Reducing antipsychotic drugs in stable patients with chronic schizophrenia or schizoaffective disorder: a randomized controlled pilot trial.

As the course of schizophrenic disorders is often chronic, treatment guidelines recommend continuous maintenance treatment to prevent relapses, but antipsychotic drugs can cause many side effects. It, therefore, seems reasonable to try to reduce doses in stable phases of the illness or even try to stop medication. We conducted a 26 weeks, randomized, rater blind, feasibility study to examine individualized antipsychotic dose reduction versus continuous maintenance treatment (Register Number: NCT02307396). We included chronic, adult patients with schizophrenia or schizoaffective disorder, who were treated with any antipsychotic drug except clozapine, who had not been hospitalized in the last 3 years and who were in symptomatic remission at baseline. The primary outcome was relapse of positive symptoms. Symptom severity, social functioning and side effects were also examined as secondary outcomes. 20 patients were randomized. Relapse rates in the two groups were not significantly different. No patient had to be hospitalized. One patient in the control group dropped out. The mean reduction of antipsychotic dose in the individualized dose-reduction group was 42%, however only one patient discontinued drug completely. There were no significant differences in efficacy or safety outcomes. This randomized trial provides evidence, that reduction of antipsychotic medication in chronic stable schizophrenic patients may be feasible. The results need to be confirmed in a larger trial with a longer follow-up period.

Patient-doctor interaction, psychobehavioural characteristics and mental disorders in patients with suspected allergies: do they predict "medically unexplained symptoms"?

In approximately 20% of patients with suspected allergies, no organic symptom explanation can be found. Limited knowledge about patients with "medically unexplained symptoms (MUS)" contributes to them being perceived as "difficult" and being treated inadequately. This study examined the psychobehavioural characteristics of patients presenting for a diagnostic allergy work-up. Patients were interviewed and completed various self-rating questionnaires. Patient-Doctor interaction was evaluated, and the organic explicability of the patients' symptoms was rated by allergists. Patients with vs. those without MUS differed in several respects. Mental comorbidity, female sex, dissatisfaction with care, and a problematic countertransference (the interviewer's feelings towards the patient) independently predicted MUS. Patients whose symptoms could be explained organically reported more psychobehavioural problems than a control group of immuno-therapy patients. There were no differences in patient-doctor interaction. In patients with suspected allergies, recognition of psychological burden and concurrent mental disorders is important. Mental comorbidity and a difficult patient-doctor interaction may predict MUS.

Cognitive decline in the behavioral variant of frontotemporal dementia.

BACKGROUND: Only a small number of studies on the natural disease course in behavioral variant frontotemporal dementia (bvFTD) have been conducted. This is surprising because knowledge about the progression of symptoms is a precondition for the design of clinical drug trials. METHODS: The aim of the present study was to examine the cognitive decline of 20 patients with mild bvFTD over one year using the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery (CERAD-NAB). RESULTS: Within an average follow-up interval of 13 months, patient scores declined significantly in the Mini-mental-State-Examination (MMSE) and the CERAD-NAB subtests of naming, verbal and nonverbal memory. No significant changes were found in the CERAD-NAB subtests of category fluency, recognition, and visuoconstruction. The average annualized decline on the MMSE was 4.0 ± 4.9 points. Ceiling effects were detected in Figures Copy, Word List Recognition and Modified Boston Naming Test. Though the included patient group was rather homogeneous regarding severity of dementia, the cognitive changes were very heterogeneous. CONCLUSION: Given the heterogeneity of cognitive decline, the design of a test battery for clinical trials in FTD will be challenging. A cognitive battery should definitely include the MMSE, Word List Learning and Word List Delayed Recall.

Characteristics of oligosymptomatic versus polysymptomatic presentations of somatoform disorders in patients with suspected allergies.

