of low and high MAO subjects, including the apparent relationship between the scale content and the clinical features of bipolar affective disorder.
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The behavioral, cognitive, and electrophysiological effect of a single dose of dextroamphetamine (0.5 milligram per kilogram of body weight) or placebo was examined in 14 normal prepubertal boys (mean age, 10 years 11 months) in a double-blind study. When amphetamine was given, the group showed a marked decrease in motor activity and reaction time and improved performance on cognitive tests. The similarity of the response observed in normal children to that reported in children with "hyperactivity" or minimal brain dysfunction casts doubt on pathophysiological models of minimal brain dysfunction which assume that children with this syndrome have a clinically specific or "paradoxical" response to stimulants.
Techniques were developed for measurement of signal to noise ratio and response variability in single trial evoked potentials. These techniques were extended and verified using a digital computer simulation of signal plus noise trials. When applied to real data the measures appear to have high reliability and to demonstrate that human evoked potentials are more variable than would be expected from background noise variation alone. Empirical equations are presented which can be applied to existing single trial EP data to estimate both signal-to-noise ratio and its expected variance.
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Much biological research is directed at using biological variables to predict traditional symptom-based psychiatric categories. In this article, the authors discuss the need for a research strategy in which biological variables actually define psychiatric groups.
This study replicates and extends earlier work by finding that low levels of platelet monoamine oxidase (MAO) activity correlate with sensation seeking, high ego strength, positive affect, and high leisure time activity levels, somewhat similar psychological correlates also being found for plasma amine oxidase activity. Although there are several ways in which a schizophrenia/MAO relationship may exist and still be congruent with the present data, these results pose difficulties for theories which link low MAO activity levels specifically to schizophrenia. Nothing in the present findings, however, is incongruent with the possibility of an association between low platelet MAO activity and bipolar affective disorder.
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14 normal volunteers were given 0.5 mg physostigmine or saline placebo i.v. in a randomized double blind trial. Subjects were pretreated with 0.5 mg methscopolamine i.m. on both days. Pain ratings and average evoked responses were obtained to brief electrical stimuli administered to the forearm. Pain response criterion was significantly higher on physostigmine than on placebo. Average evoked response component P100 was significantly smaller on physostigmine than placebo, especially for higher intensity stimuli. These results are consistent with central cholinergic modulation of pain and arousal systems in man.
Visual average evoked responses (AERs) to four intensities of light were studied in hospitalized depressed patients receiving placebo, d-amphetamine, l-amphetamine, lithium and d- and l-amphetamine combined with lithium. For the assessment of the subjective effects of the drugs, the patients completed a 34-item mood and behavior self-rating scale. AER responses to repeated doses of the amphetamines were consistent within the same individual but varied greatly between different individuals. For the patient group considered as a whole, only minor AER changes occurred in response to either d- or l-amphetamine; nonetheless, these minor changes were attenuated by lithium co-administration. There were indications, however, that AER baseline measures could be used as predictors of change in self-rating due to both d- and l-amphetamine, as patients who had larger AER amplitudes on baseline also tended to have larger increases in activation ratings and reductions in depression ratings. The amount of increase in AER amplitude or amplitude/intensity slope seen with amphetamine was also significantly correlated with the amount of increase in activation or euphoria ratings with amphetamine administration. These effects were most prominent in the same P100 component that we have previously found to differentiate bipolar and unipolar depressed patient groups.
Biochemical and electrophysiological factors were studied longitudinally in a rapidly cycling manic-depressive patient. Slow changes in mood, motor activity, sleep, and urinary norepinephrine levels during the course of each depressed and manic episode are reported, as well as rapid alterations in many variables at the time of mood switch. Urinary concentrations of norepinephrine and its metabolite, 3-methoxy-4-hydroxyphenyl glycol (MHPG) were significantly lower in depression than in mania; norepinephrine but not MHPG excretion increased prior to the switch. We postulate that the slow behavioral and biological changes preceding switches in this patient are an important manifestation of the cyclic process in manic-depressive illness.
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The relationship between suicides and suicide attempts and two biological measures, platelet monoamine oxidase levels (MAO) and average evoked response (AER) augmenting, was examined in 79 off-medication psychiatric patients and in 68 college student volunteers chosen from the upper and lower deciles of MAO activity levels. In the patient sample, male individuals with low MAO and AER augmenting, a pattern previously associated with bipolar affective disorders, showed a significantly increased incidence of suicide attempts in comparison with either non-augmenting low MAO or high MAO patients. Within the normal volunteer group, all male low MAO probands with a family history of suicide or suicide attempts were AER augmenters themselves. Four completed suicides were found among relatives of low MAO probands where as no high MAO proband had a relative who committed suicide. These findings suggest that the combination of low platelet MAO activity and AER augmenting may be associated with a possible genetic vulnerability to psychiatric disorders.
A patient with unusually regular and rapid switches from mania to depression was studied for 113 consecutive days through five switches. Average evoked responses (AERs) to four intesities of light were recorded from vertex and occipital leads; telemetered activity records and behavioral ratings were also collected. Late AER components (P200) tended to change amplitude synchronously with the switches, vertex P200 amplitude decreased and occipital P200 amplitude increased in mania. Urinary MHPG changes paralleled the changes in P200 amplitude. Early AER components (P100) and especially the amplitude/intesity slope measures for P100 decreased about 8-10 days before a switch from depression to mania. Cross-spectral and linear regression analysis helped confirm these observations. The results, taken together with AER data in recent L-dopa studies, were consistent with catecholamine potentiation prior to the switch process from depression into mania.
A population of individuals potentially at risk for psychiatric disorders was identified by screening 375 college student volunteers for low platelet monoamine oxidase (MAO) activity levels. The lower and upper 10 per cent in MAO activity were interviewed and family history data were obtained. Low-MAO probands reported more frequent psychiatric or psychological counseling and problems with the law. Families of low MAO probands had an eightfold increase in the incidence of suicide or suicide attempts over those of high-MAO probands. This suggests that reduced MAO levels, reported previously in patients with affective disorders and chronic schizophrenia, may predict a vulnerability to psychiatric disorder.