The healthy control subject in psychiatric research: impulsiveness and volunteer bias.

Exciting and demanding biomedical experiments may attract a specific subgroup of people as volunteers. In the present study of selection bias, subjects volunteering in a psychobiological study that included a potentially painful procedure (lumbar puncture) were compared with those who declined to participate, with regard to scores on personality scales administered during a previous investigation of the same subjects. Significant differences were found on the Eysenck Personality Questionnaire and Karolinska Scales of Personality Impulsiveness scale, suggesting an over-representation of impulsive individuals among the volunteers. If the specific subject of investigation has implications for the type of individual who will participate as a healthy volunteer in biomedical research, variation will be introduced, affecting the independent variable, and the conclusions that can be drawn from such research may be questionable.

Origins of individual differences in anxiety proneness: a twin/adoption study of the anxiety-related scales from the Karolinska Scales of Personality (KSP).

The genetic and environmental origins of individual differences in scores on the anxiety-proneness scales from the Karolinska Scales of Personality were explored using a twin/adoption study design in a sample consisting of 15 monozygotic twin pairs reared apart, and 26 monozygotic and 29 dizygotic twin pairs reared together. The results showed that genetic factors accounted for individual differences in scores on the psychasthenia and somatic anxiety scales. The genetic determinants were not specific to each scale, but were common to both scales. Shared-rearing environmental determinants were important for individual differences in lack of assertiveness and psychic anxiety, and were common to both scales. Individual differences in muscular tension were found to be attributable to the effects of correlated environments. The most important factor explaining individual differences for all scales was the non-shared environment component. The evidence for an aetiologically heterogeneous anxiety-proneness construct emphasizes the appropriateness of a multi-dimensional approach to anxiety proneness.

Temperamental vulnerability in attempted suicide.

The aim of this study was to explore and describe features of suicidal temperament and to describe the psychological domains of vulnerability in attempted suicide. Thirty-two suicide attempters were compared with 32 sex- and age-matched convalescent surgical controls on self-report personality inventories; the Eysenck Personality Questionnaire, the Chapman Scales, the Beck Hopelessnes Scale and the Karolinska Scales of Personality. Suicide attempters showed higher scale scores on neuroticism, psychoticism, interpersonal aversiveness, perceptual aberration, nonconformity, hopelessness, somatic anxiety, muscular tension, indirect aggression, suspicion and lower socialization. The features of suicidal temperament include hopelessness and anhedonia, anxiety, hostility and undirected anger expression, psychosis proneness, antisocial traits and interpersonal difficulties. These temperamental features might render the suicidal individual particularly vulnerable to suicidal behavior.

Relationship between personality and debrisoquine hydroxylation capacity. Suggestion of an endogenous neuroactive substrate or product of the cytochrome P4502D6.

We administered the Karolinska Scales of Personality to 225 healthy subjects in Spain selected from a group of 925 individuals previously phenotyped with regard to their capacity to hydroxylate debrisoquine. A significant relationship was found between the scores in as many as 4 of the 15 subscales (psychic anxiety, psychasthenia, inhibition of aggression and socialization) and the debrisoquine hydroxylation capacity. Poor metabolizers were more anxiety-prone and less successfully socialized than extensive metabolizers of debrisoquine. This and a previous study among subjects in Sweden suggest that there may be a relationship between personality and the activity of the enzyme hydroxylating debrisoquine (cytochrome P4502D6). This polymorphic enzyme may have an endogenous neuroactive substrate or product, such as a biogenic neurotransmitter amine.

Exploring the connections between platelet monoamine oxidase activity and behavior. II. Impulsive personality without neuropsychological signs of disinhibition in air force pilot recruits.

Platelet monoamine oxidase (MAO) activity and serum levels of the adrenal androgen metabolite dehydroepiandrosterone sulfate (DHAS) were measured in 18 male air force pilot recruits and 19 randomly selected male conscripts. Personality scales from three inventories were given, and computerized neuropsychological tests were performed: finger tapping and alternation, reaction time, perceptual maze, perspective fluctuation and lexical decision. The pilot recruits had higher scores in sensation-seeking-related scales suggesting disinhibited behavior in the social sphere, interest in sports and activities involving some danger, and a need for change. They also had higher scores on an impulsivity scale which comprises sensation-seeking content. In the neuropsychological tasks, the pilot recruits were faster in finger-tapping alternation and performed more efficiently in the perceptual-maze test than the conscripts. In a linear discriminant analysis, neuropsychological-task performance discriminated significantly between the pilot and conscript groups. In the biochemical measures, the pilot recruits had higher DHAS levels but similar MAO activity levels compared to the conscripts, which is in contrast to what has been found in other sensation-seeking groups in comparison to controls. This result is in accordance with the normal scores in one of the impulsivity scales in the pilot recruits, and with the absence of signs of disinhibition in neuropsychological tasks. It is proposed that only some aspects of the impulsivity concept might be critical for the association with low MAO activity.

