Pharmacotherapy for primary biliary cholangitis: an assessment of medication candidacy and rates of treatment.

BACKGROUND: Ursodeoxycholic acid is the preferred first-line therapy for primary biliary cholangitis. Alternative therapies, such as obeticholic acid, are recommended for patients who cannot tolerate ursodeoxycholic acid or who have an inadequate response to ursodeoxycholic acid monotherapy. Prior investigations have suggested that as many as 30% of patients with primary biliary cholangitis may have never received treatment with ursodeoxycholic acid. No prior investigations have examined usage rates of obeticholic acid in the treatment of primary biliary cholangitis. METHODS: All patients with an ICD-10 diagnosis of primary biliary cholangitis who had any records within the health system were included. A review of medical records was performed to confirm the diagnosis of primary biliary cholangitis and determine which medications had been prescribed for treatment, as well as candidacy for second-line therapies. RESULTS: A total of 495 patients met inclusion criteria. Notably, 95% of patients were taking ursodeoxycholic acid for treatment of their primary biliary cholangitis, with 67% of patients having disease that was well-controlled on ursodeoxycholic acid monotherapy. In total, 8% of patients were taking obeticholic acid (either as combination or monotherapy). Only 3% would benefit from the addition of a second line therapy but had not yet been offered medication. Only 3% of patients were not on any medication for management of their primary biliary cholangitis. CONCLUSIONS: Ursodeoxycholic acid is a readily available and generally well-tolerated medication that should be offered to all patients with primary biliary cholangitis as first-line therapy. While prior investigations have suggested that up to 30% of patients with primary biliary cholangitis may never have received treatment for the disorder, the present study suggests that patients are generally being managed according to guidelines. Moreover, a significant proportion of patients with primary biliary cholangitis will qualify for second line therapies and prescribers should be aware of the indications to use these medications.

Safe Use of POEM in a Patient With Decompensated Cirrhosis and Severe Achalasia.

Patients with both achalasia and decompensated cirrhosis can often present a therapeutic challenge because portal hypertension has generally been considered a contraindication to definitive therapies for achalasia. This case report depicts a patient who presented with progressive dysphagia, weight loss, and large-volume ascites; was diagnosed with type II achalasia and decompensated cirrhosis without esophageal varices; and underwent peroral endoscopic myotomy after preprocedural transjugular intrahepatic portosystemic shunt placement. Our case highlights the importance of multidisciplinary care and need for definitive therapies for these complex patients at high risk of malnutrition and sarcopenia.

Network analysis with either Illumina or MinION reveals that detecting vertebrate species requires metabarcoding of iDNA from a diverse fly community.

DNA obtained from invertebrates (iDNA) can be metabarcoded in order to survey vertebrate communities. However, little attention has been paid to the interaction between the invertebrate and vertebrate species. Here, we tested for specialization by sampling the dung and carrion fly community of a swamp forest remnant along a disturbance gradient (10 sites: 80-310 m from a road). Approximately, 60% of the baited 407 flies yielded 294 vertebrate identifications based on two COI fragments and 16S. A bipartite network analysis found no statistically significant specialization in the interactions between fly and vertebrate species, but uncommon fly species can carry the signal for vertebrate species that are otherwise difficult to detect with iDNA. A spatial analysis revealed that most of the 20 vertebrate species reported in this study could be detected within 150 m of the road (18 spp.) and that the fly community sourced for iDNA was unexpectedly rich (24 species, 3 families). They carried DNA for rare and common species inhabiting different layers of the forest (ground-dwelling: wild boar, Sunda pangolin, skinks, rats; arboreal: long-tailed macaque, Raffles' banded langur; flying: pin-striped tit-babbler, olive-winged bulbul). All our results were obtained with a new, greatly simplified iDNA protocol that eliminates DNA extraction by obtaining template directly through dissolving fly faeces and regurgitates with water. Lastly, we show that MinION- and Illumina-based metabarcoding yield similar results. We conclude by urging more studies that use different baits and involve experiments that are capable of revealing the dispersal capabilities of the flies carrying the iDNA.

