Weeks Of Pharmacotherapy Research Articles

Survival Outcomes of an Early Intervention Smoking Cessation Treatment After a Cancer Diagnosis

Smoking after a cancer diagnosis increases mortality and risk for a second cancer. To determine the association between time of entry into a smoking cessation intervention following a cancer diagnosis and survival outcomes. Using a prospective cohort study design, patients with cancer who smoked and received cessation treatment were assessed at 3 months, 6 months, and 9 months following tobacco treatment onset. Survival outcomes of tobacco treatment were measured and compared among patients at the MD Anderson Cancer Center Tobacco Research and Treatment Program. Treatment occurred between January 1, 2006, and March 3, 2022. Patients were excluded if they died before the tobacco treatment ended, received their diagnosis more than 6 months after beginning cessation treatment, or lacked staging information. The data analysis took place from September 2023 to May 2024. Cessation treatment consisted of 6 to 8 personalized counseling visits and 10 to 12 weeks of pharmacotherapy. More than 95% of visits were provided via telemedicine. The primary outcomes were survival as recorded in the MD Anderson Cancer Center tumor registry and 7-day point prevalence abstinence at each follow-up. The main analytical sample consisted of 4526 currently smoking patients diagnosed with cancer and receiving cessation treatment (2254 [49.8%] female; median [IQR] age, 55 [47-62] years). Survival over 15 years increased for those quitting smoking at 3 months (adjusted hazard ratio [aHR], 0.75 [95% CI, 0.67-0.83]), 6 months (aHR, 0.79 [95% CI, 0.71-0.88]), and 9 months (aHR, 0.85 [95% CI, 0.76-0.95]) of follow-up. The optimal survival outcomes were observed for patients who received tobacco treatment within 6 months of a cancer diagnosis. At the 75th percentile, their survival increased from 2.1 years (95% CI, 1.8-2.4 years) among continuing smokers (nonabstainers) vs 3.9 years (95% CI, 3.2-4.6 years) for patients who quit (abstainers). Similar but less pronounced outcomes were noted when tobacco treatment began within 6 months to 5 years following diagnosis, with survival at the 75th percentile of 4.8 years (95% CI, 4.3-5.3 years) for nonabstainers vs 6.0 years (95% CI, 5.1-7.2 years) for abstainers. The results of this prospective cohort study suggest that evidence-based smoking cessation treatment within 6 months following a cancer diagnosis maximizes survival benefit. This study supports smoking cessation as an important early clinical intervention for patients after being diagnosed with cancer.

Predicting remission after acute phase pharmacotherapy in patients with bipolar I depression: A machine learning approach with cross-trial and cross-drug replication.

Interpatient variability in bipolar I depression (BP-D) symptoms challenges the ability to predict pharmacotherapeutic outcomes. A machine learning workflow was developed to predict remission after 8 weeks of pharmacotherapy (total score of ≤8 on the Montgomery Åsberg Depression Rating Scale [MADRS]). Supervised machine learning models were trained on data from BP-D patients treated with olanzapine (N = 168) and were externally validated on patients treated with olanzapine/fluoxetine combination (OFC; N = 131) and lamotrigine (LTG; N = 126). Top predictors were used to develop a prognosis rule informing how many symptoms should change and by how much within 4 weeks to increase the odds of achieving remission. An AUC of 0.76 (NIR:0.59; p = 0.17) was established to predict remission in olanzapine-treated subjects. These trained models achieved AUCs of 0.70 with OFC (NIR:0.52; p < 0.03) and 0.73 with LTG (NIR:0.52; p < 0.003), demonstrating external replication of prediction performance. Week-4 changes in four MADRS symptoms (reported sadness, reduced sleep, reduced appetite, and concentration difficulties) were top predictors of remission. Across all pharmacotherapies, three or more of these symptoms needed to improve by ≥2 points at Week-4 to have a 65% chance of achieving remission at 8 weeks (OR: 3.74, 95% CI: 2.45-5.76; p < 9.3E-11). Machine learning strategies achieved cross-trial and cross-drug replication in predicting remission after 8 weeks of pharmacotherapy for BP-D. Interpretable prognoses rules required only a limited number of depressive symptoms, providing a promising foundation for developing simple quantitative decision aids that may, in the future, serve as companions to clinical judgment at the point of care.

One size does not fit all: notable individual variation in brain activity correlates of antidepressant treatment response.