Genetic factors for the span of apprehension test: a study of normal twins.

The Partial Report Span of Apprehension test has been found to detect cognitive deficits in some first degree relatives of schizophrenic patients. To assess the relative contribution of genetic vs. environmental factors on this measure, 19 monozygotic and 14 dizygotic female twin pairs, selected from a normal population, were tested on the Span of Apprehension test and an IQ test. Both Span of Apprehension test performance and IQ score had high heritabilities: 0.65 and 0.71, respectively. The mode of transmission for performance on the Span of Apprehension test appears to operate in a nonadditive manner. A multivariate behavioral-genetic model applied to the Span of Apprehension and IQ measures indicated that slightly less than half of the genetic effects important for the Span of Apprehension test are found in common with the genetic factors important for IQ. The phenotypic correlation between the Span of Apprehension and IQ measures can be attributed entirely to genetic factors. The influence of unique genetic components in the performance of the Span of Apprehension test in the general population heightens the promise of this measure as a genetic marker for schizophrenia.

Electrodermal responsivity in young hypotensive and hypertensive men.

Electrodermal responses were recorded during the presentation of 16 moderately intense (1000 Hz, 90dB) tones in three groups of young men: borderline hypertensives (138/79 mmHg), normotensives (112/65 mmHg), and hypotensives (104/63 mmHg). Electrodermal response habituation was measured as a decline in response over trials, number of trials to a response criterion of three successive nonresponses, and number of inversions of response amplitude (larger responses following smaller responses) in the stimulus sequence. Habituation was fastest in hypotensives. Nonspecific electrodermal responses at rest and during tone presentations were most frequent in borderline hypertensives, least frequent in the hypotensive group, with the normotensive group falling in between. There were no significant differences in electrodermal level. The rapid habituation rate in hypotensives is discussed in terms of cursory information processing associated with impulsive behaviour. The higher nonspecific electrodermal activity in borderline hypertensives is interpreted to indicate increased sympathetic nervous system activity.

Violent and nonviolent suicide attempts--a controlled Rorschach study.

Rorschach records from 20 patients who had made active, violent suicide attempts were compared with records from 20 patients who had taken drug overdoses and 20 psychiatric control patients who had not made a suicide attempt. Ego function ratings showed that violent attempters were more paranoid than both other groups and less able to cope with conflict situations, to handle dysphoric affect and to differentiate between reality and imagination. Violent attempters had lower level of cognitive maturity than controls and tended to produce fabulized combination responses, suggesting cognitive slippage, and distorted human content responses, indicating pathological object relationships. Nonviolent attempters did not differ from controls. Six patients, all from the violent attempt group, completed suicide within a follow-up period of 4 years. Compared with the survivors, they were less tolerant of dysphoric affect and showed more pronounced decline of developmental level within cards. Completers could be identified on the Rorschach at 55% sensitivity and 93% specificity.

Differences in asymmetric perception of facial expression in free-vision chimeric stimuli and reaction time.

Two forms of a Chimeric Faces Free-Vision Task used to estimate cerebral asymmetry for perceiving facial expression were given to young male subjects, n = 60 in a first session and n = 40 in a retest session. Test-retest and split-half reliabilities were high. As expected from assumptions of right-hemisphere specialization for processing expression, faces with left-sided smiles were more frequently judged as looking happier than those with right-sided smiles in both forms. However, there were individual differences in direction and extent of bias, which were systematically related to reaction time, right visual field-biased subjects being slower. Differences in lateral bias as well as in reaction time are assumed to reflect individual patterns of hemispheric activation, whereas the average left bias in the present male group may reflect right-hemisphere specialization for processing of facial expression.

Exploring the connections between platelet monoamine oxidase activity and behavior: relationships with performance in neuropsychological tasks.