The application of theranostics in different stages of prostate cancer.

Despite the remarkable achievements in treating metastatic prostate cancer over the last two decades, castrate-resistant status is still considered the lethal stage of the disease. Theranostics combines a targeting compound (ligand) with a therapeutic radioisotope (radioactive particle) injected into the blood to target the cancer cells. The most studied radioligand is 177Lu-PSMA-617, which targets PSMA, a protein found in prostate cancer cells. This new approach has shown promising results in treating metastatic castration-resistant prostate cancer. Currently, many trials are using PSMA-targeting radioligands in combination with conventional therapies in advanced prostate cancer or even in the earlier stages of the disease. Other preclinical trials are exploring the possibility of using newer ligands or radioisotopes to treat prostate cancer to increase the specificity and efficacy of this treatment.

Nonalcoholic Fatty Liver Disease After Pancreaticoduodenectomy for a Cancer Diagnosis.

Purpose: Current literature reports increased incidence of postpancreaticoduodenectomy (PD) nonalcoholic fatty liver disease (NAFLD), a precursor for nonalcoholic steatohepatitis and cirrhosis. The incidence of and risk factors (RFs) for NAFLD in the PD population, however, are not well elucidated. Methods: A cohort of 421 patients from a single institution who underwent PD for carcinoma and followed for at least 6 months were assessed retrospectively for age, gender, pathology, surgical complications (operative blood loss and length of stay [LOS]), comorbidities (diabetes, hypertension, hyperlipidemia, obesity), tobacco use, pre- and postoperative nutritional status (albumin and body mass index [BMI]), use of pancreatic enzyme replacement, and perioperative laboratory values (hemoglobin and liver function test). Cox proportional hazards model was used to examine these potential RFs as predictors of time to development of post-PD NAFLD. Results: Sixty (14.3%) patients developed post-PD NAFLD. Patients with NAFLD were younger (61.10 vs. 65.01 years old) and had higher preoperative BMI (28.92 vs. 26.61). Multivariate Cox proportional hazard model identified higher preoperative BMI, shorter postoperative LOS, and female gender as RFs for post-PD NAFLD. After excluding 12 patients with rare histology, there was a lower unadjusted hazard of developing NAFLD (p-value = 0.018) in the adenocarcinoma group than in the neuroendocrine and periampullary tumor groups. There was no statistically significant association between post-PD NAFLD and other characteristics. Conclusion: Female gender, higher preoperative BMI, and shorter LOS deserve closer monitoring for earlier detection and management of NAFLD.

Plasma Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Brown Adipose Tissue Activity in Humans.

Brown adipose tissue (BAT) activation is a possible therapeutic strategy to increase energy expenditure and improve metabolic homeostasis in obesity. Recent studies have revealed novel interactions between BAT and circulating lipid species-in particular, the non-esterified fatty acid (NEFA) and oxylipin lipid classes. This study aimed to identify individual lipid species that may be associated with cold-stimulated BAT activity in humans. A panel of 44 NEFA and 41 oxylipin species were measured using mass-spectrometry-based lipidomics in the plasma of fourteen healthy male participants before and after 90 min of mild cold exposure. Lipid measures were correlated with BAT activity measured via 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), along with norepinephrine (NE) concentration (a surrogate marker of sympathetic activity). The study identified a significant increase in total NEFA concentration following cold exposure that was positively associated with NE concentration change. Individually, 33 NEFA and 11 oxylipin species increased significantly in response to cold exposure. The concentration of the omega-3 NEFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at baseline was significantly associated with BAT activity, and the cold-induced change in 18 NEFA species was significantly associated with BAT activity. No significant associations were identified between BAT activity and oxylipins.

Acute metabolic and cardiovascular effects of mirabegron in healthy individuals.