To date, no robust electroencephalography (EEG) markers of antidepressant treatment response have been identified. Variable findings may arise from the use of group analyses, which neglect individual variation. Using a combination of group and single-participant analyses, we explored individual variability in EEG characteristics of treatment response. Resting-state EEG data and Montgomery-Åsberg Depression Rating Scale (MADRS) symptom scores were collected from 43 patients with depression before, at 1 and 12 weeks of pharmacotherapy. Partial least squares (PLS) was used to: 1) identify group differences in EEG connectivity (weighted phase lag index) and complexity (multiscale entropy) between eventual medication responders and non-responders, and 2) determine whether group patterns could be identified in individual patients. Responders showed decreased alpha and increased beta connectivity, and early, widespread decreases in complexity over treatment. Non-responders showed an opposite connectivity pattern, and later, spatially confined decreases in complexity. Thus, as in previous studies, our group analyses identified significant differences between groups of patients with different treatment outcomes. These group-level EEG characteristics were only identified in ~40-60% of individual patients, as assessed quantitatively by correlating the spatiotemporal brain patterns between groups and individual results, and by independent raters through visualization. Our single-participant analyses suggest that substantial individual variation exists, and needs to be considered when investigating characteristics of antidepressant treatment response for potential clinical applicability. https://clinicaltrials.gov, identifier NCT00519428.

The problem of timely diagnosis of primary hyperaldosteronism. Clinical case

A clinical case is presented of delayed diagnosis of primary hyperaldosteronism (PHA) due to aldosterone-producing adenoma. Suspicion of PHA arises in case of persistent combination of hypertension with hypokalemia of various severity, a specific neuromuscular syndrome, as well as a high risk of cardiomyopathy, heart failure, and deterioration of kidney function, which are not typical for banal hypertension. Unsatisfactory blood pressure control with a standard combination of pharmacotherapy, an unexpected positive effect of mineralocorticoid receptor antagonists, high blood pressure in young people, as well as a family history of early high blood pressure or stroke at a young age, paroxysmal course of hypertension itself increases the risk of PHA. For a long time, a disease in our patient was considered a banal hypertension, although the diagnostic hypothesis of PHA should appear immediately after severe neuromuscular syndrome, rapid progression of cardiomyopathy and clinically significant heart failure began to dominate in the clinical picture. A 44-year-old female patient came to the attention of rheumatologists with suspicion of inflammatory myopathy due to frequent episodes of muscle weakness whose origin remained unclear. Key complaints of pronounced paroxysmal generalized muscle weakness, especially in the limbs, numbness and paresthesias in the extremities, calf muscle cramps against the background of hypertension were regarded as a neuromuscular syndrome specific to PHA. The PHA hypothesis was supported by the presence of cardiomyopathy, heart failure, clinically significant hypokalemia, and elevated aldosterone level. Computed tomography of the retroperitoneal space confirmed the presence of adrenal adenoma. Unfortunately, with a delay, after 13 years of hypertension, the diagnosis of PHA against the background of aldosterone-producing adenoma was confirmed. Consultation with a surgeon endocrinologist was suggested, as well as administration of eplerenone 50 mg daily in combination with lercanidipine 20 mg daily. Already after 6 weeks of pharmacotherapy, a positive therapeutic effect was obtained regarding the control of hypertension, heart failure, and the severity of neuromuscular syndrome. The differential diagnosis of secondary endocrine hypertension can be successful only with the possession of skills for early clinical detection of endocrine pathology, even in subclinical disease presentation. The diagnosis of PHA makes it possible to offer a patient radical surgical treatment, as well as to choose optimal approaches to pharmacotherapy.

Mobile health contingency management for smoking cessation among veterans experiencing homelessness: A comparative effectiveness trial

