Sarah Schumacher

Is salivary alpha-amylase an indicator of autonomic nervous system dysregulations in mental disorders?—A review of preliminary findings and the interactions with cortisol

During recent years, a growing interest emerged in using salivary alpha-amylase (sAA) as a non-invasive, surrogate marker for sympathetic activity. Numerous studies applying stress protocols have demonstrated that sAA is highly sensitive to stress-related changes (in healthy subjects). Additionally, it was suggested that sAA might moreover serve as an index for pathological dysregulation of the autonomic nervous system (ANS) in patients showing psychopathology. Since then, a small but growing literature investigated sAA in patients with mental disorders. This review aims to give an overview of preliminary findings in this field of research. The results of n=15 studies are described in detail and implications for further research are discussed. Although the number of studies and the samples examined were rather small, changes in sAA, reflecting adrenergic dysregulation, could be demonstrated in psychopathology, especially in anxiety-related disorders. This field of research is still in its early stages. However, the studies included in this review revealed first evidence that the employment of sAA, as an indicator of ANS dysregulation in mental disorders, is promising.

Effect of combined cognitive-behavioural therapy and endurance training on cortisol and salivary alpha-amylase in panic disorder.

Current data point to an alteration of both the hypothalamo-pituitary-adrenal (HPA)-system and the peripheral transmission of catecholamines in anxiety disorders. There is also some evidence for the effect of several components of cognitive-behavioural interventions such as coping and control and for an effect of exercise training on the neuroendocrine stress response in healthy subjects as well as patients suffering from distinct (mental) disorders. This double-blind, controlled study investigated the effect of cognitive-behavioural therapy (CBT) in combination with either high-level endurance training or low-level exercise on salivary cortisol (sC) and on levels of salivary alpha-amylase (sAA) in patients suffering from panic disorder (PD) with and without agoraphobia. In comparison to the low-level exercise condition, there were significantly lower sC-levels in the experimental group performing high-level endurance training at a 7-month follow-up. In contrast, there were no group differences in sAA levels during the study period. In this trial, we found evidence for a decelerated effect of endurance-training on HPA-systems functioning in PD. Further studies addressing the alteration of sAA levels in this population might investigate physical exercise different in intensity and duration.

Who is stressed? A pilot study of salivary cortisol and alpha-amylase concentrations in agoraphobic patients and their novice therapists undergoing in vivo exposure.

In cognitive behavioural therapy of phobic anxiety, in vivo exposure is considered as an effective treatment strategy. Apparently, it involves the experience of stress and anxiety in patients. Given the therapists role during exposure sessions, it is conceivable that the performance is also accompanied with the experience of stress in therapists, especially when unversed in conducting psychotherapy. Studies confirmed that cognitive behavioural therapists tend to avoid therapist-guided in vivo exposure. The objective of this study was the simultaneous investigation of therapists and patients stress response during in vivo exposure. Therefore, 23 agoraphobic patients and their 23 treating therapists in training provided five saliva samples during an in vivo exposure and five samples during an ordinary therapy session. Before and during exposure session, subjective evaluations of stress and anxiety were assessed. Results suggested that therapists reported similar levels of perceived stress as patients before exposure. Both groups displayed significantly elevated salivary cortisol (sC) levels during exposure compared to the control session and a trend for alterations in salivary alpha-amylase (sAA) activity was found. Therapists reached peak concentrations of sC before start of the intervention followed by a decline during exposure, while patients displayed peak levels of cortisol secretion after 60 min of exposure. In vivo exposure seems to be a demanding intervention not only for the patient, but also for therapists in training. However, it was also demonstrated that physiological and subjective stress rather decrease during the intervention and that both groups rated exposure to be substantially successful. Based on the presented results, another potential factor contributing to the under-usage of exposure treatment is conceivable and needs to be addressed in future research.

Therapists' and patients' stress responses during graduated versus flooding in vivo exposure in the treatment of specific phobia: A preliminary observational study

Exposure therapy is considered an effective treatment strategy for phobic anxiety, however, it is rarely applied in clinical practice. The under-usage might be due to various factors of which heightened stress levels not only in patients but also in therapists are presumed to be of particular relevance. The present study aimed to investigate whether different forms of exposure might lead to varying physiological and psychological stress responses in therapists and phobic patients. 25 patients with specific phobia underwent individual cognitive behavioural therapy, performed by 25 psychotherapist trainees, applying exposure sessions in graduated form or the flooding technique. Patients and therapists provided subjective evaluations of stress and five saliva samples for analysis of salivary cortisol and alpha-amylase either during two graduated exposure sessions or during one flooding session, while a regular therapy session served as control condition. Therapists displayed heightened salivary alpha-amylase release during exposure of the flooding, but not the graduated, type. Patients showed elevated salivary cortisol during flooding exposure numerically, however, not on a statistically significant level. Therapists reported more pronounced subjective stress during flooding compared to graduated exposure. Elevated stress levels should be addressed in clinical training in order to improve application of exposure in routine practice.