Platelet MAO activity has been found to have behavioral (psychiatric and personality) correlates. The purpose of the present study was to explore the nature of the connections between platelet MAO activity and behavior by analyzing performance in neuropsychological tasks in relation to platelet MAO activity, measured in 37 male subjects. The following neuropsychological tests were given: a finger tapping and alternation test, a reaction time test, a perceptual maze test, a perspective fluctuation task (the Necker cube), and a lexical decision task. The reaction time tasks comprised a motor disinhibition task, in which auditory stimuli given simultaneously with light stimuli were signals for response inhibition. Significant relationships were obtained between low MAO activity and short response times and small variations in response times to left-sided visual stimuli, suggesting a readiness for higher right hemisphere activation in low MAO subjects, and between low platelet MAO activity and many perspective reversals, in line with expectations. Furthermore, high MAO subjects had equal tapping speed for both hands, which has been found in schizophrenic patients. Of special interest in the present results is the strong negative relationship obtained between platelet MAO activity and number of failed inhibitions in the motor disinhibition task, which in a multiple regression analysis highly significantly contributed to the prediction of platelet MAO activity. This finding is in line with the poor passive avoidance performance associated with serotonergic deficiency and syndromes of disinhibition, and thus supports the assumption that platelet MAO activity may be considered as a genetic marker for some properties of the central serotonergic system.

Birth stress, handedness and cognitive performance.

Information regarding conditions during pregnancy and delivery was obtained by extensive interviews with mothers to left-handed and right-handed students. Using the same criterion as van Strien, Bouma and Bakker (1987) for defining birth stress, the present study did not replicate their findings of higher frequency of reported birth stress in left-handers. The difference in outcome was ascribed to differences in recruitment of subjects, the present sample constituting a majority of left hand writers from a population of 921 students, while the van Strien sample was less well defined. The present study was extended by comparing left-handed and right-handed subjects (separated for sex) with and without birth stress, on verbal and nonverbal abilities, and on eye dominance, early learning difficulties and familial sinistrality. Left eye dominance was more frequent in male left-handers with birth stress. Birth stress alone had negative effects on cognitive performance, different for males and females.

Smooth pursuit eye tracking and neuro-psychological performance in healthy volunteers. Exploring a possible genetic marker for vulnerability to schizophrenia.

Eye movement dysfunction (EMD) has been repeatedly found in schizophrenics and their first-degree relatives. In the present study, smooth pursuit eye tracking was measured in healthy subjects and related to performance on computerized neuropsychological tasks assumed to involve frontal or frontoparietal functions: monitoring perspective fluctuations (Necker cube), finger tapping, trail making, reaction time (RT) and a perceptual maze test. Poor trackers performed worse on tasks requiring parallel processing (trail making with letters and digits and RT with random auditory signals for response inhibition) and made more errors and cancellations on the mazes. Results are in line with our earlier EMD results on schizophrenics, showing poor performance on frontal tasks. However, their deficiency was more pervasive, whereas the present healthy EMD subjects only had difficulties with more complex tasks. The results are of interest in view of the recent evidence that EMD may be a genetic marker for vulnerability to schizophrenia.

Circulating testosterone levels and aggression in adolescent males: a causal analysis.

Empirical analyses conducted within a causal-analytic framework (path analysis) on a sample of normal adolescent human males suggested that circulating levels of testosterone in the blood had a direct causal influence on provoked aggressive behavior (self-reports): A high level of testosterone led to an increased readiness to respond vigorously and assertively to provocations and threats. Testosterone also had an indirect and weaker affect on another aggression dimension: High levels of testosterone made the boys more impatient and irritable, which in turn increased their propensity to engage in aggressive-destructive behavior. Two somewhat parallel dimensions of behavior, intermale and irritable aggression, have been identified in animal research to be under testosterone control.

Hand preference in a population of Swedish college students.

A hand preference inventory was administered to a population of 921 Swedish college students. The questions concern writing, drawing, throwing a ball, cutting with scissors, tooth brushing, cutting with a knife, and using a hammer, each with five response alternatives: always right, mostly right, either hand, mostly left and always left. A consistent preference over all activities for the left hand was rare (4%), but common for the right hand (62%). Corresponding percentages for writing hand were 9% and 89%, thus contradicting recent reports of a dramatic increase of left-handedness. There were no sex differences. Hand preference for writing was highly correlated with that for the other activities. Self-reported parental sinistrality was more common in respondents with a consistent left hand preference. There was no association between nonright-handedness and self-reported early learning difficulties, although among females mixed handers tended to report a higher frequency of difficulties in learning to write.

Self-assessed and examiner-assessed writing hand posture in Swedish left-handers.

Writing hand posture was studied in 48 male and 54 female left-handed Swedish college students. Inverted posture was more common with examiner-assessment than with self-assessment and was more common in males. Examiner-assessed inversion frequency was lower than that reported from American samples but higher than that from Australian samples. Writing style was related to hand posture, printing being more common in non-inverted writers. Degree of lateral preference, presence of familial sinistrality and birth complications were not associated with writing hand posture.

