Low single dose gabapentin does not affect prefrontal and occipital gamma-aminobutyric acid concentrations

The γ-aminobutyric acid (GABA) system has been proposed as a target for novel antidepressant and anxiolytic treatments. Emerging evidence suggests that gabapentin (GBP), an anticonvulsant drug that significantly increases brain GABA levels, is effective in the treatment of anxiety disorders. The current study was designed to measure prefrontal and occipital GABA levels in medication-free healthy subjects after taking 0 mg, 150 mg and 300 mg GBP. Subjects were scanned on a 3T scanner using a transmit-receive head coil that provided a relatively homogenous radiofrequency field to obtain spectroscopy measurement in the medial prefrontal (MPFC) and occipital cortex (OCC). There was no dose-dependent effect of GBP on GABA levels in the OCC or MPFC. There was also no effect on Glx, choline or N-acetyl-aspartate concentrations. The previously reported finding of increased GABA levels after GBP treatment is not evident for healthy subjects at the dose of 150 and 300 mg. As a result, if subjects are scanned on a 3T scanner, low dose GPB is not useful as an experimental challenge agent on the GABA system.

The structure of psychopathological symptoms and the associations with DSM-diagnoses in treatment seeking individuals

BACKGROUND: Research on comorbidity of psychiatric disorders identifies broad superordinate dimensions as underlying structure of psychopathology. While a syndrome-level approach informs diagnostic systems, a symptom-level approach is more likely to represent the dimensional components within existing diagnostic categories. It may capture general emotional, cognitive or physiological processes as underlying liabilities of different disorders and thus further develop dimensional-spectrum models of psychopathology. METHODS: Exploratory and confirmatory factor analyses were used to examine the structure of psychopathological symptoms assessed with the Brief Symptom Inventory in two outpatient samples (n=3171), including several correlated-factors and bifactor models. The preferred models were correlated with DSM-diagnoses. RESULTS: A model containing eight correlated factors for depressed mood, phobic fear, aggression, suicidal ideation, nervous tension, somatic symptoms, information processing deficits, and interpersonal insecurity, as well a bifactor model fit the data best. Distinct patterns of correlations with DSM-diagnoses identified a) distress-related disorders, i.e., mood disorders, PTSD, and personality disorders, which were associated with all correlated factors as well as the underlying general distress factor; b) anxiety disorders with more specific patterns of correlations; and c) disorders defined by behavioural or somatic dysfunctions, which were characterised by non-significant or negative correlations with most factors. CONCLUSIONS: This study identified emotional, somatic, cognitive, and interpersonal components of psychopathology as transdiagnostic psychopathological liabilities. These components can contribute to a more accurate description and taxonomy of psychopathology, may serve as phenotypic constructs for further aetiological research, and can inform the development of tailored general and specific interventions to treat mental disorders.

Internetbasierte geleitete Selbsthilfeansätze bei Angststörungen und Depressionen

Das Spektrum internetbasierter psychologischer Behandlungsangebote bei psychischen Problemen und Erkrankungen bewegt sich zwischen webbasierten Selbsthilfeprogrammen, die das Internet als Informationsmedium verwenden, und Email-, Chat- und Video-Therapien, in welchen das Internet zu Kommunikationszwecken zwischen Hilfesuchenden und Professionellen genutzt wird. Dieser Beitrag fokussiert auf eine Beratungs- und Therapieform, die die Möglichkeiten des Internets als Informations- und Kommunikationsmedium in sogenannten geleiteten Selbsthilfeansätzen kombiniert. Internetbasierte geleitete Selbsthilfeansätze, in welchen Klienten während der Bearbeitung eines Selbsthilfeprogramms von Therapeuten via Internet (z.B. Email) unterstützt werden, wurden in den letzten Jahren intensiv erforscht. Im Bereich von Angststörungen und Depressionen liegen besonders viele Studien vor. Verschiedene Forschergruppen haben hier in der Regel große Behandlungseffekte gefunden, die mit der Wirkung von Face-to-Face-Therapien vergleichbar sind. In diesem Beitrag wird der geleitete Selbsthilfeansatz dargestellt und die empirische Evidenz diskutiert.

Ist eine wirksame psychosoziale Behandlung von Patienten mit Suchterkrankungen und komorbiden psychischen Störungen eine unmögliche Aufgabe?

