Effects of cannabidiol on fear conditioning in anxiety disorders: decreased threat expectation during retention, but no enhanced fear re-extinction.

RATIONALE: Preclinical research suggests that pharmacologically elevating cannabinoid levels may attenuate fear memory expression and enhance fear extinction. OBJECTIVES: We studied the effects of cannabidiol (CBD) on fear memory expression and fear re-extinction in 69 patients with panic disorder with agoraphobia or with social anxiety disorder. Moderation by sex, diagnosis, and serotonergic antidepressant (AD) use was explored. METHODS: A cued fear conditioning paradigm was applied before the first treatment session with 300 mg CBD/placebo augmented exposure therapy. Study medication was administered orally preceding 8 weekly sessions. Fear acquisition and suboptimal extinction took place prior to the first medication ingestion (T0). After the first medication ingestion (T1), we investigated effects on fear memory expression at retention and fear re-extinction. Subjective fear, shock expectancy, skin conductance, and startle responses to conditioned (CS+) and safety stimulus (CS-) were measured. RESULTS: Across the sample, CBD reduced shock expectancy at retention under low and ambiguous threat of shock, but fear re-extinction at T1 was unaffected by CBD. However, in AD users, re-extinction of subjective fear was impaired in the CBD condition compared to placebo. In female AD users, CBD interfered with safety learning measured with fear-potentiated startle. CONCLUSIONS: The current findings provide no evidence for enhanced fear re-extinction by CBD. However, CBD acutely decreased threat expectation at retention, without affecting other indices of fear. More studies are needed to elucidate possible interactions with AD use and sex, as well as potential effects of CBD on threat expectancies.

[Practice variation in the field of suicide prevention in Dutch mental healthcare]. / Praktijkvariatie op het gebied van suïcidepreventie in de Nederlandse ggz.

BACKGROUND: Previous studies found that the implementation of service guideline recommendations can significantly reduce the number of suicides in mental healthcare. Important barriers to suicide prevention guideline implementation are a lack of professionals' knowledge and competence towards the suicide prevention guideline.
AIM: To assess professionals' knowledge of, competence in, and adherence to the suicide prevention guideline in twelve Dutch specialist mental healthcare institutions.
METHOD: In this study, professionals working at crisis teams and outpatient care teams from each of the 12 participating mental healthcare institutions in the network of supranet Care were invited to fill in a questionnaire examining professionals' knowledge of, competence in, and adherence to the suicide prevention guideline (N = 400). Results were analyzed with multilevel regression analysis and adjusted for confounding.
RESULTS: Although professionals scored high on knowledge, competence, and adherence towards the guideline, they did not know to what extent the guideline was implemented within their own team. Outpatient care teams scored significantly lower on professionals' knowledge and reported lower levels of competence. Furthermore, we found significantly higher scores on adherence to the guideline for professionals in crisis teams compared to outpatient care teams. Healthcare professionals also reported practice variation within and across Dutch mental healthcare institutions. CONCLUSIONS Practice variation within and across teams and mental healthcare institutions is undesirable. To reduce this variation, professionals and mental healthcare institutions should share best-practices and learn from each other how the quality of care for suicidal patients can be optimized.

Predicting the course of anxiety disorders: The role of biological parameters.

OBJECTIVE: Clinical characteristics appear limited in their ability to predict course of anxiety disorders, therefore we explored the predictive value of biological parameters on course of anxiety disorders. METHODS: 907 persons with an anxiety (panic, social phobia, generalised anxiety) disorder with a baseline and two-year follow-up measure were selected from the Netherlands Study of Depression and Anxiety (NESDA). Previously, three course trajectories were distinguished which vary in terms of symptom severity and chronicity. Baseline clinical parameters like anxiety severity, anxiety duration, and disability were limited in their ability to predict the two-year course. This study explored whether metabolic syndrome, hypothalamic-pituitary-adrenal-axis functioning, inflammation markers, and neuroplasticity were indicators of two-year course and whether these parameters improved the model containing the most predictive clinical parameters only. RESULTS: Baseline diastolic blood pressure of persons with chronic moderate symptoms was significantly higher than of persons with non-chronic mild symptoms (odds ratio [OR] = 1.18, 95% confidence interval [CI95%] 1.01 to 1.38). Baseline high-density lipid cholesterol of persons with severe chronic symptoms was significantly lower than of persons with non-chronic mild symptoms (OR = 0.77, CI95% 0.62 to 0.96). The predictive ability of both parameters was however low with concordance statistics of 0.55 and 0.57 respectively. Addition of biological parameters did not improve the predictive ability of the model containing the clinical parameters. CONCLUSIONS: In addition to clinical characteristics, biological parameters did not improve the predictive ability of the model for course trajectory of anxiety disorders. Prediction of course trajectory in anxiety disorders remains difficult and warrants further research.