Tobacco cessation is reduced in U.S. military veterans experiencing homelessness. Mobile contingency management (mCM) is a promising treatment for tobacco use among populations experiencing homelessness, but past CM studies have largely been small, have relied on in-person follow-up, and/or lacked long-term biochemically verified abstinence measures. Veterans who smoked and were experiencing homelessness (N = 127) were randomly assigned to mCM treatment (4 weeks of mCM, 5 weeks of telehealth counseling, and the option of 12 weeks of pharmacotherapy) or VA standard care (3 biweekly group sessions and clinically appropriate pharmacotherapy), and all participants were randomly assigned to a $100 longer-term financial incentive for abstinence at 3-month follow-up. Participants were followed at 3-, 6-, and 12-months post-randomization, with the a priori main outcome designated as biochemically verified prolonged abstinence (with lapses) at 6-month follow-up. At 6-months, participants in the mCM group were significantly more likely to meet criteria for prolonged abstinence (OR = 3.1). Across time points, veterans in the mCM group had twice the odds of prolonged abstinence as those in the standard care group. However, by the 12-month follow-up, there was no statistically significant group difference in abstinence. Cost-effectiveness analysis indicated a modest increase in cost ($1,133) associated with an increase of one quality-adjusted life year saved for the intervention compared to standard care. mCM is a cost-effective approach to smoking cessation among veterans experiencing homelessness. Considering waning potency of this and other tobacco cessation interventions at 12-month follow-up, it is crucial to implement strategies to sustain abstinence for individuals experiencing homelessness.

Multiple Pharmacotherapy Adaptations for Smoking Cessation Based on Treatment Response in Black Adults Who Smoke

Adapting to different smoking cessation medications when an individual has not stopped smoking has shown promise, but efficacy has not been tested in racial and ethnic minority individuals who smoke and tend to have less success in quitting and bear a disproportionate share of tobacco-related morbidity and mortality. To evaluate efficacy of multiple smoking cessation pharmacotherapy adaptations based on treatment response in Black adults who smoke daily. This randomized clinical trial of adapted therapy (ADT) or enhanced usual care (UC) included non-Hispanic Black adults who smoke and was conducted from May 2019 to January 2022 at a federally qualified health center in Kansas City, Missouri. Data analysis took place from March 2022 to January 2023. Both groups received 18 weeks of pharmacotherapy with long-term follow-up through week 26. The ADT group consisted of 196 individuals who received a nicotine patch (NP) and up to 2 pharmacotherapy adaptations, with a first switch to varenicline at week 2 and, if needed, a second switch to bupropion plus NP (bupropion + NP) based on carbon monoxide (CO)-verified smoking status (CO ≥6 ppm) at week 6. The UC group consisted of 196 individuals who received NP throughout the duration of treatment. Anabasine-verified and anatabine-verified point-prevalence abstinence at week 12 (primary end point) and weeks 18 and 26 (secondary end points). The χ2 test was used to compare verified abstinence at week 12 (primary end point) and weeks 18 and 26 (secondary end points) between ADT and UC. A post hoc sensitivity analysis of smoking abstinence at week 12 was performed with multiple imputation using a monotone logistic regression with treatment and gender as covariates to impute the missing data. Among 392 participants who were enrolled (mean [SD] age, 53 [11.6] years; 224 [57%] female; 186 [47%] ≤ 100% federal poverty level; mean [SD] 13 [12.4] cigarettes per day), 324 (83%) completed the trial. Overall, 196 individuals were randomized to each study group. Using intent-to-treat and imputing missing data as participants who smoke, verified 7-day abstinence was not significantly different by treatment group at 12 weeks (ADT: 34 of 196 [17.4%]; UC: 23 of 196 [11.7%]; odds ratio [OR], 1.58; 95% CI, 0.89-2.80; P = .12), 18 weeks (ADT: 32 of 196 [16.3%]; UC: 31 of 196 [15.8%]; OR, 1.04; 95% CI, 0.61-1.78; P = .89), and 26 weeks (ADT: 24 of 196 [12.2%]; UC: 26 of 196 [13.3%]; OR, 0.91; 95% CI, 0.50-1.65; P = .76). Of the ADT participants who received pharmacotherapy adaptations (135/188 [71.8%]), 11 of 135 (8.1%) were abstinent at week 12. Controlling for treatment, individuals who responded to treatment and had CO-verified abstinence at week 2 had 4.6 times greater odds of being abstinent at week 12 (37 of 129 [28.7%] abstinence) than those who did not respond to treatment (19 of 245 [7.8%] abstinence; OR; 4.6; 95% CI, 2.5-8.6; P < .001). In this randomized clinical trial of adapted vs standard of care pharmacotherapy, adaptation to varenicline and/or bupropion + NP after failure of NP monotherapy did not significantly improve abstinence rates for Black adults who smoke relative to those who continued treatment with NP. Those who achieved abstinence in the first 2 weeks of the study were significantly more likely to achieve later abstinence, highlighting early treatment response as an important area for preemptive intervention. ClinicalTrials.gov Identifier: NCT03897439.