Auf der Grundlage von Metaanalysen und umfassenden Überblicksarbeiten werden Schlussfolgerungen über eine wirksame psychosoziale Behandlung von Patienten mit einer Komorbidität von psychischen Störungen und Sucht (Doppeldiagnosen) gezogen. Dabei wird näher auf die Studienergebnisse zu schweren und zu leichten Formen von Doppeldiagnosen eingegangen. Die Heterogenität der Patienten-, Behandlungs-, Settings- und Ergebnismerkmale erschweren allgemeingültige Schlussfolgerungen über die Wirksamkeit psychosozialer Behandlungen. Integrative, gestufte Behandlungsprogramme, die störungsspezifische Interventionen kombinieren und motivierende Gesprächsführung, kognitiv-verhaltenstherapeutische Interventionen, suchtmittelreduzierende Interventionen wie Rückfallprävention oder Kontingenzmanagement und/oder Familieninterventionen enthalten, sind Kontrollgruppen (z.B. Wartegruppen, Standardbehandlungen) meistens, anderen aktiven Behandlungen (z.B. Psychoedukation) manchmal in den drei Ergebnisbereichen (Sucht, psychische Störung und Funktionsniveau) überlegen.

Modeling corrective experiences as motivational mountain pass

Aim: The landscape metaphor allows viewing corrective experiences (CE) as pathway to a state with relatively lower 'tension' (local minimum). However, such local minima are not easily accessible but obstructed by states with relatively high tension (local maxima) according to the landscape metaphor (Caspar & Berger, 2012). For example, an individual with spider phobia has to transiently tolerate high levels of tension during an exposure therapy to access the local minimum of habituation. To allow for more specific therapeutic guidelines and empirically testable hypotheses, we advance the landscape metaphor to a scientific model which bases on motivational processes. Specifically, we conceptualize CEs as available but unusual trajectories (=pathways) through a motivational space. The dimensions of the motivational state are set up by basic motives such as need for agency or attachment. Methods: Dynamic system theory is used to model motivational states and trajectories using mathematical equations. Fortunately, these equations have easy-to-comprehend and intuitive visual representations similar to the landscape metaphor. Thus, trajectories that represent CEs are informative and action guiding for both therapists and patients without knowledge on dynamic systems. However, the mathematical underpinnings of the model allow researchers to deduct hypotheses for empirical testing. Results: First, the results of simulations of CEs during exposure therapy in anxiety disorders are presented and compared to empirical findings. Second, hypothetical CEs in an autonomy-attachment conflict are reported from a simulation study. Discussion: Preliminary clinical implications for the evocation of CEs are drawn after a critical discussion of the proposed model.

Evidence-supported psychosocial treatment for dual disorder patients

Results on the effectiveness of psychosocial treatments for patients with comorbid psychiatric and substance use disorders (dual disorders) will be discussed based on relevant meta-analyses and comprehensive reviews. Findings pertaining to severe (e.g., schizophrenia) and mild to moderate (e.g., anxiety disorders) dual disorders will be presented. The heterogeneity in patient characteristics, treatments, settings, and measured outcomes within the studies hinders the extraction of simple conclusions regarding how to effectively integrate psychiatric and addiction-oriented services into one psychosocial treatment. However, promising treatment strategies and interventions include integrative programs that comprise motivational interviewing; disorder-specific cognitive-behavioral interventions; substance use reduction interventions such as relapse prevention or contingency management; and/or family interventions. Such programs are generally superior to control groups (e.g., waiting list, treatment as usual) and are sometimes superior to other active treatments (e.g., skills training) in outcomes of substance use, psychiatric disorders, and social functioning.

