Detailed analysis of auditory brainstem responses in patients with noise-induced tinnitus.

The role of the auditory brainstem in tinnitus is questionable. This study aimed comprehensively to assess auditory brainstem responses (ABRs) in patients suffering from noise-induced tinnitus (NIT). ABRs were recorded from 13 chronic NIT patients (21 ears) and 11 (21 ears) age and hearing matched control subjects without tinnitus. ABRs were recorded with scalp electrodes placed ipsilateral and contralateral to the stimulated ear, and in three orthonormal differential configurations. The ABRs were analyzed as a function of time, frequency and voltage space. A significantly enhanced ipsilaterally recorded, time domain wave III amplitude was observed for the tinnitus patients. This finding was not confirmed by any of the other ABR measures, which were indistinguishable between subject groups. Although this may be a spurious result, it nonetheless may point to an alteration in the functioning of the putative wave III auditory brainstem generator, which deserves further study.

Impaired brain processing in noise-induced tinnitus patients as measured by auditory and visual event-related potentials.

OBJECTIVES: This study aimed to confirm that the brain processing of auditory stimuli in tinnitus patients is impaired (Attias, Urbach, Gold, & Shemesh, 1993). In addition, possible brain processing dysfunction in response to visual stimuli was assessed. DESIGN: Auditory and visual event-related potentials (ERPs) and reaction times were recorded in response to a standard oddball target detection paradigm. The subjects consisted of 21 noise-induced chronic tinnitus patients and 21 age- and hearing-matched control subjects without tinnitus. RESULTS: The tinnitus patients had significantly prolonged latencies for the auditory nontarget ERP components N1, N2, and P3 and for the auditory target ERP P3 component. The auditory P3 component was also significantly reduced in amplitude for both target and nontarget stimuli for the tinnitus patients. The visual P3 target and nontarget components were similarly significantly prolonged in latency for the tinnitus patients. Reaction times to both target and nontarget stimuli were significantly delayed for the tinnitus patients for both stimulus modalities. CONCLUSIONS: These findings point to a cortical information processing dysfunction in chronic tinnitus patients associated primarily with auditory stimuli. ERPs may provide an objective electrophysiologic tinnitus measure.

Psychological profile of help-seeking and non-help-seeking tinnitus patients.

The psychological profile of tinnitus patients who sought treatment (Help-Seeking, HS) was compared with that of patients who did not seek help (non-help-seeking, NHS) and with normal control subjects. Psychological evaluations as well as hearing, tinnitus loudness, and tinnitus pitch were measured. Overall, the psychiatric symptomatology of HS (n = 50) was more severe with poorer effective coping abilities and externalization of locus of control than NHS (n - 50). However, the psychiatric symptomatology of the NHS was remarkably more severe than that in the normals (n = 73) and more like that in the HS even though they did not turn to treatment. Tinnitus loudness was significantly lower in HS than in NHS subjects. The lower the tinnitus loudness, the higher the psychiatric symptomatology. The trend towards subclinical abnormalities in NHS indicates their vulnerability to pathology and this requires the attention of the therapist in order to increase the patient's self-awareness and to suggest preventive coping strategies or relaxation techniques.

Auditory event related potentials in chronic tinnitus patients with noise induced hearing loss.

In order to explore a possible deficit in auditory central neural activity in tinnitus with noise induced hearing loss (NIHL), auditory event related potentials (ERP) and reaction time (RT) were recorded (measures of central processing) from tinnitus patients (N = 12) and hearing and age matched controls (N = 12). Testing procedure included oddball paradigms and 1 KHz repetitive stimulus, as well as click-induced brainstem auditory evoked potentials (BAEP). ERP amplitudes (waves N1, P2 and P3) in tinnitus patients were significantly lower than in controls in all testing paradigms. No differences were found in ERP peak latencies, BAEP, RT, or response scoring. The lower ERP amplitudes may indicate attenuated or 'abnormal' auditory central processing in NIHL tinnitus patients. It is suggested that this dysfunction reflects an adaptive brain process response to the tinnitus and points to auditory central involvement in tinnitus sensation.

Sleep disturbance associated with chronic tinnitus.