Indicators to facilitate the early identification of patients with major depressive disorder in need of highly specialized care: A concept mapping study.

BACKGROUND: Early identification of the subgroup of patients with major depressive disorder (MDD) in need of highly specialized care could enhance personalized intervention. This, in turn, may reduce the number of treatment steps needed to achieve and sustain an adequate treatment response. The aim of this study was to identify patient-related indicators that could facilitate the early identification of the subgroup of patients with MDD in need of highly specialized care. METHODS: Initial patient indicators were derived from a systematic review. Subsequently, a structured conceptualization methodology known as concept mapping was employed to complement the initial list of indicators by clinical expertise and develop a consensus-based conceptual framework. Subject-matter experts were invited to participate in the subsequent steps (brainstorming, sorting, and rating) of the concept mapping process. A final concept map solution was generated using nonmetric multidimensional scaling and agglomerative hierarchical cluster analyses. RESULTS: In total, 67 subject-matter experts participated in the concept mapping process. The final concept map revealed the following 10 major clusters of indicators: 1-depression severity, 2-onset and (treatment) course, 3-comorbid personality disorder, 4-comorbid substance use disorder, 5-other psychiatric comorbidity, 6-somatic comorbidity, 7-maladaptive coping, 8-childhood trauma, 9-social factors, and 10-psychosocial dysfunction. CONCLUSIONS: The study findings highlight the need for a comprehensive assessment of patient indicators in determining the need for highly specialized care, and suggest that the treatment allocation of patients with MDD to highly specialized mental healthcare settings should be guided by the assessment of clinical and nonclinical patient factors.

The long-term association of OCD and depression and its moderators: A four-year follow up study in a large clinical sample.

BACKGROUND: Depression is the most common comorbidity in obsessive-compulsive disorder (OCD). However, the mechanisms of depressive comorbidity in OCD are poorly understood. We assessed the directionality and moderators of the OCD-depression association over time in a large, prospective clinical sample of OCD patients. METHODS: Data were drawn from 382 OCD patients participating at the Netherlands Obsessive-Compulsive Disorder Association (NOCDA) study. Cross-lagged, structural equation modeling analyses were used to assess the temporal association between OCD and depressive symptoms. Assessments were conducted at baseline, two-year and four-year follow up. Cognitive and interpersonal moderators of the prospective association between OCD and depressive symptoms were tested. RESULTS: Cross-lagged analyses demonstrated that OCD predicts depressive symptoms at two-year follow up and not vice a versa. This relationship disappeared at four-year follow up. Secure attachment style moderated the prospective association between OCD and depression. CONCLUSIONS: Depressive comorbidity in OCD might constitute a functional consequence of the incapacitating OCD symptoms. Both OCD and depression symptoms demonstrated strong stability effects between two-year and four-year follow up, which may explain the lack of association between them in that period. Among OCD patients, secure attachment represents a buffer against future depressive symptoms.

Moving Perspectives on Patient Competence: A Naturalistic Case Study in Psychiatry.