Symptom-based subtypes of depression and their psychosocial correlates: A person-centered approach focusing on the influence of sex

BACKGROUND: Reducing the complexity of major depressive disorder by symptom-based subtypes constitutes the basis of more specific treatments. To date, few studies have empirically derived symptom subtypes separated by sex, although the impact of sex has been widely accepted in depression research. METHODS: The community-based sample included 373 males and 443 females from the Zurich Program for Sustainable Development of Mental Health Services (ZInEP) manifesting depressive symptoms in the past 12 months. Latent Class Analysis (LCA) was performed separately by sex to extract sex-related depression subtypes. The subtypes were characterized by psychosocial characteristics. RESULTS: Three similar subtypes were found in both sexes: a severe typical subtype (males: 22.8%; females: 35.7%), a severe atypical subtype (males: 17.4%; females: 22.6%), and a moderate subtype (males: 25.2%; females: 41.8%). In males, two additional subgroups were identified: a severe irritable/angry-rejection sensitive (IARS) subtype (30%) comprising the largest group, and a small psychomotor retarded subtype (4%). Males belonging to the severe typical subtype exhibited the lowest masculine gender role orientation, while females of the typical subtype showed more anxiety disorders. The severe atypical subtype was associated with eating disorders in both sexes and with alcohol/drug abuse/dependence in females. In contrast, alcohol/drug abuse/dependence was associated with the severe IARS subtype in males. LIMITATIONS:The study had a cross-sectional design, allowing for no causal inferences. CONCLUSIONS:This study contributes to a better understanding of sex-related depression subtypes, which can be well distinguished on the basis of symptom profiles. This provides the base for future research investigating the etiopathogenesis and effective treatment of the heterogeneous depression disorder.

Preliminary Evidence for a Nexus between Rumination, Behavioural Avoidance, Motive Satisfaction and Depression

The present study tested a theoretically derived link between rumination and depressive symptoms through behavioural avoidance and reduced motive satisfaction as a key aspect of positive reinforcement. Rumination, behavioural avoidance, motive satisfaction and levels of depression were assessed via self-report measures in a clinical sample of 160 patients with major depressive disorder. Path analysis-based mediation analysis was used to estimate the direct and indirect effects as proposed by the theoretical model. Operating in serial, behavioural avoidance and motive satisfaction partially mediated the association between rumination and depressive symptoms, irrespective of gender, medication and co-morbid anxiety disorders. This is the first study investigating the associations between behavioural avoidance, rumination and depression in a clinical sample of depressed patients. The findings are in line with an understanding of rumination in depression as also serving an avoidance function. Copyright © 2014 John Wiley & Sons, Ltd.

General distress, hopelessness—suicidal ideation and worrying in adolescence: Concurrent and predictive validity of a symptom-level bifactor model for clinical diagnoses

BACKGROUND: Clinical disorders often share common symptoms and aetiological factors. Bifactor models acknowledge the role of an underlying general distress component and more specific sub-domains of psychopathology which specify the unique components of disorders over and above a general factor. METHODS: A bifactor model jointly calibrated data on subjective distress from The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale. The bifactor model encompassed a general distress factor, and specific factors for (a) hopelessness-suicidal ideation, (b) generalised worrying and (c) restlessness-fatigue at age 14 which were related to lifetime clinical diagnoses established by interviews at ages 14 (concurrent validity) and current diagnoses at 17 years (predictive validity) in a British population sample of 1159 adolescents. RESULTS: Diagnostic interviews confirmed the validity of a symptom-level bifactor model. The underlying general distress factor was a powerful but non-specific predictor of affective, anxiety and behaviour disorders. The specific factors for hopelessness-suicidal ideation and generalised worrying contributed to predictive specificity. Hopelessness-suicidal ideation predicted concurrent and future affective disorder; generalised worrying predicted concurrent and future anxiety, specifically concurrent generalised anxiety disorders. Generalised worrying was negatively associated with behaviour disorders. LIMITATIONS: The analyses of gender differences and the prediction of specific disorders was limited due to a low frequency of disorders other than depression. CONCLUSIONS: The bifactor model was able to differentiate concurrent and predict future clinical diagnoses. This can inform the development of targeted as well as non-specific interventions for prevention and treatment of different disorders.

Varying expectancies and attention bias in phobic and non-phobic individuals.

