Breathing-focused Yoga as Augmentation for Unipolar and Bipolar Depression: A Randomized Controlled Trial: Le yoga axé sur la respiration comme traitement d'appoint pour la dépression unipolaire et bipolaire: Un essai randomisé contrôlé.

OBJECTIVE: Patients with depression frequently experience persistent residual symptoms even with optimal interventions. These patients often use complementary treatments, including yoga, as a preferred alternative or adjunctive treatment. There is evidence for the benefit of yoga for depression, but this has not been rigorously evaluated, particularly in bipolar depression. We aimed to determine the feasibility and benefit of manualized breathing-focused yoga in comparison to psychoeducation as augmentation to pharmacotherapy for improving residual symptoms of depression in unipolar and bipolar patients. METHODS: Using a randomized single-blind crossover design, 72 outpatients with unipolar or bipolar depression were augmented with the two 8-week interventions at separate times, as add-ons to current first-line antidepressants and mood stabilizers. The primary outcome measure was the Montgomery-Åsberg Depression Rating Scale (MADRS). Due to the high dropout of participants after crossover at Week 8, analysis focused on between-group comparisons of yoga and psychoeducation during the initial 8 weeks of the study. RESULTS: There was a significant decline in depressive symptoms, as measured by the MADRS, following 8 weeks of yoga. However, there was no significant difference in MADRS ratings between intervention groups. Similar improvements in self-rated depressive symptoms and well-being were also observed across time. CONCLUSIONS: Both yoga and psychoeducation may improve residual symptoms of unipolar and bipolar depression as add-on to medications. In-class group sessions and long study durations may reduce feasibility for this population. Larger trials with parallel group design and shorter duration may be more feasible.

Functional connectivity in obsessive-compulsive disorder and its subtypes.

BACKGROUND: Obsessive-compulsive disorder (OCD) is an anxiety disorder with significant morbidity whose pathophysiology is not fully understood. Neuroimaging studies have characterized OCD in terms of elevated striatal and prefrontal reactivity to emotion provocation. This neural model may be informed by investigation of functional connectivity in OCD, identifying alterations in how sensory information is integrated into frontostriatal regions. METHODS: The current study employed functional magnetic resonance imaging (fMRI) to compare neural activity and connectivity in 31 OCD patients (12 washing and 19 checking subtypes) and 17 healthy volunteers in an emotion provocation paradigm using visual stimuli. RESULTS: OCD status was associated with hyper-activation of the posterior cingulate (PCg) in response to emotion provocation. Additionally, OCD patients demonstrated elevated PCg functional connectivity with the visual cortices and frontostriatal regions. Exploratory analyses suggested that stimulus-provoked activity and connectivity was elevated for checking subtypes in motor cortices, and elevated in washing subtypes in the anterior insula and orbitofrontal cortex. CONCLUSIONS: The PCg's role in moderating connectivity between the visual cortex and frontolimbic regions is muted in OCD, consistent with the PCg's suggested role in regulating attention towards emotional stimuli. Exploratory analyses suggest distinct PCg connectivity profiles in OCD subtypes, with checking linked to motor activation, but washing linked to a network supporting emotional salience. The study was not powered to fully investigate the effects of medication, patients often endorsed secondary symptom subtypes that muddied washing/checking distinctions, and the emotion provocation paradigm was of limited intensity compared to life stressors.

Cognitive change in cognitive-behavioural therapy v. pharmacotherapy for adult depression: a longitudinal mediation analysis.

BACKGROUND: Although cognitive-behavioural therapy (CBT) is a well-established treatment for adult depression, its efficacy and efficiency may be enhanced by better understanding its mechanism(s) of action. According to the theoretical model of CBT, symptom improvement occurs via reductions in maladaptive cognition. However, previous research has not established clear evidence for this cognitive mediation model. METHODS: The present study investigated the cognitive mediation model of CBT in the context of a randomized controlled trial of CBT v. antidepressant medication (ADM) for adult depression. Participants with major depressive disorder were randomized to receive 16 weeks of CBT (n = 54) or ADM (n = 50). Depression symptoms and three candidate cognitive mediators (dysfunctional attitudes, cognitive distortions and negative automatic thoughts) were assessed at week 0 (pre-treatment), week 4, week 8 and week 16 (post-treatment). Longitudinal associations between cognition and depression symptoms, and mediation of treatment outcome, were evaluated in structural equation models. RESULTS: Both CBT and ADM produced significant reductions in maladaptive cognition and depression symptoms. Cognitive content and depression symptoms were moderately correlated within measurement waves, but cross-lagged associations between the variables and indirect (i.e. mediated) treatment effects were non-significant. CONCLUSIONS: The results provide support for concurrent relationships between cognitive and symptom change, but not the longitudinal relationships hypothesized by the cognitive mediation model. Results may be indicative of an incongruence between the timing of measurement and the dynamics of cognitive and symptom change.

