Exploring the effectiveness of a specialized therapy programme for burnout using subjective report and biomarkers of stress.

The increasing prevalence of stress-related disorders such as burnout urges the need for specialized treatment approaches. Programmes combining psychotherapy and regenerative interventions emerge to be the most successful. However, evaluated therapy programmes are scarce and usually involve subjective symptom quantification without consideration of physiologic parameters. The aim of the present exploratory, single-group study was the multimodal investigation of the effectiveness of a specialized holistic therapy programme by assessing symptoms and biological markers of chronic stress. Seventy-one in-patients (39 men/32 women; age 46.8 ± 9.9 years) of a specialized burnout ward with the additional diagnosis of burnout (Z73.0) in conjunction with a main diagnosis of depressive disorder (F32 or F33) according to the International Classification of Diseases (ICD)-10 were included in the study. In addition to symptomatology, the stress-responsive biomarkers heart rate variability (HRV) and serum brain-derived neurotrophic factor (BDNF) were measured in patients at admittance to and discharge from the burnout ward applying a 6-week specialized treatment programme. At discharge, patients showed a significant reduction of symptom burden and a significant increase in serum BDNF, while HRV remained unchanged. The findings implicate that the therapy programme may have beneficial effects on symptomatology and neuroplasticity of patients with burnout. As therapy was often supplemented by psychopharmacological treatment, a relevant influence of antidepressant medication especially on BDNF has to be considered.

Quantification of network perfusion in ASL cerebral blood flow data with seed based and ICA approaches.

Independent component analysis (ICA) or seed based approaches (SBA) in functional magnetic resonance imaging blood oxygenation level dependent (BOLD) data became widely applied tools to identify functionally connected, large scale brain networks. Differences between task conditions as well as specific alterations of the networks in patients as compared to healthy controls were reported. However, BOLD lacks the possibility of quantifying absolute network metabolic activity, which is of particular interest in the case of pathological alterations. In contrast, arterial spin labeling (ASL) techniques allow quantifying absolute cerebral blood flow (CBF) in rest and in task-related conditions. In this study, we explored the ability of identifying networks in ASL data using ICA and to quantify network activity in terms of absolute CBF values. Moreover, we compared the results to SBA and performed a test-retest analysis. Twelve healthy young subjects performed a fingertapping block-design experiment. During the task pseudo-continuous ASL was measured. After CBF quantification the individual datasets were concatenated and subjected to the ICA algorithm. ICA proved capable to identify the somato-motor and the default mode network. Moreover, absolute network CBF within the separate networks during either condition could be quantified. We could demonstrate that using ICA and SBA functional connectivity analysis is feasible and robust in ASL-CBF data. CBF functional connectivity is a novel approach that opens a new strategy to evaluate differences of network activity in terms of absolute network CBF and thus allows quantifying inter-individual differences in the resting state and task-related activations and deactivations.

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 doctor's 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.

Theta burst TMS increases cerebral blood flow in the primary motor cortex during motor performance as assessed by arterial spin labeling (ASL).

Theta burst stimulation (TBS) is a novel variant of repetitive transcranial magnetic stimulation (rTMS), which induces changes in neuronal excitability persisting up to 1h. When elicited in the primary motor cortex, such physiological modulations might also have an impact on motor behavior. In the present study, we applied TBS in combination with pseudo continuous arterial spin labeling (pCASL) in order to address the question of whether TBS effects are measurable by means of changes in physiological parameters such as cerebral blood flow (CBF) and if TBS-induced plasticity can modify motor behavior. Twelve right-handed healthy subjects were stimulated using an inhibitory TBS protocol at subthreshold stimulation intensity targeted over the right motor cortex. The control condition consisted of within-subject Sham treatment in a crossover design. PCASL was performed before (pre TBS/pre Sham) and immediately after treatment (post TBS/post Sham). During the pCASL runs, the subjects performed a sequential fingertapping task with the left hand at individual maximum speed. There was a significant increase of CBF in the primary motor cortex after TBS, but not after Sham. It is assumed that inhibitory TBS induced a "local virtual lesion" which leads to the mobilization of more neuronal resources. There was no TBS-specific modulation in motor behavior, which might indicate that acute changes in brain plasticity caused by TBS are immediately compensated. This compensatory reaction seems to be observable at the metabolic, but not at the behavioral level.

