Impulsive aggression in adults with attention-deficit/hyperactivity disorder.

OBJECTIVE: DSM-IV criteria for attention-deficit/hyperactivity disorder (ADHD) include examples of 'impulsivity'. This term can refer to various dysfunctional behaviours, including some examples of aggressive behaviour. However, impulsive aggression is not included in the DSM-IV criteria for ADHD. The associations of impulsive aggression with ADHD were investigated. METHOD: Seventy-three male adults with DSM-IV ADHD, and their informants, completed questionnaires. Impulsive aggression was assessed by ratings of two criteria for borderline personality disorder (BPD), involving hot temper and/or self-harm. RESULTS: Logistic regression indicated that features of DSM-IV ADHD were predictors of comorbid impulsive aggression. However, compared with ADHD features, verbal IQ and comorbid psychopathology were more strongly associated with impulsive aggression. CONCLUSION: The findings support the inclusion of features of impulsive aggression, such as hot temper/short fuse, in the ADHD syndrome in adults. These overlap with features of BPD. The findings inform the selection of research samples.

Characteristics of adults with attention-deficit/hyperactivity disorder and past conduct disorder.

OBJECTIVE: DSM-IV Attention-deficit/hyperactivity disorder (ADHD) comorbid with DSM-IV conduct disorder (CD) in childhood/adolescence has been proposed as a 'distinct subtype'. The present study investigated subsequent psychopathological characteristics of this proposed subtype in adults. METHOD: Questionnaires were completed by 71 adults (mean age 29.6 years) with ADHD and their informants. RESULTS: The 39 subjects with a history of past CD, when compared with the remaining subjects, were associated with significantly increased ratings of aspects of ADHD-related impulsivity, with features of all three DSM-IV 'Clusters' of personality disorders (PDs) (in particular of 'Cluster B' PDs) and with other psychopathology. Also, there were significant correlations between the number of endorsed past CD criteria and various self-ratings of psychopathology. CONCLUSION: The results indicate the psychopathological characteristics of adults with a history of the proposed 'ADHD with CD' subtype. The findings are relevant to future studies of ADHD subtypes in adults.

Profile of neurocognitive impairments associated with female in-patients with anorexia nervosa.

BACKGROUND: Although many studies have reported impairments of neurocognitive performance in patients with anorexia nervosa (AN), these have involved a wide range of assessment methods and some findings are inconsistent. METHOD: Twenty-five female in-patients with a DSM-IV diagnosis of AN, identified from three units specializing in the treatment of eating disorders, volunteered for the study. Twenty-five non-clinical control subjects were recruited, matched for age, gender and estimated IQ. Subjects were assessed with a range of computer-administered neurocognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), which has been validated in many studies of neuropsychiatric disorders. RESULTS: The patient group showed significant but moderate impairments (i.e. less than one standard deviation below the mean performance of the control group) on tests of spatial recognition memory, a planning task and rapid visual information processing, while a subgroup of patients (n = 14) showed greater degrees of impairments on at least one of these tests. The degrees of impairments did not correlate with body mass index (BMI). No impairments were observed on tests of spatial span, pattern recognition memory, spatial working memory, matching-to-sample, paired associates learning and set-shifting. CONCLUSIONS: The findings, in relation to a mean BMI of 15.3, are compatible with, in general, subtle impairments in neurocognition in AN. However, in those patients with relatively severe degrees of impairments, these may have adverse effects on complex tasks of social and occupational functioning. Further research is needed on the nature of relevant causal mechanisms, including the effects of potentially confounding variables.

Impaired spatial working memory in adults with attention-deficit/hyperactivity disorder: comparisons with performance in adults with borderline personality disorder and in control subjects.

OBJECTIVE: This study investigated a previous claim that working memory may be 'particularly impaired' in adult attention-deficit/hyperactivity disorder (ADHD), compared with other psychiatric disorders which affect frontal lobe-mediated executive functions. METHOD: Performance on spatial working memory (SWM) and two additional tasks were investigated for adult patients selected on the basis of DSM-IV ADHD (n = 19), adult patients selected on the basis of borderline personality disorder (BPD) (n = 19), and non-clinical control subjects (n = 19). Groups were matched for age, verbal IQ and gender. RESULTS: Analysis of variance showed that the ADHD group had significant impairment of SWM performance relative to the non-clinical controls. Although there was a trend towards impairment in the BPD group relative to non-clinical controls, this did not reach significance. CONCLUSION: The results are consistent with the claim that aspects of working memory are 'particularly impaired' in adult ADHD. Also, the BPD group had a longer deliberation time for one of the additional tasks, compared with the ADHD group, which indicated that the patient groups may have different patterns of neuropsychological impairments.