A novel immunoassay for quantitative drug abuse screening in serum

An immunoassay was established which enables a reliable quantification of serological drug samples. The assay is based on a competitive ELISA. In total nine drugs (amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), tetrahydrocannabinol (THC), phencyclidine (PCP), methadone, morphine, cocaine and benzoylecgonine) were tested. All reagents had to pass through a stringent validation process. Within the established test for three out of the nine drugs no cross-reactivity with any tested compounds, e.g. serum, other antibodies or chemically related molecules was detectable for the tested antibodies. Furthermore, a sensitive and selective detection was possible, even in the presence of up to 9 drugs or of various anti-drug antibodies. After exclusion of cross-reactivities antibodies against three drugs (methadone, MDMA, benzoylecgonine) were validated, which allowed a specific and sensitive quantification. For the competitive measurements CVs in the range of 2-17% could be reached with LLOQs of 10ng/mL and LODs of 150ng/mL for methadone, 250ng/mL for MDMA and 400ng/mL for benzoylecgonine. Anonymized serum samples (n=10) provided by the office of criminal investigation Berlin were analyzed for verification purposes. Evaluation of these data showed a correlation (CV) of ≈0.9 with standard GC-MS methods. A miniaturization on microarray was possible by using the anti-MDMA antibody for the detection of MDMA in serum. The microarray increased the through-put drastically and enabled the simultaneous quantification of various drugs.

Clinical and neurobiological effects of aerobic exercise in dental phobia: A randomized controlled trial

Physical activity has shown to be effective in anxiety disorders. For specific phobia, no studies are available that systematically examined the effects of an aerobic exercise intervention on phobic fear within a randomized‐controlled design. Therefore, we investigated the acute effect of a standardized aerobic training on clinical symptoms of dental phobia as well as on stress‐related neurobiological markers.

Habituation of stress in psychotherapists performing subsequent in vivo exposures—A case series.

In the treatment of phobic patients, in vivo exposure is a highly effective, yet rarely applied approach. Among other factors, stress experienced by therapists while performing this intervention might contribute to the reluctance of its application. Also, this technique is still strongly associated to traditional behavior therapy and rarely considered by other orientations in the sense of technical eclecticism. It is investigated whether therapist trainees show a habituation of perceived psychological and physiological stress across several exposure sessions. Psychological and physiological stress was assessed in 5 inexperienced therapist trainees before, during and after 3 subsequent in vivo exposures. Salivary cortisol levels served as a marker for the physiological stress response. Due to the small sample size, only descriptive statistics are reported. On a descriptive level, therapists displayed peak levels of cortisol at onset of exposure session and decreasing concentrations over the course of each session. Overall, levels of cortisol concentrations decreased across the 3 subsequent sessions. With regard to psychological stress, within session, but not across session, habituation was determined. The presented findings provide first and only descriptive indications of habituation of physiological stress after performance of several exposure sessions in novice therapists. Application of this powerful intervention needs to be addressed in clinical training and should be encouraged to be used as a tool regardless of psychotherapeutic orientation. ¿Psicoterapeutas muestran habituación de estrés a través de sesiones de exposiciones en vivo? - Una serie de casos En el tratamiento de pacientes fóbicos, la exposición en vivo es muy efectiva, pero es una técnica aplicada raramente. El estrés experimentados por terapeutas mientras llevan a cabo la intervención puede contribuir a la reticencia de usar este método, entre otras razones. Adicionalmente, la técnica sigue siendo fuertemente asociada con la terapia conductual tradicional y raramente es considerada por otras orientaciones en la moda de eclecticismo técnico. Es investigado si los terapeutas aprendices demuestran una habituación de estrés percibido psicológico y fisiológico a través de varias sesiones de exposición. Estrés psicológico y fisiológico fue observado en cinco terapeutas aprendices sin experiencia antes, durante y después de tres exposiciones consecutivas. Niveles de cortisol salival fueron usados como la señal de respuestas al estrés. Debido al pequeño número de participantes, solo estadísticas descriptivas son reportadas. A nivel descriptivo, terapeutas mostraron niveles máximos de cortisol al inicio de la sesión de exposición y la concentraciones redujeron a través del curso de cada sesión. En general, los niveles de concentración de cortisol disminuyeron a través de las tres sesiones consecutivas. Con respecto al estrés psicológico se determinó habituación dentro de la sesión pero no a través de la sesión. Los hallazgos presentados proveen los primeros y únicos indicativos descriptivas de habituación de estrés fisiológico después de varias sesiones de exposición en terapeutas aprendices. Aplicaciones de esta intervención poderosa necesitan ser discutidas en el contexto de la formación clínica y se debe alentar la utilización de estas como un instrumento clínico, independiente de la orientación del psicoterapeuta.