AIMS: To quantify acute energy expenditure, supraclavicular skin temperature and cardiovascular responses to four doses of the ß3-adrenoceptor agonist, mirabegron. MATERIALS AND METHODS: A total of 17 individuals (11 men, six women) participated in this ascending-dose study, receiving single 50-, 100-, 150- and 200-mg doses of mirabegron on four separate days with 3 to 14 days wash-out between each dose. All variables were measured each visit from baseline to 180 minutes post mirabegron treatment. To determine brown adipose tissue (BAT) thermogenic efficacy at each dose, energy expenditure and supraclavicular skin temperature were compared from baseline to 180 minutes post mirabegron treatment. To examine safety, changes in cardiovascular variables at 100, 150 and 200 mg were compared with the standard clinical dose of 50 mg. RESULTS: Energy expenditure significantly increased after the 100- (35.6 ± 5.4 kJ/h) and 200-mg (35.6 ± 13.1 kJ/h) doses (P ≤ 0.05), and trended towards an increase after 150 mg (24.1 ± 13.6 kJ/h). Supraclavicular skin temperature increased after 50- (0.22 ± 0.1°C), 100- (0.30 ± 0.1°C) and 150-mg mirabegron doses (0.29 ± 0.1°C; P ≤ 0.05). The change in systolic blood pressure was greater after 150- (7.1 ± 1.3 mm Hg) and 200-mg doses (9.3 ± 1.9 mm Hg) than after the 50-mg dose (2.2 ± 1.3 mm Hg; P ≤ 0.05). The change in heart rate was greater after 200 mg (9.0 ± 2.2 bpm) compared with 50 mg (2.9 ± 1.4 bpm; P ≤ 0.05). CONCLUSIONS: A 100-mg dose of mirabegron increases energy expenditure and supraclavicular skin temperature in a ß3-adrenoceptor-specific manner, without the off-target elevations in blood pressure or heart rate observed at higher doses.

Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans.

AIMS/HYPOTHESIS: Increasing brown adipose tissue (BAT) activity is a possible therapeutic strategy to increase energy expenditure and glucose and lipid clearance to ameliorate obesity and associated comorbidities. The thiazolidinedione (TZD) class of glucose-lowering drugs increase BAT browning in preclinical experimental models but whether these actions extend to humans in vivo is unknown. The aim of this study was to determine the effect of pioglitazone treatment on adipocyte browning and adaptive thermogenesis in humans. METHODS: We first examined whether pioglitazone treatment of cultured human primary subacromioclavicular-derived adipocytes induced browning. Then, in a blinded, placebo-controlled, parallel trial, conducted within the Baker Institute clinical research laboratories, 14 lean male participants who were free of cardiometabolic disease were randomised to receive either placebo (lactose; n = 7, age 22 ± 1 years) or pioglitazone (45 mg/day, n = 7, age 21 ± 1 years) for 28 days. Participants were allocated to treatments by Alfred Hospital staff independent from the study via electronic generation of a random number sequence. Researchers conducting trials and analysing data were blind to treatment allocation. The change in cold-stimulated BAT activity, assessed before and after the intervention by [18F]fluorodeoxyglucose uptake via positron emission tomography/computed tomography in upper thoracic and cervical adipose tissue, was the primary outcome measure. Energy expenditure, cardiovascular responses, core temperature, blood metabolites and hormones were measured in response to acute cold exposure along with body composition before and after the intervention. RESULTS: Pioglitazone significantly increased in vitro browning and adipogenesis of adipocytes. In the clinical trial, cold-induced BAT maximum standardised uptake value was significantly reduced after pioglitazone compared with placebo (-57 ± 6% vs -12 ± 18%, respectively; p < 0.05). BAT total glucose uptake followed a similar but non-significant trend (-50 ± 10% vs -6 ± 24%, respectively; p = 0.097). Pioglitazone increased total and lean body mass compared with placebo (p < 0.05). No other changes between groups were detected. CONCLUSIONS/INTERPRETATION: The disparity in the actions of pioglitazone on BAT between preclinical experimental models and our in vivo human trial highlight the imperative to conduct human proof-of-concept studies as early as possible in BAT research programmes aimed at therapeutic development. Our clinical trial findings suggest that reduced BAT activity may contribute to weight gain associated with pioglitazone and other TZDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02236962 FUNDING: This work was supported by the Diabetes Australia Research Program and OIS scheme from the Victorian State Government.