OBJECTIVE: Psychobehavioral characteristics of patients with somatoform disorders (SFDs), are increasingly discussed as possible positive criteria for this diagnostic group. However, little is known about psychobehavioral differences, or similarities, between the different SFD presentations, i.e., polysymptomatic [multisomatoform/somatization disorders (MSD)] versus mono- or oligosymptomatic courses [pain disorder (PD), undifferentiated somatoform disorder (USD)]. METHODS: This is a cross-sectional study including 268 consecutive allergology inpatients. After an Structured Clinical Interview for DSM-IV, patients completed several self-rating questionnaires. Results were compared within the different SFD presentations as well as between patients with versus without SFDs. RESULTS: We identified 72 patients with an SFD. There were fewer and smaller psychobehavioral differences within patients with the different SFD presentations (MSD, USDs, PDs) than between patients with undifferentiated versus no SFD. Patients with one of the three different SFD subdiagnoses scored similarly on many measures referring to psychosocial distress (e.g., psychological distress, mental health-related quality of life, dissatisfaction with care). The number of reported symptoms, somatic symptom severity, a self-concept of bodily weakness, the degree of disease conviction, and physical health-related quality of life discriminated the different SFD presentations not only from patients without SFDs but also from each other. CONCLUSIONS: Patients diagnosed with one of the different SFD subtypes share many psychobehavioral characteristics, mostly regarding the reporting of psychosocial distress. Perceived somatic symptom severity and physical impairment as indicators of bodily distress could either further define categorical subdivisions of SFD or dimensionally graduate one general SFD category defined by bothering bodily symptoms and disproportionate psychosocial distress.

Predictors of treatment outcomes after removal of amalgam fillings: associations between subjective symptoms, psychometric variables and mercury levels.

OBJECTIVE: This analysis aimed to study predictors of different treatment outcomes and associations between subjective symptoms, psychometric variables and mercury levels in patients who subjectively attributed their health problems to dental amalgam. MATERIAL AND METHODS: A secondary and retrospective analysis of data of a recently published randomized clinical trial was performed. Seventy-eight patients [44% female, mean (SD) age 35 (6) years, randomly assigned to either amalgam removal or a health promotion program] were included into statistical analysis. Prior to intervention and 12 months later, questionnaires for assessing symptoms, psychological distress and health status were presented, and mercury levels in blood and urine were determined. RESULTS: The patients' personality profile at study onset was characterized by slightly reduced extraversion and slightly elevated emotional instability. Overall, subjective symptoms decreased slightly and there were no statistically significant differences in the decrease of symptoms after intervention between both groups. Decrease of mercury levels after intervention was closely associated with removal of amalgam fillings (r(mult) = 0.64 in regression analysis). Statistically significant correlations could be found between mercury levels and subjective symptoms with respect to baseline (r = 0.29-0.39) and to changes after intervention (r = 0.24-0.42), but not for psychological distress (r = 0.05-0.25) and health related quality of life (r = -0.03-0.18). Prediction of symptom improvement after intervention was poor (r(mult) = 0.44). CONCLUSIONS: Results contribute some new aspects to the inconsistent findings in the literature with respect to associations between symptoms and subtoxic mercury levels. More emphasis should be placed on exploring individual vulnerability for amalgam sensitivity.

Psychobehavioral predictors of somatoform disorders in patients with suspected allergies.