Patient competence, defined as the ability to reason, appreciate, understand, and express a choice is rarely discussed in patients with obsessive compulsive disorder (OCD), and coercive measures are seldom used. Nevertheless, a psychiatrist of psychologist may doubt whether OCD patients who refuse treatment understand their disease and the consequences of not being treated, which could result in tension between respecting the patient's autonomy and beneficence. The purpose of this article is to develop a notion of competence that is grounded in clinical practice and corresponds with the experiences of patients with obsessions and/or compulsions. We present a naturalistic case study giving both the patient's and the therapist's perspective based on in-depth interviews and a narrative analysis. The case study shows that competence is not merely an assessment by a therapist, but also a co-constructed reality shaped by the experiences and stories of patient and therapist. The patient, a medical student, initially told her story in a restitution narrative, focusing on cognitive rationality. Reconstructing the history of her disease, her story changed into a quest narrative where there was room for emotions, values and moral learning. This fitted well with the therapist's approach, who used motivational interventions with a view to appealing to the patient's responsibility to deal with her condition. We conclude that in practice both the patient and therapist used a quest narrative, approaching competence as the potential for practical reasoning to incorporate values and emotions.

[Psychiatric comorbidity: theoretical and clinical dilemmas]. / Psychiatrische comorbiditeit: theoretische en klinische dilemma's.

BACKGROUND: The high prevalence of psychiatric comorbidity is usually considered to be a problematic artefact of the DSM. Clinicians appear to be reluctant to register comorbid diagnoses. AIM: To provide insight into the concept of 'psychiatric comorbidity', so that the phenomenon can be dealt with more efficiently in clinical practice. METHOD: We studied the literature and performed a theoretical analysis. RESULTS: The high prevalence of psychiatric comorbidity is closely linked to the structure of the DSM and is leading increasingly to practical and theoretical problems. These problems have stimulated the development of several valuable alternative models of psychopathology. In the context of these developments, however, the use of terms such as 'artificial' has led to a needless and unfruitful polarisation of the debate. The debate needs to focus primarily on the usefulness of various models for patient care and research. CONCLUSION: Psychiatric comorbidity is an inevitable consequence of a categorical approach to psychopathology, which is basically legitimate. As long as the dsm in its current form constitutes an important part of our diagnostic 'arsenal', we advise clinicians to register comorbid classifications in as much detail as possible and at the same time to give close attention to the correct interpretation of the phenomenon.

[Complex PTSD following early-childhood trauma: emotion-regulation training as addition to the PTSD guideline]. / Complexe PTSS na vroegkinderlijk trauma: emotieregulatietraining als aanvulling op de PTSS-richtlijn.

BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms in individuals who have experienced repeated trauma (sexual and/or physical) in early childhood can lead to problems associated with emotion regulation, interpersonal functioning and self-image. This so-called complex PTSD is often accompanied by a comorbid personality disorder. Although ptsd is associated with structural and functional abnormalities in emotion-regulation areas in the brain, it is not known whether complex PTSD shows similar abnormalities. Experts take the view that before individuals with complex PTSD are given appropriate therapy they should receive a course of emotion-regulation therapy such as the one tested by Zlotnick e.a. (1997) in a randomised controlled trial (RCT).   AIM: To replicate Zlotnick's RCT in the Netherlands and to find out whether complex PTSD patients show specific structural and functional brain abnormalities and whether psychological recovery is linked to the 'normalisation' of these abnormalities. METHOD: In a RCT with complex PTSD patients (n = 71) who had experienced trauma in early childhood, we compared normal individual treatment with treatment supported by 'Before and beyond', which consists of emotion-regulation therapy combined with cognitive group therapy. In a subsample (n= 33) we also performed an mri (repeated, n = 9) in which individuals were required to execute an emotional memory and attention task. RESULTS: In complex PTSD, structural abnormalities in the brain seemed to be more extensive than in PTSD and brain activity in complex PTSD seemed to be strikingly different from the brain activity seen in PTSD patients who had experienced only single trauma. The results of the RCT indicate that 'Before and beyond' is a clinically meaningful treatment (with minimal drop-out) for complex PTSD patients with a variety of personality disorders. The psychological recovery of patients who received the emotion regulation and cognitive group treatment was associated with normalisation of brain function. CONCLUSION: Treatment guidelines for ptsd patients cannot be applied directly and automatically to complex PTSD because there is no scientific evidence to justify such a step. The neurobiological profile of PTSD differs from that of complex PTSD. Patients with complex PTSD seem to react favourably to emotion regulation therapy. This treatment therefore could be a useful addition to the current PTSD guideline for this specific group. There is a need for further research that focuses on complex PTSD patients.

