The intensity dependence of auditory evoked ERP components predicts responsiveness to reboxetine treatment in major depression.

INTRODUCTION: The intensity (loudness)-dependent amplitude change (IDAP) of auditory evoked event-related potential (ERP) components has been suggested as an indicator of central serotonergic neurotransmission. In patients with major depression, associations of high IDAP with favorable SSRI treatment outcome have been reported. This is the first study to assess the predictive value of the IDAP in SNRI treatment. METHODS: We evaluated the pre-treatment intensity-dependent change of auditory evoked P1, N1, P2, and P1/N1 and N1/P2 peak-to-peak amplitudes in 14 inpatients with major depressive episode (DSM IV) in the course of 24 days of treatment with the SNRI reboxetine (6-12 mg/d). RESULTS: Our data revealed a highly significant correlation between lower intensity-dependent N1 amplitude slopes prior to reboxetine treatment and stronger decrease of HDRS total score at Fz ( r = 0.86, P < 0.001), Fcz ( r = 0.91, P < 0.001), and Cz ( r = 0.93, P < 0.001). CONCLUSION: This result corroborates the hypothesis of the IDAP as a differential indicator of serotonergic versus noradrenergic antidepressant psychopharmacotherapy.

The movement-related potential in children with migraine and tension-type headache.

Migraine is characterized by an elevated contingent negative variation (CNV) in adults and children. In the present study the movement-related potential preceding self-initiated movements, the Bereitschaftspotential, was investigated in 30 children (mean age 12 years) who were suffering from migraine and tension-type headache and in 16 healthy age-matched controls. Children pressed a button 80 times with the right index finger while movement-related potentials were recorded from frontal and central electrodes. Whereas healthy children evidenced positive movement-related potentials at left and midline positions, children with migraine and tension-type headache showed negative movement-related potentials at midline leads without lateralization. Negativity was even more pronounced in cases of migraine with than without aura symptoms.

Novelty-elicited mismatch negativity in patients with schizophrenia on admission and discharge.

OBJECTIVE: Given recent reports of differences between mismatch negativity (MMN) elicited by always novel sounds (novelty-elicited MMN) and that elicited by repeated rare deviants (conventional MMN), we investigated novelty-elicited MMN and P3a in patients with schizophrenia before and after a nonstandardized inpatient treatment. DESIGN: Electrophysiological and clinical assessment of patients on admission and discharge from hospital. Assessment of control subjects on 2 sessions. SETTING: Inpatient treatment in a psychiatric university hospital. SUBJECTS: 20 patients with schizophrenia and 21 healthy control subjects of similar age and sex. Selection of patients with first- to third-episode schizophrenia. OUTCOME MEASURES: Early and late component MMN amplitudes and latencies, P3a amplitudes and latencies, Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Extrapyramidal Symptom Scale (EPS), Abnormal Involuntary Movement Scale (AIMS) and chlorpromazine equivalents. RESULTS: In patients with schizophrenia, novelty-elicited MMN was unimpaired on admission, and there was a statistically significant reduction of the late MMN component with treatment. Improvements in symptom expression were associated with increased latencies of the early MMN component. CONCLUSION: Results indicate differences in information processing between conventional and novelty-elicited MMN. Some components of the novelty-elicited MMN might be more state dependent than those of the conventional MMN.

Conditioned blocking and schizophrenia: a replication and study of the role of symptoms, age, onset-age of psychosis and illness-duration.

Measures of selective attention processing like latent inhibition (LI) and conditioned blocking (CB) are disturbed in some patients with schizophrenia. [LI is the delay in learning about the associations of a stimulus that has been associated with no event (versus de novo learning); CB is the delay in learning the associations of a stimulus-component when the other component has already started to acquire these associations.] We proposed: (1) to replicate the reported decreases of CB in patients without paranoid-hallucinatory symptoms; (2) to see if CB depends on the age of illness-onset and its duration, as reported for LI. We studied 101 young and old, acute and chronically ill patients with schizophrenia, of whom 62 learned a modified 'mouse-in-house' CB task, and compared them with 62 healthy controls matched for age, education and socio-economic background. CB was more evident in patients with a diagnosis of paranoid schizophrenia than other subtypes. An unusual persistence of high CB scores through testing was associated with productive symptoms (including positive thought disorder). Reduced CB related to the expression of (a) Schneider's first rank symptoms of ideas-of-reference and (b) to negative symptoms like poor rapport and poor attention. CB was less evident in the older patients and those with an earlier illness-onset. In contrast to the similar LI test of selective attention, CB is found in patients with paranoid schizophrenia and its expression is not related closely to illness duration. This implies that the two tests reflect the activity of different underlying processes. We suggest that reduced CB on initial test-trials in nonparanoid schizophrenia reflects the unusual persistence of controlled information processing strategies that would normally become automatic during conditioning. In contrast, continued CB during testing reflects an unusual persistence of automatic processing strategies.

Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy.

Patients with schizophrenia show impairments of attention and neuropsychological performance, but the extent to which this is attributable to antipsychotic medication remains largely unexplored. We describe here the putative influence of the dose of antipsychotic medication (chlorpromazine equivalents, CPZ), the antipsychotic serum concentration of dopamine (DA) D2-blocking activity and the approximated central dopamine D2-receptor occupancy (DA D2-occupancy), on conditioned blocking (CB) measures of attention and performance on a neuropsychological battery, in 108 patients with schizophrenia (compared with 62 healthy controls). Antipsychotic serum concentration and D2-occupancy were higher in patients with a paranoid versus non-paranoid diagnosis, and in female versus male patients (independent of symptom severity). Controlling for D2-occupancy removed the difference between high CB in paranoid and impaired low CB in non-paranoid patients. Similar partial correlations for antipsychotic drug dose and serum levels of DA D2-blocking activity with performance of the trail-making and picture completion tests (negative) and the block-design task (positive) showed the functional importance of DA-related activity. High estimates of central DA D2-occupancy were related to impaired verbal fluency but were associated with improved recall of stories, especially in paranoid patients. This, the first study of its kind, tentatively imputes a role for DA D2-related activity in left frontal (e.g. CB, verbal fluency) and temporal lobe functions (verbal recall) as well as in some non-verbal abilities mediated more in the right hemisphere in patients with schizophrenia.

Fear reduction in patients with dental treatment phobia.

In a clinical trial, we examined short- and medium-term reduction of dental fear in patients with dental phobia. Ninety-one patients selected one of two treatments or no intervention before oral surgery (control group). One group comprised a one-session psychological treatment and included 25 patients. The second group chose oral selected midazolam and included 30 patients. Thirty-six patients chose the control group. In total, 50 patients completed the study (10 controls, 20 in the midazolam group, an d 20 in the treated group). The degree of fear was assessed by the Corah Dental Anxiety Scale. Before the operation, both interventions caused the degree of fear to fall significantly compared with the control group. Two months later, the midazolam group showed a return to baseline fear, whereas the psychologically treated group showed further improvement. Medium-term results after one year showed that compliance and reduction of fear remained only in the psychologically treated group.

Comparison between one-session psychological treatment and benzodiazepine in dental phobia.

To compare the effects of a single session of psychological treatment and acute administration of benzodiazepine, 50 dental phobic patients were allocated either to psychological treatment, benzodiazepine, or no treatment for anxiety. Psychological treatment consisted of stress management training and imaginal exposure to phobic stimuli with homework assignments. Benzodiazepine was administered 30 min before dental treatment. Both treatment conditions led to less anxiety during dental surgery than did the control condition. Phobic patients in the benzodiazepine condition showed a relapse after dental treatment, whereas those in the psychological treatment condition showed further improvement until the follow-up 2 months later. Of the latter group, 70% continued dental treatment; only 20% and 10% returned in the benzodiazepine and control conditions, respectively.

A comparison of psychological and pharmacological treatment of pediatric migraine.

A comparison was carried out of the efficacy of psychological and drug treatments for children with migraine. Forty-three children aged between 8 and 16 years (mean age: 11.3 years) who suffered from migraine received either progressive relaxation or cephalic vasomotor feedback, both with stress management training, or metoprolol, a beta-blocker. Psychological treatment was administered in ten sessions lasting six weeks and the drug treatment lasted ten weeks. Relaxation and stress management training reduced the headache index (frequency x intensity of headache episodes), more effectively than metoprolol with cephalic vasomotor feedback and stress management training in between. An overall improvement over time was found with regard to frequency and intensity of headache episodes and analgesics intake. When comparing pre- to post-treatment data, children treated with relaxation training improved significantly in headache frequency and intensity, whereas those treated with cephalic vasomotor feedback improved significantly in headache frequency and duration as well as mood. The clinical improvement was stable at an 8-months follow-up.