OBJECTIVE: To explore a combination of health-related psychobehavioral features as potential positive criteria for somatoform disorders (SFD). Currently, SFD can only be diagnosed in the absence of sufficient organic symptom explanation, resulting in low criterion validity and delay of appropriate therapy. METHODS: Cross sectionally, we studied various psychobehavioral characteristics of 197 inpatients with suspected allergies. At the beginning of the medical work-up, patients were interviewed and completed a set of self-rating questionnaires (Illness Perception Questionnaire-Revised, Whiteley Index-7, Cognitions About Body And Health Questionnaire, Scale for the Assessment of Illness Questionnaire, Health Attitude Survey, Reassurance Questionnaire, and Patient Health Questionnaire). Organic explicability of the presenting symptoms was assessed by allergists at the end of the work-up. Forty-eight patients with SFD were compared with 149 patients without SFD, and predictive models were set up. To control for effects of the work-up situation, we also investigated 47 patients with an established diagnosis of hymenoptera venom allergy. RESULTS: In the work-up group, various self-reported psychobehavioral features discriminated patients with SFD from patients without SFD. In logistic regression analysis, self-reported dissatisfaction with medical care, disease conviction, reduced symptom controllability, and reduced body scanning independently predicted SFD. A predictive model based on these psychobehavioral characteristics had high sensitivity and specificity (area under the curve = 0.86, 95% Confidence Interval = 0.79-0.93; p < .001), which was comparable to the Patient Health Questionnaire-15, an established SFD screening tool assessing somatization. CONCLUSIONS: Psychobehavioral characteristics in patients with SFD cannot solely be attributed to the uncertainty of a work-up situation. Their predictive value is comparable to that of the traditional measuring of symptom number and severity; hence, they should be considered as SFD positive criteria in Diagnostic and Statistic Manual of Mental Disorders, 5th Edition.

Does a specific dental amalgam syndrome exist? A comparative study.

OBJECTIVE: The aim of this article was to investigate whether there is evidence for a specific syndrome of health problems attributed to dental amalgam. MATERIAL AND METHODS: A secondary and retrospective analysis of two different databases was performed: (a) 90 patients (47% female, mean (SD) age 34 (6) years) of a clinical trial to remove amalgam fillings who attribute their health complaints to dental amalgam, and (b) 116 patients (62% female, mean (SD) age 37 (8) years) from an outpatient unit for environmental medicine who attribute their symptoms to environmental sources other than amalgam. RESULTS: The samples differed in age, sex, and educational level. No statistically significant differences between either of the groups were found in overall psychological distress, intensity of the symptoms, or in numbers of self-reported symptoms in the Symptom Check List after controlling for age, sex, and education (Mean Global Severity Index 0.62 versus 0.63). Patients from the amalgam group showed mean values for private and public self-consciousness similar to the population norm, while patients from the comparison group had statistically significantly decreased mean values. While the amalgam group more frequently reported mental symptoms, patients from the comparison group had a higher prevalence of somatic symptoms. CONCLUSIONS: The results showed some differences in symptomatology, while general psychological distress was similar in both groups, indicating no strong evidence for an amalgam-specific syndrome.

Accelerated clinical decline in well-educated patients with frontotemporal lobar degenerations.

Education seems to protect against symptoms of neurodegeneration, but highly educated individuals experience faster cognitive decline after the onset of dementia. No studies on the effects of education on the clinical course in frontotemporal lobar degenerations (FTLD) exist. The aim of the study was to explore the effect of education on the rate of clinical deterioration in patients with FTLD. Thirty-five patients with FTLD were recruited and followed up for 20 months in average. A correlation was calculated between years of education and monthly rate of change on the clinical dementia rating scale sum of the boxes (CDR-SOB). A linear regression analysis with the CDR-SOB monthly rate of change as dependent, and the educational years and other variables possibly associated with the rate of clinical decline as independent variables was performed. There was a significant positive association between education and CDR-SOB monthly rate of change, indicating a faster decline in the well-educated. Education was the only significant predictor of clinical deterioration.

Double-blind placebo-controlled provocation study in patients with subjective Multiple Chemical Sensitivity (MCS) and matched control subjects.

INTRODUCTION: Multiple Chemical Sensitivity (MCS) is an acquired disorder with recurrent symptoms referable to multiple organ systems. No widely accepted test of physiologic function correlates with symptoms and it has not been recognized as a distinct entity by the scientific community. Few double-blind placebo-controlled studies have been done. The objectives of this study were to test two hypotheses: that patients with MCS can distinguish reliably between solvents and placebo, and that there are significant differences in objective biological and neuropsychological parameters between solvent and placebo exposures. METHODS: Twenty patients with MCS and 17 controls underwent six exposure sessions (solvent mixture and clean air in random order, double-blind) in a challenge chamber. Positive reactions were defined as subjective perception of being exposed to solvents, blood pressure or heart rate change of > or = 10%, rash or clinical signs of hypoxia, or symptom severity rise after exposure. RESULTS: No differences between the groups with regard to sensitivity, specificity, and accuracy were found. Cognitive performance was not influenced by solvent exposure, and did not differ between the groups. There was no difference between the groups in serum cortisol levels measured before and after exposures. CONCLUSION: The hypotheses were not confirmed.

