Maintenance electroconvulsive therapy for intractable Parkinson's disease.

The authors administered electroconvulsive therapy (ECT) to four patients with intractable Parkinson's disease who were free from depression or dementia. After an initial "acute" phase, subjects received bitemporal maintenance ECT every 3 to 4 weeks for up to 12 months. Serial measures of mood, cognition, and motor function were performed. One subject developed cognitive impairment after seven maintenance treatments, and another developed delusions during the acute phase of the study. The two subjects completing the 12-month maintenance phase noted significant reductions in "off" time without impairment of cognitive functioning.

Modification of CAPS-1 for diagnosis of PTSD in Afghan refugees.

A DSM-III-R based instrument for the assessment of posttraumatic stress disorder (PTSD), the Clinician-Administered PTSD Scale (CAPS-1), was modified to accommodate cultural differences and translated into the Afghan languages Pushto and Farsi (Dari) and administered to 30 Afghan refugees living in the United States. The modified CAPS-1 was found to be practical and reliable. Inter-item correlations were calculated on the frequency and intensity scores for the 17 cardinal symptoms and the eight associated features items of the modified CAPS-1. The four reexperiencing items demonstrated significant independence from the avoidance and arousal symptom clusters. However, the avoidance and arousal symptom clusters were not found to be independent cardinal components of PTSD in our participants. The CAPS-1 criteria for diagnosis of PTSD were met by 50% of the subjects evaluated.

Amplitude/intensity functions of auditory event-related potentials predict responsiveness to bupropion in major depressive disorder.

Patients diagnosed with major depressive disorder (MDD) and enrolled in an open-label safety surveillance study of a sustained release formulation of bupropion hydrochloride (100 to 300 mg/day) were evaluated with the Hamilton Rating Scale for Depression (HAM-D) immediately before and 6 to 12 weeks after the initiation of drug treatment. Auditory event-related potentials (ERPs) recorded under a stimulus intensity modulation paradigm were also obtained at these times. Patients were classified as responders and nonresponders based on post-treatment HAM-D scores, with responders having HAM-D scores less than 10 and nonresponders having scores greater than 10. Consistent with our previous findings, responders exhibited significantly larger positive slope coefficients for P2 ERP component amplitudes as a function of auditory stimulus intensity obtained at baseline and were not affected by bupropion treatment. Thus, these results further support our previous finding that ERP amplitude/intensity functions measured under a stimulus intensity modulation paradigm provide information about the likelihood of a positive therapeutic response to antidepressant pharmacotherapy in patients with MDD and extends these results to bupropion, a pharmacologically atypical antidepressant agent.

Event-related potential amplitude/intensity slopes predict response to antidepressants.

We measured event-related potential (ERP) component amplitudes to four intensities of randomly presented tones. Patients diagnosed with major depressive disorder were tested prior to and following a clinical trial of antidepressant medication. Slope of P2 amplitude as a function of stimulus intensity was calculated for each subject and condition. Subjects were divided into two groups (responders and nonresponders) based on their Hamilton Rating Scale for depression scores following treatment. Responders had significantly larger P2 slopes prior to treatment than did nonresponders. P2 slopes did not differ significantly between responders and nonresponders following antidepressant treatment. These data support the conclusion that P2 amplitude/intensity slope may be a predictor of response to treatment with antidepressant medication.

Inefficacy of propranolol in attenuation of drug-induced parkinsonian tremor.

We investigated the tremolytic effect of long-acting propranolol (propranolol-LA) in six subjects with drug-induced parkinsonism (DIP), using a double-blind, placebo-controlled, crossover experimental design. Subjects received propranolol-LA for 2 weeks and placebo for 2 weeks, with no change in neuroleptic treatment. Tremor frequency and amplitude were objectively quantified at the end of each 2-week period by computerized tremorgram recording. There were no significant differences in attenuation of DIP tremor by propranolol-LA and placebo. Previous investigations reported in the literature have found propranolol to attenuate the tremor of idiopathic parkinsonism (IPD). It is expected that DIP and IPD tremor would respond similarly to propranolol if a solely peripheral or spinal cord tremolytic action were operative. A possible differential attenuation of IPD tremor and DIP tremor provides support for the concept of a higher central tremolytic mechanism of beta-adrenergic receptor-blocking drugs.

Increases in heart rate variability with successful treatment in patients with major depressive disorder.

We obtained Hamilton Rating Scale for Depression (HAM-D) scores and recorded 5 minutes of rhythm strip both before and after a therapeutic trial of antidepressant medications in 17 patients diagnosed with major depressive disorder (MDD). We calculated the standard deviation (SD) of interbeat intervals and the mean squared successive difference (MSSD) as measures of heart-rate variability (HRV). We then calculated Spearman rank-ordered correlation coefficients between the HRV measures and the HAM-D scores. Changes in SD and MSSD correlated with post-treatment HAM-D scores and with changes in HAM-D scores. These relationships were strongest in patients who responded positively to nontricyclic antidepressant medications. HRV before treatment was not predictive of treatment response, nor did HRV reliably reflect the severity of depressive symptoms. These findings indicate that pharmacologic treatment leading to improvement in MDD is associated with increased HRV. Hence, brief measures of HRV could be developed as a useful adjunctive, physiologic measure of treatment response to pharmacotherapy in clinical trials and other settings. Further, increased HRV associated with successful treatment of MDD may reflect improved autonomic function, decreasing the risk of cardiovascular mortality found in patients with MDD.