Sustained attention and planning deficits but intact attentional set-shifting in neuroleptic-naïve first-episode schizophrenia patients.

INTRODUCTION: The nature of deficits in tests of sustained attention, planning and attentional set-shifting has not been investigated in neuroleptic-naïve first-episode (FE) schizophrenia patients. Based on previous literature of chronic and medicated FE schizophrenia patients, we predicted that the neuroleptic-naïve patients would show deficits in these cognitive processes. METHODS: Twenty-nine neuroleptic-naïve FE schizophrenia patients and 33 healthy controls - matched by age, gender, and nicotine consumption - performed 3 tests from the Cambridge Automated Neuropsychological Test Battery (CANTAB) thought to measure these cognitive processes: the Rapid Visual Information Processing task (RVIP, sustained attention), the Stockings of Cambridge task (SOC, planning), and the Intradimensional/Extradimensional set-shifting task (IDED, attention shifting). RESULTS: The patients were significantly impaired in the sensitivity index (A') of the RVIP, and in the number of problems solved with minimum moves on the SOC. Nevertheless, the groups did not differ regarding the number of participants who failed at the crucial extradimensional shift stage of the IDED. CONCLUSION: Sustained attention and planning abilities are already impaired in neuroleptic-naïve FE schizophrenia patients, whereas set-shifting abilities as measured with the IDED task seem to be intact at illness onset. Since chronic schizophrenia patients have been shown to have impaired IDED performance, we tentatively propose that IDED performance deteriorates over time with illness chronicity and/or medication.

[Acceptance of Psychiatric and Somatic Advance Directives: A Comparison in Psychiatric Patients and Professionals]. / Akzeptanz von psychiatrischen und somatischen Patientenverfügungen: ein Vergleich unter psychiatrischen Patienten und Fachpersonen.

OBJECTIVE: Assessment of the attitudes towards somatic and psychiatric advance directives in the German speaking part of Switzerland. METHODS: Questionnaire for psychiatric patients, psychiatrists, psychologists, psychiatric nurses and peers assessing the attitudes towards three exemplary advance directives. RESULTS: The attitudes were mainly positive in all participating groups. Compared to professionals (79-100 %), the somatic advance directive found approval in significantly less patients (46 %). There were no significant group differences regarding the psychiatric advance directives, but patients (58 % and 84 %) were slightly more agreeing compared to professionals (31-50 % and 62-70 %). CONCLUSION: Psychiatric advance directives seem to be broadly accepted. The development of campaigns might help to raise the awareness about these instruments and increase their usage in clinical practice.

Psychiatric advance directives in Switzerland: Knowledge and attitudes in patients compared to professionals and usage in clinical practice.

BACKGROUND: Psychiatric advance directives (PAD) were shown to be effective in the reduction of coercion and strengthening of the patients` autonomy. Therefore, the Swiss legislation was revised and stipulates that PAD must be taken into account during involuntary hospitalization. This study aimed to analyze knowledge on and attitudes towards this instrument in patients and healthcare practitioners and their usage in clinical practice. METHODS: We developed a structured questionnaire and included patients (n = 110), psychiatrists (n = 205), psychologists (n = 85), nurses (n = 268) and peers (n = 16) to rate their knowledge on and attitudes towards PAD. We registered the existing PAD in patients and peers. The response rate varied between 17% (nurses), 19% (psychologists) 21% (psychiatrists), 33% (peers) and 56% (patients). RESULTS: Only 7% of the participating patients had a PAD. Compared to the other groups, patients had the least knowledge on PAD. Psychiatrists were significantly more critical towards PAD. Concerns that PAD impede necessary and adequate treatment, restrict professionals and result in conflicts between patients and HCP were most frequently named as reason for critical attitudes. CONCLUSIONS: Although being explicitly mentioned in the Swiss legislation the usage of PAD is small. Proactive information and training of psychiatrists might be helpful for a reduction of skeptical attitudes. This might improve the attitudes and lead to active support of patients during the preparation of PAD.