Sleep disturbance is a common and frequent complaint reported by tinnitus sufferers. Recent studies have shown that when insomnia and depression are associated with tinnitus there is decreased tolerance and increased discomfort with the tinnitus. The purpose of this study was to assess the reported prevalence and severity of sleep disturbance in chronic tinnitus patients. Patients (n = 80) were military personnel without major psychiatric disturbance and their tinnitus was associated with noise-induced permanent hearing loss (NIHL). Mini Sleep Questionnaire (MSQ) scores for sleep disturbance were found to be higher than those of normal controls in 77% of the patients. Highest MSQ scores in tinnitus patients with a sleep complaint were for delayed sleep, morning awakenings, mid-sleep awakenings, morning fatigue, and chronic fatigue. In contrast, a complaint of excessive daytime sleep (EDS) was not common. The self-rated severity of the tinnitus was greater in subjects with higher sleep disturbance scores. Self-rated depressive symptomatology was also highly correlated with sleep disturbance. Retrospective examination of sleep records and polysomnographic data for 10 patients with a complaint of chronic tinnitus revealed a combined effect for the tinnitus condition when associated with another conventional sleep disorder. In spite of the common complaint of sleep disturbance in tinnitus, only a minority seek a sleep examination.

Comparison between self-hypnosis, masking and attentiveness for alleviation of chronic tinnitus.

The efficacy of self-hypnosis (SH), masking (MA) and attentiveness to the patient's complaints (AT) in the alleviation of tinnitus was evaluated. Forty-five male patients close in age with chronic tinnitus related to acoustic trauma were assigned to three matched subgroups: SH, AT or MA. The therapeutic stimuli in the SH and MA sessions, recorded on audio cassettes, were given to the patients for use when needed. SH significantly reduced the tinnitus severity; AT partially relieved the tinnitus; MA did not have any significant effect.

Vitamin B12 deficiency in patients with chronic-tinnitus and noise-induced hearing loss.

INTRODUCTION: This study examines the incidence of vitamin B12 deficiency in three groups of noise-exposed subjects: patients with chronic tinnitus and noise-induced hearing loss (NIHL), patients with NIHL only, and subjects demonstrating normal hearing. MATERIALS AND METHODS: A group of 113 army personnel exposed to military noise was studied. The mean age was 39 years. Chronic tinnitus and NIHL existed in 57 subjects. NIHL alone was observed in 29 subjects, and 27 subjects had normal audiograms. All subjects were queried about noise exposure and dietary habits. Vitamin B12 serum levels were measured. RESULTS: Patients with tinnitus and NIHL exhibited vitamin B12 deficiency in 47% of cases (blood levels < or = 250 pg/mL). This was significantly more (P < .023) compared with NIHL and normal subjects who exhibited vitamin B12 deficiency in 27% and 19%, respectively. CONCLUSION: These observations suggest a relationship between vitamin B12 deficiency and dysfunction of the auditory pathway. Some improvement in tinnitus and associated complaints were observed in 12 patients following vitamin B12 replacement therapy. The authors recommend that routine vitamin B12 serum levels be determined when evaluating patients for chronic tinnitus.

Efficacy of self-hypnosis for tinnitus relief.

The efficacy of self-hypnosis (SH) on tinnitus relief was compared with two control procedures: 1) presentation of a brief auditory stimulus (BAS) to the ear with tinnitus; 2) waiting list (WL), i.e. patients receiving no formal treatment. The results have shown that 73% of SH subjects reported disappearance of tinnitus during treatment sessions, as compared with only 24% in the BAS group. Moreover, the short-term (1 week) and long-term (2 months) symptom profiles of only SH subjects revealed a significant improvement. Thus, SH may well be a beneficial method for the relief of tinnitus.

Cyclic AMP second-messenger signal amplification in depression.

Beta-adrenergic-mediated cyclic AMP accumulation was reduced in lymphocytes obtained from depressed patients from that observed in an age- and sex-matched group of control subjects. Among the depressed patients, those not responding to treatment showed significantly lower pretreatment responses to isoproterenol compared with patients who exhibited significant clinical improvement during antidepressant treatment. Late-night (terminal) insomnia was significantly associated with the blunted response to beta-adrenergic stimulation. In depressed patients with the lowest isoproterenol response, the effect of forskolin (which acts distal to the receptor and directly stimulates the catalytic subunit) on cyclic AMP accumulation was also significantly decreased. This suggests that post-receptor modulations of signal amplification also play a role in the reduced response to beta-adrenergic stimulation in depression.