The effects of varenicline, bupropion, nicotine patch, and placebo on smoking cessation among smokers with major depression: A randomized clinical trial.

Improving treatment outcomes for smokers with major depressive disorder (MDD) can have significant public health implications. To evaluate the safety and efficacy of smoking cessation pharmacotherapy among smokers with MDD. Secondary analysis of a randomized, double-blind, active- (nicotine patch) and placebo-controlled trial of 12 weeks of either varenicline or bupropion with a 12-week follow-up. Community volunteers 18-75 years of age; smoke 10+ cigarettes/day; with clinically stable MDD (N = 2635) or no psychiatric disorder (N = 4028), from 140 sites in 16 countries. Twelve weeks of pharmacotherapy (placebo[PLA], nicotine replacement therapy[NRT], bupropion[BUP], varenicline[VAR]) plus brief cessation counseling. Primary safety outcome: the occurrence of ≥1 treatment-emergent, moderate to severe neuropsychiatric adverse event (NPSAE). Primary efficacy outcome: biochemically confirmed continuous abstinence(CA) during the final 4 weeks of treatment (Weeks 9-12). A total of 6653 participants (56% female; 39% MDD) ~47 years old. Risk of NPSAEs did not differ by medication for MDD. MDD had higher risk (p < .0001) for NPSAEs than the NPC. Efficacy (6653; intent-to-treat): CA rates for MDD versus NPC respectively were 31.2% versus 38.0% VAR; 23.0% versus 26.1% BUP; 22.6% versus 26.4% NRT; and 13.4% versus 13.7% PLA but no differential treatment effect was noted within the cohorts. All active treatments differed from PLA but VAR showed the largest effect. Results suggest that for MDD smokers, inclusive of those with recurrent episode, varenicline plus counseling may be the best pharmacological option for the treatment of smoking given its greater efficacy effect size and similar risk of NPSAEs. ClinicalTrials.gov Identifier: NCT01456936. https://clinicaltrials.gov/ct2/show/NCT01456936.

ASSOCIATION BETWEEN C-REACTIVE PROTEIN AND GLYCOSYLATED HEMOGLOBIN IN TYPE-2 DIABETES MELLITUS: AN INDIAN PERSPECTIVE

Background: Diabetes mellitus (DM) is a complex metabolic disorder that alters the glucose status of the human body. There has been a steady increase in the prevalence of DM in the past few decades leading to macro-and microvascular complications. There has been mounting evidence suggesting that inammation plays a role in the pathophysiology of DM. Methods: Asingle centre prospective study was conducted on 50 consecutive patients with de novo or prior Type-2 DM (T2DM) history between JANUARY 2021 to OCTOBER 2021. CRP and HbA1c samples were taken at the start of the study and were retaken after 12 weeks of pharmacotherapy and lifestyle modication. The relationship between CRPand HbA1c was analysed. Results: The mean HbA1c and CRP for the initial 50 participants were 9.6500 ± 1.8816 and 1.1520 ± 0.9984, respectively. At the 12th-week follow up, the mean HbA1c fell to 7.3952 ± 1.3155 (P&lt;0.05), and the mean CRP was reduced to 0.2857 ± 0.5237 (P&lt;0.05). Furthermore, the rise in HbA1c was correlated with a statistically signicant rise in CRP. Conclusion: This study establishes a positive correlation between serum CRP and HbA1c. Improving glycemic control can help reduce the risk of adverse events associated with sustained inammation

Dosing Time Matters? Nighttime vs. Daytime Administration of Nifedipine Gastrointestinal Therapeutic System (GITS) or Amlodipine on Non-dipper Hypertension: A Randomized Controlled Trial of NARRAS.