Correction to: Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans.

The baseline insulin data given in Table 1 for the placebo group were incorrectly reported as 51 ± 10 pmol/l instead of 48 ± 10 pmol/l. This mistake also impacts on data reported in Table 4.

Relationships Between Measures of the Ability to Perform Vision-Related Activities, Vision-Related Quality of Life, and Clinical Findings in Patients With Glaucoma.

IMPORTANCE: To our knowledge, few studies have combined an objective measure of vision-related performance (VRP) and subjective measures of vision-related quality of life (VRQoL) with clinically related visual parameters, particularly in a large, prospective, cohort study setting. OBJECTIVE: To examine the relationships between clinical visual assessments and both a VRP and 2 self-reported VRQoL measurements. DESIGN, SETTING, AND PARTICIPANTS: Patients (N = 161) with moderate-stage glaucoma recruited from the Glaucoma Service at Wills Eye Hospital, Philadelphia, Pennsylvania, were enrolled from May 2012 to May 2014 in an ongoing prospective, 4-year longitudinal observational study. This report includes cross-sectional results from the baseline visit. Patients received a complete ocular examination, automated visual field (VF) test and Cirrus optical coherence tomographic scan. Contrast sensitivity was measured with the Pelli-Robson and the Spaeth-Richman Contrast Sensitivity (SPARCS) tests. Vision-related performance was assessed by the Compressed Assessment of Ability Related to Vision (CAARV) test. Vision-related QoL was assessed by the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) and a modified Glaucoma Symptom Scale (MGSS). MAIN OUTCOMES AND MEASURES: Correlations between clinical measures and CAARV, NEI-VFQ-25, and MGSS scores. RESULTS: A total of 161 patients were enrolled in the study. The strongest correlation was found between SPARCS score in the better eye and total CAARV score (r = 0.398; 95% CI, 0.235-0.537; P < .001). The CAARV score also correlated with the Pelli-Robson score (r = 0.353; 95% CI, 0.186-0.499; P = .001), VF mean deviation (r = 0.366; 95% CI, 0.200-0.510; P < .001), and VA (r = -0.326, 95% CI = -0.476 to -0.157; P = .003) in the better eye. There were more statistically significant correlations between contrast sensitivity tests and VF mean deviation with VRQoL measurements than with other clinical measures (visual acuity, intraocular pressure, Disc Damage Likelihood Scale, and mean retinal nerve fiber layer thickness). The MGSS scores were lower (worse) in women compared with men (P = .03 for binocular, P = .01 for better eye, and P = .05 for the worse eye). Structural measures (eg, Disc Damage Likelihood Scale, and retinal nerve fiber layer thickness) were generally not informative with respect to VRP or VRQoL. CONCLUSIONS AND RELEVANCE: Contrast sensitivity tests and VF mean deviation were associated with both objective measures of the ability to act and subjective measurements of VRQoL. The strongest correlation was between SPARCS score (contrast sensitivity) in the better eye and total CAARV score. Therefore, measurement of contrast sensitivity should be considered when evaluating patients' VRQoL. The results of this study were limited by the patient population and apply only within the bounds of the tested cohort.

Social and demographic determinants for breastfeeding in a rural, suburban and city area of South East China.

