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Biomedical subjects

A O Hamm

Publications and source records attributed to A O Hamm.

12 recordsLinked to original sources

Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14 : 1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism.

OBJECTIVES: There is evidence from recent controlled clinical studies that replacement therapy of hypothyroidism with T4 in combination with a small amount of T3 may improve the well-being of the patients. As the issue is still the subject of controversial discussion, our study was assigned to confirm the superiority of a physiological combination of thyroid hormones (absorbed molar ratio 14 : 1) over T4 alone with regard to mood states and cognitive functioning. DESIGN AND PATIENTS: After a run-in period with the T4 study medication for 4 weeks, a controlled, randomized, double-blind, two-period (each 12 weeks), cross-over study without washout between the treatment periods was performed in 23 hypothyroid patients (three males, 20 females, age 23-69 years, 21 subjects after surgery/radioiodine, two with autoimmune thyroiditis) to compare the effects of the previous individual T4 dose (100-175 micro g) with a treatment in which 5% of the respective T4 dose was substituted by T3. MEASUREMENTS: Standard hormonal characteristics and standardized psychological tests to quantify mood and cognitive performance were measured after the run-in period and at the end of each treatment period. In 12 subjects, the concentration-time profiles of fT3 and fT4 were compared after the last administration of the respective study medication. TSH, fT3 and fT4 were measured with immunological assays. CLINICAL RESULTS: Replacement therapy with T4 and T4/T3 was not different in all steady-state hormonal, metabolic and cardiovascular characteristics except for TSH, which was more suppressed after T4/T3. The efficacy of replacement therapy with the T4/T3 combination was not different from the T4 monotherapy with regard to all psychological test scores describing mood and cognitive functioning of the patients. Mood was even significantly impaired by the T4/T3 combination in eight subjects, with TSH < 0.02 mU/l, compared to patients with normal TSH (Beck Depression Inventory: 8.25 +/- 5.01 vs. 4.07 +/- 5.60, P = 0.026). PHARMACOKINETIC RESULTS: The area under the concentration-time curve (AUC(0-8h)) of fT3 was significantly higher after T4/T3 compared to the T4 monotherapy (42.8 +/- 9.03 pmol x h/l vs. 36.3 +/- 8.50 pmol x h/l, P < 0.05) and was significantly correlated to serum TSH (r(s) = -0.609, P < 0.05). After T4/T3, patients with a history of Graves' disease or autoimmune thyroiditis had significantly higher serum trough levels of fT3 whereas the fT4 concentrations were significantly lower in patients with a nonautoimmune background. CONCLUSION: Replacement therapy of hypothyroidism with T4 plus T3 does not improve mood and cognitive performance compared to the standard T4 monotherapy. There is even a higher risk of signs of subclinical hyperthyroidism associated with impaired well-being of the patients, which is clearly caused by significant fluctuations in the steady-state fT3 serum concentrations.

Adult↗

The effect of neuroleptic medication on prepulse inhibition in schizophrenia patients: current status and future issues.

RATIONALE: Prepulse inhibition (PPI) of the startle reflex is a powerful tool for investigating sensorimotor gating in both animals and humans. Evidence of impaired PPI in patients with schizophrenia suggests that PPI performance might serve as a promising model to investigate the neurobiological mechanisms of this disorder. Animal data show that experimentally induced PPI deficits can be removed by the administration of antipsychotic agents. Recent clinical studies suggest that neuroleptic medication is capable of improving deficient PPI performance in schizophrenia patients as well. OBJECTIVES: The present paper reviews the published data on PPI performance in schizophrenia patients, focussing on medication effects. Using a modified meta-analytic approach, the consistency of PPI deficits in schizophrenia patients across studies is explored. In particular, methodological issues of defining PPI deficits and assessing PPI improvements are considered. METHOD: Literature search produced 12 original studies that investigated PPI performance in schizophrenia patients using comparable experimental conditions. Percentage change scores were calculated to compare the actual amount of PPI observed in schizophrenia patients and healthy controls across studies. RESULTS: Results revealed that the amount of PPI in medicated schizophrenia patients was fairly consistent across all studies. For medicated schizophrenia patients, the amount of PPI varied between 30% and 65% for the critical lead intervals. Moreover, medicated patients showed around 20% less PPI than healthy controls. Whether these group differences were statistically significant depended on the composition of the control group that showed large variability across studies. CONCLUSIONS: To delineate the effects of neuroleptic medication on PPI performance more precisely, future research should not further rely on between-group comparisons. Rather, future clinical research should take advantage of longitudinal designs to disentangle state-dependent medication effects from more stable, trait-linked factors that contribute to PPI deficits in schizophrenia.

Antipsychotic Agents↗

Sensorimotor gating and attitudes related to schizotypal proneness.