Effectiveness of the implementation of guidelines for anxiety disorders in specialized mental health care.

OBJECTIVE: To examine the effect of implementing anxiety disorders guidelines on guideline adherence and patient outcomes in specialized mental health care. METHOD: A treatment setting in which guidelines were implemented (intervention condition) was compared with one in which guidelines were only disseminated (control condition). RESULTS: Of 61.7% of 81 intervention-condition patients received treatment according to the guidelines vs. 40.6% of 69 control-condition patients (P = 0.01). At 1-year follow-up, intervention-condition patients showed a greater decrease in anxiety symptoms (d = 0.48, P < 0.05); higher percentages of response (52.6% vs. 33.8%; P = 0.025) and remission (33.3% vs.16.9%; P = 0.026); and a greater decrease in the rate of phobic avoidance (d = 0.34, P < 0.05). At 2-year follow-up, control-condition patients had experienced a longer period of treatment, which had eroded most of these differences, except for phobic avoidance. CONCLUSION: Systematic guideline implementation results in earlier gains and shorter treatment times.

[Anxiety, obsessive-compulsive disorder and trauma in the DSM-5]. / Angst, obsessieve-compulsieve stoornis en trauma in de DSM-5.

BACKGROUND: The 12 anxiety disorders which were defined in the DSM-IV, have been increased to 27 disorders in the DSM-5. These 27 disorders have been subdivided into three chapters: 1. anxiety disorders, 2. obsessive-compulsive and related disorders (OCRD) and 3. trauma and stressor-related disorders. AIM: To describe the most important differences between the DSM-IV and DSM-5 classifications of the above-mentioned disorders. METHOD: Survey of the relevant literature. RESULTS: Within the chapter on anxiety disorders in DSM-5 the classifications of 'panic disorder' and 'agoraphobia' have been separated. In addition, DSM-5 allows the specification 'with panic attacks' to be applied to all psychiatric disorders. New additions to the group ocrd are: 'trichotillomania' and 'body dysmorphic disorder'. Also newly added to the group are the new classifications 'excoriation disorder' and 'hoarding disorder'. The DSM-IV group of adjustment disorders has been merged with the group of stress disorders. In accordance with the system adopted elsewhere in DSM-5, the disorders which are 'usually first diagnosed in infancy, childhood and adolescence' and which resemble the disorders defined in the three chapters have been added to these chapters. Two extra categories are defined in each of the three chapters. CONCLUSION: The three chapters in DSM-5 are little more than a re-arrangement of the disorders defined in DSM-IV. The revision has not led to any clarification of or insight into the relationship between and the etiology of these disorders.

Age of onset in obsessive-compulsive disorder: admixture analysis with a large sample.

BACKGROUND: Research into age of onset in obsessive-compulsive disorder (OCD) has indicated significant differences between patients with early and late onset of the disorder. However, multiple criteria have been used arbitrarily for differentiating between early- and late-onset OCD, rendering inconsistent results that are difficult to interpret. METHOD: In the current study, admixture analysis was conducted in a sample of 377 OC patients to determine the number of underlying populations of age of onset and associated demographic and clinical characteristics. Various measures of anxiety, depression, co-morbidity, autism, OCD, tics and attention deficit hyperactivity disorder (ADHD) symptoms were administered. RESULTS: A bimodal age of onset was established and the best-fitting cut-off score between early and late age of onset was 20 years (early age of onset ≤19 years). Patients with early age of onset were more likely to be single. Early age of onset patients demonstrated higher levels of OCD severity and increased symptoms on all OCD dimensions along with increased ADHD symptoms and higher rates of bipolar disorder. CONCLUSIONS: It is suggested that 20 years is the recommended cut-off age for the determination of early versus late age of onset in OCD. Early age of onset is associated with a generally graver OCD clinical picture and increased ADHD symptoms and bipolar disorder rates, which may be related to greater functional implications of the disorder. We propose that age of onset could be an important marker for the subtyping of OCD.

Trajectories of functioning after remission from anxiety disorders: 2-year course and outcome predictors.