Interference during the implicit learning of two different motor sequences.

It has been demonstrated that learning a second motor task after having learned a first task may interfere with the long-term consolidation of the first task. However, little is known about immediate changes in the representation of the motor memory in the early acquisition phase within the first minutes of the learning process. Therefore, we investigated such early interference effects with an implicit serial reaction time task in 55 healthy subjects. Each subject performed either a sequence learning task involving two different sequences, or a random control task. The results showed that learning the first sequence led to only a slight, short-lived interference effect in the early acquisition phase of the second sequence. Overall, learning of neither sequence was impaired. Furthermore, the two processes, sequence-unrelated task learning (i.e. general motor training) and the sequence learning itself did not appear to interfere with each other. In conclusion, although the long-term consolidation of a motor memory has been shown to be sensitive to other interfering memories, the present study suggests that the brain is initially able to acquire more than one new motor sequence within a short space of time without significant interference.

Deficient associative learning in drug-naive first-episode schizophrenia: results obtained using a new visual within-subjects learned irrelevance paradigm.

One of the key features of schizophrenia is the inability to filter out irrelevant stimuli which consequently leads to stimulus overload. There are different methods which aim at investigating these deficient filter mechanisms; one of these is the learned irrelevance (LIrr) paradigm. LIrr refers to the retardation of associative learning that occurs if the conditioned stimulus (CS) and the unconditioned stimulus (US) are preexposed in an explicitly unpaired manner prior to the establishment of the association between the stimuli. In the present study we used a recently developed computerized within-subject visual LIrr test. We measured 11 drug-naive first-episode schizophrenia patients and compared their performance to that of 17 healthy control subjects. LIrr was observed to be intact in normal individuals but disrupted in drug-naive first-episode schizophrenia patients. After one month elapsed, 5 of the 11 patients and 16 of the 17 control subjects were retested in a follow-up study. By this time, patients had been medicated with antipsychotic drugs for at least 3 weeks. While healthy controls exhibited a robust LIrr effect, patients still failed to show LIrr. Correlations were found between the performance of unmedicated patients and the depression component of the PANSS psychopathology scale.

Repeated measurements of learned irrelevance by a novel within-subject paradigm in humans.

Learned irrelevance (LIrr) refers to the retardation of classical conditioning following preexposure of the to-be-associated stimuli. Healthy volunteers have been tested on three occasions with a new LIrr paradigm avoiding methodological problems which afflict traditional paradigms. A significant LIrr effect was demonstrated on each occasion. Thus, the new paradigm enables repeated measurements of LIrr and might be useful in evaluating long-term effects of medication in psychiatric disorders exhibiting aberrant LIrr.

A biological perspective on differences and similarities between burnout and depression.

To compare and contrast burnout and depression is not only a conceptual issue, but may deliver important directions for treatment approaches and stabilize the awareness of disease which is essential for affected individuals. Because of the symptomatic overlap, it is a subject of multidimensional research and discussion to find specific signatures to differentiate between the two phenomena or to present evidence that they are different aspects of the same disorder. Both pathologies are regarded as stress-related disorders. Therefore, in this review burnout and depression are discussed on the basis of biological parameters, mainly heart rate variability (HRV) and brain-derived neurotrophic factor (BDNF), which are crucial to the stress response system. It emerges that instead of finding one specific discriminating marker, future research should rather concentrate on elaborating indices for burnout and depression which integrate combinations of parameters found in genetics, neurobiology, physiology and environment.

CBT reduces CBF: cognitive-behavioral therapy reduces cerebral blood flow in fear-relevant brain regions in spider phobia.