The Effect of Intravenous Citalopram on the Neural Substrates of Obsessive-Compulsive Disorder.

This study investigated the effect of an intravenous serotonin reuptake inhibitor on the neural substrates of obsessive-compulsive disorder (OCD), as intravenous agents may be more effective in treating OCD than conventional oral pharmacotherapy. Eight OCD subjects and eight control subjects received alternate infusions of citalopram and placebo during functional magnetic resonance imaging, in a randomized, symptom-provocation, crossover design. Compared with baseline, OCD subjects displayed significant changes in prefrontal neural activity after the citalopram infusion relative to placebo, and these changes correlated with reductions in subjective anxiety.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 5. Complementary and Alternative Medicine Treatments.

BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. METHODS: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Complementary and Alternative Medicine Treatments" is the fifth of six sections of the 2016 guidelines. RESULTS: Evidence-informed responses were developed for 12 questions for 2 broad categories of complementary and alternative medicine (CAM) interventions: 1) physical and meditative treatments (light therapy, sleep deprivation, exercise, yoga, and acupuncture) and 2) natural health products (St. John's wort, omega-3 fatty acids; S-adenosyl-L-methionine [SAM-e], dehydroepiandrosterone, folate, Crocus sativus, and others). Recommendations were based on available data on efficacy, tolerability, and safety. CONCLUSIONS: For MDD of mild to moderate severity, exercise, light therapy, St. John's wort, omega-3 fatty acids, SAM-e, and yoga are recommended as first- or second-line treatments. Adjunctive exercise and adjunctive St. John's wort are second-line recommendations for moderate to severe MDD. Other physical treatments and natural health products have less evidence but may be considered as third-line treatments. CAM treatments are generally well tolerated. Caveats include methodological limitations of studies and paucity of data on long-term outcomes and drug interactions.

Inhibition of the cortex using transcranial magnetic stimulation in psychiatric populations: current and future directions.

Several lines of evidence suggest that deficits in γ-aminobutyric acid (GABA) inhibitory neurotransmission are implicated in the pathophysiology of schizophrenia, bipolar disorder, major depressive disorder and obsessive-compulsive disorder. Cortical inhibition refers to a neurophysiological process, whereby GABA inhibitory interneurons selectively attenuate pyramidal neurons. Transcranial magnetic stimulation (TMS) represents a noninvasive technique to measure cortical inhibition, excitability and plasticity in the cortex. These measures were traditionally specific to the motor cortex, which is an important limitation when nonmotor neurophysiological processes are of primary interest. Recently, TMS has been combined with electro encephalography (EEG) to derive such measurements directly from the cortex. This review focuses on neurophysiological studies related to inhibitory and excitatory TMS paradigms, linking dysfunctional GABAergic neurotransmission to disease states. We review evidence that suggests cortical inhibition deficits among psychiatric populations and demonstrate how each disorder has a specific neurophysiological response to treatment. We conclude by discussing the future directions of TMS combined with EEG, demonstrating the potential to identify biological markers of neuropsychiatric disorders.

Effects of anxiolytic treatment on potentiated startle during aversive image anticipation.

OBJECTIVE: Heightened anticipation of future events has been characterized as a feature of certain anxiety disorders. In functional magnetic resonance imaging studies, anticipation of fearful/threatening images has been shown to robustly activate the insular cortex and amygdala in healthy subjects, in subjects with high trait anxiety, and in some with anxiety disorders. Blood oxygenation level dependent activation in response to negative image anticipation is also sensitive to anxiolytic treatment, suggesting that image anticipation probes anxiety systems. It is not clear, however, if behavioral responses to image anticipation are also sensitive to anxiolytics. This study tested the hypothesis that anxiety behaviors during anticipation of negative images are sensitive to anxiolytic treatment. METHOD: This study examined the effects of alprazolam and pregabalin treatment on potentiated startle during affective image anticipation. RESULTS: There was an effect of anticipation type (negative versus neutral versus positive) on startle reactivity and subjective ratings, suggesting that the task was effective in assaying negative anticipatory arousal. Both treatments significantly reduced overall startle magnitude. However, neither treatment specifically affected potentiated startle during aversive anticipation. CONCLUSION: These data suggest that potentiated startle in response to anticipation of aversive images is not sensitive to anxiolytic treatments in a healthy population, limiting its use as a predictive model of anxiolytic activity. This article is a US Government work and is in the public domain in the USA.

