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.

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.

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.

Quantitative studies of the effects of aging, meclofenoxate, and dihydroergotoxine on intraneuronal lipopigment accumulation in the rat.

Intraneuronal lipopigment accumulation is associated with ageing and certain diseases, and there are many claims that this can be influenced by drugs, particularly meclofenoxate (centrophenoxine). The various unsubstantiated or conflicting reports of the effects of this drug in animal studies indicate the need for methods for the demonstration of lipopigment accumulation in adequately defined, easily-identified, and relatively homogeneous neuronal populations; this study has validated two such methods by demonstrating significant differences between groups of rats at different ages in respect of measured lipopigment autofluorescence intensity from the most heavily pigmented regions of a subpopulation of Purkinje cells, and of the area overlying intraneuronal lipopigment in a region of the hippocampus. These methods were then used to investigate the effects of daily (5 days per week) intraperitoneal injections of meclofenoxate or dihydroergotoxine, over a period of 12 weeks, before sacrifice at 13.5 months. No significant effects of meclofenoxate were detected, but dihydroergotoxine administration was associated with a significant increase in mean area overlying intraneuronal lipopigment in the CA3a region of the hippocampus. The results do not confirm that meclofenoxate can induce a reduction in intraneuronal lipopigment, but suggest that chronic dihydroergotoxine administration was associated with an increase in intraneuronal volume of lipopigment in the cell bodies of CA3a hippocampal neurones.

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)

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.

Lipopigment in rat hippocampal and Purkinje neurones after chronic phenytoin administration.

The accumulation of lipopigment may indicate ageing, certain diseases and cellular damage, while phenytoin, which has been claimed to cause selective clinical cerebellar dysfunction and degeneration, has been reported to produce increased lipopigment accumulation in rat Purkinje neurones. In the present study, 8 rats received phenytoin, 300 mg/kg/day for 20 weeks, and were compared with a control group of 9 rats in respect of lipopigment in Purkinje and hippocampal neurones. Neuronal lipopigment was identified by fluorescence microscopy. The results did not indicate that phenytoin administration was associated with an increase in the area corresponding to (i.e. within the outlines of) neuronal lipopigment in Purkinje neurones, although the relatively small number of animals limits the power of the study. However, in hippocampal neurones, a two-way analysis of variance for numbers of discrete regions of lipopigment demonstrated a significant interaction (P = 0.003) between, firstly, size categories of discrete regions of lipopigment and, secondly, phenytoin administration or a control procedure. In hippocampal neurones, phenytoin administration was accompanied by a decrease in the numbers of discrete lipopigment regions in the smaller size categories and an increase in the numbers in the larger size categories. This finding indicates the need for further investigation into the effects of phenytoin on brain regions other than the cerebellum, as intellectual deterioration may be related to chronic use of this drug.

MAO inhibitors in mental disease: their current status.

Available MAOIs seem to be mainly indicated for the heterogeneous group of patients with depressive syndromes. Although groups of patients with all the recognized major subtypes of depression (including "endogenous depression") probably respond in varying degrees, MAOIs appear to be particularly indicated for out-patients with "neurotic depression" complicated by panic disorder or hysteroid dysphoria, which involves repeated episodes of depressed mood in response to feeling rejected. MAOIs can also be effective in several anxiety syndromes, in particular panic disorder. Other reports have claimed success in a variety of other syndromes including bulimia, anorexia nervosa, obsessive-compulsive neurosis, atypical facial pain and some other types of chronic pain, childhood attention deficit disorder and delusions of infestation by parasites. The nature of any underlying personality disorder is an important response variable and the assessment of personality should be encouraged in further studies. The development of new drugs raises the prospect of a range of MAOIs targeted at specific patient populations. Tranylcypromine also merits further investigation as clinical experience suggests that it can produce a dramatic response in some patients with phenelzine-resistant disorders. This may be due, at least in part, to its amphetamine-like effects.

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.

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 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.

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.

The effects of ageing and a vitamin E-deficient diet on the lipopigment content of rat hippocampal and Purkinje neurones.

This study examined associations between a vitamin E-deficient diet, ageing and aspects of the morphology of neuronal lipopigment in rat hippocampal and Purkinje neurones. Groups of rats given a standard diet were killed at 6, 12, 18 and 25 months of age, while a group which had received a vitamin E-deficient diet from 1-18 months were killed at 18 months of age. Lipopigment within a neuronal cell body consists of a number of discrete regions of varying size. These were identified by fluorescence microscopy and a photograph for each individual neurone was projected onto paper, so that the outlines of the discrete regions of lipopigment could be drawn and subjected to morphometric measurements. Both ageing and vitamin E deficiency in relation to hippocampal neurones and vitamin E deficiency in relation to Purkinje neurones (in which ageing effects were not examined), were associated with a significant (< 0.05) increase in the mean total area (per rat) enclosed by the lipopigment outlines. For both vitamin E deficiency and ageing this increase was associated with both an increase in the number of relatively large discrete lipopigment regions and a decrease in the number of relatively small discrete lipopigment regions. The findings in relation to vitamin E deficiency could be explained by an increased rate of lipopigment formation, involving processes which also occur in ageing.

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.

The evaluation of autofluorescence emission spectra derived from neuronal lipopigment.

A method for measuring the emission spectra from regions of neuronal lipopigment in tissue sections is described and illustrated. Each emission spectrum was derived from the means of six sets of readings, from either six regions of lipopigment from six neurones which were presumed to be from a homogeneous cell population, or from one region of one neurone. Characteristics of the emission spectra from lipopigment in various forms of neuronal ceroid-lipofusinoses (NCLs) and in brains without evidence of NCL are presented and discussed. The results indicate that the classification of lipopigments should not be restricted to the two categories of 'lipofuscin' and 'ceroid'. This method may aid the identification of various pathogenic mechanisms in neurones, and provide another means of investigating the effects of certain drugs on cerebral function.

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.