BACKGROUND: Anxiety disorders are associated with substantial functional limitations but the course of functioning following symptom remission remains largely unknown. METHOD: Using data from the Netherlands Study of Depression and Anxiety (NESDA), we examined the 2-year trajectories of functioning in participants with chronic (n = 586) or remitting anxiety disorders (n = 385) and in healthy controls (n = 585). In participants with remitting anxiety disorders, we identified predictors of functioning from among sociodemographic, clinical and vulnerability variables. Data were analysed using linear mixed models (LMMs). Functioning was assessed with the World Health Organization Disability Assessment Schedule II (WHO DAS II). RESULTS: At baseline, participants with remitting anxiety disorders functioned significantly better than those with chronic anxiety disorders, but significantly worse than controls. In both anxiety disorder groups, most impairment was reported in social functioning, occupational functioning and cognition. During the follow-up, functioning improved in both groups, probably due to treatments received. Participants who achieved symptom remission experienced moderate improvements in social functioning and cognition but not in occupational functioning. Of those who remitted, 45.8% reported functioning scores similar to healthy controls whereas 28.5% still functioned at the level of those with chronic anxiety disorders. Worse functioning was predicted by severe anxiety disorders, use of psychological treatment, co-morbid depressive disorders and maladaptive personality traits. CONCLUSIONS: In anxiety disorders, symptom remission is accompanied by improvements in functioning but significant functional impairments may persist because of co-morbid disorders, lower functioning prior to the onset of the anxiety disorder or residual subthreshold anxiety symptoms.

A brief cognitive-behavioral intervention for treating depression and panic disorder in patients with noncardiac chest pain: a 24-week randomized controlled trial.

BACKGROUND: Most patients with noncardiac chest pain experience anxiety and depressive symptoms. Commonly they are reassured and referred back to primary care, leaving them undiagnosed and untreated. Some small studies have suggested efficacy of 12 cognitive behavioral therapy (CBT) sessions. Our aim was to examine efficacy of brief CBT in reducing anxiety and depressive symptoms in patients with noncardiac chest pain and comorbid panic and/or depressive disorders. METHODS: In this 24-week randomized controlled trial comparing CBT (n = 60) versus treatment as usual (TAU, n = 53), we included all adults who presented at the cardiac emergency unit of a university hospital with noncardiac chest pain, scored ≥8 on the hospital anxiety and depression scale (HADS) and were diagnosed with a comorbid panic and/or depressive disorder with the Mini International Neuropsychiatric Interview. CBT consisted of six individual sessions. Main outcome was disease severity assessed with the clinical global inventory (CGI) by a blinded independent rater. RESULTS: ANCOVA in the intention-to-treat and completer sample showed that CBT was superior to TAU after 24 weeks in reducing disease severity assessed with CGI (P < .001). Secondary outcomes on anxiety (HADS-anxiety, state trait anxiety inventory (STAI)-trait) and depressive symptoms (Hamilton depression rating scale) were in line with these results except for HADS-depression (P = .10), fear questionnaire (P = .13), and STAI-state (P = .11). CONCLUSIONS: Brief CBT significantly reduces anxiety and depressive symptoms in patients with noncardiac chest pain who are diagnosed with panic and/or depressive disorders. Patients presenting with noncardiac chest pain should be screened for psychopathology and if positive, CBT should be considered.

An evaluation of irreversible psychosurgical treatment of patients with obsessive-compulsive disorder in the Netherlands, 2001-2008.

Admissions for irreversible psychosurgical treatment of obsessive-compulsive disorder (OCD) by the Working Group for Indication Psychosurgery in the Netherlands were analyzed, and the postsurgical effects on symptom severity and quality of life were evaluated. The data were extracted from patient records in the period 2001-2008, and there was a postoperative assessment with a semistructured interview. Fourteen patients applied, having severe OCD with mostly one or more comorbid disorders. The mean Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score was 32 points. Four of seven patients in whom psychosurgery was deemed useful were operated on. The decrease of the Y-BOCS score from registration to after surgery was 9 points (range, 3-17 points). An improvement in social function was present in three of four patients. In conclusion, psychosurgery can be a valuable treatment option for patients with severe OCD in whom other treatments fail.

[The characterisation of anxiety disorders: staging and profiling based on common sense]. / De karakterisering van angststoornissen: stageren en profileren met gezond verstand.

