Dysfunctional pain modulation in somatoform pain disorder patients.

To date, pain perception is thought to be a creative process of modulation carried out by an interplay of pro- and anti-nociceptive mechanisms. Recent research demonstrates that pain experience constitutes the result of top-down processes represented in cortical descending pain modulation. Cortical, mainly medial and frontal areas, as well as subcortical structures such as the brain stem, medulla and thalamus seem to be key players in pain modulation. An imbalance of pro- and anti-nociceptive mechanisms are assumed to cause chronic pain disorders, which are associated with spontaneous pain perception without physiologic scaffolding or exaggerated cortical activation in response to pain exposure. In contrast to recent investigations, the aim of the present study was to elucidate cortical activation of somatoform pain disorder patients during baseline condition. Scalp EEG, quantitative Fourier-spectral analyses and LORETA were employed to compare patient group (N = 15) to age- and sex-matched controls (N = 15) at rest. SI, SII, ACC, SMA, PFC, PPC, insular, amygdale and hippocampus displayed significant spectral power reductions within the beta band range (12-30 Hz). These results suggest decreased cortical baseline arousal in somatoform pain disorder patients. We finally conclude that obtained results may point to an altered baseline activity, maybe characteristic for chronic somatoform pain disorder.

[The pupillary response test as a method to differentiate various types of dementia]. / Der Rezeptortest bei der Pupillometrie als Methode zur Differenzierung des dementiellen Syndroms.

AIM: Pupillometry is a non-invasive measurement technique based on the pupillary response to specific sensoric, mental and emotional variables. After topical application of a cholinergic antagonist (tropicamide) an increased pupillary dilatation response in Alzheimers s disease patients was described ("receptor test"). The aim of the present study was to evaluate the usefulness of the 0.01% tropicamide receptor test in differentiating types of dementia. METHOD: 425 patients (159 men, 266 women, mean age 75 years) of the Memory Clinic of the SMZ Ost Vienna, Austria were included in the study. 195 patients suffered from a dementia in Alzheimer's disease with late onset (ICD-10: F00.1), 42 from dementia in Alzheimer's disease with early onset (F00.0), 71 from vascular dementia (F01), 34 from Lewy-Body dementia (F03) and 83 from mixed dementia (F00.2). All patients were investigated by means of a computer-assisted pupillometer. The pupillary diameter of the left eye was measured 4 times (baseline=0 minutes, after 20, 40 and 60 minutes). 4 minutes after baseline one drop of 0.01% tropicamide solution was installed onto the left eye of the patients. RESULTS: At baseline the pupillary diameter was largest in Lewy-Body dementia, smallest in vascular dementia. Significant differences were observed between vascular dementia and early-onset dementia in Alzheimer's disease as well as between Lewy-Body dementia and all other dementia syndromes (except dementia in Alzheimer's disease with early onset). The 0.01% tropicamide receptor test made it possible to differentiate early-onset dementia in Alzheimer's disease from vascular and mixed dementia. CONCLUSION: Utilizing pupillometry in combination with the 0.01% tropicamide receptor test allows to discriminate between different dementia types of, as demonstrated in our study.

High prevalence of restless legs syndrome in somatoform pain disorder.

UNLABELLED: Patients with somatoform pain often complain of sleep disorders, but sleep disorders are not an integrated part of the diagnosis of this disorder. Restless legs syndrome is associated with painful symptoms and sleep disturbances. The aim of our study was to evaluate the prevalence of restless legs syndrome (RLS) in somatoform pain disorder. METHOD: In this study 100 consecutive patients (mean age: 46.4; SD: 11.4; women: 58) diagnosed with somatoform pain disorder (SPD) were clinically investigated for the occurrence of RLS at the behavioral medicine clinic for pain outpatients in the department of psychiatry within the Medical University of Vienna. The pain parameters of SPD were assessed using a pain questionnaire and visual analogue scales (VAS). The severity of RLS was established using the questionnaire of the International Restless Legs Syndrome Study Group (IRLSSG). RESULTS: The prevalence of restless legs syndrome found in somatoform pain disorder was 42%. Interrupted sleep was found in 83.3% in somatoform pain disorder with comorbid RLS and in 64.1% in somatoform pain disorder without RLS. Patients with continuous somatoform pain had a significant higher occurrence of RLS (Sample: 55%; with RLS: 71.4% and without RLS: 43.1%). The pain parameters increased parallel to the severity of RLS. Additionally, RLS was associated with higher psychosocial disability in family life. CONCLUSIONS: The prevalence of RLS is high in our sample of patients with somatoform pain disorder. There seems to be a difference in pain profile between patients with and without RLS. RLS may increase the pain level and prolong pain in somatoform pain disorder. RLS should be considered when a somatoform pain disorder is diagnosed.