Event-related perturbations in an electrophysiological measure of auditory sensitivity: effects of probability, intensity and repeated sessions.

It is often held that novel or salient stimuli are followed by a brief period of orienting or alerting during which sensory processes are facilitated. Evidence for such a period of facilitation was sought in a paradigm in which evoked responses to weak auditory probe stimuli were examined when given in the presence of salient foreground stimuli, which were varied in probability and intensity, and which were given in two replicate sessions. The background probe stimuli consisted of a continuous train of auditory pip stimuli delivered at a rate of 40 pips per second. Under such conditions of repetitive stimulation a steady-state rhythm (SSR), which is believed to reflect summated early and middle latency evoked responses, is established in the EEG at a corresponding frequency of 40 Hz. The 40 Hz SSR was extracted using a digital averaging and filtering technique and examined continuously for changes in amplitude and latency. The rhythm showed a brief episode during which the latencies of response were decreased. The reduction in latency was greatest at 186 ms after the foreground stimulus, at which time the latencies of individual peaks in the rhythm were reduced by about 3.5 ms. The magnitude of the latency reduction response was larger for intense and for rare stimuli, and showed long-term decrement during the second session. Event-related potential and heart rate responses to the foreground stimulus were also affected by probability, intensity and session, but not in the same pattern. It was hypothesized that the latency shift in the 40 Hz SSR reflects a brief period of sensitization during alerting or orienting responses.

Auditory and visual event-related perturbations in the 40 Hz auditory steady-state response.

The effects of salient auditory and visual 'foreground' stimuli on responses to 'background' probe stimuli were investigated. The foreground stimuli were given at long and aperiodic intervals and required a discriminative judgment. Simultaneously, evoked potentials were obtained in response to background probe auditory stimuli presented in a continuous train at about 40/sec. The 40 Hz steady-state rhythm (SSR) evoked under such conditions was extracted using digital averaging and filtering techniques and examined continuously for evidence of change in latency or amplitude during the period surrounding the foreground stimulus. Within the first 200-300 msec after the onset of an acoustic foreground stimulus the latencies of individual peaks in the rhythm were momentarily reduced by a mean of 5.5 msec. A shift in the 40 Hz rhythm was also seen following visual foreground stimuli, although the shift was about one-third that following acoustic stimuli. A latency shift of comparable magnitude was not produced by deliberate manipulation of intensity or signal-to-noise ratio of the stimuli used to evoke the rhythm. The latency shift response is discussed in terms of a transient period of sensory facilitation during orienting or alerting associated with the foreground stimuli.

HLA antigens in tardive dyskinesia.

Fifty-three male, Caucasian, neuroleptic-treated patients with chronic schizophrenia were examined for the presence of tardive dyskinesia (TD) and were tissue typed. The group with TD (n = 25) was compared to the group without TD (n = 28). HLA-DR4 was more prevalent in the group with TD than in the group without TD, with a relative risk of 3.04 for TD with HLA-DR4 present, although this finding is not statistically significant when corrected for the number of nonparametric comparisons. Other investigations reported an association between HLA-B44 and TD, or between HLA-B44 and neuroleptic-induced parkinsonism. Potential explanations relating the findings of these investigations are discussed.

Psychophysiological correlates of posttraumatic stress disorder in Vietnam veterans.

We measured event-related brain potential (ERP) component amplitudes and heart rate (HR) to four intensities of randomly presented tones in two matched groups of drug-free male Vietnam veterans: 12 patients diagnosed with posttraumatic stress disorder (PTSD) and 6 normal combat veterans. Subjects were evaluated with structured diagnostic interviews and anxiety and depression rating scales. We found a significant group X intensity interaction for P2 peak amplitude at CZ. Subjects were classified as augmenters or reducers: positive P2 slopes as a function of stimulus intensity implying augmentation and negative slopes implying reduction. Nine of 12 PTSD subjects were reducers (sensitivity of 75%) and 5 of 6 normals were augmenters (specificity of 83.3%). By the third and fourth second following tone onset, the mean HR of PTSD subjects increased more than twice that of the normals. HR change scores were significantly responsive to the manipulation of stimulus intensity and to the difference between our two groups. P2 reduction differentiates Vietnam veterans with combat-related PTSD from combat veteran controls, and PTSD subjects are more autonomically arousable than their combat veteran peers.

Blink rates in schizophrenia.