Breastfeeding is a traditional practice in China, yet few studies have explored its current trend after socioeconomic reform. This study aims to characterize breastfeeding rates and possible associations with sociodemographic factors using a breastfeeding questionnaire administered to 1,385 mothers of 6-year-old children. Rates were lowest among city residents and negatively associated with parental and grandmother education levels as well as mothers' professional occupational status. These findings highlight the impact of urbanization on maternal and child health and the effect of marketing tactics for breast milk substitutes (BMS). Public health education promoting breastfeeding should target urban families, particularly those educated.

Open-label study of high (30 mg) and moderate (20 mg) dose escitalopram for the treatment of obsessive-compulsive disorder.

This study sought to investigate the efficacy of escitalopram at different dosages for the treatment of obsessive-compulsive disorder (OCD). Thirty individuals were enrolled in a 16-week, open-label trial of escitalopram and randomly assigned to the 20 or 30 mg study arm. Study measures assessing OCD symptoms, anxiety, depression, and quality of life were administered at baseline and weeks 2, 4, 8, 12, and 16. For the 23 study completers, pretreatment and posttreatment analyses revealed significant improvements (P<0.05) on clinician-rated and self-rated measures of OCD symptoms, quality of life, anxiety, and depression. Approximately half of the sample (n = 12) satisfied full medication response criteria and less than one-quarter (n = 5) were partial medication responders. Intention-to-treat analyses showed similar improvements (P<0.05) on all study measures. At study completion, a superior responder rate and more improvement on the Yale-Brown Obsessive Compulsive Scale (P<0.05) was reported for those in the 30 versus 20 mg study arm. The difference between the two groups, however, disappeared when initial differences in baseline depression and anxiety scores were used as analysis covariates. These results suggest that the 30 mg (vs. 20 mg) dose of escitalopram may provide a superior reduction in OCD symptoms for those sufferers with comorbid depression and/or anxiety.

Autonomic and prefrontal cortex responses to autobiographical recall of emotions.

The present study combined measures of regional cerebral blood flow (rCBF) using positron emission tomography (PET) with measures of the autonomic nervous system using skin conductance (SC), heart rate (HR), and the high frequency band of heart rate variability (HRV) in ten healthy participants who were exposed to autobiographical scripts of memories for three target emotions: anger, happiness, and sadness. According to the results, anger was the only emotion to show a significant increase in sympathetic activity, accompanied by a significant decrease in HRV when compared with a neutral script. Anger was also the only emotion to show significant changes in rCBF in the prefrontal cortex. By contrast, the results for the happy and sad conditions showed no significant increase in sympathetic activity and no changes in rCBF in the prefrontal cortex in comparison with the neutral script. The findings suggest that a relative increase in sympathetic activity with a reciprocal decrease in parasympathetic activity may be necessary to generate frontal activity in autobiographical recall of emotions.

Open-label escitalopram treatment for pathological skin picking.

Pathological skin picking is characterized by dysfunctional, repetitive and excessive manipulation of the skin resulting in noticeable tissue damage. This study sought to assess the effectiveness of escitalopram in treating pathological skin picking. Twenty-nine individuals with pathological skin picking were enrolled in an 18-week, open-label trial of escitalopram. Study measures assessing skin picking severity and impact, anxiety, depression, and quality of life were given at baseline and weeks 2, 4, 6, 10, 14, and 18. The mean maximally tolerated dose was 25.0 mg (standard deviation=8.4). For the 19 study completers, pre-post-treatment analyses revealed significant improvements (P<0.05) on measures of skin picking severity and impact, quality of life, and self-rated anxiety and depression. Completer as well as intent-to-treat analyses indicated that approximately half of the sample satisfied full medication response criteria and one-quarter were partial medication responders. Correlational analyses indicated that changes in depression, anxiety, and quality of life co-occurred with reductions in skin picking severity but not impact. A high percentage of variance in severity, however, remained unexplained. These results suggest that escitalopram can be an effective agent in reducing pathological skin picking. The lack of medication response in a subset of our sample suggests the possibility of pathological skin picking subtypes.

Autonomic reactivity to induced emotion as potential predictor of response to antidepressant treatment.