Pest controllers: a high-risk group for Multiple Chemical Sensitivity (MCS)?

INTRODUCTION: Based on the assumption that professional groups with frequent chemical exposure are at an increased risk for developing Multiple Chemical Sensitivity (MCS), a sample of 45 professional pest controllers was investigated. METHODS: The examination of the pest controllers consisted of a physical and laboratory examination with urine screening for pyrethroid metabolites, a psychiatric interview, a neuropsychological test battery, and a chemical sensitivity questionnaire. RESULTS: Persistent or serious work related health problems and chemical sensitivity were not reported. In urine, cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Br(2)CA) was detected in 11%, 4-fluoro-3-phenoxybenzoic acid (F-PBA) in 7%. 3-phenoxybenzoic acid (3-PBA) exceeded the reference range in 9%, cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane-1-carboxylic acid (Cl(2)CA) in 20%. Increased liver enzymes and blood count deviations were rather common. 38% had psychiatric disorders. With few exceptions, neuropsychological testing results were normal. CONCLUSIONS: The results do not support the hypothesis that work-related insecticide exposure promotes chemical sensitivity.

Neuropsychological and positron emission tomography correlates in idiopathic environmental intolerances.

OBJECTIVES: It has been hypothesized that people with subjective hypersensitivity to chemicals may indeed suffer from neuronal damage due to widely distributed environmental toxins and that such deficits of diagnostic importance can be demonstrated with the help of functional neuroimaging even in single cases. In this study, a small group of well-characterized patients with idiopathic environmental intolerance were examined in order to identify such changes. METHODS: Twelve patients with idiopathic environmental intolerance were investigated neuropsychologically and underwent cerebral F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET). The imaging results were compared with findings from 17 healthy controls. RESULTS: Six patients showed deficits in verbal learning and memory, three of them also had a reduced information processing speed. In the individual analyses, 11 patients showed normal cerebral glucose metabolism. In the group analysis of the patients, no areas with significantly reduced glucose metabolism could be found. CONCLUSIONS: No consistent pathological cognitive performance and functional imaging pattern was found. It appears premature to claim specific neuropsychological or neuroimaging findings characteristic of idiopathic environmental intolerance. Therefore cerebral F-18 FDG PET should not be used to corroborate or rule out suspected idiopathic environmental intolerance, a syndrome whose potential biological underpinnings still need to be clarified.

Psychiatric morbidity and toxic burden in patients with environmental illness: a controlled study.

OBJECTIVE: Patients with environmental illness experience a large number of psychological symptoms. The nature of these symptoms and their pathogenesis (toxicogenic versus psychogenic) is controversial. The objective was to (1) characterize the nature of the psychological symptoms according to well-established diagnostic criteria, and (2) to investigate the association between toxicological factors and psychological symptoms. METHODS: Toxic burden, somatic morbidity, and psychiatric morbidity were assessed in 309 outpatients with environmental illness and 59 semiconductor industry workers matched for age and gender. Psychiatric disorders were assessed by a structured psychiatric interview (SCID), and distress was assessed by the Symptom-Checklist-90-Revised (SCL-90-R). Routine and specific laboratory tests in blood and urine samples were used to assess chemical exposures. RESULTS: Overall psychiatric morbidity was significantly higher in patients than in controls according to SCID (75% versus 24%). Somatoform, mood, and anxiety disorders were significantly more frequent in patients with environmental illness. They also revealed marked stress on the SCL-90-R somatization subscale and scored significantly higher than controls on most of the other subscales. Industry workers from the control group tended to have higher urine metal concentrations than environmental illness patients and similar concentrations of solvents in blood. CONCLUSION: Our data extend previous findings of high psychiatric morbidity in patients with environmental illness. They do not support the notion of a direct causal link between chemical exposure and the psychological symptoms.