Lithium modulation of second messenger signal amplification in man: inhibition of phosphatidylinositol-specific phospholipase C and adenylate cyclase activity.

The activity of phosphatidylinositol-specific phospholipase C was significantly reduced in platelets obtained from 20 euthymic manic-depressive patients on therapeutic lithium doses (mean blood level 0.85 mEq/l) compared to an age- and sex-matched group of 36 control subjects. The activities of prostaglandin E1-, aluminum/NaF-, and forskolin-stimulated platelet adenylate cyclase activity were also measured in a similar group of 16 lithium-treated and 22 control subjects. A marked reduction in both postreceptor (aluminum/NaF and forskolin) and receptor-stimulated (prostaglandin E1) platelet adenylate cyclase activity was observed in the lithium-treated group (mean blood level 0.81 mEq/l). These findings support the hypothesis that lithium's therapeutic mode of action in manic-depressive psychosis is mediated by the combined down-regulation of both principal second messenger systems, inositol phosphates and cyclic adenosine monophosphate, by reducing the activity of phosphatidylinositol-specific phospholipase C and adenylate cyclase.

Cyclic AMP signal transduction in posttraumatic stress disorder.

Cyclic adenosine 3',5'-monophosphate (cAMP) signal transduction was examined in lymphocytes and platelets obtained from patients with posttraumatic stress disorder. Intact lymphocytes from the posttraumatic patients (N = 10) showed significantly lower basal, isoproterenol-, and forskolin-stimulated cAMP levels than those from 10 healthy control subjects. In platelet membrane preparations, basal, forskolin-, aluminum chloride plus sodium fluoride-, and prostaglandin E1-stimulated adenylate cyclase activity levels were all significantly lower in the posttraumatic group than in the control group. The authors discuss the potential role of their findings as a biological marker for posttraumatic stress disorder.

Utility of neuroleptic blood levels in the treatment of acute psychosis.

Twenty-two acutely psychotic patients were treated with a flexible dose of haloperidol in a 5-week study. The neuroleptic blood levels of all patients were measured; however, for 10 of the patients, the treating physician remained blind to the drug blood level. The Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions (CGI) scale were administered at study entry and once a week by a blind rater. No clinical differences were seen between the two groups at any time point. However, blood levels within an operative therapeutic range of 10-20 ng/ml were seen at the same rate in both groups of patients. These data do not contradict other findings which suggest a correlation between clinical outcome and blood level but rather suggest that responsible clinicians using clinical signs can maintain the "average patient" within the range of therapeutic blood levels, even without the laboratory monitoring of such levels.

Hormone and forskolin-stimulated cyclic AMP accumulation in human lymphocytes: reliability of longitudinal time measurements.

Reliability of measurement of lymphocyte cyclic AMP synthesis in intact cells was estimated by taking 3 successive blood samples during a one-month period from 11 healthy volunteers. Isoproterenol and prostaglandin E1-stimulated cyclic AMP accumulation were used to evaluate the activity of these two receptor activities in human lymphocytes. Forskolin-stimulated cyclic AMP accumulation was used to evaluate the activity of the Ns/catalytic subunit. Only for forskolin was significant reliability observed. For isoproterenol and prostaglandin E1 significant reliability was observed only for male subjects.

Heritability of forskolin and hormone-stimulated adenylate cyclase activity in human lymphocytes.

Isoproterenol, prostaglandin E1 and forskolin-stimulated cyclic AMP accumulation were compared in intact lymphocytes obtained from nine monozygotic and nine sib pairs matched for age and sex. Heritability was calculated by three different methods, two based on the intraclass correlation coefficients and one based directly on the variances. Only for forskolin is a significant proportion of variance (0.68-0.91) attributable to genetic factors, suggesting that forskolin-stimulated activity may prove to be a valuable genetic marker in studies of human pathology. Neither basal nor isoproterenol and prostaglandin E1-stimulated activity show significant heritability in intact human lymphocytes. The individual differences observed in levels of beta-adrenergic and prostaglandin stimulated receptor activity in human lymphocytes are, therefore, most likely due to environmental factors.