The magnitude of the startle eyeblink response is diminished when the startle eliciting probe is shortly preceded by another stimulus. This so called prepulse inhibition is interpreted as an automatic sensorimotor gating mechanism. There is substantial support for prepulse inhibition deficits in subjects suffering from schizophrenia spectrum disorders and in psychosis-prone normals as well. Thus, prepulse inhibition deficits may reflect vulnerability on the hypothesized psychopathological continuum from "normal" to "schizophrenia." The present experiment investigated the amount of prepulse inhibition in a sample selected for "belief in extraordinary phenomena," an attitude related to measures of psychosis-proneness. Believers and skeptics were tested in an acoustic prepulse-inhibition paradigm. As expected presentation of prepulses clearly diminished magnitude of startle response, with greatest inhibition effects gained by lead intervals of 60 and 120 msec. Patterns of response were identical for believers and skeptics, i.e., attitude towards extraordinary phenomena did not seem to be related to functional information-processing deficits as has been observed in psychosis-prone normals.

Adult↗

Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients.

BACKGROUND: The magnitude of the startle eyeblink response is reduced if the startle eliciting stimulus is shortly preceded by another stimulus. There is evidence that schizophrenia patients exhibit impairments in this so-called prepulse inhibition. Our study investigated whether prepulse inhibition is affected by neuroleptic drug treatment as is suggested by animal research. METHODS: Prepulse inhibition was tested in five unmedicated and 20 medicated inpatients with schizophrenia, and 12 normal controls. RESULTS: The unmedicated schizophrenia patients showed a strong impairment of sensorimotor gating as indexed by the absence of prepulse inhibition. By contrast, the medicated patients showed a pronounced prepulse inhibition that did not differ from that of the normal controls. There was a substantial covariation between the rated severity of the positive syndrome and the amount of prepulse inhibition--i.e., the patients whose positive symptoms were rated as more severe showed less prepulse inhibition. CONCLUSIONS: These data suggest that the impaired sensorimotor gating of schizophrenia patients is not a stable vulnerability indicator, but may rather be related to the positive syndrome and may be improved by treatments with neuroleptic medication.

Adult↗

Fear appears fast: temporal course of startle reflex potentiation in animal fearful subjects.

The temporal course of startle reflex modulation and autonomic response patterns to fear-relevant and fear-irrelevant pictures in subjects with high and low levels of animal fear was investigated. Thirty-eight high-fear and 48 low-fear volunteers viewed photos of snakes and spiders and pictures of neutral and pleasant content. The slides were presented for 6 s or for only 150 ms, depending on the group. Acoustic startle probes were presented at five different times after slide onset. Relative potentiation of the startle responses started 300 ms after onset of snake/spider pictures in fearful subjects. This fear-potentiated startle effect was maintained for the later probe times and was identical in the 150-ms condition. Fear-relevant pictures also prompted a sympathetically dominated autonomic response profile in fearful persons. These data support the idea that fear can be activated very rapidly, requiring only minimal stimulus input.

Adolescent↗

Fear and the startle reflex: blink modulation and autonomic response patterns in animal and mutilation fearful subjects.

The present study was designed to examine the pattern of startle reflex modulation and autonomic responses for individuals high in animal or blood-injury fear when viewing pictures of their feared objects. Sixteen individuals in each fear group and 16 low-fear control individuals viewed 32 color slides depicting fear-relevant, unpleasant but fear-unrelated, neutral, and pleasant scenes. Free viewing times were assessed in a second phase of the procedure as an index of avoidance behavior. Exposure to pictures of feared objects resulted in a consistent startle reflex potentiation and behavioral avoidance in both fear groups. This activation of the basic aversive system was independent of the autonomic pattern of the fear responses, which differed for the high-fear groups. These results suggest that the probe startle response indexes the organism's basic motivational disposition and add new information to the assessment of fear.

Adult↗

Affective learning: awareness and aversion.

In two studies, we investigated the influence of aversive and nonaversive reinforcers on startle reactivity, visceral responses, and self-report during Pavlovian conditioning. Furthermore, we assessed how awareness of the stimulus contingencies affect conditioned discrimination in the different response systems. Conditioned potentiation of the startle response was only observed in the context of aversive learning. Moreover, blink potentiation occurred without awareness of the relationship between the conditioned and unconditioned stimulus. In contrast, skin conductance conditioning was independent of the aversiveness of the reinforcer and was only obtained for those individuals who could correctly verbalize the stimulus contingency in a postconditioning recognition test. Cardiac responses varied with the task demands of the situation and covaried with individual response stereotypes.

Adult↗

Emotional learning, hedonic change, and the startle probe.

