René Bridler

Schizophrenia and smoking: Evidence for a common neurobiological basis?

Several previous investigations have suggested that the gene for the alpha 7-nicotinic receptor may play a role in the pathogenesis of schizophrenia and may be responsible for the heavy smoking among schizophrenic patients. In a study of 129 healthy controls and 127 schizophrenic, schizoaffective, and bipolar patients we have aimed 1) to confirm the potential association between schizophrenia and the alpha 7-nicotinic receptor, 2) to test the diagnostic specificity of alpha 7-receptor subunits with respect to psychiatric diagnoses, and 3) to investigate potential receptor differences between smokers and nonsmokers in the general population. Our analysis included the two dinucleotide polymorphisms D15S1360 and L76630 that are localized in a genomic fragment containing the alpha 7-nicotinic receptor gene CHRNA7. Highly significant differences (P < 0.0001) between the allele distributions of patients and controls were detected for these two markers with all three diagnostic subgroups contributing to the discrimination. An independently ascertained replication sample of 24 patients confirmed this finding. Our results suggested an unspecific vulnerability that depended on the severity of overall psychopathology in terms of the co-occurrence of psychopathology with no clear-cut boundary between the diagnostic entities. In comparison with healthy controls, this vulnerability was lowest among schizophrenics, intermediate among bipolars, and highest among schizoaffectives. As to the question of alpha 7-receptor differences between smokers and nonsmokers among the healthy control subjects, our analysis revealed no significant differences, thus indicating that the differences between patients and controls are more than just a smoker/nonsmoker distinction. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:173-177, 2000.

Psychopharmacological treatment of 2195 in-patients with borderline personality disorder: A comparison with other psychiatric disorders

Patients with borderline personality disorder (BPD) are usually prescribed a variety of psychotropic drugs; however, none is recommended in the guidelines nor has any been approved for this indication. As data on drug prescriptions for BPD are sparse, cross-sectional data from the European Drug Safety Project AMSP were used to analyse drug prescriptions of 2195 in-patients with BPD between 2001 and 2011, and the mean values, confidence intervals and regression analyses were calculated. 70% of all BPD patients were medicated with antipsychotics and/or antidepressants, 33% with anticonvulsants, 30% with benzodiazepines, and 4% with lithium; 90% received at least one, 80%≥2, and 54%≥3 psychotropic drugs concomitantly (mean: 2.8). Prescription rates for quetiapine, the single drug most often used in BPD (22%), increased significantly over time. In view of the high percentage of young females with BPD, 18-40 year-old female patients with BPD were compared with patients of the same age but with depression (unipolar and bipolar) and schizophrenia. Typical sedative antipsychotics and anticonvulsants were prescribed more often in BPD than in the other diagnostic groups, with the exception of bipolar depression; this was true for the single substances quetiapine, levomepromazine, chlorprothixene, carbamazepine, and valproate. A limitation of the study was the use of clinical data without verifying the diagnoses by structured interviews. Contrary to the guidelines, about 90% of in-patients with BPD received psychotropic drugs. Polypharmacy was common, and antipsychotics with sedative profiles such as quetiapine and mood-stabilizing anticonvulsants such as valproate appear to be preferred.

Quantifying Insufficient Coping Behavior under Chronic Stress: A Cross-Cultural Study of 1,303 Students from Italy, Spain and Argentina

The question of how to quantify insufficient coping behavior under chronic stress is of major clinical relevance. In fact, chronic stress increasingly dominates modern work conditions and can affect nearly every system of the human body, as suggested by physical, cognitive, affective and behavioral symptoms. Since freshmen students experience constantly high levels of stress due to tight schedules and frequent examinations, we carried out a 3-center study of 1,303 students from Italy, Spain and Argentina in order to develop socioculturally independent means for quantifying coping behavior. The data analysis relied on 2 self-report questionnaires: the Coping Strategies Inventory (COPE) for the assessment of coping behavior and the Zurich Health Questionnaire which assesses consumption behavior and general health dimensions. A neural network approach was used to determine the structural properties inherent in the COPE instrument. Our analyses revealed 2 highly stable, socioculturally independent scales that reflected basic coping behavior in terms of the personality traits activity-passivity and defeatism-resilience. This replicated previous results based on Swiss and US-American data. The percentage of students exhibiting insufficient coping behavior was very similar across the study sites (11.5-18.0%). Given their stability and validity, the newly developed scales enable the quantification of basic coping behavior in a cost-efficient and reliable way, thus clearing the way for the early detection of subjects with insufficient coping skills under chronic stress who may be at risk of physical or mental health problems.