Background: Non-dipper hypertension is often characterized by a blunted decrease of nocturnal blood pressure (BP) and is associated with increased risk of target organ damage and cardiovascular (CV) events, while the optimal treatment strategy is yet to be established. This trial was designed to evaluate whether nocturnal BP reduction and arterial stiffness improvement differ from antihypertensive agents and time of administration.Methods: Young and middle-aged adults (18–65 years) with non-dipper hypertension were randomly assigned to nifedipine GITS (gastrointestinal therapeutic system) 30 mg or amlodipine besylate 5 mg once daily for 8 weeks, either taken in the morning or at night. Dose was doubled at 4-week if BP is not at goal. Twenty-four hour ambulatory BP monitoring (ABPM) and arterial stiffness were evaluated before and after 8 weeks of pharmacotherapy. The primary efficacy measure was the average nighttime systolic BP reduction.Results: A total of 98 non-dipper hypertensive patients (mean age 46.3 years) were randomized during Dec, 2016 and Dec, 2020, of whom 72 (73%) patients completed all ABPM and follow-up evaluations. Nighttime systolic BP significantly reduced at 8 weeks vs. baseline with nifedipine GITS or amlodipine, irrespective of dosing at nighttime (−9.9 vs −9.9 mmHg, P > 0.05) or daytime (−11.5 vs. −10.9 mmHg, P > 0.05). No difference was seen between these two agents, when combining the data of nighttime and daytime dosing together (−10.8 vs. −10.5 mmHg, respectively, P = 0.898). Daytime, 24-h systolic BP, diastolic BP at different time and pulse wave velocity reduced significantly and comparably, and recovery of dipping rhythm were similar among groups.Conclusion: Nighttime dosing of long-acting antihypertensive preparations, nifedipine GITS or amlodipine demonstrated similar effects on nocturnal BP reduction, dipping rhythm restoration and arterial elasticity improvement in younger subjects with non-dipper hypertension. These effects were comparable with morning dosing.

Liver stiffness assessment as an alternative to hepatic venous pressure gradient for predicting rebleed after acute variceal bleed: A proof-of-concept study.

Background and AimHepatic venous pressure gradient (HVPG), although an important determinant in predicting rebleeding after an episode of acute variceal bleed (AVB), is seldom utilized in clinical practice. We aimed to study the role of liver stiffness measurement (LSM) after variceal bleeding as a potential noninvasive predictor of rebleed.MethodsThis was a post hoc analysis of clinical trial of patients undergoing HVPG (postbleed HVPG) and LSM (postbleed LSM) assessment within 3–5 days of index AVB. HVPG response was assessed after 4 weeks of pharmacotherapy. Comparative assessment of long‐term rebleeding rates stratified using postbleed LSM, postbleed HVPG, and HVPG response was performed. Decision curve analysis (DCA) was conducted to identify the most appropriate tool for routine use.ResultsLong‐term clinical and HVPG response data were available for 48 patients post‐AVB, of whom 45 patients had valid postbleed LSM. Rebleeding occurred in 13 (28%) patients over a median follow‐up of 4 years with no early rebleeds. Postbleed LSM >30 kPa and baseline HVPG >15 mm Hg were optimal cutoffs for identifying patients at high risk of rebleeding. Time‐dependent receiver operating characteristic curves and competing risk analysis accounting for death showed similar discriminative values for all three stratification tools. At usual risk thresholds, HVPG response had maximum benefit on DCA followed by postbleed LSM. On DCA, 50–60 additional HVPGs were required to detect one additional patient at high risk of rebleed.ConclusionLiver stiffness measurement during AVB can potentially be used as an alternative to portal pressure indices in decompensated cirrhosis to identify those at high risk of late‐onset rebleed.

Antidepressants normalize brain flexibility associated with multi-dimensional symptoms in major depressive patients

BackgroundThe fundamental pathophysiology of major depressive disorder (MDD) could be characterized by functional brain networks which tightly and dynamically connect into groups as communities, making the flexible brain possible to external multifarious demands. We aim to scrutinize what brain dynamics go awry in MDD and antidepressants effects on multi-dimensional symptoms. MethodsThirty-five patients and thirty-five controls underwent resting-state functional magnetic resonance imaging (MRI). Patients were scanned before and after 8 or 12 weeks of pharmacotherapy. Group independent component analysis decomposed resting-state images to instinct networks and networks' integrated flexibility was calculated. Network flexibility between patients at baseline and after therapy were compared. ResultsAll patients completed the clinical trial and MRI scans. Following antidepressants treatment, we found significant normalization of reduced network flexibility in default mode network (DMN) and cognitive control network (CCN) of MDD patients. Selectively significant correlations between network flexibility and multi-dimensional symptoms such as anxiety/somatization and hysteresis factor were also found. Conclusions“Hypoflexible” CCN may involve in anxiety syndrome. Low flexibility in DMN may be indicative of hysteresis. These suggest an important pathophysiology of depressive manifestation of MDD. The antidepressant-induced normalization of the “hypoflexibility” suggests a selective pathway through which antidepressants may alleviate symptoms in depression.