New aspects of psychiatric morbidity in idiopathic environmental intolerances.

OBJECTIVE: To understand idiopathic environmental intolerances (IEI)-formerly multiple chemical sensitivities (MCS)-it is helpful to outline its characteristic psychiatric morbidity. METHOD: We applied a standardized interview according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (SCID) to 305 environmental patients with and without IEI. RESULTS: Somatoform, affective and anxiety disorders were the most frequent diagnoses but only slightly differed between patients with or without IEI. In both groups, current substance-related disorders were rare. We found a clearly higher prevalence of psychotic, especially current delusional disorders, in IEI. CONCLUSION: Somatization, depression, and anxiety are frequent in IEI but nonspecific. Psychotic disorders are more common in IEI than in other types of environmental illness. It appears worthwhile to study personality and cognitive style to explain the pivotal features of IEI.

Self-reported chemical sensitivity in Germany: a population-based survey.

OBJECTIVES: Environmental clinics are frequented by patients with fears and complaints related to environmental triggers. A dose-independent overreaction to small doses of widely used and generally non-toxic chemicals is referred to as multiple chemical sensitivity (MCS), but no clearly defined clinical syndrome with objective physical findings has been delineated so far. We aimed to obtain information about symptoms, supposed environmental triggers, the frequency of self-reported chemical sensitivity, and of the diagnosis MCS in Germany. METHODS: We conducted a representative survey among 2032 adult Germans. RESULTS: We found self-reported chemical sensitivity in 9% and physician-diagnosed MCS in 0.5% of our representative sample. Physical complaints were common in the whole study population and in chemically sensitive individuals, but there was no clear-cut symptom constellation among the latter. The most common complaints were headache, fatigue, sleep disturbances, joint pain, mood changes and nervousness. A subjective connection between complaints and environmental triggers was denied by 67% of the whole group and by 35% of the self-reported chemically sensitive. Factor analysis of environmental triggers suggested that a specific exposure situation rather than chemical similarity is the basis for individual trigger combinations. CONCLUSIONS: The prevalence of subjective sensitivity towards chemicals is similar to such rates reported from other countries. There is a relatively low awareness of the MCS-concept, and it appears to be diagnosed less frequently than, e.g., in the USA. Since symptoms and triggers in chemically sensitive individuals did not differ from the general population, our data do not suggest the existence of a widespread new syndrome related to chemical sensitivities in Germany. We outline the limitations of self-reported chemical sensitivity as the major criterion for such a contentious diagnosis as MCS.

Psychiatric morbidity and low self-attentiveness in patients with environmental illness.

Controversy surrounds the origin of symptoms attributed to environmental pollutants or widely used chemicals, and the authors believed that a psychiatric evaluation could advance understanding of this contentious condition. They assessed psychiatric morbidity, somatization, and self-attentiveness in patients seen in their Environmental Clinic. Two hundred ninety-five consecutive patients underwent SCID-I and -II interviews and were investigated with self-rating scales for self-attentiveness and somatization. The authors found a high prevalence of mental disorders (66% had a current SCID diagnosis, and 75% had a lifetime SCID diagnosis) and a low level of self-attentiveness, which was not necessarily associated with psychiatric disease. Among patients visiting an Environmental Clinic, mental disorders were common and needed to be diagnosed and treated by standard interventions. Patients who did not meet diagnostic criteria for a psychiatric disorder had relatively low somatization scores and low private self-attentiveness. These "externalizers" could benefit from an intervention that teaches them to focus on their internal and emotional lives. In these patients, the authors consider low self-attentiveness a major feature that may act as a pathogenic factor for environmental illness.