Further parameters of insight and neuropsychological deficit in schizophrenia and other chronic mental disease.

Evidence has begun to accumulate which suggests that lack of awareness of illness in schizophrenia is related to and possibly the result of a cognitive deficit involving prefrontal cerebral dysfunction. This study further explores this relationship along with other domains of self-awareness in chronic schizophrenics and other subjects with serious mental disorders. One hundred eight schizophrenics and 21 bipolar subjects from three separate sites in Britain, Germany, and Canada were administered the Wisconsin Card Sorting Test and three measures of self-awareness. Lack of illness awareness and other domains of self-knowledge were significantly more related to poorer neuropsychological performance in schizophrenia patients than in the other subjects. The results support the hypothesis that lack of illness awareness is related to defective frontal lobe functioning as indexed by neuropsychological measures.

Disgust implicated in obsessive-compulsive disorder.

Psychiatric classificatory systems consider obsessions and compulsions as forms of anxiety disorder. However, the neurology of diseases associated with obsessive-compulsive symptoms suggests the involvement of fronto-striatal regions likely to be involved in the mediation of the emotion of disgust, suggesting that dysfunctions of disgust should be considered alongside anxiety in the pathogenesis of obsessive-compulsive behaviours. We therefore tested recognition of facial expressions of basic emotions (including disgust) by groups of participants with obsessive-compulsive disorder (OCD) and with Gilles de la Tourette's syndrome (GTS) with an without co-present obsessive-compulsive behaviours (GTS with OCB; GTS without OCB). A group of people suffering from panic disorder and generalized anxiety were also included in the study. Both groups with obsessive-compulsive symptoms (OCD; GTS with OCB) showed impaired recognition of facial expressions of disgust. Such problems were not evident in participants with panic disorder and generalized anxiety, or for participants with GTS without obsessions or compulsions, indicating that the deficit is closely related to the presence of obsessive-compulsive symptoms. Participants with OCD were able to assign words to emotion categories without difficulty, showing that their problem with disgust is linked to a failure to recognize this emotion in others and not a comprehension or response criterion effect. Impaired recognition of disgust is consistent with the neurology of OCD and with the idea that abnormal experience of disgust may be involved in the genesis of obsessions and compulsions.

The efficacy of complaints management training in facilitating benzodiazepine withdrawal.

The study aimed at evaluating the efficacy of complaints management training (CMT) compared to that of anxiety management training (AMT) in patients undergoing benzodiazepine withdrawal. CMT focused on techniques to alleviate reported withdrawal symptoms. Nineteen patients were randomly allocated either to CMT or to AMT. Both groups received 9 weekly treatment sessions and were assessed every other week. Withdrawal was designed to be gradual over the first 4 weeks. CMT proved more successful than AMT in terms of abstinence rate, reported number of severe withdrawal symptoms, depression and anxiety. At follow-up after 6 months, there was no difference between groups in terms of abstinence rate.

On the relation among psychological distress, diabetes-related health behavior, and level of glycosylated hemoglobin in type I diabetes.

This study aimed at investigating the relation between psychological diabetes-related health behavior, and metabolic aspects of diabetes. Fifty-one adult patients with type I diabetes mellitus took part in the study. Psychological status, health, and self-care behavior were assessed by means of questionnaires. Level of glycosylated hemoglobin (HbA(1c) served as the index of metabolic control. Depression was slightly elevated among women as was trait anxiety and blood-injury phobia or fear of medical interventions in all patients. Depression and anxiety were not related to duration of diabetes or presence of diabetes complications. As could be expected, patients who frequently checked their blood glucose level had a significantly lower level of HbA(1c) than those with infrequent checks. Patients with a marked blood-injury phobia carried out fewer daily checks of blood glucose level than those without, but blood-injury phobia was not directly related to HbA(tc) level. A higher level of HbA(tc) was, however, associated with mood deterioration. As depression was not related to health behavior, its effect on metabolic control is likely to be mediated via endocrine rather than behavioral variables.