The specificity of clinical characteristics in adults with attention-deficit/hyperactivity disorder: a comparison with patients with borderline personality disorder.

Characteristics of DSM-IV attention-deficit/hyperactivity disorder (ADHD) in adults can also be found as part of other psychiatric disorders. This study investigated the specificity of adult ADHD features in relation to patients with borderline personality disorder (BPD), a syndrome which shares some of its intrinsic features with ADHD and often co-occurs with ADHD. A group of 20 adult patients selected on the basis of a diagnosis of ADHD and 20 patients selected on the basis of a diagnosis of BPD were assessed by the self-report Attention Deficit Scales for Adults (ADSA). The two groups were matched for age, verbal IQ and gender. Of the nine ADSA scales, seven showed significant inter-group differences, in particular involving attention, organisation and persistence. The 'Consistency/Long-Term' scale, which mainly reflects impaired task and goal persistence, was the best discriminator between the groups. Furthermore, ratings on this scale correlated significantly with the error score of a computer-administered task of spatial working memory, the performance of which has been reported to be impaired in patients with ADHD. The results provide further validation for the ADSA scales and support a previous claim that 'long-term consistencies', i.e., related to task and goal persistence, is 'the centrepiece behavioural issue' for adults with ADHD.

Diazepam produces disinhibitory cognitive effects in male volunteers.

RATIONALE: Diazepam has well known amnestic and sedative effects but effects on fronto-executive function remain largely uninvestigated, especially on neuropsychologically validated tests of risk taking and orbitofrontal cortex function. OBJECTIVES: We aimed to determine the impact of diazepam on a variety of executive tasks. METHODS: The effects of 5, 10 and 20 mg of diazepam on a battery of neuropsychological tests were investigated using a randomised, double blind, placebo-controlled design. Seventy-five adult men were recruited. The Rogers et al. (1999b) test of risk-taking was given along with tasks from the CANTAB battery. RESULTS: Diazepam impaired performance on the Tower of London test of planning, without influencing visual pattern recognition memory. Subjects who had taken diazepam made more risky choices on the risk-taking task. On two speeded reaction time tasks diazepam impaired discrimination sensitivity and increased the bias to respond. CONCLUSIONS: In contrast to the well-known sedative effects of diazepam, we demonstrate disinhibitory effects on two speeded reaction time tasks. Our results show that diazepam can impair performance on reaction time tasks both by impairing sensitivity and by increasing the bias to respond. Furthermore diazepam impaired performance on tests of planning and risky decision making that depend predominantly on dorsolateral and orbitofrontal regions of the prefrontal cortex, respectively.

Neurocognitive deficits in decision-making and planning of patients with DSM-III-R borderline personality disorder.

BACKGROUND: Repeated, self-damaging behaviour occurring in the context of borderline personality disorder (BPD) may reflect impairments in decision-making and planning cognition. However, there has been no systematic neuropsychological examination of these particular cognitive functions in patients diagnosed with BPD. Such investigations may improve our understanding of the possible role of brain dysfunction in BPD and improve the characterization of the psychological difficulties associated with this disorder. METHOD: Forty-two psychiatric patients with a diagnosis of DSM-III-R BPD (41 of whom gave a history of self-harm), without a history of specified 'psychoses' or current major affective disorder, were clinically assessed before completing computerized tasks of decision-making and planning previously shown to be sensitive to frontal lobe dysfunction, and tests of spatial and pattern visual recognition memory previously shown to be sensitive to frontal lobe damage and temporal lobe damage respectively. The performance of the BPD patient group was compared with that of a non-clinical control group consisting of 42 subjects. RESULTS: The performance of the BPD patients on the decision-making task was characterized by a pattern of delayed and maladaptive choices when choosing between competing actions, and by impulsive, disinhibited responding when gambling on the outcome of their decisions. BPD patients also showed impairments on the planning task. There was no evidence of impaired visual recognition memory. Additional analyses suggested only limited effects of current medication and history of previous substance use disorder. CONCLUSIONS: These findings suggest that BPD is associated with complex impairments in dissociable cognitive processes mediated by circuitry encompassing the frontal lobes. These impairments may mediate some of the behavioural changes evident in BPD. Further work is needed to examine the specificity of these findings.

Associations of past conduct disorder with personality disorders in 'non-psychotic' psychiatric inpatients.