A multiple-response analysis of aversive learning was conducted in human subjects. For each subject, two pictorial stimuli were presented--one paired with electric shock. After training, the magnitude of the acoustic startle eyeblink reflex elicited in the context of the shocked picture increased dramatically and was significantly larger than for reflexes elicited during the nonshocked stimulus. Five different picture contents were tested in separate groups: Reflex potentiation was larger for pictures rated as pleasant than pictures rated as unpleasant. Conditioned responses were also evident for skin conductance, heart rate, and affective judgments. Different systems reflected different aspects of the acquired fear response: Conductance change covaried with arousal, and startle probe magnitude varied with affective valence (pleasure). The neurophysiological implications of the data are elucidated, and parallels drawn between animal and human subjects findings.

Adult↗

Looking at pictures: affective, facial, visceral, and behavioral reactions.

Colored photographic pictures that varied widely across the affective dimensions of valence (pleasant-unpleasant) and arousal (excited-calm) were each viewed for a 6-s period while facial electromyographic (zygomatic and corrugator muscle activity) and visceral (heart rate and skin conductance) reactions were measured. Judgments relating to pleasure, arousal, interest, and emotional state were measured, as was choice viewing time. Significant covariation was obtained between (a) facial expression and affective valence judgments and (b) skin conductance magnitude and arousal ratings. Interest ratings and viewing time were also associated with arousal. Although differences due to the subject's gender and cognitive style were obtained, affective responses were largely independent of the personality factors investigated. Response specificity, particularly facial expressiveness, supported the view that specific affects have unique patterns of reactivity. The consistency of the dimensional relationships between evaluative judgments (i.e., pleasure and arousal) and physiological response, however, emphasizes that emotion is fundamentally organized by these motivational parameters.

Analysis of Variance↗

Fear conditioning, meaning, and belongingness: a selective association analysis.

Twenty-three subjects rated the belongingness of pairs of conditionable (photographic slides) and unconditioned (e.g., shock, tone, human scream) stimuli. Forty new subjects were then classically conditioned, using rating-defined high (angry face/scream) and low (landscape/scream) belongingness pairs. Finger-pulse responses to the high-belongingness pairs showed superior acquisition and resistance to extinction. Another 40 subjects were conditioned to compound stimuli: a slide (either landscape or angry face) that was the same over trials, and a yellow or blue background that was the discriminant cue for the unconditioned stimulus (scream). When the angry face (the high-belongingness slide) was the invariant part of the compound, relatively poorer differential pulse-volume and skin-conductance conditioning was observed. Thus, depending on the task, a priori belongingness rendered stimuli selectively conditionable, either enhancing or inhibiting visceral response associations.

Association↗

The fear potentiated startle effect. Blink reflex modulation as a result of classical aversive conditioning.

A differential conditioning study examined whether an acoustic startle probe, presented during extinction of an aversively conditioned visual stimulus, potentiated the reflex eyeblink response in humans and whether this potentiation varied with the change in affective valence of the conditioned stimulus. Sixty college students were randomly assigned to view a series of two slides, depicting either unpleasant/highly arousing, unpleasant/moderate arousing, neutral/calm, pleasant/moderate arousing or pleasant/highly arousing scenes and objects (duration: 8 sec). During preconditioning (8 trials) and extinction (24 trials) acoustic startle probes (white noise bursts [50 ms; 95 dBA] were administered during and between slide presentation). During acquisition (16 trials) CS+ was reinforced by an electric shock. Startle response magnitudes significantly increased from preconditioning to extinction and were substantially larger to CS+. Conditioned startle reflex augmentation linearly increased with the pleasantness of the slides. Furthermore, subjects showed a greater post-conditioning increase of judged aversiveness to slides that they had previously reported to be more pleasant, exactly paralleling the startle reflex results.

Adult↗

Sensitization and aversive conditioning: effects on the startle reflex and electrodermal responding.

Animal data suggest that shock sensitization as well as aversive learning potentiates the acoustic startle reflex. The present experiment tested, whether this shock sensitization also occurs in human subjects and whether it precedes aversive conditioning. Sixty subjects viewed--prior to conditioning--a series of slides of different emotional contents including the to be conditioned stimuli (CSs). Afterwards, the experimenter attached the shock electrodes and initiated shock exposure. Then, subjects were randomly assigned to view a series of two slides, each for eight acquisition trials in which one slide was followed by a shock. Subsequently, extinction trials (12 for each slide) were administered. During preconditioning, acquisition, and extinction, startle probes occurred unpredictably during and between slide viewing. Preconditioning data replicated previous results by Lang and his associates, showing that the startle response magnitude is directly related to the affective valence induced by the slides. Shock exposure strongly facilitated the startle reflex magnitude. This shock sensitization was absent for the skin conductance response. Course of learning also varied for both response systems. The data suggest that startle reflex potentiation indexes the acquisition of an avoidance disposition, which is preceded by a general sensitization of the protective reflexes. Skin conductance learning follows arousal changes and is modulated by cognitive processes.

Adult↗