White matter connectivity differences between treatment responders and non-responders in patients with panic disorder

BackgroundPanic disorder (PD) is a prevalent and highly disabling mental condition. However, less is known about relationships between biomarkers that may together predict a better response to pharmacological treatment. The objective of the present study was to compare the brain white matter (WM) connectivity between treatment-responsive patients with panic disorder (RPD) and non-responsive patients with panic disorder (NRPD) after 12 weeks of pharmacotherapy. MethodsSixty-four patients with PD were enrolled in this study (RPD, n = 37; NRPD, n = 27). All patients were examined by using magnetic resonance imaging at 3 Tesla. The Panic Disorder Severity Scale (PDSS), Albany Panic and Phobia Questionnaire (APPQ), Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) were administered at baseline of the study. Fractional anisotropy (FA) data were compared using tract-based spatial statistics (TBSS). ResultsTBSS results showed that the FA values of the patients with NRPD were significantly higher than of those with RPD in the WM regions such as the precentral gyrus, parahippocampal gyrus, posterior corona radiata, posterior thalamic radiation, posterior parts of the corpus callosum, and precuneus. Symptom severity scales, such as ASI-R scores, showed significant positive correlations of the FA values with the fronto-temporal WM regions in NRPD. ConclusionsThese results suggest that structural changes to areas such as the fronto-limbic regions and the posterior part of default mode network, could influence medication response in PD. Further studies with a larger number of patients should be performed to confirm our findings.

Venlafaxine and sertraline does not affect the expression of genes regulating stress response in female MDD patients.

The aim of this study was to analyze the expression of 3 genes involved in the regulation of HPA axis: GR, HSP90 and FKBP5, in patients with major depressive disorder (MDD) before antidepressant treatment and after 8 weeks of pharmacotherapy. Additionally, we analyzed the level of glucocorticoid receptor isoforms before and after treatment. The study included 30 female patients (aged 18-60 years), with major depres- sive disorder diagnosed on the basis of the Structured Clinical Interview for DSM-IV (SCID). Antidepressant treatment included use of sertraline or venlafaxine. The assessment of patients' mental state (severity of depression) was checked by the Hamilton Depression Rating Scale (HDRS). After 8 weeks of treatment, the same clinical and molecular tests were performed. All of the patients underwent dexamethasone suppression test (DST). MRNA was isolated from the peripheral blood to evaluate the expression of the studied genes using real-time PCR with TaqMan probes. The concentration of GR isoforms (α and β) in serum was also determined using ELISA. Statistical analysis was performed using Statistica v.12.0 software. The abnormal cortisol level was only seen in 20% of patients. Dysregulation on HPA axis was observed in 10% of patients. We observed significant clinical improvement after 8 weeks of pharmacotherapy in all patients. Almost the whole group of patients (except one patient) showed full remission of symptoms. We observed significant moderate correlation between cortisol level after DST before treatment and after 8 weeks of pharmacotherapy (r2 = 0.44). The results showed no significant difference in the expression of 3 analyzed genes compared before and after 8 weeks of therapy. The results of ELISA showed decreased level of α isoform after pharmacotherapy, independent of drug. The results showed no significant changes in the expression of genes involved in the stress axis activity during antidepressant therapy.

Reported maladaptive decision-making in unipolar and bipolar depression and its change with treatment

Mood disorder patients frequently experience difficulty making decisions and may make sub-optimal decisions with adverse life consequences. However, patients’ styles for decision-making when ill and after treatment have received little study to date. We assessed healthy controls (HC, n = 69) and patients with major depressive disorder (MDD, n = 61) or bipolar disorder (BP, n = 26) in a current major depressive episode using the Melbourne Decision-making Questionnaire. A subset of participants was re-evaluated after completing six weeks of pharmacotherapy. HC demonstrated significantly greater use of the healthy vigilance style, and significantly lower use of maladaptive decision-making styles, than the MDD and depressed BP patients. After six weeks of treatment, neither the MDD nor BP patients reported meaningful improvements in the vigilance style of decision-making, but scores on most maladaptive decision-making styles declined. BP patients who remitted reported significantly lower buckpassing and procrastination scores than healthy controls. Among MDD patients, however, the maladaptive passive buckpassing style of decision-making did not significantly diminish. For MDD patients, reported decision-making styles may remain impaired even after achieving remission. Among BP patients, low levels of adaptive vigilance decision-making may be a trait component of the illness, whereas for MDD patients, reported maladaptive passive decision-making styles are persistent.