What does the WHOQOL-Bref measure? Measurement overlap between quality of life and depressive symptomatology in chronic somatoform pain disorder.

INTRODUCTION: Quality of life has become an important outcome criterion for psychiatric interventions. Especially in chronic disorders with no complete recovery, the improvement of quality of life is an important treatment goal. Nevertheless, there are methodological problems in assessing quality of life. There is a possible measurement overlap between quality of life and psychopathology, especially depression, which may invalidate research results. This study addresses the quality of life of patients with chronic somatoform pain and its relation to depressive symptoms. METHOD: One hundred out-patients with somatoform pain disorder at the Behavioural Medicine Pain Clinic in the Department of Psychiatry of the Medical University of Vienna were diagnosed using the SCID for Diagnostic and Statistical Manual of Mental Disorder (DSM-IV). The patients filled out the World Health Organisation Quality of Life Assessment-Bref (WHOQOL-Bref) and the Beck Depression Inventory (BDI). Pain intensity (average pain, maximum pain, minimal pain) and disability (work, leisure and family life) were assessed using visual analogue scales. RESULTS: Quality of life in somatoform pain disorder was reduced compared to the norm population, especially in the physical and psychological domains. There were highly significant negative correlations between, on the one hand, depressive symptomatology (BDI) and, on the other hand, the physical quality of life domain (r=-0.655, p<0.01), the psychological domain (r=-0.735, p<0.01), the social domain (r=-0.511, p<0.01) and the environmental domain (r=-0.561, p<0.01). In all domains of the WHOQOL-Bref and in the global score, significant differences between the group of patients with severe or very severe depressive symptoms and the group with no or only mild depressive symptoms were found. DISCUSSION: While the WHOQOL-Bref showed a poor quality of life of patients with chronic somatoform pain disorder in general and especially in the physical and in the psychological domains, the high correlation of physical and psychological quality of life scores with depressive symptomatology points to a measurement overlap. It is suggested that assessment of subjective quality of life should always be checked for the influence of depressive symptomatology on the quality of life score.

On the pharmacotherapy of sleep bruxism: placebo-controlled polysomnographic and psychometric studies with clonazepam.

OBJECTIVES: Sleep bruxism (SB) is a parasomnia defined as a stereotyped movement disorder characterized by grinding or clenching of the teeth during sleep. Pathophysiologically, SB is the result of biological and psychosocial influences. Treatment comprises behavioral, orthodontic and pharmacological interventions. While benzodiazepines and muscle relaxants have been reported by clinicians to reduce bruxism-related motor activity, placebo-controlled studies are lacking. Thus, the aim of the present study was to investigate the acute effects of clonazepam (Rivotril) as compared with placebo, utilizing polysomnography and psychometry. METHOD: Ten drug-free outpatients (6 females, 4 males), aged 46.5 +/- 13.1 years, suffering from SB (ICD-10: F45.8; ICSD: 306.8) and having been treated by bite splints were included in the trial. Comorbidity was high: 7 patients presented nonorganic insomnia related to adjustment or anxiety disorders (5 patients) or depression (2 patients); all patients had a concomitant movement disorder (6 restless legs syndrome, 4 periodic leg movement disorder). After one adaptation night, patients received placebo and 1 mg clonazepam 1/2 hour before lights out in a single-blind, nonrandomized study design. Objective sleep quality was determined by polysomnography, subjective sleep and awakening quality by rating scales, objective awakening quality by psychometric tests. Clinical evaluation was based on the Pittsburgh Sleep Quality Index (PSQI), the Zung Depression (SDS) and Anxiety (SAS) Scales, the Quality of Life Index, the Epworth Sleepiness Scale and the International Restless Legs Syndrome Study Group (IRLSSG) Scale. RESULTS: On admission, SB patients exhibited deteriorated PSQI, SAS, SDS and IRLSSG measures. As compared with placebo, 1 mg clonazepam significantly improved the mean bruxism index from 9.3 to 6.3/h of sleep. Furthermore, it significantly improved the total sleep period, total sleep time, sleep efficiency, sleep latency and time awake during the total sleep period, and increased stage 2 sleep and movement time. Periodic leg movements decreased significantly, while the apnea index and apnea-hypopnea index increased marginally, but remained within normal limits. Subjective sleep quality improved as well, while in mood, performance and psychophysiology no changes were observed. CONCLUSION: Acute clonazepam therapy significantly improved not only the bruxism index but also objective and subjective sleep quality, with unchanged mood, performance and psychophysiological measures upon awakening, suggesting good tolerability of the drug.

Insomnia in somatoform pain disorder: sleep laboratory studies on differences to controls and acute effects of trazodone, evaluated by the Somnolyzer 24 x 7 and the Siesta database.

Patients with chronic pain often suffer from sleep disturbances, specifically decreased deep sleep, and thus may get into a vicious circle which maintains their pain condition. Utilizing polysomnography and psychometry, objective and subjective sleep and awakening quality was investigated in 11 patients with nonorganic insomnia (F51.0) related to somatoform pain disorder (SPD; F45.4) as compared with age- and sex-matched healthy controls of the Siesta normative database. Patients demonstrated a markedly deteriorated Pittsburgh Sleep Quality Index, a decreased Quality of Life Index, slightly increased self-reported anxiety (Zung SAS) and depression scores (Zung SDS), as well as an increased Epworth Sleepiness Scale and International Restless Legs Syndrome Scale score. Subjective sleep and awakening quality was markedly reduced, while somatic complaints were increased. Polysomnographic evaluation by a recently developed automatic sleep classifier (Somnolyzer 24 x 7) based on the rules of Rechtschaffen and Kales demonstrated reduced slow-wave sleep (SWS), the target variable in the present study, a decreased stage shift index, increased SWS latency and stage 4 sleep (S4) latency and an increased frequency of shifts from S2 to wakefulness (W) in patients as compared with controls. Minimal oxygen saturation was found decreased, periodic leg movements (PLMs) were increased. In the morning, patients showed deteriorated well-being, drive, mood and wakefulness. There were no significant noopsychic or psychophysiological differences between patients and controls (except for a reduced numerical memory and a slightly increased morning diastolic blood pressure in patients). Subsequent evaluation of the acute effects of 100 mg of a controlled-release formulation of trazodone (Trittico retard) in the patients demonstrated an increase in the target variable SWS, accompanied by a reduction in the number of awakenings and stage shifts. It normalized the frequency of shifts from S2 to W and reduced the frequency of shifts from W to S1, from S1 to S2, as well as from any stage to S1 and S2. Trazodone, however, also significantly reduced the total sleep period and S2 and increased the latency to S1. Moreover, the drug increased the reduced minimal O(2 )saturation, reduced the arousal index and the PLMs-in-wake index and normalized the increased morning diastolic blood pressure. In conclusion, our study demonstrated that SPD induced significant changes in subjective and objective sleep and awakening quality, which were partially mitigated by trazodone therapy. The data on the target variable SWS support our hypothesis of a key-lock principle in the diagnosis and drug treatment of sleep disorders. Our study provided the first evidence on the usefulness of the Somnolyzer 24 x 7 and the Siesta database in clinical practice.

Quality of life in nonorganic and organic sleep disorders: II. Correlation with objective and subjective quality of sleep and awakening.

OBJECTIVE: The purpose of this study of 100 patients suffering from sleep-disorders was to determine correlations between their subjective health-related quality of life (HRQoL) and objective variables in sleep initiation and maintenance, sleep architecture, objective quality of awakening, psychophysiological parameters and subjective quality of sleep and awakening. METHODS: Objective measurements were obtained from overnight diagnostic polysomnography. Subjective HRQoL was determined from the Quality of Life Index (QLI, Mezzich and Cohen) completed prior to the adaptation night. Other measurements included subjective and objective quality of sleep and awakening (psychometry) the evening before and morning after polysomnographic investigations. RESULTS: 63% of the patients were suffering from nonorganic and 37% from organic sleep disorders (SDs). Within the first group, nonorganic insomnia predominated; within the second, sleep apnea. Subjective HRQoL correlated well with subjective sleep and awakening quality, especially in nonorganic SDs. There were only a few correlations of objective measurements with subjective HRQoL: in the total group of SD patients HRQoL correlated with sleep stage S2, and in nonorganic SDs with attention scores and psychophysiological measurements (mainly the pulse rate in the evening and morning). CONCLUSION: Our findings suggest only a weak relationship between objective sleep variables and subjective HRQoL in both organic and nonorganic SDs. However, we found various significant correlations of HRQoL with subjective measurements of sleep, especially in nonorganic SDs.

Quality of life in nonorganic and organic sleep disorders: I. Comparison with normative data.

Subjective health-related quality of life (HRQoL) was investigated in 100 patients with disturbed sleep (39 women aged 52 +/- 13 years and 61 men aged 53 +/- 10 years) referred to the sleep laboratory and compared with HRQoL in 100 normal healthy adults. Measurements included the Quality of Life Index (QLI) (Mezzich and Cohen), and objective (polysomnographic) and subjective (psychometric) quality of sleep and awakening. Statistical analysis (Mann-Whitney U-test) showed HRQoL to be significantly reduced in sleep disorders (SDs), with a more pronounced reduction in nonorganic than in organic SDs. Patients with nonorganic hypersomnia were more disturbed than those with nonorganic insomnia. Within organic SDs, patients with apnea were more disturbed than those with obstructive snoring. Out of ten elementary HRQoL components, seven were disturbed in SDs: physical well-being, psychological well-being, self-care and independent functioning, occupational functioning, interpersonal functioning, personal fulfillment, and overall quality of life. No differences between patients and normal healthy subjects where found in the components social support, community and services support or spiritual fulfillment. Patients suffering from nonorganic SDs had significantly worse scores in physical and psychological well-being and overall quality of life than those with organic SDs. Patients with both SDs and additional diagnoses of affective disorders had more profoundly reduced HRQoL than those with anxiety disorders. Follow-up of 51 patients (31 with nonorganic SDs and 20 with organic SDs) one year after sleep laboratory investigation and subsequent treatment found significantly improved HRQoL compared with pre-treatment. Moreover, patients diagnosed and treated in the sleep laboratory showed lower re-hospitalization rats.

Sleep disturbances in somatoform pain disorder.

UNLABELLED: Patients with chronic somatoform pain often complain about sleep disorders. However, sleep disorder/disturbances are not an integrated part of the somatoform disorders in the DSM-IV and the ICD-10. Sleep is important for recreation. Deprivation of deep sleep stages is experimentally linked to muscle pain. Therefore, sleep disorder may play an important part in the persistence of somatoform pain disorder. The aim of the study was to evaluate the frequency of sleep disorder in patients with somatoform pain disorder and to correlate it with comorbid depression, pain parameters and psychosocial parameters. METHOD: In this study, 147 patients (mean age: 48.8 years; SD: 11.0) with the diagnosis of a somatoform pain disorder were studied with regard to affective comorbidity, pain duration (months), maximum pain within the last month, minimum pain within the last month and medium pain within the last month, psychosocial disability within the last month and the presence of a sleep disorder. RESULTS: Eighty-four percent of the patients had a sleep disorder. The patients with a sleep disorder had significantly higher maximum and medium pain, a significantly higher level of psychosocial disability and a significantly lower overall subjective well-being. The medium pain and psychosocial disability in leisure and social activities are significant predictors for sleep disorder. CONCLUSIONS: The presence of a sleep disorder may be a hint for higher pain intensity and a higher level of psychosocial disability. Sleep disorder may be a factor in the persistence and aggravation of pain as well as psychosocial disability. Therefore, sleep disorder should be integrated in the therapeutic targets. It is suggested that sleep disorder should be a diagnostic criterion in somatoform pain disorder.

Visualizing central effects of S-adenosyl-L-methionine (SAMe), a natural molecule with antidepressant properties, by pharmaco-EEG mapping.

In a double-blind, placebo-controlled, cross-over study, the central effects of the natural molecule S-adenosyl-L-methionine (SAMe), or ademetionine (ADE), used in low doses as a nutraceutical and in higher doses as a pharmaceutical, were investigated by means of EEG mapping and psychometry. Ten young, normal healthy volunteers of both sexes, with a mean age of 25.2+3.9 yr received, in random order, infusions of 800 mg ADE in 250 ml of isotonic solution, and placebo consisting of 250 ml of isotonic solution administered over 30 min for 7 d, with a wash-out period of 3 wk in between. EEG recordings and psychometric tests were carried out 0, 1, 3 and 6 h after drug administration on days 1 and 7. While there were no significant changes in psychometric findings, multivariate analyses of the EEG results based on MANOVA/Hotelling T 2 tests demonstrated significant encephalotropic effects of ADE compared to placebo. ADE-induced changes were characterized by a decrease in total power, an increase in absolute delta power and a decrease in absolute alpha and beta power, further by an increase in relative delta and beta power and a decrease in relative alpha power, a slowing of the delta/theta centroid, an acceleration of the alpha centroid as well as a slowing of the centroid of the total power spectrum. These changes are typical of classical antidepressants of the thymoleptic type such as imipramine and amitriptyline. Time-efficacy calculations demonstrated a significant central effect of ADE in the first hour after the first infusion, declining slowly until the third hour and thereafter steeply until the sixth hour; a further significant effect was after 1 wk of daily infusions and in the third hour after one superimposed infusion on day 7 of subacute treatment. Our pharmaco-EEG findings suggest both inhibitory and excitatory drug effects at the neurophysiological level, underlying the antidepressant properties well-documented in clinical trials.

Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone.

Utilizing polysomnography (PSG) and psychometry, objective and subjective sleep and awakening quality was investigated in 11 drug-free patients (five females, six males) aged 35-75 years (mean age 54.1 +/- 11.4) suffering from nonorganic insomnia (F 51.0) related to a depressive episode (F 32) or recurrent depressive disorder (F 33). as compared with 11 age- and sex-matched normal controls (five females, six males) aged 36-75 years (mean age 53.0 +/- 13.5). PSG demonstrated decreased sleep efficiency, total sleep time (TST), total sleep period (TSP) and sleep stage S2, as well as increased wakefulness during TSP, early morning awakening, sleep latency to S1, S2, S3 and sleep stage S1 in depressed patients. Subjective sleep quality and the total score of the Self-Assessment of Sleep and Awakening Quality Scale (SSA) were deteriorated as were morning and evening well being, drive, mood and fine motor activity right. Evening and morning blood pressure, the O2 desaturation index and periodic leg movement (PLM) index were increased. In a subsequent acute, placebo-controlled cross-over design study, the acute effects of 100 mg of trazodone, a serotonin reuptake inhibitor with a sedative action due to 5-HT2 and alpha1 receptor blockade, were investigated in the patients. As compared with placebo, trazodone induced an increase in sleep efficiency (primary target variable), TST, TSP and SWS (S3 + S4), as well as a decrease in wakefulness during the TSP, early morning awakening and S2. There was no change in rapid eye movement (REM) sleep with the exception of an increase in the REM duration in minutes. Trazodone also caused an improvement in subjective sleep quality, affectivity, numerical memory and somatic complaints. All respiratory variables remained within normal limits. Critical flicker frequency and moming diastolic blood pressure were decreased. The present study demonstrated that depression induced significant changes in objective and subjective sleep and awakening quality, which were counteracted by 100 mg of trazodone, thus suggesting a key-lock principle in the treatment of depression.