German validation of the Conners Adult ADHD Rating Scales-self-report (CAARS-S) I: factor structure and normative data.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. Instruments for diagnosing ADHD in childhood are well validated and reliable, but diagnosis of ADHD in adults remains problematic. Attempts have been made to develop criteria specific for adult ADHD, resulting in the development of self-report and observer-rated questionnaires. To date, the Conners Adult ADHD Rating Scales (CAARS) are the international standard for questionnaire assessment of ADHD. The current study evaluates a German version of the CAARS self-report (CAARS-S). METHODS: Eight hundred and fifty healthy German control subjects were recruited to fill out the CAARS-S and to answer questions on sociodemographic variables. Explorative and confirmative factor analyses were conducted to obtain the factor structure for the German model and to replicate the factor structure of the original American model. Analyses on gender, age, and education level were calculated for normative data. RESULTS: The explorative factor analysis of the German sample results in a six-factor solution that explained 52% of the variance. A confirmative analysis that was based on the 42 items of the original American model showed a high model-fit. Analyses of normative data showed significant influences of age, gender, and education level on the emerging subscales. CONCLUSION: Even though the explorative factor analysis yields a solution different from the American original, the confirmative factor analysis results in such a high model-fit that use of the American version is justified with respect to international multicenter studies, for which this instrument will be highly valuable.

Body dissatisfaction and restrained eating in male juvenile and adult athletes.

Athletes of light-weight sport classes are under a constant strain to control eating and body shape, which can make them prone to develop eating disorders. In the present study, cognitive control of eating (restrained eating) and body dissatisfaction were investigated in male elite athletes of light-weight and heavy-weight classes at different ages. Body dissatisfaction was assessed under hunger and satiety. Adult light-weight rowers had extremely high scores of restrained eating and a more pronounced body dissatisfaction under hunger compared to satiety in contrast to heavy-weight rowers. Juvenile light-weight rowers had a pronounced cognitive control of eating behavior while body dissatisfaction was not affected by weight-class or hunger. The results suggest that extensive participation in a light-weight sport increases the cognitive control of eating behavior but not the disinhibition of cognitive control of eating. High levels of cognitive control of eating in the adult lightweight rowers are accompanied with body dissatisfaction under hunger but not under satiety.

No changes in event-related potentials with estrogen or estrogen plus progesterone treatment in healthy older hysterectomized women: results from a double-blind, placebo-controlled study.

RATIONALE: The potential to improve cognition in older women with estrogen or estrogen/progesterone therapy is currently a matter of intense debate. Only a few studies conducted so far have used electrophysiological indicators of cognitive information processing as outcome measures in randomised placebo controlled studies. OBJECTIVES: This study was undertaken to measure changes in event-related potentials (ERPs) after short (4 weeks) or prolonged (24 weeks) hormone treatment in older women. METHODS: A randomised, double-blind, placebo-controlled study in hysterectomized older women (aged 58-75 years) was performed (n = 51). The participants received orally estradiol (2 mg estradiol valerate), estradiol plus progesterone (100 mg micronized progesterone) or placebo for 24 weeks. Using four different paradigms, early and late ERPs were assessed at baseline and after 4 and 24 weeks of treatment. RESULTS: Strong hormone increases were observed in the two active treatment groups. However, no significant effects on any of the assessed ERPs were observed in either of the two treatment groups. Similar non-significant findings were obtained for reaction time and error rate. CONCLUSIONS: Estradiol or estradiol/progesterone treatment appears to have no strong effects on several ERP markers of information processing in older hysterectomized women. The current negative findings might suggest a reduced sensitivity of the aged brain to gonadal steroids.

Time course of intranasally administered cholecystokinin-8 on central nervous effects.