Soluble Fas ligand (sFasL) as a predictor of reduction of general psychopathology in schizophrenia after antipsychotic treatment

IntroductionDysregulation of the apoptotic process is associated with the etiopathogenesis of schizophrenia, which is observed at the brain and peripheral blood levels. A significant negative correlation between the duration of the disease and serum sFasL concentration was demonstrated by other authors. It was shown that an increased rate of apoptosis is more pronounced in neuroleptic-free patients with the first-episode of schizophrenia than in patients with chronic disease.AimSearch for a predictor of good response to antipsychotic treatment based on the analysis of the sFasL plasma level and its relationship with clinical symptoms.MethodsFifty-three patients with chronic schizophrenia and 46 healthy individuals were enrolled in the study. The concentration of sFasL was measured by ELISA. Clinical assessments (PANSS, SANS, SAPS) and blood analyses were conducted three times: during the active phase of disease (at admission), after 4 weeks of pharmacotherapy, and after reaching remission.ResultsIn the schizophrenia group, non-altered levels of sFasL (P = 0.1; U Mann-Whitney test), compared to the control, were detected at admission. The initial level of sFasL correlated negatively (r = −0.33; P = 0.04; Spearman's rank) with blood leukocyte count. Despite clinical improvement, no significant changes in the level of sFasL were observed. However, the sFasL level correlated negatively with the PANSS general psychopathology reduction after 4 weeks of pharmacotherapy (r = −0.7; P = 0.04) and after remission (r = −0.39; P = 0.026).ConclusionsThe results indicate a possible role of sFasL in apoptosis of blood leukocytes and suggest that the reduction of sFasL level can predict level of PANSS general psychopathology after antipsychotic treatment in schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Differential therapeutic effects of 12-week treatment of atomoxetine and methylphenidate on drug-naïve children with attention deficit/hyperactivity disorder: A counting Stroop functional MRI study

Methylphenidate and atomoxetine are effective in treating attention-deficit/hyperactivity disorder (ADHD) with underlying distinct pharmacological mechanisms. To relate neural mechanisms to clinical response, we conducted a comparative trial to differentiate the changes in brain activation of drug-naïve children with ADHD when performing neuropsychological tasks after 12 weeks of pharmacotherapy. We randomized 50 drug-naïve children with ADHD, aged 7–17, to treatment with methylphenidate (n=25) or atomoxetine (n=25). These children were scanned twice with functional magnetic resonance imaging (fMRI) during the counting Stroop task before and after treatment. Focused attention and impulsivity were assessed twice by using the Conner's Continuous Performance Test (CCPT). The final sample for fMRI analysis comprised 20 in the methylphenidate group and 22 in the atomoxetine group. Atomoxetine decreased activations in the dorsal anterior cingulate cortex and dorsolateral prefrontal cortex, which correlated with improvement in focused attention assessed by the CCPT. In contrast, methylphenidate increased activations in the inferior frontal gyrus, which correlated with the decreasing severity of impulsivity assessed by the CCPT. The current findings suggest that differential therapeutic effects on neuronal changes induced by 12-week treatment atomoxetine and methylphenidate may contribute to behavioral improvement.

High insulin-like growth factor-1 in patients with bipolar I disorder: A trait marker?