Neuropsychological test performance and CSF levels of monoamine metabolites in healthy volunteers and patients with Alzheimer's dementia.

Fifteen patients (51-78 yrs) with mild to moderately severe Alzheimer's dementia and 18 healthy subjects of the same age were examined by clinical rating scales and a battery of neuropsychological tests. Levels of the monoamine metabolites homovanillic acid (HVA), 3-methoxy-4-hydroxyphenyl glycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the lumbar cerebrospinal fluid (CSF). Correlations between clinical, psychological and biochemical measures were calculated in order to elucidate whether monoaminergic mechanisms are of importance for the maintenance of cognitive abilities in normal and pathological aging. The patients' performance was severely impaired in all neuropsychological tests. The mean levels of monoamine metabolites, however, did not differ between patients and volunteers. The correlations between psychological test scores and CSF metabolite levels were generally low, but mostly negative, associating a poor performance to a high activity of brain monoaminergic neurons. Thus, among the volunteers high 5-HIAA and MHPG levels correlated with poor performance in the Picture completion and the Trail making tests--measures of visuo-perceptual and visuo-motor skills. In the demented patients poor performance in the memory tests was associated with high levels of HVA and 5-HIAA. The results indicate that monoamine neuron activity is not a primary determinant for cognitive abilities in healthy elderly subjects or in demented patients. The slight negative correlation between cognitive function and metabolite concentrations in the patients may reflect a disturbance in a dopaminergic-cholinergic balance due to degenerative changes of central cholinergic pathways.

Cognitive sex differences: speed and problem-solving strategies on computerized neuropsychological tasks.

Skill, strategy, and laterality measures obtained through computerized neuropsychological tasks, a reaction time (RT) test, and a visuospatial problem-solving test, the Perceptual Maze Test, were analyzed in relation to sex and handedness of 56 high-school students. Boys were significantly faster than girls on most RT subtasks (including a response-inhibition task) and made more two-choice RT response errors for right-sided stimuli, which may be interpreted as resulting from a less cautious strategy. In maze performance, boys were superior to girls. An analysis of separate phases of the maze-solution process suggested that boys preferentially used an impulsive-global strategy. Girls, using a more reflective-sequential task-solving strategy, were significantly slower, without hitting more targets. Compared to all other groups, left-handed girls (strongly left-handed) had lower performance on maze tasks with no target information, particularly in left-sided solution pathways. Results were interpreted as reflecting differences in hemispheric competence and activation patterns between the sexes. Signs of a less differentiated lateralization and slight dysfunction of visuospatial skills in the left-handed girls were discussed.

Thrombocyte monoamine oxidase activity and personality traits in women with severe premenstrual syndrome.

Women with premenstrual syndrome (PMS) of such severity that they actively had sought medical attention for their symptoms were compared with healthy female students with regard to platelet MAO activity and temperamental correlates by means of the Karolinska Scales of Personality (KSP), scales from the Eysenck Personality Questionnaire (EPQ) and Eysenck's IVE inventory. The women with PMS were divided into two groups; irritability and depression as predominating symptom. No variation in platelet MAO was found during the menstrual cycle, either in patients or in controls. Both PMS groups had significantly lower platelet MAO activity than the controls. There was no difference between the two groups with PMS. Also with regard to personality traits there were considerable differences between the females with PMS and the controls. There were few differences between the two groups of PMS patients. Thus, the patients scored significantly higher as regards somatic anxiety, muscular tension, indirect aggression, verbal aggression and neuroticism and lower as regards socialization than the controls.

Markers for vulnerability to psychopathology: temperament traits associated with platelet MAO activity.

The functional linkage between platelet MAO activity and psychopathology was explored by analyzing temperamental correlates in 40 male subjects by means of scales from the Eysenck Personality Questionnaire (EPQ), the Zuckerman Sensation Seeking Inventory, and the Karolinska Scales of Personality (KSP). Linear correlations were found with two sensation seeking scales, replicating earlier findings. However, nonlinear correlations predominated. Subjects with intermediate platelet MAO activity had higher scores in conformity scales and lower scores in anxiety and hostility scales than low and high MAO subgroups. Low MAO subjects showed a pattern of higher scores in KSP Impulsiveness, EPQ Neuroticism, and KSP Somatic Anxiety and Irritability and lower scores in KSP Socialization, in line with personality profiles found in alcoholics, psychopaths, and suicide attempters who also tend to have low platelet MAO activity. High MAO subjects scored lower in sensation seeking and conformity scales and higher in KSP Psychasthenia, Muscular Tension and Suspicion scales, consistent with clinical links between high platelet MAO activity and anxiety and paranoia.