The gut and brain peptide cholecystokinin (CCK) exerts a number of central nervous effects. Among them are effects on attention and stimulus processing as revealed by modulations of event-related potentials (ERPs). In the present study the time course of central nervous effects after an intranasal administration of CCK-8 was investigated by means of ERPs. ERPs were recorded in an oddball paradigm 15, 30, 60, 90, 120, and 240 min after administration. Following the double-blind intranasal administration of CCK-8 and placebo, the late positive complex (LPC) of the ERP was significantly increased following CCK-8 compared to placebo. This effect was more pronounced in women than in men. The enhancement of the LPC by intranasal CCK-8 was not restricted to a specific recording time but reached its maximum 120 min after administration in men and women. Moreover, results tentatively indicate that 30 min after administration of CCK-8 the LPC increased only in women but not in men. The early effect of intranasal CCK-8 on LPC in women is unlikely to be caused by changes in plasma CCK-8 levels and suggests a direct nose-brain pathway.

[Psychological descriptors of excessive use of analgesic medication]. / Psychologische Deskriptoren des Schmerzmittelabusus und des medikamenteninduzierten Kopfschmerzes.

INTRODUCTION: Patients suffering from migraine and tension-type-headache are at risk of misusing analgesics and therefore developing chronic drug-induced headache. The present study compares migraine patients with and without abuse to identify psychological descriptors promoting drug abuse. METHODS: We examined 21 in-patients with migraine and drug-abuse and 21 out-patients with migraine and no drug-abuse who were comparable regarding age and diverse pain variables (intensity, frequency, duration, etc. ). Psychometric questionnaires measured the constructs "pain-", "depression", "self-efficacy" and "pain-coping". Using a standardized interview we investigated the external (environment) and internal (mental factors) conditions of all patients during medication intake. RESULTS: Migraineurs who misused medications showed significantly greater disability, greater helplessness and anxiety due to pain and a tendency towards more marked general depression than non-abusers. The extent of the helpless and depressive coping with pain was best suited for distinguishing the patients with and without drug abuse, followed by the fact that those with abuse receive drugs from several doctors at the same time and demand that the drugs free them of all complaints. CONCLUSIONS: These findings suggest that migraine patients with drug abuse often take analgesics not according to their headache, but rather depending on certain other factors.

Dexamethasone blocks sleep induced improvement of declarative memory.

To investigate the role of glucocorticoids for effects of early and late nocturnal sleep on declarative and procedural memory, 2 mg dexamethasone (versus placebo) were administered to healthy men 7 h prior to retention sleep. The retention sleep interval covered either the early or late half of nocturnal sleep. Following placebo, recall of a paired associate list (declarative memory) benefitted more from early than late sleep and recall of mirror tracing skills (procedural memory) benefitted more from late than early sleep. Dexamethasone did not affect slow wave sleep dominating early sleep, but blocked the beneficial effect of early sleep on recall of paired associates. Conversely, dexamethasone reduced rapid eye movement sleep dominating late sleep, but did not affect late sleeps beneficial effect on mirror tracing skills. The natural inhibition of endogenous glucocorticoid secretion during early sleep seems to be essential for a sleep-related facilitation of declarative memory.

Beneficial treatment of age-related sleep disturbances with prolonged intranasal vasopressin.

Disturbed sleep is common in the elderly and is characterized by disordered sleep architecture with reduced time spent in slow wave sleep (SWS) and in rapid eye movement (REM) sleep. At present, no treatments are available to fully compensate for these disorders. In the elderly, vasopressin content is decreased at various brain sites. Investigating the effects of a 3-month intranasal vasopressin administration on sleep and cognitive functions in two elderly subjects in a foregoing pilot study, the authors found that the most pronounced influence of the peptide was a marked increase in SWS. This placebo-controlled, double-blind, randomized study examined the influences of a 3-month period of daily intranasal vasopressin treatment (20 IU before bedtime and after awakening) on nocturnal sleep in 26 healthy elderly subjects (mean age, 74.2 years). Intranasal treatment of vasopressin increased (1) the total sleep time, on average, by 45 minutes (p < 0.002); (2) time spent in SWS by 21 minutes (p < 0.025); and (3) time in REM sleep in the second half of the night by 10 minutes (p < 0.01). Vasopressin promotes sleep time and improves sleep architecture after prolonged intranasal administration in elderly subjects, although scores of subjective sleep quality did not change. Results suggest that age-related deterioration of sleep architecture can benefit from intranasal treatment with vasopressin. But a potential use in clinical settings will also depend on demonstrating improved subjective sleep quality, which remained unaffected by vasopressin in this study of elderly subjects.

