Heart rate variability: A biomarker of selective response to mindfulness-based treatment versus fluoxetine in generalized anxiety disorder.

BACKGROUND: Mindfulness-based interventions (MBIs) are effective for some, but not all patients with anxiety disorders, but no clinical features have been consistently able to differentiate which patients are more likely to respond. In this study, we tested heart rate variability (HRV), a proposed correlate of regulated emotional response, as a moderator of treatment response to an MBI compared with pharmacotherapy. METHODS: Seventy-seven patients with GAD had HRV data collected before randomization to pharmacological treatment with fluoxetine or Body-in-Mind Training (an MBI focused on bodily movement attention). HRV was used to predict treatment response measured by the Hamilton anxiety rating scale at 0 (baseline), 5, and 8 weeks (end of the intervention). RESULTS: The HF (nu) index of HRV was a strong moderator of treatment response between BMT and fluoxetine (estimate = 4.27 95%CI [1.19, 8.19]). Although fluoxetine was overall slightly superior to BMT in this study, no differences were found between groups in patients with high HF (nu) scores (estimate = -1.85 CI95% [-9.21, 5.52]). In contrast, patients with low HF (nu) achieved lower anxiety rating scores with fluoxetine treatment when compared with BMT (estimate = -10.29, 95% CI [-17.59, -2.99]). LIMITATIONS: A relatively small sample of patients was included. CONCLUSIONS: HRV was able to identify a subgroup for which MBI was less effective than pharmacotherapy and is a promising candidate as a selective biomarker for treatment response between an MBI and fluoxetine.

Heart rate variability as a predictor of improvement in emotional interference in Generalized Anxiety Disorder.

BACKGROUND: Generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders but the least successfully treated. The search for accessible clinical, psychological and biological markers is crucial for developing more effective and personalized interventions. AIMS: To evaluate if changes in heart rate variability (HRV) between rest and stress conditions before interventions could predict improvement in emotional interference (EI) in a cognitive task after three different treatment modalities in patients with GAD. METHOD: This is a post-hoc analysis study reporting data from a larger randomized controlled trial (NCT03072264) assessing a mindfulness-based intervention (BMT), fluoxetine (FLX), and an active comparison group (QoL) in adult patients diagnosed with GAD. We assessed pulse plethysmography (PPG) data using a Shimmer3 GSR to measure HRV. Regression analyses were performed using the variation between baseline and endpoint EI scores as dependent variables and contrasts considering changing in HRV*group interaction in the baseline. RESULTS: 106 individuals were included. The correlations between HRV changing from rest to task predicted improvement in IE only in the FLX versus control group contrast (estimated = -80.24; SE = 27.31; p = 0.005) and not in the BMT and control group contrast. CONCLUSION: More flexible HRV at baseline predicted EI improvement only in the FLX group. This finding is clinically relevant since it may help us develop more personalized interventions for GAD.

Panic attack provocation in panic disorder patients with a computer simulation.

BACKGROUND: Computer simulations (CS) and virtual reality exposure are promising techniques for research and treatment of panic disorder with agoraphobia (PDA). The objective of this study was to ascertain whether a given CS was a stimulus capable of producing panic attacks (PAs), anxiety and psychophysiological changes in patients with PDA. METHODS: Thirty PDA patients and 30 healthy subjects were recruited for this study. Subjects were exposed to a 3-min CS of a situation relevant to agoraphobic patients. Anxiety, panic symptoms, PAs, heart rate, skin conductance and respiration were recorded before, during and after the CS exposure. RESULTS: The CS effectively induced anxiety, hyperventilation and electrodermal responses in PDA patients but not in healthy subjects. Forty percent of PDA patients had a PA while none of the control subjects had a PA. A subgroup of patients who were less sensitive to the CS than the other subgroup of PDA patients and did not present full-blown PAs still had more panic symptoms, higher anxiety levels and more respiratory irregularities than the controls. LIMITATIONS: Low immersion and low sense of presence, lack of interaction with the environment. CONCLUSIONS: Exposure to the CS produced effects similar to in vivo exposure, respiratory and caffeine challenges. Subsequent studies should: make direct comparisons between CS and other challenges for PDA; investigate if CS can be a tool for predicting effects of medication; determine the potential of CS as a desensitization technique for situational PAs.

Negative Affect Mediates Impulsivity in Generalized Anxiety Disorder.

INTRODUCTION: Although anxiety and impulsivity are intuitively thought to be inversely correlated, increased impulsivity has been associated both with generalized anxiety disorder (GAD) diagnosis and GAD symptoms in non-clinical samples. The emotional dysregulation model of GAD posits that patients experience more frequent and intense negative emotions while having poor regulatory control over emotional states and greater negative reactivity to their emotions. We hypothesized that poor regulatory control in the presence of negative emotions might explain the increased impulsivity found in GAD patients. In this study, we examined if negative affect mediates the relationship between GAD and impulsivity. METHODS: Thirty-four GAD patients and 35 healthy controls were included, and evaluated with measurements of impulsivity, negative and positive emotions, the severity of worrying and GAD symptoms, depression, and 5-factor personality traits. RESULTS: Global impulsivity scores and the attentional facet of impulsivity were higher in the patient group when compared to the controls. Negative affect was correlated with global impulsivity in the patient group only and explained impulsivity in our regression model while worrying and depressive symptoms did not. An indirect relationship was found between diagnosis and impulsivity through negative affect. CONCLUSION: Our study showed that the cardinal symptom of GAD - worrying - was not independently related to impulsivity in our sample. Increased impulsivity in GAD seems to be mediated by the increased presence of negative emotions, as it is common in mood and impulse-control disorders, indicating an unspecific shared vulnerability factor to psychopathology.

Tranylcypromine Plus Amitriptyline for Electroconvulsive Therapy-Resistant Depression: A Long-Term Study.

BACKGROUND: Few therapeutic options are available for patients with electroconvulsive therapy-resistant major depressive disorder (ECT-r MDD), leaving a substantial proportion of this population beyond treatment possibilities. The combination of monoamine oxidase inhibitors and tricyclic antidepressants could be a potential strategy for managing ECT-r MDD, and the specific association of amitriptyline and tranylcypromine may offer additional tolerability advantages. Although promising, in our knowledge, no studies have examined until now the effectiveness of this combination in ECT-r MDD. METHODS: We report a retrospective cohort of 31 patients with ECT-r MDD treated in an open-label fashion with the combination of amitriptyline and tranylcypromine. RESULTS: Overall, 80.6% of the sample met response criteria at the end of the first 12 weeks of treatment. Seventy-six percent (19 of 25) of the responders were followed for a mean of 9.37 ± 3.86 years. During this follow-up period, none of the patients had a recurring depressive episode. The combination was well tolerated, whereas minor adverse effects were common, and no severe or life-threatening events were reported throughout the study. CONCLUSIONS: These findings indicate that the combination tranylcypromine and amitriptyline is a potentially safe and effective candidate for future investigation in the treatment and long-term maintenance of ECT-r MDD.

Predictors of Pharmacotherapy Response in Generalized Anxiety Disorder: A Systematic Review.

BACKGROUND: Pharmacotherapy for generalized anxiety disorder (GAD) may be effective in reducing symptoms in the majority of patients. The study of moderators and predictors of treatment response may help clinicians both to select appropriate interventions to maximize the probability of response and to inform the general prognosis. METHODS: A systematic literature search of electronic databases, selected authors, and reference lists was used to identify articles that reported trials of drug monotherapy in GAD. Data on predictors and moderators were extracted. Quality of evidence was determined by the presence of a priori hypotheses, number of variables investigated, adequate quality of the measurement, and use of interaction-effects testing. RESULTS: From the 98 articles meeting inclusion criteria, 24 reported a total of 22 factors associated with treatment response. The reported results were heterogeneous, ranging over sociodemographic, clinical, comorbidity, genetic, and functional-imaging studies. Major depressive symptoms were found to moderate treatment outcome in favor of antidepressants versus benzodiazepines. Neuroticism, previous treatment, genetic polymorphisms (including serotonin receptor gene 2A), and functional activation of the anterior cingulate cortex and amygdala were identified as potential predictors of treatment response. CONCLUSIONS: Correlates of poor emotion regulation predicted poor treatment response, but subclinical depression was the only variable capable of informing treatment selection in this review. Future research should focus on further exploring the value of depression as a moderator and on a narrower list of potential genetic, brain-imaging, and temperament predictors of response to pharmacotherapy in GAD.

Pathological generosity: an atypical impulse control disorder after a left subcortical stroke.

Changes in socio-emotional behavior and conduct, which are characteristic symptoms of frontal lobe damage, have less often been described in patients with focal subcortical injuries. We report on a case of pathological generosity secondary to a left lenticulocapsular stroke with hypoperfusion of several anatomically intact cortical areas. A 49-year-old man developed excessive and persistent generosity as he recovered from a left lenticulocapsular hematoma. His symptoms resembled an impulse control disorder. (99m)Tc-HMPAO SPECT demonstrated hypoperfusion mostly in the ipsilateral striatum, dorsolateral, and orbitofrontal cortex. This case study adds pathological generosity to the range of behavioral changes that may result from discrete unilateral lesions of the lenticular nucleus and nearby pathways. In our particular case, post-stroke pathological generosity was not ascribable to disinhibition, apathy, mania, or depression. Because pathological generosity may lead to significant distress and financial burden upon patients and their families, it may warrant further consideration as a potential type of impulse control disorder.

'Impulsive compulsivity' in obsessive-compulsive disorder: a phenotypic marker of patients with poor clinical outcome.

Although traditionally obsessive-compulsive disorder (OCD) and impulse control disorders (ICD) have represented opposing ends of a continuum, recent research has demonstrated a frequent co-occurrence of impulsive and compulsive behaviours, which may contribute to a worse clinical picture of some psychiatric disorders. We hypothesize that individuals with 'impulsive' OCD as characterized by poor insight, low resistance, and reduced control towards their compulsions will have a deteriorative course, greater severity of hoarding and/or symmetry/ordering symptoms, and comorbid ICD and/or substance use disorders (SUD). The sample consisted of 869 individuals with a minimum score of 16 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Of these, 65 had poor insight, low resistance, and reduced control towards compulsions ('poor IRC') and 444 had preserved insight, greater resistance and better control over compulsions ('good IRC'). These two groups were compared on a number of clinical and demographic variables. Individuals with poor IRC were significantly more likely to have a deteriorative course (p < 0.001), longer duration of obsessions (p = 0.017), greater severity of symmetry/ordering (p < 0.001), contamination/cleaning (p < 0.001) and hoarding (p = 0.002) symptoms, and comorbid intermittent explosive disorder (p = 0.026), trichotillomania (p = 0.014) and compulsive buying (p = 0.040). Regression analysis revealed that duration of obsessions (p = 0.037) and hoarding severity (p = 0.005) were significant predictors of poor IRC. In the absence of specific measures for impulsivity in OCD, the study highlights the utility of simple measures such as insight, resistance and control over compulsions as a phenotypic marker of a subgroup of OCD with impulsive features demonstrating poor clinical outcome.

Dementia developing in late-onset and treatment-refractory obsessive-compulsive disorder.

BACKGROUND: Although several studies have been conducted in an attempt to characterize the phenotype and underlying pathophysiology of individuals with early-onset obsessive-compulsive disorder (OCD), the literature on patients who develop OCD later in life remains sparse. OBJECTIVE: To describe clinical outcomes in the 7-year follow-up of a patient with late-onset OCD. METHOD: Single case report. RESULTS: A 64-year-old woman exhibiting a 7-year history of treatment-refractory late-onset OCD developed significant cognitive deterioration. We suggest that the association between late-onset treatment refractory OCD and dementia may stem from at least 3 different scenarios. First, dementia may be an inexorable end-point of some forms of malignant, primary, and late-onset obsessional illness. Second, late-onset OCD and dementia may result from a common pathophysiologic basis, such as in fronto-temporal dementia. Finally, the association between both conditions may result by the interaction between vulnerability toward OCD-type symptoms and the nonspecific effects of a neurodegenerative process. In our case, although subclinical OCD was likely to be "unmasked" by cognitive decline and/or bilateral caudate vascular lesions, ensuing cognitive deterioration could be ascribed to development of Alzheimer dementia. CONCLUSION: Our observation suggests that treatment refractoriness in an individual with late-onset OCD may indicate underlining organicity.