ObjectivesNeurotrophic factors exert substantial effects on the central nervous system. The present study investigates the roles of insulin-like growth factor-1 (IGF-1), β-nerve growth factor (β-NGF), and brain-derived neurotrophic factor (BDNF) in bipolar disorder. MethodsBaseline levels of culture-stimulated IGF-1, β-NGF, and BDNF were compared in 116 patients with bipolar I disorder and 123 healthy controls. Neurotrophic factors were also compared in patients before and after 6 weeks of pharmacotherapy. A multivariate logistic regression analysis was used to investigate the influence of the neurotrophic factors analyzed in quartile form, in relation to confounding variables, such as age, sex, and body mass index. ResultsIGF-1 was significantly higher in patients (mean=514.57, SD=259.78) than in healthy controls (mean=316.82, SD=270.00, p<0.0001) at baseline. Furthermore, higher levels of IGF-1 substantially increased the risk for bipolar I disorder. IGF-1 level was not significantly changed at 6-weeks (mean=506.41, SD=313.66). No changes in BDNF or β-NGF-1 levels were found following the 6-week treatment period. IGF-1 and β-NGF were negatively correlated in healthy controls, but not in patients. Severity of manic symptoms was not associated with any of the neurotrophic factors. LimitationsWe did not measure cortisol, growth hormone, or IGF-1 receptors. This study is cross-sectional in design. ConclusionsElevated IGF-1 levels may be a trait marker for bipolar disorder. Further studies are needed to thoroughly investigate the role of IGF-1 in relation to other neuroendocrine factors and biological markers for bipolar disorder.

Auditory P3 in antidepressant pharmacotherapy treatment responders, non-responders and controls

Event-related potentials (ERPs), derived from electroencephalographic (EEG) recordings, can index electrocortical activity related to cognitive operations. The fronto–central P3a ERP is involved in involuntary processing of novel auditory information, whereas the parietal P3b indexes controlled attention processing. The amplitude of the auditory P3b has been found to be decreased in major depressive disorder (MDD). However, few studies have examined the relations between the P3b, the related P3a, and antidepressant treatment response. We tested 53 unmedicated individuals (25 females) with MDD, as well as 43 non-depressed controls (23 females) on the novelty oddball task, wherein infrequent deviant (target) and frequent standard (non-target) tones were presented, along with infrequent novel (non-target/distractor) sounds. The P3a and P3b ERPs were assessed to novel and target sounds, respectively, as were their accompanying behavioral performance measures. Depression ratings and the antidepressant response status were assessed following 12 weeks of pharmacotherapy with three different regimens. Antidepressant treatment non-responders had smaller baseline P3a/b amplitudes than responders and healthy controls. Baseline P3b amplitude also weakly predicted the extent of depression rating changes by week 12. Females exhibited larger P3a/b amplitudes than males. With respect to task performance, controls had more target hits than treatment non-responders. ERP measures correlated with clinical changes in males and with behavioral measures in females. These results suggest that greater (or control-like) baseline P3a/b amplitudes are associated with a positive antidepressant response, and that gender differences characterize the P3 and, by extension, basic attentive processes.

The DRD4 Exon III VNTR, Bupropion, and Associations With Prospective Abstinence

DRD4 Exon III Variable Number of Tandem Repeat (VNTR) variation was found to interact with bupropion to influence prospective smoking abstinence, in a recently published longitudinal analyses of N = 331 individuals from a randomized double-blind placebo-controlled trial of bupropion and intensive cognitive-behavioral mood management therapy. We used univariate, multivariate, and longitudinal logistic regression to evaluate gene, treatment, time, and interaction effects on point prevalence and continuous abstinence at end of treatment, 6 months, and 12 months, respectively, in N = 416 European ancestry participants in a double-blind pharmacogenetic efficacy trial randomizing participants to active or placebo bupropion. Participants received 10 weeks of pharmacotherapy and 7 sessions of behavioral therapy, with a target quit date 2 weeks after initiating both therapies. VNTR genotypes were coded with the long allele dominant resulting in 4 analysis categories. Covariates included demographics, dependence measures, depressive symptoms, and genetic ancestry. We also performed genotype-stratified secondary analyses. We observed significant effects of time in longitudinal analyses of both abstinence outcomes, of treatment in individuals with VNTR long allele genotypes for both abstinence outcomes, and of covariates in some analyses. We observed non-significantly larger differences in active versus placebo effect sizes in individuals with VNTR long allele genotypes than in individuals without the VNTR long allele, in the directions previously reported. VNTR by treatment interaction differences between these and previous analyses may be attributable to insufficient size of the replication sample. Analyses of multiple randomized clinical trials will enable identification and validation of factors mediating treatment response.

Dopamine transporter binding in social anxiety disorder: the effect of treatment with escitalopram

Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed to unfamiliar people or to possible scrutiny by others. The literature on dopamine ligands and dopamine genotypes in SAD is however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram. DAT single photon emission computed tomography (SPECT) using (123)I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy, and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects' Liebowitz Social Anxiety Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration.