Rapid tryptophan depletion in drug-free depressed patients with seasonal affective disorder

The authors of a large number of Norwegian detective stories, particularly from the first part of this century, are occupied with neurologists and neurobiological problems. A survey of this literature shows. One Norwegian neurologist has written four detective stories. Not one single neurologist can be found as a detective hero. On the other hand there are numerous examples of the neurologist as a criminal or even a murderer. Neurological symptoms and signs (mostly functional pareses and epileptic fits) are used to construct the plot in other novels. The most striking finding is a detective story where the criminal is a neurobiologist, the plot is based on neurobiology and the author discusses neurological phenomena throughout the entire book.     

Effects of light treatment on sleep structure in seasonal affective disorder

Twelve outpatients with seasonal affective disorder (depression, winter type) were treated by 1 h of bright light exposure for five mornings. The intervention produced a significant reduction in depression scores, but no change was seen in the sleep electroencephalographic variables recorded after light treatment. Significant changes were seen, however, in ratings of subjective sleepiness. The acrophase of the circadian sleepiness rhythm was phase advanced, the mean level of the sleepiness rhythm was diminished, and the mean values of sleepiness scores were reduced at 8 and 10 a.m. This minimal influence of bright light on sleep structure is unlikely to explain the well-documented antidepressant effect.     

The competition of affective responses in human subjects.

"The present study is an attempt to study competing responses in human affective behavior. The following hypothesis was tested: a reduction of the magnitude of a conditioned anxiety response can be produced by the simultaneous elicitation of certain other affects. The procedure… consisted of the simultaneous tachistoscopic presentation of two letters, one having an anxiety response conditioned to it under hypnosis, and the other a response of either sadness, contentment, or delight. In the control condition the other letter was affectively neutral. The competing affects hypothesis was confirmed for the pairing of contentment and anxiety (only)." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Greater improvement in summer than with light treatment in winter in patients with seasonal affective disorder

OBJECTIVE: The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. METHOD: By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: during winter when the patients were depressed, during winter following 2 weeks of light therapy, and during the following summer. They compared the three conditions by using Friedman's analysis of variance and the Wilcoxon signed ranks test. RESULTS: The patients' scores on the depression scale were significantly higher after 2 weeks of light therapy in winter than during the following summer. CONCLUSIONS: Light treatment for 2 weeks in winter is only partially effective when compared to summer. Further studies will be necessary to assess if summer's light or other factors are the main contributors to this difference.     

Effects of fluoxetine versus bright light in the treatment of seasonal affective disorder

BACKGROUND: Disturbances of serotonergic neurotransmission appear to be particularly important for the pathophysiology of winter depression. This study investigated whether fluoxetine has antidepressant effects comparable to bright light in the treatment of seasonal affective disorder (winter type). METHOD: A randomized, parallel design was used with rater and patients blind to treatment conditions. One week of placebo (phase I) was followed by 5 weeks of treatment (phase II) with fluoxetine (20 mg per day) and a placebo light condition versus bright light (3000 lux, 2 h per day) and a placebo drug. There were 40 patients (20 in each treatment condition) suffering from seasonal affective disorder (SAD) according to DSM-III-R who had a total score on the Hamilton Depression Scale of at least 16. RESULTS: Forty patients entered phase II and 35 completed it (one drop-out in the fluoxetine group and four in the bright light group). Fourteen (70%) of the patients treated with bright light and 13 (65%) of those treated with fluoxetine were responders (NS). The remission rate in the bright light group tended to be superior (bright light 50%, fluoxetine 25%; P = 0.10). Light therapy improved HDRS scores significantly faster, while fluoxetine had a faster effect on atypical symptoms. Light treatment in the morning produced a significantly faster onset of improvement, but at the end of treatment the time of light application seemed not to be crucial. CONCLUSION: Both treatments produced a good antidepressant effect and were well tolerated. An apparently better response to bright light requires confirmation in a larger sample.     

Antisaccade performance in patients with schizophrenia and affective disorder.

The authors examined psychotic patients with schizophrenia, major depression, and bipolar disorder; "normal" participants; and 1st-degree relatives of patients with schizophrenia on an antisaccade task in which participants were instructed to move their eyes in the opposite direction of a target that moved unpredictably and abruptly either to the left or right of central fixation. Patients with schizophrenia were found to make significantly more errors than their relatives, and the latter made more errors than the controls. The poor performance of the relatives could not be attributed to their having a psychiatric disorder. Comparison of the 3 patient groups indicated that antisaccade deficits were more pronounced in schizophrenia and bipolar disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of isoproterenol infusions on heart rate variability in patients with panic disorder

Some evidence suggests that patients with panic disorder have a decreased cardiac vagal and a relatively higher sympathetic activity. In this study, spectral analysis of the time series of heart rate before and after isoproterenol infusions was used to study heart rate variability in six panic disorder patients and 11 normal control subjects. These preliminary data reveal a significant increase of sympathovagal ratios only in the patient group after isoproterenol administration. The findings suggest a relative increase in cardiac sympathetic and a relative decrease in cardiac vagal function in patients with panic disorder during isoproterenol infusions.     

Suggestibility in hypochondriacal patients and healthy control subjects. An experimental case-control study

The effects of slow freezing and thawing on enzyme compartmentalization and ultrastructure were studied in rat liver slices frozen in dry ice, isopentane/ethanol-dry ice, or liquid nitrogen, and stored at -80 degrees C for 1-14 days. Non-frozen slices served as controls. Frozen liver slices were thawed in a Karnovsky fixative and processed for transmission electron microscopy (TEM). After all freezing protocols, the outer zone of frozen-thawed tissue was ultrastructurally very similar to that of non-frozen liver. Towards the center of the tissue, the ultrastructure progressively deteriorated. Comparison with 50-microm cryostat sections prepared for TEM showed that thawing and not freezing is the detrimental step for fair preservation of ultrastructure. After thawing, homogenization, and differential centrifugation, distribution patterns of soluble marker enzymes were analyzed (cytosol, lactate dehydrogenase; mitochondrial matrix, glutamate dehydrogenase; lysosomes, acid phosphatase). The enzyme activities were not affected by storage for 2 weeks and the activity distributions showed that protein leakage from compartments was only minimally increased in frozen-thawed tissue compared with that from non-frozen tissue, irrespective of the method of freezing. In conclusion, fairly large tissue slices (20x5x3 mm) may be frozen and stored at -80 degrees C for biochemical, ultrahistochemical or ultrastructural studies. For ultrastructural analysis, only the periphery of the tissue slice should be used.     

Diurnal and long-term variations of lymph capillary pressure in healthy subjects

The practical value of the detection of clonality within the T-cell receptor gamma locus by polymerase chain reaction for the diagnosis of cutaneous T-cell lymphomas is well known. However, studies dealing with this subject so far, with special emphasis on the sensitivity of the technique in comparison to, for example, Southern blotting have used mixtures of DNA in various concentrations instead of using mixtures of the cells involved, which would reflect the in vivo situation in a more realistic scope. The purpose of this study was therefore to determine the sensitivity and the limitations of the PCR assay by dilution experiments, using mixtures of cells. Furthermore we studied its applicability to cutaneous T-cell proliferative disorders. Two clonal T-cell lines (MyLa and Jurkat) served as positive control. Dilutions of MyLa cells, cultured normal human keratinocytes and peripheral blood mononuclear cells from lymphoma negative volunteers were used to assess the sensitivity of the PCR-DGGE assay. Skin samples from 4 patients with cutaneous T-cell lymphoma, 1 lesional lymph node, 2 blood samples from a patient with Sézary syndrome and 4 lymphoma-negative tissue samples were analysed. Two samples were uncertain for diagnosis of lymphoma. The PCR-DGGE assay consisted of a 2-round nested PCR with consensus primers within the TCR-gamma locus followed by electrophoretic separation of the product along a denaturing urea/formamide gradient gel. PCR-DGGE sensitivity was, to our knowledge, for the first time investigated for mixtures of lymphocytes (clonal and polyclonal) and keratinocytes. Clonal T-cells were detected in a concentration between 1-0.1% in keratinocytes, whereas the sensitivity was generally lower upon dilution in peripheral blood mononuclear cells or in a mixture of keratinocytes and peripheral blood mononuclear cells. Nevertheless, T-cell clonality was detected in 2 blood samples of a patient with Sézary syndrome, which were negative by Southern blot analysis. The crucial point of this work was the new approach to establish the sensitivity of the PCR-DGGE, in a way which more closely mimics the condition of clinical specimens. Instead of mixing and amplifying DNA extracted from clonal T-cell lines and polyclonal bone marrow cells, we amplified DNA from clonal and polyclonal cells which had been mixed in various ratios before DNA extraction. Polymerase chain reaction in conjunction with denaturing gradient gel electrophoresis is a sensitive and versatile molecular tool for the assessment of clonality of suspect cutaneous lesions. The determination of sensitivity using DNA extracted from premixed cells more closely corresponds to the actual test situation when testing skin samples.     

Autobiographical memory style in seasonal affective disorder and its relationship to future symptom remission.

Autobiographical memory was examined in participants with seasonal affective disorder (SAD). In Experiment 1, participants with SAD performed an autobiographical memory task (AMT) in the winter when depressed. The AMT required participants to generate autobiographical memories to positive and negative cue words. Symptom levels were reassessed in the summer, when participants were remitted. The number of overly general memories to positive cues generated when the SAD participants were depressed predicted symptom levels when remitted, over and above initial symptom levels, with greater winter overgenerality being associated with high levels of summer symptoms. However, this was dependent on the exact measure of depressive symptoms used. The degree of overgenerality of memories in SAD participants was further investigated in Experiment 2. Results revealed that SAD participants did not show elevated recall of overgeneral memories relative to controls. The results as a whole indicate that, even when levels of general memories are no greater in a given target group than in controls, the absolute level of general memories to positive cues words is still independently related to symptom outcome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of tryptophan depletion on responses to yohimbine in healthy human subjects

There is considerable evidence that both the norepinephrine (NE) and serotonin (5-HT) systems are involved in the regulation of human anxiety and fear responses. To assess the modulating effects of central 5-HT levels on NE function, 11 healthy human subjects were studied with placebo-controlled challenge tests involving tryptophan depletion followed by administration of the alpha-2-adrenergic antagonist yohimbine 0.4 mg/kg IV. Five of the 11 subjects reported a marked increase in feelings of nervousness (> or = 25 mm on a 100 mm analog scale) following the combination test, while 1/11 had this response to yohimbine alone. No subjects had an increase in nervousness during other control tests. The increase in nervousness after the tryptophan depletion-yohimbine test was statistically significant for the whole group, but there were no other unique changes in behavioral, physiologic or biochemical (MHPG, cortisol) variables with this test. These data are discussed in terms of possible functional interactions between the 5-HT and NE neurotransmitter systems.     

Circadian profiles of cortisol, prolactin, and thyrotropin in seasonal affective disorder

To determine whether circadian profiles of various plasma hormones are abnormal in patients with winter seasonal affective disorder (SAD), we obtained 24-hour profiles of plasma cortisol, prolactin, and thyrotropin in subsets of a sample of 22 depressed patients with SAD on and off light therapy and in subsets of a sample of 24 normal controls. Cortisol levels did not differ between patients and controls, and levels in patients were not affected by light therapy. Prolactin levels were lower in patients than in controls throughout the day (p < 0.03) but were unaffected by light therapy. Independent of patient vs. control status, prolactin levels were higher in women than in men throughout the day (p < 0.003). Thyrotropin levels were no different in patients and controls, but levels in patients were lower following light therapy (p < 0.05).     

Prediction of acute and late responses to light therapy from vocal (pitch) and self-rated activation in seasonal affective disorder

It was hypothesized that pre-treatment activation plays a role in the response to light therapy in Seasonal Affective Disorder (SAD). In 55 SAD patients (DSMIII-R) energetic and tense activation was assessed before light therapy via self-rating (AD-ACL) and voice sound characteristics (mean pitch and variation in pitch). These variables were studied in relation to the "acute" response to 4 days of light therapy (30 min, 10000 lux) and to a "late" response (11 (10) days after light therapy had stopped). Acute response was defined as the percent change in 3 times daily self-rated depressed mood (AMS) with respect to the average of 4 baseline days. "Late" response was defined as the percent change in HRSD or AMS scores between baseline and 11 (10) days after light therapy. It was found that patients having high pitched voices with small variation in this pitch benefitted more from light therapy than the patients with low pitch and large variation in pitch levels. This effect was only significant after the first day of light exposure. No other significant relations were found between baseline activation and acute or late responses to light therapy. Hence, light therapy seems to give extra comfort in "tense" patients, who become rapid responders to light therapy.     

One-footed and externally disturbed two-footed postural control in patients with chronic low back pain and healthy control subjects. A controlled study with follow-up

STUDY DESIGN: A study of postural control during one-footed and externally disturbed two-footed stance among healthy control subjects and patients with chronic low back pain at the beginning of a functional back restoration program and 6 months later at follow-up examination. OBJECTIVES: To study postural control cross-sectionally among control subjects and patients with low back pain, and to evaluate the effects of functional restoration on the postural control parameters in a follow-up examination. SUMMARY OF BACKGROUND DATA: Deficits of motor skills and coordination have been reported in association with musculoskeletal disorders. It has been found that patients with chronic low back pain have impaired psychomotor control, but the impairment is reversible with successful low back rehabilitation. It is insufficiently known how functional activation and intensive physical training affect postural control. METHODS: Sixty-one healthy volunteers (32 men, 29 women) and altogether 99 patients with low back pain participated in the study. Sixty-eight patients (33 men, 35 women) had moderate and 31 (18 men, 13 women) had severe low back pain. Postural stability was measured with a force platform. In two-footed stance, vibration stimulation on calf and back muscles was used to disturb the balance. Center point of force-velocity (cm/sec), average position shift in anteroposterior direction (cm), and maximal position shift in lateral direction (cm) were used as the parameters. RESULTS: Reliability of all tests was acceptable. Center point of force-velocity was the most sensitive parameter and the one-footed measurement the most sensitivetest for evaluating postural stability. At the beginning, the patients with severe low back pain had poorer one-footed postural control compared with the control subjects (P = 0.0003). The subgroup of patients with moderate low back pain participated in the restoration program. The outcome of the restoration program was considered good if the disability because of low back pain (Oswestry index) decreased during the restoration program and poor if the disability increased or did not change. The one-footed postural stability remained primarily at the same level as the initial results in the control and good outcome groups, but became significantly poorer in the poor outcome group. The difference between poor outcome and control groups was statistically significant (P = 0.04). CONCLUSIONS: Impaired postural stability seems to be one factor in multidimensional symptomatology of patients with chronic low back trouble. Postural stability is easily disturbed in case of impairment in strength, coordination, or effective coupling of muscles in the lumbar and pelvic area. Patients with chronic low back pain seem to experience impairment in these functions, which should be taken into consideration when back rehabilitation programs are planned.     

Identical effects of indomethacin on renal function in healthy uninephrectomized subjects and in healthy control subjects

1. Animal studies have shown that prostaglandins are important for renal function after unilateral nephrectomy. In order to investigate the importance of prostaglandins for renal function in the fully adapted remnant kidney in healthy uninephrectomized subjects, the acute effects of indomethacin on renal haemodynamics, lithium clearance, urinary excretion rates of prostaglandin E2, sodium and water, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and arginine vasopressin were measured in 14 healthy uninephrectomized subjects (median time after nephrectomy 1.7 years) and in 14 matched healthy control subjects. In addition, nine healthy control subjects were studied without indomethacin and served as a time-control group. 2. Before indomethacin ingestion there was a significantly higher single-kidney urinary excretion rate of prostaglandin E2 in the uninephrectomized group (uninephrectomized group, 349.2 fmol/min; control group, 76.6 fmol/min; time-control group, 96.3 fmol/min). 3. Indomethacin ingestion resulted in equal changes in all parameters in both groups. These were significant decreases in glomerular filtration rate (-11.3% versus -14.6%), renal plasma flow (-6.5% versus -13.0%), urinary flow rate (-49.8% versus -49.4%), fractional sodium excretion (-44.5% versus -47.4%), lithium clearance (33.2% versus -23.8%) and urinary excretion rate of prostaglandin E2 (-93.8% versus -86.7%) (uninephrectomized versus control subjects, values are medians). In the time-control group no changes were observed in these parameters. 4. It is concluded that healthy uninephrectomized subjects with a fully adapted remnant kidney have a normal renal response to acute indomethacin-induced inhibition of prostaglandin synthesis.     

Clinical correlates of anhedonia and perceptual aberration in first-episode patients with schizophrenia and affective disorder.

Examined the association between scales measuring physical anhedonia, social anhedonia, and perceptual aberration and premorbid functioning, clinical state, and current level of adjustment in 91 psychotic Ss. The patients were examined at the onset of their 1st psychotic episode and again 18 mo later. For patients with schizophrenia, anhedonia was significantly related to premorbid functioning. No association was found between the scales and clinical state or level of adjustment at intake or follow-up. In affective disorder patients, no correlation was found between premorbid functioning (a stable characteristic) and scale scores, but moderately large correlations emerged between the scales and clinical state and level of adjustment at both assessment times. These results suggest that schizophrenic and affective disorder patients endorse items on these scales for different reasons. The authors hypothesize that for patients with schizophrenia the scales assess enduring personality characteristics, whereas for the affective disordered patients they assess clinical condition at the time of testing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Event-related potentials during an auditory discrimination with prepulse inhibition in patients with schizophrenia, obsessive-compulsive disorder and healthy subjects

Prepulse inhibition (PPI) is a measure of the influence of a stimulus (S1) on the response elicited by a second stimulus (S2) occurring shortly afterwards. Most S1/S2 measures of gating have used behavioural startle and the P50 event-related potential (ERP) amplitudes to detect PPI in a simple paired stimulus paradigm. We report on two behavioural (reaction time, RT, and the electromyographically recorded response of the musculus orbicularis oculi, EMG) and 5 ERP measures of PPI where S2 was the target in an auditory two-tone discrimination. Subjects were 21 healthy controls (CON), 11 obsessive-compulsive (OCD) and 9 schizophrenic patients (SCH). The prepulse 100 ms before S2 induced more omission errors and longer RTs compared to 500ms S1-S2 interval in all subjects. PPI was also evident in EMG, P50, N1, P3 but not P2 or N2 amplitudes of CON subjects. SCH patients showed attenuation of PPI on the same measures. OCD patients were characterized only by their slow RT and a marginal attenuation of PPI of the EMG response. A correlational analysis implied separate relationships of ERP indices of PPI to the cognitive and psychomotor consequences of the prepulse on behavioural and discrimination responses. However, SCH patients showed a general rather than a specific impairment of these indices.     

Reduced benzodiazepine sensitivity in patients with panic disorder: comparison with patients with obsessive-compulsive disorder and normal subjects

OBJECTIVE: The authors sought to replicate their previous finding of reduced response to diazepam in patients with panic disorder, to test whether this effect was specific for panic disorder, and to determine whether this reduced response was merely an artifact of resistance to sedation from anxiety-related overarousal. METHOD: The effects of four increasing intravenous doses of diazepam on saccadic eye movement velocity and accuracy (the latter being a saccadic variable that is unaffected by sedation), short-term memory, and self- and observer-rated sedation were assessed in 18 patients with panic disorder, 15 patients with obsessive-compulsive disorder, and 14 normal comparison subjects. The ratios of effect to blood level areas under the curve for both ascending and descending limbs of the effect/blood level curves were compared for each variable. RESULTS: Patients with panic disorder showed significantly less diazepam effect on saccadic velocity and accuracy for the ascending limb of the blood level curve than comparison subjects. Patients with obsessive-compulsive disorder showed similar differences from comparison subjects but only for saccadic velocity. There were no group differences in diazepam effects on memory and sedation. CONCLUSIONS: Patients with panic disorder are less sensitive than comparison subjects to diazepam. Although this difference is not an artifact of resistance to sedation, it may not be specific for panic disorder but rather may reflect a more nonspecific aspect of anxiety disorders.     

Effects of bright light on sleepiness, melatonin, and 25-hydroxyvitamin D(3) in winter seasonal affective disorder

Sixteen patients with winter seasonal affective disorder and 13 healthy controls were exposed to 3300 lx of cool-white fluorescent light for either 1 hour or 15 min in the morning for 2 weeks during the winter. Subjective sleepiness, melatonin concentration in saliva, and serum 25-hydroxyvitamin D(3) concentration were measured before and after the 2-week trial as well as the following summer when the patients were well. There were no significant differences in the baseline values between the patients and healthy subjects. No significant differences in the outcome measures were observed in the patients or the controls in the two groups of each after the trial. The exposure to bright light resulted in a significant decrease in subjective sleepiness early in the evening in the patients but not in the control subjects. The reduction of depressive symptoms was associated with the decrease in subjective sleepiness but not with the changes in the melatonin or vitamin D concentrations.