Intranasal angiotensin II directly influences central nervous regulation of blood pressure.

Intranasal administration of some peptides has been shown to directly influence central nervous functions, thus pointing to a nose-brain pathway for these substances in humans. The present study investigated whether intranasal administration of angiotensin II (ANG II) affects central nervous functions of cardiovascular control in a different way from intravenously administered ANG II. In a balanced cross-over design 12 healthy men were treated with ANG II intravenously (2.5 microg), ANG II intranasally (400 microg), and placebo. Angiotensin II, vasopressin, norepinephrine, and epinephrine plasma levels were assessed every 10 min; blood pressure, heart rate, and systemic vascular resistance were measured by a Dinamap, and by continuous, noninvasive body plethysmography. Also, feelings of activation and mood were measured. Intranasal and intravenous administration invoked equivalent increases in plasma levels of ANG II, and induced an acute rise in blood pressure of comparable size and duration. However, subsequent blood pressure profiles differed dependent on intravenous and intranasal ANG II administration; after intravenous ANG II administration blood pressure remained enhanced at an intermediate level, but it returned to normal or even decreased below normal levels after intranasal ANG II administration. Intranasal ANG II also counteracted the decrease in norepinephrine levels observed after intravenous administration of ANG II. Intranasal but not intravenous ANG II enhanced plasma concentrations of vasopressin. This diverging pattern of effects bears similarities with effects of intracerebroventricular administration of ANG II in animals, suggesting that the effects after intranasal administration reflect a direct central nervous action of ANG II.

Enhanced selective attention after low-dose administration of the benzodiazepine antagonist flumazenil.

Although recognized for their sedative properties, benzodiazepines are also known to impair sustained and selective attention. Flumazenil at low doses may act to antagonize benzodiazepine-induced effects. This study examined whether low doses of flumazenil would improve event-related brain potential (ERP) indicators of selective attention and induce feelings of activation and anxiety in healthy men. Data from 11 men (24-30 years) who received intravenous flumazenil (0.2 mg, plus 0.3 mg 30 minutes later) and placebo were analyzed according to a double-blind crossover design. ERPs were recorded while subjects performed an auditory selective attention task. Mismatch negativity (MMN), processing negativity (PN), and the P3 component were extracted from the ERP as markers of preattentive mismatch processing, selective attention, and stimulus processing within working memory, respectively. Counting accuracy and performance on a letter cancellation test were used as behavioral indicators of attention. Mood was assessed by an adjective checklist and the State-Trait Anxiety Inventory. Flumazenil significantly increased PN over frontocortical areas, indicating improved selective attention (p < 0.05). Increases in the P3 amplitude and MMN after drug treatment remained nonsignificant. Subjects felt more activated and extraverted after flumazenil treatment than after placebo (p < 0.05). Anxiety was not increased. The findings of this study confirm the concept that flumazenil administered at a low dose in humans exerts effects opposite to those of benzodiazepines.

Neuropsychological effects of vasopressin in healthy humans.