Phobic individuals display an attention bias to phobia-related information and biased expectancies regarding the likelihood of being faced with such stimuli. Notably, although attention and expectancy biases are core features in phobia and anxiety disorders, these biases have mostly been investigated separately and their causal impact has not been examined. We hypothesized that these biases might be causally related. Spider phobic and low spider fearful control participants performed a visual search task in which they specified whether the deviant animal in a search array was a spider or a bird. Shorter reaction times (RTs) for spiders than for birds in this task reflect an attention bias toward spiders. Participants' expectancies regarding the likelihood of these animals being the deviant in the search array were manipulated by presenting verbal cues. Phobics were characterized by a pronounced and persistent attention bias toward spiders; controls displayed slower RTs for birds than for spiders only when spider cues had been presented. More important, we found RTs for spider detections to be virtually unaffected by the expectancy cues in both groups, whereas RTs for bird detections showed a clear influence of the cues. Our results speak to the possibility that evolution has formed attentional systems that are specific to the detection of phylogenetically salient stimuli such as threatening animals; these systems may not be as penetrable to variations in (experimentally induced) expectancies as those systems that are used for the detection of non-threatening stimuli. In sum, our findings highlight the relation between expectancies and attention engagement in general. However, expectancies may play a greater role in attention engagement in safe environments than in threatening environments.

High-Dose Benzodiazepine Dependence: A Qualitative Study of Patients' Perceptions on Initiation, Reasons for Use, and Obtainment

BACKGROUND High-dose benzodiazepine (BZD) dependence is associated with a wide variety of negative health consequences. Affected individuals are reported to suffer from severe mental disorders and are often unable to achieve long-term abstinence via recommended discontinuation strategies. Although it is increasingly understood that treatment interventions should take subjective experiences and beliefs into account, the perceptions of this group of individuals remain under-investigated. METHODS We conducted an exploratory qualitative study with 41 adult subjects meeting criteria for (high-dose) BZD-dependence, as defined by ICD-10. One-on-one in-depth interviews allowed for an exploration of this group's views on the reasons behind their initial and then continued use of BZDs, as well as their procurement strategies. Mayring's qualitative content analysis was used to evaluate our data. RESULTS In this sample, all participants had developed explanatory models for why they began using BZDs. We identified a multitude of reasons that we grouped into four broad categories, as explaining continued BZD use: (1) to cope with symptoms of psychological distress or mental disorder other than substance use, (2) to manage symptoms of physical or psychological discomfort associated with somatic disorder, (3) to alleviate symptoms of substance-related disorders, and (4) for recreational purposes, that is, sensation-seeking and other social reasons. Subjects often considered BZDs less dangerous than other substances and associated their use more often with harm reduction than as recreational. Specific obtainment strategies varied widely: the majority of participants oscillated between legal and illegal methods, often relying on the black market when faced with treatment termination. CONCLUSIONS Irrespective of comorbidity, participants expressed a clear preference for medically related explanatory models for their BZD use. We therefore suggest that clinicians consider patients' motives for long-term, high-dose BZD use when formulating treatment plans for this patient group, especially since it is known that individuals are more compliant with approaches they perceive to be manageable, tolerable, and effective.

Evidence for chronic low-grade systemic inflammation in individuals with agoraphobia from a population-based prospective study.

BACKGROUND Anxiety disorders have been linked to an increased risk of incident coronary heart disease in which inflammation plays a key pathogenic role. To date, no studies have looked at the association between proinflammatory markers and agoraphobia. METHODS In a random Swiss population sample of 2890 persons (35-67 years, 53% women), we diagnosed a total of 124 individuals (4.3%) with agoraphobia using a validated semi-structured psychiatric interview. We also assessed socioeconomic status, traditional cardiovascular risk factors (i.e., body mass index, hypertension, blood glucose levels, total cholesterol/high-density lipoprotein-cholesterol ratio), and health behaviors (i.e., smoking, alcohol consumption, and physical activity), and other major psychiatric diseases (other anxiety disorders, major depressive disorder, drug dependence) which were treated as covariates in linear regression models. Circulating levels of inflammatory markers, statistically controlled for the baseline demographic and health-related measures, were determined at a mean follow-up of 5.5 ± 0.4 years (range 4.7 - 8.5). RESULTS Individuals with agoraphobia had significantly higher follow-up levels of C-reactive protein (p = 0.007) and tumor-necrosis-factor-α (p = 0.042) as well as lower levels of the cardioprotective marker adiponectin (p = 0.032) than their non-agoraphobic counterparts. Follow-up levels of interleukin (IL)-1β and IL-6 did not significantly differ between the two groups. CONCLUSIONS Our results suggest an increase in chronic low-grade inflammation in agoraphobia over time. Such a mechanism might link agoraphobia with an increased risk of atherosclerosis and coronary heart disease, and needs to be tested in longitudinal studies.

Vitamin D Deficiency and Depressive Symptomatology in Psychiatric Patients Hospitalized with a Current Depressive Episode: A Factor Analytic Study.

BACKGROUND Low vitamin D levels have been associated with depressive symptoms in population-based studies and non-clinical samples as well as with clinical depression. This study aimed to examine the association of vitamin D levels with the severity and dimensions of depressive symptoms in hospitalized patients with a current episode of depression taking into account confounding variables. METHODS We investigated 380 patients (mean age 47 ± 12 years, 70% women) who were consecutively hospitalized with a main diagnosis of an ICD-10 depressive episode. All patients self-rated depressive symptom severity with the Hospital Anxiety and Depression Scale (HADS-D), the Beck Depression Inventory-II (BDI-II), and the Brief Symptom Inventory. A principal component analysis was performed with all 34 items of these questionnaires and serum levels of 25-hydroxyvitamin D3 (25-OH D) were measured. RESULTS Vitamin D deficiency (< 50 nmol/l), insufficiency (50-75 nmol/l), and sufficiency (> 75 nmol/l) were present in 55.5%, 31.8% and 12.6%, respectively, of patients. Patients with vitamin D deficiency scored higher on the HADS-D scale and on an anhedonia symptom factor than those with insufficient (p-values ≤ 0.023) or sufficient (p-values ≤ 0.008) vitamin D. Vitamin D deficient patients also scored higher on the BDI-II scale than those with sufficient vitamin D (p = 0.007); BDI-II cognitive/affective symptoms, but not somatic/affective symptoms, were higher in patients with vitamin D deficiency (p = 0.005) and insufficiency (p = 0.041) relative to those with sufficient vitamin D. Effect sizes suggested clinically relevant findings. CONCLUSIONS Low vitamin D levels are frequent in hospitalized patients with a current episode of depression. Especially 25-OH D levels < 50 nmol/l were associated with cognitive/affective depressive symptoms, and anhedonia symptoms in particular.

European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe

PURPOSE: Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given. METHODS: We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders. RESULTS: We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences. DISCUSSION: The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD. CONCLUSION: Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm.

The Process-Outcome Mindfulness Effects in Trainees (PrOMET) study: protocol of a pragmatic randomized controlled trial

Background Mindfulness has its origins in an Eastern Buddhist tradition that is over 2500 years old and can be defined as a specific form of attention that is non-judgmental, purposeful, and focused on the present moment. It has been well established in cognitive-behavior therapy in the last decades, while it has been investigated in manualized group settings such as mindfulness-based stress reduction and mindfulness-based cognitive therapy. However, there is scarce research evidence on the effects of mindfulness as a treatment element in individual therapy. Consequently, the demand to investigate mindfulness under effectiveness conditions in trainee therapists has been highlighted. Methods/Design To fill in this research gap, we designed the PrOMET Study. In our study, we will investigate the effects of brief, audiotape-presented, session-introducing interventions with mindfulness elements conducted by trainee therapists and their patients at the beginning of individual therapy sessions in a prospective, randomized, controlled design under naturalistic conditions with a total of 30 trainee therapists and 150 patients with depression and anxiety disorders in a large outpatient training center. We hypothesize that the primary outcomes of the session-introducing intervention with mindfulness elements will be positive effects on therapeutic alliance (Working Alliance Inventory) and general clinical symptomatology (Brief Symptom Checklist) in contrast to the session-introducing progressive muscle relaxation and treatment-as-usual control conditions. Treatment duration is 25 therapy sessions. Therapeutic alliance will be assessed on a session-to-session basis. Clinical symptomatology will be assessed at baseline, session 5, 15 and 25. We will conduct multilevel modeling to address the nested data structure. The secondary outcome measures include depression, anxiety, interpersonal functioning, mindful awareness, and mindfulness during the sessions. Discussion The study results could provide important practical implications because they could inform ideas on how to improve the clinical training of psychotherapists that could be implemented very easily; this is because there is no need for complex infrastructures or additional time concerning these brief session-introducing interventions with mindfulness elements that are directly implemented in the treatment sessions.