Contingent negative variation in childhood migraine.

Adult migraineurs without aura have an increased amplitude of the Contingent Negative Variation (CNV) between attacks. Given the potential diagnostic importance of this finding and the difficulties associated with diagnosing migraine in childhood it seemed important to assess CNV in children suffering from this disorder. Ninety-seven children aged between 8 and 14 years were recruited. Forty-two suffered from migraine, 34 from tension-type headache. Twenty-one healthy controls were also studied. CNV was recorded from Fz, Cz and Pz referenced to linked earlobes during 20 trials consisting of two tones of moderate intensity with an interstimulus interval (ISI) of 4 sec and an intertrial interval (ITI) of 10 to 14 sec. The second tone of each trial required a button press. EOG was recorded from the left eye. The 10 CNV responses with the least EOG artefact were selected and averaged. Children with migraine had a highly significantly more negative mean CNV amplitude at all three electrode sites than children with tension-type headache and also a more pronounced Post-Imperative-Negative-Variation (PINV). Migrainous children differed from controls only at Cz (ISI). There was also a highly significant increase of mean CNV amplitude and PINV at all three electrode sites in the control group compared to the tension headache group.

EMG biofeedback treatment of torticollis: a controlled outcome study.

Successful treatment of torticollis with electromyographic (EMG) biofeedback has been reported in a number of single case and single group studies. The present investigation represents the first controlled outcome study. Twelve torticollis patients were randomly assigned to EMG biofeedback or relaxation training and graded neck exercises (RGP). The procedure involved three sessions of baseline assessment, 15 sessions of EMG BF or RGP, 6 sessions of EMG BF or RGP plus home-management, 6 sessions of home-management alone, and follow-up 3 months after the end of treatment. A variety of outcome measures were used including physiological (EMG from the two sternocleidomastoid muscles, skin conductance level), behavioral (angle of head deviation, range of movement of the head), and self-report (depression, functional disability, body concept), therapist and "significant other" reports and independent observer assessment of videos. In both groups, neck muscle activity was reduced from pre- to posttreatment. This reduction was greater in the EMG biofeedback group. There was evidence of feedback-specific neck muscle relaxation in the EMG biofeedback group. Therefore, the outcome was not due to nonspecific factors and could be attributed to feedback-specific effects. Changes in skin conductance level showed that neck muscle relaxation was not simply mediated by a general reduction of "arousal." Significant improvements of extent of head deviation, and range of movement of the head, as well as reductions of depression were present, which were not different in the two groups. At the end of treatment, no patient was asymptomatic. Any therapeutic benefit was generally maintained at follow-up. The results and the procedural simplicity of RGP make the issue of cost-efficacy of EMG biofeedback a pertinent one. Further controlled outcome studies of EMG biofeedback treatment of torticollis with larger samples are required.

Effects of diazepam on approach, self-reported fear and psychophysiological responses in snake phobics.

The effects of diazepam was assessed on a number of measures of phobic anxiety. Snake-phobic subjects underwent two sessions on either diazepam or placebo in a crossover design. In addition to a habituation series, a slide with the phobic object was displayed as well as a live snake which subjects were asked to approach. The anxiolytic effect of diazepam was manifest in only one measure of fear, namely self-rated fear at the point of closest approach when it also attained the highest level. The result would indicate that diazepam has an anxiolytic only on high levels of subjective anxiety. The magnitude of the phasic cardiac reaction to the slide was highly and positively correlated with self-rated fear of the slide.

Safety-signal therapy in agoraphobics: a preliminary test.

It has been argued that persistent avoidance behaviour is strongly influenced by safety signals, and that agoraphobic avoidance behaviour is a clinical example of this influence. It was proposed that agoraphobic avoidance can be reduced by the judicious use of safety signals, and specifically, by training patients to travel towards rather than away from safety. A safety-signal technique in which the patient travelled towards the therapist at the most fear-inducing situations was compared with conventional therapist-assisted exposure. In the second part of the treatment programme, both groups of agoraphobics were given homework assignments. The safety-signal technique resulted in slightly better clinical gains than those achieved by therapist assisted exposure, but after these relatively brief programmes, the improvements in both groups were weak. Global clinical outcome was influenced by age, chronicity and long-term benzodiazepine use.