Animal research indicated that vasopressin (VP) exerts its principle behavioral influence, the improvement of memory formation, through an action on septo-hippocampal and connected limbic structures. Here human research is reviewed with the notion of a comparable effect of VP in healthy humans. Although the human studies yielded less consistent results than those in rats, they indicate that VP is able to improve declarative memory formation which is the type of memory essentially relying on hippocampal function. The effect appears to center on the encoding process for memory. In examinations of event-related brain potentials (ERPs) VP was consistently found to increase the 'mismatch negativity' (MMN) and the P3 components which are ERP potentials closely linked to the hippocampal processing of novel, unexpected and salient events. Enhanced processing of these stimulus aspects is considered to precipitate memory encoding. The regulation of voluntary selective attention and arousal do not appear to be primary targets of VP effects in humans. A mediation of effects by peripheral changes can be excluded since the central nervous effects were observed in studies using intranasal VP administration providing a direct access to brain functions.

Systemic immune changes following meal intake in humans.

Food intake represents a high intestinal antigen exposition requiring host defense. Besides local immune activation, this defense includes a coordinate systemic immune response, which may serve to support local immunity. This study examined influences of a standardized high-protein meal on peripheral blood mononuclear cell counts; on the in vitro mitogen-stimulated production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interferon-gamma; on the in vivo plasma levels of tumor necrosis factor-alpha and interleukin-6; and on plasma concentrations of cortisol and growth hormone. Ten healthy men (18-35 yr) participated in two experimental sessions in a balanced order. On one occasion, subjects fasted; on the other, they received a high-protein meal at 1230. Blood was sampled every 15 min. Whereas the numbers of neutrophils and platelets were increased for more than 2.5 h after meal intake (P < 0.01) lymphocyte counts decreased (P < 0.01). Meal intake also decreased the production of interferon-gamma but did not affect the production and plasma levels of the other cytokines. Changes in immune cell distribution and function were accompanied by a strong postprandial rise in plasma cortisol concentrations. Some of the systemic immune changes, like the emigration of lymphocytes, probably into extravascular abdominal tissues, may serve to support local immune defense.

Regulation of human thought by neuropeptide ACTH 4-10: an analysis of the EEG's dimensional complexity.

The neuroactive 4-10 fragment of adrenocorticotropin (ACTH 4-10) has been found to impair electroencephalographic (EEG) signs of selective attention in previous studies. It was hypothesized that this effect reflects a more general influence of the peptide weakening the mutual inhibition among frontocortical neuronal networks. Therefore, ACTH 4-10 was expected to loosen attentional control not only over external input but also over internal thoughts. This study examined the effects of ACTH 4-10 on the dimensional complexity of the EEG recorded while subjects solved tasks of convergent analytical thinking and of divergent creative thinking and during mental relaxation. Subjects were tested 30 min after i.v. administration of placebo or ACTH 4-10 (2 mg). ACTH 4-10 enhanced dimensional complexity of the EEG. The effect primarily concerned frontocortical recordings during convergent thinking, which, following placebo, was associated with the lowest EEG dimension. ACTH 4-10 also impaired behavioral performance on tasks of convergent thought, when presented verbally. Results suggest that ACTH 4-10 counteracts the inhibitory control among cortical neuronal networks necessary for orderly analytical thinking.

Verbal memory after three months of intranasal vasopressin in healthy old humans.

In animals, evidence has been accumulated that vasopressin (VP) improves learning and memory. In humans, this effect was not consistently demonstrated, and attempts to restore age-related memory deficits by VP also remained inconsistent. Assuming that in old subjects a beneficial effect on memory occurs only after prolonged treatment with VP, we conducted a study in 26 healthy elderly persons receiving 40 IU of VP for three months through the intranasal route. The trial was randomized, placebo-controlled and held double-blind. Memory was assessed by the Auditory Verbal Learning Test (AVLT) requiring the subject to learn repeatedly presented lists of 15 words. Results demonstrated no general effect of long-term treatment with VP on memory in aged humans. However, recall of an interfering word list was improved, indicating a diminished proactive interference by the peptide. Additionally, VP influenced recall depending on the serial position of an item: it improved the primacy effect (i.e. recall of the first words of a list) and impaired the recency effect. This result may indicate an improved semantic encoding (i.e. a primary effect on processes of attention) after long-term administration of VP.