The relationship between testosterone and sexual function in depressed and healthy men.

AIM: Men with Major Depressive Disorder (MDD) report high rates of sexual dysfunction, as do healthy males with low levels of testosterone. The objective of this study is to evaluate the effects of depression and low testosterone across various domains of sexual function. METHODS: Untreated depressed males (N = 44) and age-matched healthy controls (N = 50) had blood samples drawn to determine morning levels of total testosterone (TT) and bioavailable testosterone (BT). In addition, questionnaires regarding depressive symptoms as well as sexual function were administered. MAIN OUTCOME MEASURES: Sexual function outcomes were measured using the Sex Effects (SexFX) Scale and depression severity was assessed with the Hamilton Rating Scale for Depression-17 item (HAMD-17). RESULTS: Using TT criteria, 27.9% of men were categorically defined as hypogonadal compared to 19.3% using BT criteria. Within both TT and BT hypogonadal groups, men with MDD had lower scores on all domains of sexual function compared to healthy controls with hypogonadism. Testosterone levels interacted with MDD status to affect orgasm and desire, although not arousal. Multiple linear regression analyses revealed that depression status was the main factor influencing sexual function. Hypogonadal status was not a predictor of sexual function in this sample, although age did play a minor role in the domain of arousal. CONCLUSION: While testosterone levels appear to influence sexual function, specifically orgasm, the presence of MDD appears to be a stronger factor and has high predictive value for sexual outcomes.

A randomized controlled trial of atomoxetine in generalized social anxiety disorder.

The current mainstays of social anxiety disorder pharmacotherapy are serotonergic agents, with less known about the efficacy of more noradrenergic drugs. Atomoxetine (ATM), a highly selective norepinephrine reuptake inhibitor, is currently approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). We describe the first controlled trial of ATM with respect to efficacy and tolerability in adults with the generalized subtype of social anxiety disorder (GSAD) without comorbid ADHD. Twenty-seven outpatients with clinically prevailing diagnoses of GSAD by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized in a 1:1 ratio to 10 weeks of double-blind flexible-dose treatment with either ATM 40-100 mg per day (n = 14) or placebo (n = 13). Primary efficacy outcome was score at end point on the Liebowitz Social Anxiety Scale in the intention-to-treat sample. There were no significant group differences in patients completing the study (ATM, 79%; placebo, 77%). Whereas ATM was well tolerated, there were no significant differences in clinical efficacy between ATM and placebo for GSAD. There were few responders overall (ATM, 21%; placebo, 33%), but proportions were similar in each group (chi [1, 26] = 0.47; P = 0.67). Analysis of variance with repeated measures on the Liebowitz Social Anxiety Scale was performed to detect any differential change in social anxiety symptoms between groups. A significant time effect was found (F = 8.71; P = 0.007), but the time-by-treatment interaction was nonsignificant (F = 0.013; P = 0.91). Although the small sample size limits confidence in the reported results, the comparable, and low, response rates for ATM and placebo suggest that in the absence of comorbid ADHD, ATM is unlikely to be an effective agent for the treatment of GSAD.

The role of outcome expectancy in therapeutic change across psychotherapy versus pharmacotherapy for depression.

BACKGROUND: Patient outcome expectancy - the belief that treatment will lead to an improvement in symptoms - is linked to favourable therapeutic outcomes in major depressive disorder (MDD). The present study extends this literature by investigating the temporal dynamics of expectancy, and by exploring whether expectancy during treatment is linked to differential outcomes across treatment modalities, for both optimistic versus pessimistic expectancy. METHODS: A total of 104 patients with MDD were randomized to receive either cognitive behavioral therapy (CBT) or pharmacotherapy for 16 weeks. Outcome expectancy was measured throughout treatment using the Depression Change Expectancy Scale (DCES). Depression severity was measured using both the Hamilton Depression Rating Scale and Beck Depression Inventory-II. RESULTS: Latent growth curve models supported improvement in expectancy across both treatments. Cross-lagged panel models revealed that both higher optimistic and lower pessimistic expectancy at mid-treatment predicted greater treatment response in pharmacotherapy. For CBT, the associative patterns between expectancy and depression differed as a function of expectancy type; higher optimistic expectancy at pre-treatment and lower pessimistic expectancy at mid-treatment predicted greater treatment response. LIMITATIONS: The sample size limited statistical power and the complexity of models that could be explored. CONCLUSIONS: Results suggest that outcome expectancy improved during treatment for depression. Whether outcome expectancy represents a specific mechanism for the reduction of depression warrants further investigation.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 5. Complementary and Alternative Medicine Treatments.