In Need of Psychiatric Help - Leave a Message after the Beep

Background/Aim: Every day, a substantial proportion of the general population experiences the distressing and frightening signs of an upcoming psychiatric illness. The consequences can be enormous because severe psychiatric disorders typically cause the loss of the ability to work and often mean a long-term burden for both the patients and their families. Even though most developed countries have an exceptionally high density of general practitioners and psychiatrists in private practice, getting a mental health appointment and seeing a doctor is often very difficult for patients with acute psychiatric symptoms. This study aimed at quantifying the time delay involved in seeking medical attendance when psychiatric disorders begin to develop. Methods: Two female actors with well-proven experiences of realistically simulating the clinical presentation of depression and psychotic disorders made systematic phone calls to 106 psychiatrists in private practice and 106 general practitioners (GPs) of the Zurich City area. The actors asked for an appointment at the doctors earliest convenience due to acute psychiatric symptoms. We assessed (1) the number of phone calls it took to reach each doctor; (2) the time it took to book an appointment; (3) the time span between the first phone call and the earliest available appointment, and (4) the possibility of personal contact with a doctor prior to booking the appointment. Results: A total of 383 phone calls were made by the two actors (227 to psychiatrists and 156 to GPs) which resulted in analyzable data from 102 psychiatrist and 106 GP practices. Two thirds (68%) of the phone calls to the psychiatrists in private practice were answered by voice mail, compared to 21% among the GPs. A personal contact was established with 56% of the psychiatrists and 95% of the GPs. On average, 7.3 phone calls were necessary to successfully book an appointment with a psychiatrist. Almost half of the psychiatrists (45.6%) were not accepting new patients so appointments were able to be booked in less than one third of cases (30.4%). The situation was significantly better with GPs (p < 0.002) but depended on clinical diagnosis (p < 0.01). The waiting time to seeing a psychiatrist often far exceeded 7 days. Conclusions: A high density of psychiatrists in private practice does not necessarily improve the long and troublesome circumstances of obtaining a mental health appointment in acute psychiatric situations. Under these circumstances, a considerable proportion of patients might give up prior to seeing a doctor. This has important implications - many patients could miss the potential benefits from timely therapeutic interventions which can significantly modify both the acute and long-term course of the illness. The situation might be improved if psychiatrists and GPs joined forces in the form of group practices or networks as this would readily ensure (1) a rapid mental health triage by assessing and categorizing the urgency of mental health-related problems, and (2) timely therapeutic interventions whenever indicated.

Inflammatory processes and schizophrenia: two independent lines of evidence from a study of twins discordant and concordant for schizophrenic disorders

The concept of twin concordance involves quantifying the resemblance between co-twins in an “objective” and reproducible way. Yet, quantifying resemblance in the case of complex psychiatric traits like schizophrenic disorders leads to methodological problems, as the yes–no dichotomy of diagnostic schemata does not allow one to assess between-subject differences in psychopathology patterns sufficiently accurately. Therefore, we relied on a multidimensional, quantitative concordance measure that provided a high resolution and differentiation when assessing the resemblance of psychopathology patterns. This concordance measure was central to our investigations into the potential link between schizophrenic disorders and aberrancies of the inflammatory response system. Specifically, we aimed to determine the extent to which (1) the observed variation of between-subject psychopathology concordance among 100 schizophrenic patients and (2) the observed variation of within-pair psychopathology concordance among 71 twin pairs can be explained by immunoglobulin M (IgM) levels. To accomplish this goal, we had to “gauge” in a first step the concordance measure’s performance by (1) comparing the psychopathology patterns of 269 index cases suffering from functional psychoses with the respective patterns of the 350 “affecteds” among their first-degree relatives; (2) systematically comparing the psychopathology patterns of 100 unrelated patients with a diagnosis of schizophrenic disorders with each other; and (3) detailing the within-pair concordance of elementary traits among 2734 healthy twin pairs. As to the role of active immune processes in the context of schizophrenic disorders, we found that there exists a 20–30% subgroup of patients for whom aberrancies of the inflammatory response system, as quantified through IgM levels, appeared to be linked to the pathogenesis of schizophrenic disorders (r = 0.7515/0.8184, p < 0.0001). The variation of within-pair psychopathology concordance among twins with schizophrenic disorders was found to be “explainable” in part by chronically elevated IgM levels (24.5% of observed phenotypic variance; p = 0.0434), thus suggesting that monozygotic twins concordant for schizophrenic disorders may possess a less “robust” variant of the inflammatory response system which can more easily be triggered by exogenous factors than the more “robust” variants of discordant pairs. Though the underlying biological mechanisms remain to be detected, our data have cleared the way for an early identification of patients with schizophrenic disorders for whom the inflammatory response system may be a target for therapeutic intervention. Moreover, our results will likely lead to new treatment strategies that involve elements of personalized medicine.

Contents Vol. 49, 2016

Founded 1897 as ‘Monatsschrift für Psychiatrie und Neurologie’, continued 1957–1967 as ‘Psychiatria et Neurologia’, continued 1968–1983 as ‘Psychiatria Clinica’ Founders: C. Wernicke and Th. Ziehen Successors: K. Bonhoeffer (1912–1938), J. Klaesi (1939–1967), E. Grünthal (1953–1973), N. Petrilowitsch (1968–1970), Th. Spoerri (1971–1973), P. Berner (1974–1999), E. Gabriel (1974–2004), Ch. Mundt (2000–2011)