BACKGROUND: Clinicians need to be well informed about staging and profiling so that they can divide patients with anxiety disorders into groups according to the phase and severity of their illness. The group to which the patient is assigned determines the types of treatment he or she receives. AIM: To investigate ways in which clinicians can be helped to apply staging and profiling procedures to patients with anxiety disorders. METHOD: We searched the literature for articles about the staging and profiling of anxiety disorders. RESULTS: There seems to be practically no literature relating to the staging and profiling of anxiety disorders. However, in daily practice clinicians do attempt to classify their patients and use forms of staging when deciding on special types of treatment for their patients and when assessing the length of treatment required. The revised Dutch guidelines on anxiety disorders include a generalised form of staging, called 'stepped care’. These revisions have been made on the basis of consensus decisions reached by the guideline committee. CONCLUSION: The revised guidelines on anxiety disorders assist clinicians with the application of staging in their daily practice. However, because of the lack of scientific data, our article closes with the presentation of a research agenda.

The cardiac anxiety questionnaire: cross-validation among cardiac inpatients.

OBJECTIVE: General anxiety symptoms are common in patients with cardiac disease and considered to have an adverse effect on cardiac prognosis. The role of specific cardiac anxiety, however, is still unknown. The aim of this study is to examine the factor structure, reliability, and validity of the Dutch version of the Cardiac Anxiety Questionnaire (CAQ), which was specifically designed to assess heart focused anxiety. METHODS: Two hundred thirty-seven patients admitted for an acute coronary syndrome (ACS) and a control group of 49 patients admitted for an exacerbation of rheumatoid arthritis (RA) completed the CAQ, the Agoraphobic Cognitions Questionnaire, Mobility Inventory, Beck Depression Inventory, Beck Anxiety Inventory, and the State-Trait Anxiety Inventory. RESULTS: Although the original three-factor solution (fear, avoidance, and attention) was acceptable (model fit parameters: CFI = 0.89 and TLI = 0.87), our data were best explained by a four-factor model including safety seeking behaviors. Internal consistency and test-retest reliability were good. The CAQ had moderate correlations with the other anxiety and depression questionnaires. Recently admitted ACS patients had significantly higher scores than RA patients, even after controlling for general anxiety and depressive symptoms (p < 0.001). CONCLUSION: The CAQ is a reliable and valid instrument to assess cardiac anxiety in patients hospitalized with ACS. These results enable longitudinal studies to examine the relationship of heart-focused anxiety with cardiac prognosis and to evaluate interventions specifically targeted at anxiety in cardiac patients.

One-year follow up of cardiac anxiety after a myocardial infarction: a latent class analysis.

INTRODUCTION: Longitudinal elevated depressive symptom scores are associated with a less favorable cardiac outcome. Although anxiety has received less attention, meta-analysis suggests that high baseline levels of general anxiety might worsen cardiac outcome. The objective of this study was to explore the longitudinal course of cardiac anxiety after a myocardial infarction (MI). METHODS: The Cardiac Anxiety Questionnaire (CAQ) was administered to 194 patients hospitalized for MI after admission, and one, three, six and twelve months after discharge. Latent class growth analysis (LCGA) was performed to identify groups based on cardiac anxiety course. Between group differences were checked on relevant socio-demographic, cardiac and psychiatric variables. RESULTS: LCGA identified three groups with stable CAQ levels over time, indicative of high (7.7%), intermediate (45.4%) and low (30.4%) levels of cardiac anxiety, respectively. A fourth group (16.5%) reported high levels of cardiac anxiety that decreased over time. Between group differences were of particular interest for the two subgroups that started high in cardiac anxiety, since these may differentiate patients with spontaneous remission from those who might be in need of treatment. Patients in whom cardiac anxiety persisted were less often employed, had more diabetes mellitus, a history of acute coronary syndrome, depressive symptoms, anxiety and avoidance at baseline and a lower quality of life at follow-up. CONCLUSION: This first study addressing cardiac anxiety after an MI identified four trajectories. Future studies should focus on cardiac outcome and treatment strategies for cardiac anxiety in the subgroup with persistent high anxiety levels.