Distinct factors have been identified as potential predictors of antidepressant treatment response. Although autonomic function changes have been described in depressive subjects, their value as predictors of antidepressant response has not been systematically evaluated. Eight un-medicated patients with major depressive order (MDD) have their skin conductance (SC) and heart rate variability (HRV) measured at basal condition and during four induced emotional states: happy, angry, sad and neutral. The high frequency (HF) and low frequency (LF) power parameters of HRV were assessed. Subsequently, patients were treated with fluoxetine 20 mg/day for 8 weeks. The antidepressant response was measured with the Beck Depression Inventory (BDI). The BDI percentage reduction correlated significantly with HRV responses during sad condition in LF power, and during happy condition with LF/HF ratio. The BDI percentage reduction also correlated significantly with HR responses in happy and in neutral conditions, and also with SC responses in neutral condition. These preliminary findings indicate that automatic responses to induced emotions may predict antidepressant response in MDD patients. Confirmatory studies are warranted.

Single modality versus dual modality treatment for trichotillomania: sertraline, behavioral therapy, or both?

BACKGROUND: Trichotillomania is a psychiatric condition characterized by chronic hair pulling. Both cognitive behavioral therapy (CBT) and the selective serotonin reuptake inhibitors (SSRIs) have shown promise in the treatment of trichotillomania, with comparison studies favoring CBT over pharmacotherapy. However, no randomized, controlled studies to date have compared the efficacy of individual SSRI or CBT treatment to the combination of both treatment modalities. METHOD: In this study, which ran from February 2000 through April 2003, subjects who met DSM-IV criteria for trichotillomania were randomly assigned to treatment with sertraline or placebo in a double-blind study design. Following 12 weeks of active pharmacotherapy, subjects not demonstrating significant trichotillomania symptom improvement had habit reversal training (HRT) added to their treatment regimen. Primary outcome measures were the Hair Pulling Scale and the Clinical Global Impressions scale. RESULTS: Thirteen subjects completing the 22-week study received single modality treatment of either sertraline or HRT, and 11 received both modalities of treatment. Trichotillomania symptoms in both groups improved, although the dual modality treatment group demonstrated larger gains and were much more likely to reach responder status at final evaluation. CONCLUSION: These results suggest that the combination of sertraline and HRT may be more efficacious in the treatment of trichotillomania than either approach alone.

Current posttraumatic stress disorder and history of trauma in trichotillomania.

Though some researchers and clinicians postulate that trauma and posttraumatic stress disorder (PTSD) may be implicated in the etiologic underpinnings of trichotillomania (TTM), very little research to date has examined such postulations. To address this gap in the literature, the current study assessed the prevalence of trauma and PTSD in 42 individuals seeking treatment for TTM. Relations between symptoms of PTSD and TTM also were examined, as were differences in TTM symptoms between those with and without PTSD. Findings revealed that approximately 76% reported a history of at least one traumatic event, and 19% met criteria for PTSD. Furthermore, negative correlations were demonstrated between symptoms of PTSD and characteristics of TTM, and the PTSD group reported less severe TTM characteristics. Findings suggest that the prevalence of PTSD in TTM may be higher than in the general population and that a history of greater number of types of traumas is associated with a longer duration of hair pulling as well as the scalp as the primary pulling site. The authors also speculate that in traumatized individuals, TTM may represent a form of coping vis-à-vis self-soothing or self-harm.

The Tridimensional Personality Questionnaire: changes during psychological treatment of social phobia.

Thirty-nine individuals completed 12 weekly group sessions of psychological therapy for social phobia (social anxiety disorder). Before and after treatment, participants filled out the Tridimensional Personality Questionnnaire (TPQ, [Cloninger C.R., 1987a. A systematic method for clinical description and classification of personality variants. Archives of General Psychiatry, 44, 573-58]) and measures of social anxiety and depression. Treatment led to a significant reduction in social anxiety, depression, harm avoidance, and reward dependence. However, only pre-post changes in harm avoidance and depression were significantly correlated with pre-post changes in social anxiety. These results suggest that harm avoidance shows state-dependent changes during the course of treatment for social phobia. The implications of these findings for the trait/state distinction of the TPQ scales are discussed.