BACKGROUND: Imaging studies have provided evidence that cognitive-behavioral therapy (CBT) is able to change brain activation in phobic patients in response to threatening stimuli. The changes occurred in both emotion-generating and modulatory regions. In this study, we use a data-driven approach to explore resting state cerebral blood flow (CBF) measured by arterial spin labeling (ASL), before and after CBT. METHODS: Eight female patients with spider phobia were scanned before and 1 month after an exposure-based group therapy for spider phobia. Each MRI session consisted of an ASL resting state measurement acquired before and after a symptom provocation task involving the showing of spider pictures in the scanner. The first ASL acquisition measured anticipatory anxiety and the second measured postprocessing of phobia-relevant stimuli. RESULTS: Cognitive-behavioral therapy significantly reduced spider phobic symptoms in all patients. Symptom reduction during anticipatory anxiety was accompanied by reduced bilateral CBF in the parahippocampal gyrus, ventral anterior thalamus, Brodmann area 8, and the anterior cingulate cortex. During postprocessing of phobia-relevant stimuli, patients showed reduced CBF in the bilateral insula, components of the motor cortex, and areas associated with language functions. CONCLUSIONS: Longitudinal CBF dynamics following CBT were in concordance with results from several studies using BOLD fMRI to investigate the effects of psychotherapy on brain activity. CBF can be quantified by ASL, with the principal advantage of sensitivity to slow variations in neural activity and task independence. Therefore, ASL may be a suitable method for monitoring and evaluating the efficacy of psychotherapy or pharmacotherapy approaches.

Reduced cerebral blood flow within the default-mode network and within total gray matter in major depression.

The default-mode network (DMN) was shown to have aberrant blood oxygenation-level-dependent (BOLD) activity in major depressive disorder (MDD). While BOLD is a relative measure of neural activity, cerebral blood flow (CBF) is an absolute measure. Resting-state CBF alterations have been reported in MDD. However, the association of baseline CBF and CBF fluctuations is unclear in MDD. Therefore, the aim was to investigate the CBF within the DMN in MDD, applying a strictly data-driven approach. In 22 MDD patients and 22 matched healthy controls, CBF was acquired using arterial spin labeling (ASL) at rest. A concatenated independent component analysis was performed to identify the DMN within the ASL data. The perfusion of the DMN and its nodes was quantified and compared between groups. The DMN was identified in both groups with high spatial similarity. Absolute CBF values within the DMN were reduced in MDD patients (p<0.001). However, after controlling for whole-brain gray matter CBF and age, the group difference vanished. In patients, depression severity was correlated with reduced perfusion in the DMN in the posterior cingulate cortex and the right inferior parietal lobe. Hypoperfusion within the DMN in MDD is not specific to the DMN. Still, depression severity was linked to DMN node perfusion, supporting a role of the DMN in depression pathobiology. The finding has implications for the interpretation of BOLD functional magnetic resonance imaging data in MDD.

Learned irrelevance and associative learning is attenuated in individuals at risk for psychosis but not in asymptomatic first-degree relatives of schizophrenia patients: translational state markers of psychosis?

Learned irrelevance (LIrr) refers to a form of selective learning that develops as a result of prior noncorrelated exposures of the predicted and predictor stimuli. In learning situations that depend on the associative link between the predicted and predictor stimuli, LIrr is expressed as a retardation of learning. It represents a form of modulation of learning by selective attention. Given the relevance of selective attention impairment to both positive and cognitive schizophrenia symptoms, the question remains whether LIrr impairment represents a state (relating to symptom manifestation) or trait (relating to schizophrenia endophenotypes) marker of human psychosis. We examined this by evaluating the expression of LIrr in an associative learning paradigm in (1) asymptomatic first-degree relatives of schizophrenia patients (SZ-relatives) and in (2) individuals exhibiting prodromal signs of psychosis ("ultrahigh risk" [UHR] patients) in each case relative to demographically matched healthy control subjects. There was no evidence for aberrant LIrr in SZ-relatives, but LIrr as well as associative learning were attenuated in UHR patients. It is concluded that LIrr deficiency in conjunction with a learning impairment might be a useful state marker predictive of psychotic state but a relatively weak link to a potential schizophrenia endophenotype.