In schizophrenia, blink rates are frequently elevated and the peak of the electroencephalographic alpha rhythm is often absent or of a lower frequency. Emerging evidence suggests that both blinks and the alpha rhythm may be controlled by a linked neuroanatomical circuit that begins in rostral pons and involves several subcortical structures as well as the occipital cortex. Blink-alpha abnormalities in schizophrenia further suggest that this blink-alpha neurocircuit may be a locus of the pathophysiological process of this disorder.

Urine screening for abused drugs in new admissions to a VA hospital.

The urine samples from two groups of Veteran's Administration patients newly admitted to general psychiatry units were screened in 1985 and in 1987-88 for abused drugs. The results were compared with urine samples from controls with similar age distributions admitted to an alcohol and drug abuse unit or to medical-surgical units. About 40% of all newly admitted patients were positive for one or more controlled drugs, but there were no significant differences among patient groups in the percentage of urine samples positive for these drugs. Marijuana and benzodiazepines were detected frequently in all patient groups and often in combination, although opiates also were frequently detected in the urine samples from the medical-surgical patients. There was a clear decrease in drug-positive samples with age in all patient groups, much of which could be accounted for by decreased marijuana detection.

Event-related perturbations in an electrophysiological measure of auditory function: a measure of sensitivity during orienting?

The effects of salient foreground stimuli in evoked potentials to weak background probe stimuli were examined in situations requiring passive observation or discriminative judgments of foreground tone stimuli. The background probe stimuli consisted of a continual train of weak acoustic stimuli presented at a rate of about 40 stimuli per second. Under such conditions, a 40-Hz steady-state rhythm (SSR) is established, which has been proposed to consist of the algebraic summation of individual middle-latency components evoked by stimuli in the train. The 40-Hz SSR was averaged over trials and extracted from the composite event-related potential signal using narrow-band digital filtering, for continuous examination of latency and amplitude during the course of the period immediately preceding and following the foreground stimulus. The foreground stimulus was followed by a brief period (peaking at about 200 ms) during which the latency of response to the background probe stimuli was reduced. The extent of this latency reduction was in proportion to the magnitude of the simultaneous slow-wave ERP responses and, to a lesser extent, heart rate responses. It is proposed that the results may reflect a transient period of sensitization during orienting, at a presumably early level in the auditory system, and that the method thus offers a means for determining the extent and temporal course of such effects.

Effects of repeated drug holidays on serum haloperidol concentrations, psychiatric symptoms, and movement disorders in schizophrenic patients.

In a crossover experiment the authors investigated the effects of repeated weekly, 2-day, haloperidol drug holidays on serum haloperidol concentrations, mental status, and neuroleptic-induced movement disorders in seven chronic schizophrenic patients. Haloperidol concentrations decreased about 64% during the initial 36 hours of drug holiday and subsequently increased slightly during the next 24 hours of drug holiday. Two-day weekly drug holidays for 6 weeks resulted in an average reduction of 25% in serum haloperidol concentrations at all drug holiday points. Mental status and movement disorders scores, rated by observers blind to the drug-holiday condition, were not significantly affected by drug holidays.

HLA antigens in drug-induced parkinsonism.

The results of two epidemiological studies suggest a hereditary predisposition to develop drug-induced parkinsonism. We investigated human leukocyte antigen (HLA) antigen prevalence rates in patients with neuroleptic-induced parkinsonism. Fifty-two male, white, neuroleptic-treated, chronic in-patients with DSM-III-diagnosed schizophrenia were examined for the presence of parkinsonism. Subjects were tested for 23 type A, 43 type B, 4 type C, and 10 type DR HLA antigens. The group of schizophrenic patients with parkinsonism (n = 29) was compared with the group of schizophrenic patients without parkinsonism (n = 23). There were no significant differences between the two groups with respect to age, duration of neuroleptic exposure, or anticholinergic drug exposure. One HLA antigen, B44, was significantly more prevalent in the group with parkinsonism than in the group without parkinsonism. We derived a relative risk of 7.16 for drug-induced parkinsonism with HLA-B44 present in this group of schizophrenic patients. These data indicate that HLA-B44 may play a role in genetic or immunologic susceptibility to develop drug-induced parkinsonism in white schizophrenic individuals.

Serum haloperidol and neuroleptic receptor levels in chronic psychosis.

Serum haloperidol and serum dopamine blocking activity were measured, and steady state levels were compared in 22 chronic male schizophrenic patients. Haloperidol levels were measured by high pressure liquid chromatography (HPLC), and dopamine blocking activity was measured by a radioreceptor assay (NRRA). Clinical status was determined by the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS). Patients were stabilized on individual doses of haloperidol for at least three weeks and dosages ranged from five to 200 mg per day. All measures were determined on two occasions, one week apart. All measures (AIMS, BPRS, HPLC, and NRRA) showed a high degree of repeated test reliability. The behavioral measures showed a high degree of interobserver reliability on both occasions. There were significant correlations at both time points among haloperidol dosage, serum haloperidol levels, and dopamine blocking activity. Although the correlations between serum levels measured by HPLC and NRRA were positive and significant on both occasions, they never accounted for more than 58 percent (coefficient of variation) of the total variance.