Spontaneous and directed application of verbal learning strategies in bipolar disorder and obsessive-compulsive disorder.

OBJECTIVES: Individuals with bipolar disorder exhibit neuropsychological impairments when they are euthymic (neither depressed nor manic). One of the most consistently reported cognitive problems in euthymic individuals with bipolar disorder is impairment in verbal episodic memory. Recent findings suggest that episodic memory difficulties in these individuals are attributable to difficulties using organizational strategies during encoding. The purpose of the present study was (i) to investigate whether difficulties using organizational strategies in bipolar disorder are due to a failure in spontaneously initiating verbal organization strategies or are due to difficulties implementing such strategies, and (ii) to compare the characteristics of verbal organizational impairment in bipolar disorder with those observed in individuals with obsessive-compulsive disorder (OCD). METHODS: Study participants were 20 individuals with bipolar I disorder (BP-I), 20 individuals with OCD, and 20 healthy control participants matched for age, gender, and education. Participants completed a verbal encoding paradigm that involved spontaneous and directed use of verbal organization strategies during encoding of word lists. RESULTS: Compared with control subjects, both BP-I and OCD participants showed impaired verbal organization in the spontaneous encoding condition. In the directed encoding condition, OCD patients organized the word lists as well as control participants whereas BP-I participants exhibited lower verbal organization than both control and OCD participants. OCD and BP-I participants' free recall performance did not differ from that of control participants in the spontaneous encoding condition. In the directed encoding condition, BP-I participants recalled fewer words than OCD or control participants. CONCLUSIONS: Episodic memory difficulties in OCD are associated with difficulties spontaneously initiating verbal organization strategies during encoding whereas the ability to implement verbal organization when instructed to do so is preserved. BP-I participants, on the other hand, exhibit difficulties in both spontaneously initiating verbal organization strategies and in the ability to implement such strategies when instructed to do so.

Ventromedial prefrontal cortex and amygdala dysfunction during an anger induction positron emission tomography study in patients with major depressive disorder with anger attacks.

CONTEXT: Although a variety of functional neuroimaging studies have used emotion induction paradigms to investigate the neural basis of anger in control subjects, no functional neuroimaging studies using anger induction have been conducted in patient populations. OBJECTIVE: To study the neural basis of anger in unmedicated patients with major depressive disorder with anger attacks (MDD + A), unmedicated patients with MDD without anger attacks (MDD - A), and controls. DESIGN: We used positron emission tomography, psychophysiologic measures, and autobiographical narrative scripts in the context of an anger induction paradigm. SETTING: Academic medical center. PARTICIPANTS: Thirty individuals, evenly divided among the 3 study groups. INTERVENTIONS: In separate conditions, participants were exposed to anger and neutral autobiographical scripts during the positron emission tomography study. Subjective self-report and psychophysiologic data were also collected. MAIN OUTCOME MEASURES: Voxelwise methods were used for analyses of regional cerebral blood flow changes for the anger vs neutral contrast within and between groups. RESULTS: Controls showed significantly (P<.001) greater regional cerebral blood flow increases in the left ventromedial prefrontal cortex during anger induction than patients with MDD + A, whereas these differences were not present in other between-group analyses. Also, in controls, an inverse relationship was demonstrated between regional cerebral blood flow changes during anger induction in the left ventromedial prefrontal cortex and left amygdala, whereas in patients with MDD + A there was a positive correlation between these brain regions during anger induction. There was no significant relationship between these brain regions during anger induction in patients with MDD - A. CONCLUSION: These results suggest a pathophysiology of MDD + A that is distinct from that of MDD - A and that may be responsible for the unique clinical presentation of patients with MDD + A.