(Reprinted by permission of SAGE Publications, Inc., from The Canadian Journal of Psychiatry 2016; 61:576-587. Copyright © 2016 by the Authors [https://doi.org/10.1177/0706743716660290]).

Lamotrigine in the treatment of recurrent brief depression.

Recurrent brief depression is a well-recognized subtype of depressive illness with brief episodes of depression alternating with periods of euthymia. The symptoms are often severe, with frequent association to suicidal ideation. Literature suggests frequent nonresponse to first-line antidepressants. Lamotrigine is an anticonvulsant with antidepressant properties, and reported effectiveness in bipolar depression. We report on two patients with recurrent brief depression, nonresponsive to selective serotonin reuptake inhibitors and venlafaxine, and who responded to therapeutic doses of lamotrigine.

Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder.

Importance: For a small percentage of obsessive-compulsive disorder (OCD) cases exhibiting additional neuropsychiatric symptoms, it was proposed that neuroinflammation occurs in the basal ganglia as an autoimmune response to infections. However, it is possible that elevated neuroinflammation, inducible by a diverse range of mechanisms, is important throughout the cortico-striato-thalamo-cortical circuit of OCD. Identifying brain inflammation is possible with the recent advance in positron emission tomography (PET) radioligands that bind to the translocator protein (TSPO). Translocator protein density increases when microglia are activated during neuroinflammation and the TSPO distribution volume (VT) is an index of TSPO density. Objective: To determine whether TSPO VT is elevated in the dorsal caudate, orbitofrontal cortex, thalamus, ventral striatum, dorsal putamen, and anterior cingulate cortex in OCD. Design, Setting, and Participants: This case-control study was conducted at a tertiary care psychiatric hospital from May 1, 2010, to November 30, 2016. Participants with OCD (n = 20) and age-matched healthy control individuals (n = 20) underwent a fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide PET scan. It is a high-quality second-generation TSPO-binding PET radiotracer. All participants were drug and medication free, nonsmoking, and otherwise healthy. Main Outcomes and Measures: The TSPO VT was measured in the dorsal caudate, orbitofrontal cortex, thalamus, ventral striatum, dorsal putamen, and anterior cingulate cortex. Compulsions were assessed with the Yale-Brown Obsessive Compulsive Scale. Results: In the OCD and healthy groups, the mean (SD) ages were 27.4 (7.1) years and 27.6 (6.6) years, respectively, and 11 (55%) and 8 (40%) were women, respectively. In OCD, TSPO VT was significantly elevated in these brain regions (mean, 32%; range, 31%-36% except anterior cingulate cortex, 24%; analysis of variance, effect of diagnosis: P < .001 to P = .004). Slightly lower elevations in TSPO VT (22%-29%) were present in other gray matter regions. The Yale-Brown Obsessive Compulsive Scale measure of distress associated with preventing compulsive behaviors significantly correlated with TSPO VT in the orbitofrontal cortex (uncorrected Pearson correlation r = 0.62; P = .005). Conclusions and Relevance: To our knowledge, this is the first study demonstrating inflammation within the neurocircuitry of OCD. The regional distribution of elevated TSPO VT argues that the autoimmune/neuroinflammatory theories of OCD should extend beyond the basal ganglia to include the cortico-striato-thalamo-cortical circuit. Immunomodulatory therapies should be investigated in adult OCD, rather than solely childhood OCD, particularly in cases with prominent distress when preventing compulsions.

The effect of bupropion XL and escitalopram on memory and functional outcomes in adults with major depressive disorder: results from a randomized controlled trial.