The aim was to investigate associations of a history of features of DSM-III-R conduct disorder (CD) with features of DSM-III-R personality disorders (PDs) and psychopathy, in inpatient psychiatric practice. Fifty-six psychiatric inpatients, without a history of specified 'psychoses', were assessed by the SCID structured interview for DSM-III-R PDs and the 'Psychopathy Checklist Revised' (PCL-R). In a sample in which 59% had borderline PD, significant associations between a history of CD criteria and the adult features of antisocial PD (APD) were relatively specific compared with other PDs, but were weaker in women. However, significant correlations between the number of positive CD criteria and PCL-R scores were similar in both genders. The relatively specific associations between CD and adult features of APD are likely to be relevant to psychiatric patients who show various presentations of PD, if these include some adult features of APD. The findings inform the understanding of the development and classification of PDs.

Diurnal variations in endocrine and psychological responses to 0.2 mg/kg naloxone administration in patients with major depressive disorder and matched controls.

BACKGROUND: There is evidence that the endogenous opioid system (EOS) is involved in the modulation of mood and neuroendocrine function. Furthermore, the possible involvement of the EOS in major depression has been postulated, although a clear role has not been established. METHODS: The affective and endocrine responses to naloxone administration in seven female depressives and in seven matched controls and their diurnal variations were investigated. Subjects had an i.v. bolus of either 0.2 mg/kg naloxone or saline at two time points (09:00 or 18:00 h) and for 2 days in a single-blind, cross-over design. RESULTS: The basal cortisol plasma levels, both in the morning and in the afternoon, showed higher values (P<0.05) in the depressives. There was a naloxone-induced increase in the adrenocorticotrophic hormone (ACTH), cortisol, and luteinizing hormone (LH) plasma levels, plus a subjective dysphoric effect in both groups. The depressives showed a greater dysphoric effect both in the morning and afternoon (P<0.05), and a blunted cortisol response in the afternoon (P<0.05). There were no differences between groups or time of day in the ACTH or LH responses. LIMITATIONS: The sample size was small, but by studying each patient as their own control, plus a matched control for every patient, softens this effect. Finding patients with a major depressive episode free of medication is difficult, and this aspect contributes to the size of the sample. CONCLUSIONS: These results suggest that opioid mechanisms may be involved in the HPA axis changes and possibly in mood changes found in depression. The discrepancy between increased sensitivity in depression to mood changes and decreased change in cortisol may indicate a ceiling effect for the latter.

Associations of self-reported past "psychotic" phenomena with features of personality disorders.

Patients with borderline personality disorder (BPD) may present with "psychotic" phenomena, which can be defined as a range of specified "altered experiences of reality." This study investigated the associations between self-reported past psychotic phenomena and features of DSM-III-R personality disorders (PDs) in 57 inpatients without a previous diagnosis of the main disorders that involve delusions and hallucinations. The present findings include associations between past psychotic phenomena and features of BPD, between repeated self-harm and a report that "thoughts seemed put into head," and between psychotic phenomena and features of other PDs, particularly schizotypal PD. There was a high prevalence of BPD in the present sample. Dissociation, in the context of the features of BPD, may be a causal factor for the development of some of the psychotic phenomena presented by patients with PD.

Lipopigment Changes in Purkinje Cells in Alzheimer's Disease.

Cerebellar tissue was examined from 22 patients with Alzheimer's disease (AD) and from an age-matched group of 20 non-diseased subjects. Intraneuronal lipopigment in the bodies of 1344 Purkinje cells (PCs) (32 per brain) was identified by fluorescence microscopy. The mean total area (per PC) of the outlines of discrete regions of lipopigment in a PC perikaryon for the AD-related group of PCs was significantly greater than the mean for the comparison group (p<0.001). Also, the two groups of PCs showed significant (

Alzheimer's disease: distribution of changes in intraneuronal lipopigment in the frontal cortex.

Brains from 22 patients with Alzheimer's disease (AD) and 20 non-diseased subjects were examined. Intraneuronal lipopigment in 2,440 nucleolated neurons throughout the depth of cortex was identified by fluorescence microscopy. In the AD brains, the mean total area per neuron of the outlines of lipopigment was significantly increased in the region adjacent to the brain surface (sixths 1-3), and analysis of variance showed a significant interaction between depth of cortex (in sixths) and AD for this lipopigment variable (p = 0.012). After relating this lipopigment variable to the size of neuronal bodies, the results indicate that this change occurs in pyramidal neurons, although other neuronal types may also be affected. At least one of three AD-related changes in lipopigment was found in each sixth of the depth of cortex.

DSM-III-R self-defeating personality disorder criteria evaluated by patients' self-report questionnaire: relationships with other personality disorders and positive predictive powers of the individual criteria.

A self-report questionnaire for DSM-III-R personality disorders (PDs) was completed by 64 patients in adult psychiatric practice and their informants. Various correlations and associations of the number of patients' positive criteria (scores) for the controversial category of self-defeating PD (SDPD) are reported. When evaluated by a patient's self-report, the highest correlations of SDPD scores were with borderline PD in relation to individual PDs, and cluster C in relation to the 3 DSM-III-R PD clusters. Criteria 2 and 7 had positive predictive powers of 0.75 and 0.67 for membership of the subgroup based on scores of 5 or more positive criteria for SDPD. Positive ratings for criterion 5, involving anhedonia, were significantly associated with informants' ratings. SDPD features appear to be present in many psychiatric patients with PD and should be evaluated in PD assessment.

Effects of naloxone on diurnal rhythms in mood and endocrine function: a dose-response study in man.

This study investigated diurnal variations in the affective and endocrine response to opioid blockade in man and whether there were effects related either to the dose of naloxone or the time of day at which it was given. Normal male subjects were given an intravenous bolus of either 0.2 mg/kg (study 1) or 1 mg/kg naloxone (study 2) or control infusions at two time points (0900 or 1800 hours) in a single-blind crossover design. Before and following each infusion, mood was measured by the Profile of Mood States (POMS) and a visual analogue scale (VAS), and blood samples taken at 15-min intervals. Cortisol, LH ACTH and vasopressin (study 2 only) were measured. Blood pressure and heart rate were also monitored. The lower dose of naloxone had no effect on overall mood (POMS), though tension and confusion were increased in the afternoon. The VAS showed increased depression in the afternoon, and heightened tension, sleepiness and reduced ability to concentrate at both times of day. The higher dose increased overall dysphoria at both time points, though the tension and depression subscales were not altered. VAS depression and tension were increased, and there were changes in sleepiness. Subjective reports showed that 45% of the subjects correctly identified the drug treatment at the lower dose compared with 89% at the higher one. ACTH increased after both doses of naloxone irrespective of time of day. Cortisol was also raised by naloxone; the effect was greater in the afternoon for the lower dose, but not the higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of chronic chlorpromazine or lithium administration on ageing-related lipopigment in rat Purkinje neurones.

Ageing-related accumulation of neuronal lipopigment is considered to be debris from processes of renewal of cellular constituents, but can also reflect cell damage and certain diseases. Chlorpromazine (an example of a class of drug chronically administered in psychiatric practice) has been reported to reduce neuronal lipopigment accumulation, and the present study investigated the effects of 28 weeks of chlorpromazine administration on lipopigment in rat Purkinje neurones. The effects of 26 weeks of lithium administration (also chronically administered in psychiatric practice) were also studied. Lipopigment was identified by fluorescence microscopy and the area enclosed by an outline of each discrete region of lipopigment was measured. While lithium administration was not associated with significant changes in lipopigment variables, chlorpromazine administration was associated with a significant (p=0.001) reduction in the number of discrete lipopigment regions and with significant (p=0.001) differences in the numbers of discrete lipopigment regions in various size categories. The findings are similar to those associated with the administration of acetyl-L-carnitine (which has been reported to reduce some morphological and behavioural associations of brain ageing) and are compatible with a reduction in the rate of lipopigment formation. This could reflect an adverse effect of chlorpromazine administration (i.e. reduced functional activity of neurones) or a beneficial effect (i.e. a reduction in ageing-related changes).

Associations between self-induced vomiting and personality disorder in patients with a history of anorexia nervosa.

Fifty-five patients of an eating disorders service with a history of anorexia nervosa (AN), defined by a history of refusal to maintain body weight above a level of 15% below that expected, completed a modified version of the revised Personality Diagnostic Questionnaire (PDQ-R) based on DSM-III-R personality disorders (PD). The subjects were divided into 2 groups based on AN subtypes: vomiters, defined by a history of self-induced vomiting, and non-vomiters, who had maintained low weight mainly or only by diet +/- excessive exercise. Vomiters showed significantly higher scores on self-report measures of borderline and antisocial PD criteria. Discriminant analysis based on PD scores for all 13 DSM-III-R PD categories correctly predicted AN subtype membership based on vomiting history in 85.5% of patients. The implications of PD comorbidity for the development and management of eating disorders are discussed.

DSM-III-R narcissistic personality disorder evaluated by patients' and informants' self-report questionnaires: relationships with other personality disorders and a sense of entitlement as an indicator of narcissism.

Modified versions of the revised Personality Diagnostic Questionnaire (PDQ-R) for DSM-III-R personality disorders (PDs) were completed by 60 patients and their informants. Patients' ratings gave a mean number of 4.5 PDs per subject and narcissistic (NAR) PD in 42%. Informants' ratings gave NAR PD in 38%. For patients and informants, NAR PD scores (i.e., the number of positive NAR PD criteria for each subject) were significantly correlated with histrionic (HIS) and borderline (BOR) PD scores and with scores of some PDs outside DSM-III-R's "cluster B." Also, there were significant correlations between patients' and informants' NAR PD scores and between NAR PD scores and total number of positive criteria (i.e., for all 13 PDs) for patients and informants. For patients' ratings, there were significant associations between NAR PD and HIS, BOR, and passive-aggressive (PAG) PDs and, for informants' ratings, between NAR and HIS PDs. There was no significant association between patients' and informants' diagnoses of NAR PD. Grandiosity, the most characteristic feature of narcissism, is related to NAR PD criteria 3 through 6. The patients' evaluation of criterion 6 (i.e., "Has a sense of entitlement ...") shows satisfactory item-total correlation and endorsement frequency, together with "fair to good" reliability when patients' and informants' ratings are compared (kappa = 0.62). The identification of a sense of entitlement by the patient may be a relatively reliable and valid indicator of narcissism.

Assessment of DSM-III-R personality disorders by self-report questionnaire: the role of informants and a screening test for co-morbid personality disorders (STCPD)

A modified version of the revised Personality Diagnostic Questionnaire (PDQ-R), based on DSM-III-R personality disorders (PDs), was completed by 60 psychiatric patients. An informant's version was also completed by 60 relatives or friends nominated by each subject. Discrete DSM-III-R PDs were rare; the mean number of PDs per subject was 4.5. Cluster analysis showed that only antisocial PD was a basis for classification of patients, while most patients formed two groups which were mainly distinguished by quantitative differences related to the total scores of positive PD criteria. A shorter version of the questionnaire can be used as a screening test for co-morbid PDs (STCPD) which can predict the number of co-morbid DSM-III-R PDs. The total scores of positive PD criteria from the STCPD were usually (and significantly) higher than the corresponding scores from informants' questionnaires, but when an informant's total score exceeded that of the patient, this indicated a subject's under-reporting.

Changes in intraneuronal lipopigment in Alzheimer's disease.

Brains were examined from 22 patients with Alzheimer's disease (AD) (mean age 80.5, S.D. 11.5) and were compared with brains from 20 nondiseased subjects (mean age 81.1, S.D. 10.2). Intraneuronal lipopigment in all layers of a region of the superior frontal cortex was identified by fluorescence microscopy. The areas enclosed by the outlines of discrete regions of lipopigment autofluorescence were measured and assigned to a range of size categories. AD was associated with significant (p less than 0.05) decreases in the mean number (per neuron) of discrete regions of yellow lipopigment autofluorescence in the three smallest size categories and a significant increase in one of the larger size categories. Also, AD was associated with a significant decrease in the mean number (per neuron) of discrete regions of lipopigment autofluorescence (p less than 0.001). Significant (p less than 0.05) correlations were obtained between the Blessed dementia score (obtained within 2 years of death) and these lipopigment variables. The changes in neuronal lipopigment in AD may reflect an increased rate of lipopigment formation related to membrane and lysosomal abnormalities.

The morphology of lipopigment in rat Purkinje neurons after chronic acetyl-L-carnitine administration: a reduction in aging-related changes.

The aging-related accumulation of neuronal lipopigment is considered to be cellular debris from processes of renewal of cellular constituents, but it can also reflect cell damage and certain diseases. Acetyl-L-carnitine (AC) has been reported to reduce some morphological and behavioral associations of brain aging and the present study investigated the effects of 37 weeks of AC administration on lipopigment in rat Purkinje neurons. Lipopigment was identified by fluorescence microscopy and the area enclosed by an outline of each discrete region of lipopigment was measured. Acetyl-L-carnitine was associated with a significant (p = 0.05) reduction in the number of discrete lipopigment regions and there was a significant (p = 0.001) association of AC administration with numbers of lipopigment regions in various size categories. As AC administration was associated with a reduction in some of the aging-related morphological changes in lipopigment, this compound is a candidate for evaluation as a long-term prophylactic agent for the adverse effects of cerebral aging.