Cholecystokinin-induced effects on selective attention depend on level of activation.

Cholecystokinin (CCK)-like peptides, such as ceruletide, have been found to improve selective attention as indicated by the processing negativity (PN) of the event-related brain potential. The present study compared effects of ceruletide and placebo after intravenous administration of ceruletide on the PN in healthy subjects classified into two groups scoring high versus low on self-reported activation. Following placebo, PN (at Fz) was somewhat larger in subjects with low than high activation (p < 0.1). Administration of the CCK analog decreased PN in low-activation subjects but increased PN in the highly activated group (p < 0.01). Results suggest that the effects of CCK on selective attention depend on a modulation of central nervous mechanisms underlying activation.

Event-related brain potentials during identification of tachistoscopically presented pictures.

In the present study in 20 healthy subjects, event-related potentials (ERPs) were used to investigate the identification of picture stimuli. Each of 36 landscape pictures and 36 scrambled pictures was presented by a tachistoscope repeatedly until the subject made an identification response. Presentation of one picture was finished after 12 exposures. On the average, landscapes were identified after 5.8 +/- 0.4 exposures; identification responses to scrambles were always wrong and occurred after 11.8 +/- 0.1 exposures. Latencies and amplitude measures were assessed for P2, P3, N400, and the slow wave (SW). Changes in P2 across stimulus presentations did not differ between landscapes and scrambles excluding this component from being indicative for the processing of stimulus meaning. Amplitude of P3 generally declined across presentations, but increased prior to identification for landscape pictures. N400 rapidly declined across presentations of landscapes, but less rapidly for scrambles. The SW increased across stimulus presentations. This increase was more pronounced for landscape than scrambled pictures. The pattern of ERP changes can be interpreted in a framework of a stepwise inhibition of spreading activation within semantic memory with progressing picture identification.

Ceruletide improves event-related potential indicators of cognitive processing in young but not in elderly humans.

The effect of intravenously administered ceruletide, a cholecystokinin (CCK) analogue, on neurophysiologic signs of stimulus processing was tested in 16 young (19-28 years) and 16 aged (70-86 years) healthy subjects. Placebo or 2.5 micrograms ceruletide was infused within 30 minutes according to a double-blind within-subject crossover design. Thereafter, auditory event-related brain potential (AERP) responses to stimuli of an "oddball" task (including the random presentation of frequent standard tones and rare target tones) were recorded. Amplitudes of the P2, P3, and SW components of the AERP were reduced in aged subjects (p < 0.05, p < 0.001, and p < 0.01, respectively), and latencies (from stimulus onset) of the N2 and P3 components were prolonged (p < 0.05 and p < 0.01, respectively). Together, these changes indicate impaired cognitive processing capabilities in aged compared with young subjects. Ceruletide enhanced P3 and also the subsequent slow-wave (SW) component that occurs 500 to 700 ms poststimulus in young subjects (p < 0.05 and p < 0.001, respectively). The peptide did not at all affect AERPs in the elderly subjects. Results demonstrate the capability of ceruletide after systemic administration to enhance central nervous system indicators of cognitive processing such as P3 and SW in young subjects. However, despite the clear effect of the CCK analogue in young subjects, it remained ineffective in the group of aged subjects and, thus, failed to compensate for the decline in AERP signs of working memory functioning in the elderly subjects.

The angiotensin converting enzyme inhibitors fosinopril and enalapril differ in their central nervous effects in humans.

BACKGROUND: Although the antihypertensive actions of different angiotensin converting enzyme (ACE) inhibitors are comparable, they may affect central nervous activity, mood and well-being differently. Thus, central nervous actions of ACE inhibitors may represent an essential factor determining compliance with antihypertensive therapy. OBJECTIVE: To compare central nervous effects of the biochemically different ACE inhibitors fosinopril and enalapril in healthy men. METHODS: In a double-blind cross-over study, auditory event-related brain potentials and heart rate variability were assessed 6 h after oral intake of placebo, enalapril (10 mg) and fosinopril (20 mg) with the doses being equipotent with regard to systemic ACE inhibition. Plasma concentrations of noradrenaline, adrenaline, vasopressin and cortisol were determined 3 and 6 h after drug intake. Central nervous effects mediated via direct systemic hypotensive actions were avoided (although not completely ruled out) by including only subjects (n = 14) who displayed no substantial drop in blood pressure following intake of the ACE inhibitors. RESULTS: Enalapril, but not fosinopril, enhanced the N1 component and the N1-P2 amplitude of the event-related brain potential (P < 0.05). In addition, enalapril enhanced plasma noradrenaline concentrations (P < 0.05). A similar effect of fosinopril failed to reach significance. There was no clear-cut effect of ACE inhibition on heart rate variability, and also plasma concentrations of adrenaline, vasopressin and cortisol remained unaffected. CONCLUSION: The results suggest an enhancing effect of enalapril on mechanisms regulating stimulus-induced cortical arousal and central nervous sympathetic outflow. The effects diverging between enalapril and fosinopril indicate that access to human brain functions differs among the various types of ACE inhibitors.

Corticosteroid receptor mediated effects on mood in humans.

The present double-blind cross-over study aimed to discriminate effects of dexamethasone (DEX) and cortisol (CORT) on mood in ten healthy men. DEX is assumed to predominantly activate glucocorticoid receptors (GR) whereas CORT binds central nervous mineralocorticoid receptors (MR) as well as GR. Mood was assessed by an extensive adjective checklist (Eigenschaftswoerterliste) every morning during two 7-day experimental periods. During one of these periods, subjects were subchronically treated with placebo, during the other they received DEX (4 mg/day). On days 5 and 7 of these periods, (in a balanced manner) either placebo or CORT (10 mg/h) was infused during the night (9 h) before mood assessment. DEX, acutely, enhanced activation, concentration, and arousal (p < .05). During prolonged DEX administration, the energizing effect of the glucocorticoid decreased, but emotional arousability and negative feelings (anger, sadness) were significantly enhanced. CORT administered during prolonged DEX treatment, counteracted these negative feelings, and enhanced scores on a dimension of "high spirits". Sole administration of CORT also enhanced "high spirits" (p < .05) and, like DEX, activation and concentration (p < .05). Results suggest GR to mediate an energizing effect and, with prolonged activation, a dysphoric influence on mood. Predominant activation of MR appears to mediate changes towards euphoric mood.

A nose-brain pathway for psychotropic peptides: evidence from a brain evoked potential study with cholecystokinin.

The access of substances to the brain is of particular relevance for the etiology and treatment of psychiatric and neurologic diseases. This study provides functional evidence for a direct access of peptides to the human brain after intranasal administration. Effects were compared of intranasal (IN, 10 micrograms) and intravenous (i.v., 0.25 and 2.5 micrograms) administered cholecystokinin-8 (CCK) on the auditory event related potential (AERP) in 20 healthy subjects. Also, plasma concentration of cortisol and ACTH were monitored. The study was designed as a placebo-controlled, double-blind within-subject cross-over comparison. AERPs were recorded while the subject performed on an attention task (oddball task). Plasma CCK concentrations after IN administration of CCK were comparable to those after i.v. administration of 0.25 microgram CCK, but were substantially lower than those after 2.5 micrograms CCK. The P3 complex of the AERP was markedly increased following the IN administration of CCK (p < .01) compared to placebo and to the i.v. administration of 0.25 microgram. This pattern was more obvious in women than men. Increases in plasma ACTH concentrations after CCK reached significance selectively following the IN mode of administration (p < .01).