Decrements in cognitive function are a common feature of Major Depressive Disorder (MDD), and whether distinct classes of antidepressants differentially affect memory in these individuals has not been sufficiently evaluated. In this study we sought to determine the effect of escitalopram and bupropion XL on memory and psychosocial function. Forty-one individuals (18-50 years) with MDD were enrolled in an 8-week, double-blind, double-dummy, randomized controlled comparative trial of bupropion XL and escitalopram. Thirty-six participants completed pre and post memory assessments. Verbal, non-verbal and working memory were evaluated with a comprehensive neuropsychological battery. Psychosocial function was assessed with the Sheehan Disability Scale and Endicott Work Productivity Scale. Escitalopram and bupropion XL significantly improved immediate as well as delayed verbal and nonverbal memory, global function (all p≤0.001), and work productivity (p=0.045), with no significant between-group differences. Improvement in immediate verbal memory exerted a direct influence on improvement in global function (p=0.006). Treatment with either escitalopram or bupropion XL was associated with improvement in memory and psychosocial function in adults with MDD.

Paroxetine in the treatment of dysthymic disorder without co-morbidities: A double-blind, placebo-controlled, flexible-dose study.

Few published studies have evaluated selective serotonin reuptake inhibitors in dysthymia without current co-morbid major depression. In this 12-week study, 40 dysthymic patients were randomly assigned to either placebo (n=19) or 20-40 mg/day of paroxetine (n=21). At endpoint, the paroxetine group showed significantly greater improvement on the Clinical Global Impression Scale, Beck Depression Inventory, and Quality of Life Enjoyment and Satisfaction Questionnaire (p<0.05), and a trend to superiority over placebo on the Hamilton Depression Rating Scale. Response and remission were significantly higher with paroxetine than placebo (p<0.05). There were no significant differences in drop out rates or frequency of adverse effects, except for excessive sweating (greater with paroxetine, p=0.04). Reporting of multiple side effects was also higher with paroxetine than with placebo (p=0.02). Paroxetine is more effective than placebo in improving symptoms and quality of life in dysthymia, and is generally tolerable.

A meta-analysis of cortical inhibition and excitability using transcranial magnetic stimulation in psychiatric disorders.

OBJECTIVE: To evaluate transcranial magnetic stimulation (TMS) measures of inhibition and excitation in obsessive-compulsive disorder (OCD), major depressive disorder (MDD) and schizophrenia (SCZ). METHODS: Paradigms included: short-interval cortical inhibition (SICI), cortical silent period (CSP), resting motor threshold, intracortical facilitation, and motor evoked potential amplitude. A literature search was performed using PubMed, Ovid Medline, Embase Psychiatry and PsycINFO 1990 through April 2012. RESULTS: A significant Hedge's g was found for decreased SICI (g=0.572, 95% confidence interval [0.179, 0.966], p=0.004), enhanced intracortical facilitation (g=0.446, 95% confidence interval [0.042, 0.849], p=0.030) and decreased CSP (g=-0.466, 95% confidence interval [-0.881, -0.052], p=0.027) within the OCD population. For MDD, significant effect sizes were demonstrated for decreased SICI (g=0.641, 95% confidence interval [0.384, 0.898], p=0.000) and shortened CSP (g=-1.232, 95% confidence interval [-1.530, -0.933], p=0.000). In SCZ, a significant Hedge's g was shown for decreased SICI (g=0.476, 95% confidence interval [0.331, 0.620], p=0.000). CONCLUSION: Inhibitory deficits are a ubiquitous finding across OCD, MDD, SCZ and enhancement of intracortical facilitation is specific to OCD. SIGNIFICANCE: Provides a clear platform from which diagnostic procedures can be developed.

Evidence for cortical inhibitory and excitatory dysfunction in obsessive compulsive disorder.

Several lines of evidence suggest that obsessive-compulsive disorder (OCD) is associated with an inability to inhibit unwanted intrusive thoughts. The neurophysiological mechanisms mediating such inhibitory deficits include abnormalities in cortical γ-aminobutyric acid (GABA) inhibitory as well as N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms. Molecular evidence suggests that both these neurotransmitter systems are involved in OCD. Transcranial magnetic stimulation (TMS) represents a noninvasive technique to ascertain neurophysiological indices of inhibitory GABA and facilitatory NMDA receptor-mediated mechanisms. In this study, both mechanisms were indexed in 34 patients with OCD (23 unmedicated and 11 medicated) and compared with 34 healthy subjects. Cortical inhibitory and facilitatory neurotransmission was measured using TMS paradigms known as short-interval cortical inhibition (SICI), cortical silent period (CSP), and intracortical facilitation (ICF). Patients with OCD demonstrated significantly shortened CSP (p<0.001, Cohen's d=0.91) and increased ICF (p<0.009, Cohen's d=0.71) compared with healthy subjects. By contrast, there were no significant deficits in SICI. After excluding patients with OCD and comorbid major depressive disorder (MDD) from the analysis, these differences remained significant. Our findings suggest that OCD is associated with dysregulation in cortical inhibitory and facilitatory neurotransmission. Specifically, these findings suggest impairments in GABA(B) receptor-mediated and NMDA receptor-mediated neurotransmission. These findings are consistent with previously published genetic studies implicating GABA(B), and NMDA transporter and receptor genes in OCD. It is posited that dysregulation of such mechanisms may lead to the generation and persistence of intrusive thoughts that form the basis for this disorder.

Pregabalin effects on neural response to emotional faces.

Pregabalin has shown promise in the treatment of anxiety disorders. Previous functional magnetic resonance imaging (fMRI) studies indicate agents used to treat anxiety, e.g., SSRIs and benzodiazepines, attenuate amygdala, insula, and medial prefrontal cortex (mPFC) activation during emotional processing. Our prior study has shown that during anticipation of an emotional stimulus, pregabalin attenuates amygdala and insula activation but increases medial PFC activation. In this study, we examined whether, similar to SSRIs and benzodiazepines, pregabalin attenuates amygdala, insula, and medial PFC during emotional face processing. Sixteen healthy volunteers underwent a double-blind within-subjects fMRI study investigating effects of placebo, 50 mg, and 200 mg pregabalin on neural activation during an emotional face-matching task. Linear mixed model analysis revealed that pregabalin dose-dependently attenuated left amygdala activation during fearful face-matching and left anterior insula activation during angry face-matching. The 50 mg dose exhibited more robust effects than the 200 mg dose in the right anterior insula and ventral ACC. Thus, pregabalin shares some similarity to SSRIs and benzodiazepines in attenuating anger and fear-related insula and amygdala activation during emotional face processing. However, there is evidence that a subclinical 50 mg dose of pregabalin produced more robust and widespread effects on neural responses in this paradigm than the more clinically relevant 200 mg dose. Taken together, pregabalin has a slightly different effect on brain activation as it relates to anticipation and emotional face processing, which may account for its unique characteristic as an agent for the treatment of anxiety disorders.

Pregabalin influences insula and amygdala activation during anticipation of emotional images.

Pregabalin (PGB) has shown potential as an anxiolytic for treatment of generalized and social anxiety disorder. PGB binds to voltage-dependent calcium channels, leading to upregulation of GABA inhibitory activity and reduction in the release of various neurotransmitters. Previous functional magnetic resonance imaging (fMRI) studies indicate that selective serotonin reuptake inhibitors and benzodiazepines attenuate amygdala, insula, and medial prefrontal cortex activation during anticipation and emotional processing in healthy controls. The aim of this study was to examine whether acute PGB administration would attenuate activation in these regions during emotional anticipation. In this double-blind, placebo-controlled, randomized crossover study, 16 healthy controls completed a paradigm involving anticipation of negative and positive affective images during fMRI approximately 1 h after administration of placebo, 50, or 200 mg PGB. Linear mixed model analysis revealed that PGB was associated with (1) decreases in left amygdala and anterior insula activation and (2) increases in anterior cingulate (ACC) activation, during anticipation of positive and negative stimuli. There was also a region of the anterior amygdala in which PGB dose was associated with increased activation during anticipation of negative and decreased activation during anticipation of positive stimuli. Attenuation of amygdala and insula activation during anticipatory or emotional processing may represent a common regional brain mechanism for anxiolytics across drug classes. PGB induced increases in ACC activation could be a unique effect related to top-down modulation of affective processing. These results provide further support for the viability of using pharmaco-fMRI to determine the anxiolytic potential of pharmacologic agents.

Pharmacotherapy of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a prevalent psychiatric disorder that may result in significant social and occupational debilitation unless symptoms are recognized and treated appropriately. Considerable research effort has been devoted over the last 20 years to developing effective pharmacological treatments for this illness. At this time, the bulk of the agents investigated include antidepressants, anticonvulsants, atypical antipsychotics, benzodiazepines, and antiadrenergic agents. Herein, we review the existing evidence base for these different classes of psychotropics in PTSD. Emphasis is placed on discussion of evidence stemming from randomized placebo-controlled clinical trials wherever possible. A brief description of novel agents that have shown initial promise for PTSD treatment is also provided.