Quality control of antibodies for assay development.

Antibodies are used as powerful tools in basic research, for example, in biomarker identification, and in various forms for diagnostics, for example, identification of allergies or autoimmune diseases. Due to their robustness and ease of handling, immunoassays are favourite methods for investigation of various biological or medical questions. Nevertheless in many cases, additional analyses such as mass spectrometry are used to validate or confirm the results of immunoassays. To minimize the workload and to increase confidence in immunoassays, there are urgent needs for antibodies which are both highly specific and well validated. Unfortunately many commercially available antibodies are neither well characterized nor fully tested for cross-reactivities. Adequate quality control and validation of an antibody is time-consuming and can be frustrating. Such validation needs to be performed for every assay/application. However, where an antibody validation is successful, a highly specific and stable reagent will be on hand. This article describes the validation processes of antibodies, including some often neglected factors, as well as unspecific binding to other sample compounds in a multiparameter diagnostic assay. The validation consists of different immunological methods, with important assay controls, and is performed in relation to the development of a diagnostic test.

Psychotherapeutic treatment and HPA axis regulation in posttraumatic stress disorder: A systematic review and meta-analysis

Posttraumatic stress disorder (PTSD) has been associated with dysregulation of the hypothalamic-pituitary- adrenal (HPA) axis. Research over the past years has investigated potential changes of these alterations in the context of psychotherapy. Yet, no systematic review has been conducted. To summarize the current state of research on psychotherapy and HPA hormones, namely cortisol, dehydroepiandrosterone and its sulfate form (DHEA(S)), we searched for studies investigating predictions or changes in hormones over treatment course within the databases PubMed, Scopus, Medline, PsychINFO, Pilots/ProQuest, and Web of Science, and in the grey literature up to May 2018. Controlled and uncontrolled trials investigating adult samples with a clinical status of PTSD were eligible for inclusion. Twelve studies (428 participants) were included. Study quality was overall sufficient. Hormone assessment designs differed considerably. Treatment efficacy on PTSD symptom reduction was mostly high, but predictions of pre-treatment hormone concentrations on treatment efficacy were largely non-significant. Changes from pre- to post-test in basal cortisol (g = -0.07, 95% CI = -0.36; 0.21) and in the cortisol awakening response (g = -0.07, 95% CI = -0.48; 0.35) were also non-significant. Future studies require comparable designs and need to be sufficiently powered to be able to detect potential associations with HPA regulation.

Cortisol and alpha-amylase assessment in psychotherapeutic intervention studies: A systematic review

&NA; Dysregulations of the hypothalamus‐pituitary‐adrenal (HPA) axis and the autonomic nervous system (ANS), two of the most prominent stress‐responsive systems, have been associated with the development and maintenance of various mental disorders. It has been suggested that these alterations might normalize in the course of psychotherapeutic interventions. We conducted a comprehensive review of psychotherapeutic intervention effects on HPA axis and ANS regulation in adult samples with mental disorders. We searched four databases for psychotherapeutic intervention studies with mentally ill patient samples, assessing cortisol and/or alpha‐amylase before and after treatment. Study quality and confounder consideration within biomarker assessment were examined. Twenty‐five studies were included. Psychotherapeutic interventions and biomarker assessment methodology varied substantially between studies. Accordingly, meta‐analytical computations were deemed unfeasible. Study characteristics especially regarding cortisol and alpha‐amylase assessment and analysis procedures were comprehensively reviewed. Study quality and biomarker confounder consideration ratings were mostly moderate to strong. Based on the results, we provide recommendations regarding intervention design and biomarker assessment methodology to increase comparability of psychotherapeutic treatment effects in future studies.