The Impact of Teen Court on Rural Adolescents: Improved Social Relationships, Psychological Functioning, and School Experiences.

Teen Court is a prevention program aimed at diverting first time juvenile offenders from the traditional juvenile justice system and reintegrating them into the community. Few studies have examined if Teen Court impacts adolescent functioning. We examined how Teen Court participation impacted psychosocial functioning, social relationships, and school experiences in a sample of 392 rural Teen Court participants relative to two comparison samples, one from the same county as Teen Court (n = 4276) and one from a neighboring county (n = 3584). We found that Teen Court has the potential to decrease internalizing symptoms, externalizing behavior, violent behavior, parent-adolescent conflict, and delinquent friends, and increase self-esteem and school satisfaction.

L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials.

OBJECTIVE: The authors conducted two multicenter sequential parallel comparison design trials to investigate the effect of L-methylfolate augmentation in the treatment of major depressive disorder in patients who had a partial response or no response to selective serotonin reuptake inhibitors (SSRIs). METHOD: In the first trial, 148 outpatients with SSRI-resistant major depressive disorder were enrolled in a 60-day study divided into two 30-day periods. Patients were randomly assigned, in a 2:3:3 ratio, to receive L-methylfolate for 60 days (7.5 mg/day for 30 days followed by 15 mg/day for 30 days), placebo for 30 days followed by L-methylfolate (7.5 mg/day) for 30 days, or placebo for 60 days. SSRI dosages were kept constant throughout the study. In the second trial, with 75 patients, the design was identical to the first, except that the l-methylfolate dosage was 15 mg/day during both 30-day periods. RESULTS: In the first trial, no significant difference was observed in outcomes between the treatment groups. In the second trial, adjunctive L-methylfolate at 15 mg/day showed significantly greater efficacy compared with continued SSRI therapy plus placebo on both primary outcome measures (response rate and degree of change in depression symptom score) and two secondary outcome measures of symptom severity. The number needed to treat for response was approximately six in favor of adjunctive L-methylfolate at 15 mg/day. L-Methylfolate was well tolerated, with rates of adverse events no different from those reported with placebo. CONCLUSIONS: Adjunctive L-methylfolate at 15 mg/day may constitute an effective, safe, and relatively well tolerated treatment strategy for patients with major depressive disorder who have a partial response or no response to SSRIs.

Resistance training reduces subclinical inflammation in obese, postmenopausal women.

PURPOSE: Aerobic exercise is frequently prescribed to reduce inflammatory-related disease (cardiovascular disease and diabetes) risk. Resistance training (RT), however, may be key to maximizing anti-inflammatory benefits of consistent exercise. We examined the influence of RT on inflammatory biomarkers in obese, postmenopausal women. METHODS: Twenty-three women (65.6 ± 2.6 yr; body mass index, 33 kg·m) underwent 12 wk of RT (3 sets, 10 exercises, 3× per week, 8-12 repetition maximum (RM), resistance exercise (EX), N = 11) or social interaction intervention (SI, stretching, knitting, health lectures, 2× per week, control group (CON), N = 12). Both before (BT) and after (AT) RT or SI, blood was collected before (PR), immediately (PO), 2 h (2H), and 24 h (24H) after a single resistance exercise bout (RE) in EX and at the same time points in nonexercise, resting CON. For all time points, blood was analyzed for IL-6, leptin, and lipopolysaccharide (LPS)-stimulated tumor necrosis factor-α (TNF-α) (LPS-TNF) and IL-10 (LPS-IL10). PR samples were also examined for C-reactive protein, TNF-α, and adiponectin, and mRNA expression of toll-like receptor 4 (TLR4) and MC1R. Subcutaneous adipose tissue was extracted BT and AT and analyzed for mRNA expression of monocyte chemotactic protein-1, leptin, CD68, and TLR4. RESULTS: RT improved strength (44%) and reduced circulating C-reactive protein (-33%), leptin (-18%) and TNF-α (-29%) with no change in body composition. IL-6 decreased after SI in CON (-17%). LPS-TNF increased after SI or RT (CON +26%, EX +67%, respectively), whereas LPS-IL10 decreased in CON (-28%) but increased in EX (+20%). RT did not influence inflammatory biomarker gene expression in whole blood or subcutaneous adipose tissue. A single RE bout augmented LPS-TNF and LPS-IL10 at 24H in EX, particularly AT. CONCLUSION: RT reduced markers of subclinical inflammation in circulation in obese, postmenopausal women in the absence of changes in body composition. Chronic RT also enhanced response to endotoxin challenge both at rest (PR) and 24 h after an acute RE bout (24H).

A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression.

BACKGROUND: Previous reports have suggested that lamotrigine is effective as an antidepressant augmentation agent in patients with treatment-resistant unipolar depression. This study is the largest double-blind placebo-controlled study conducted to date of lamotrigine in this role. METHOD: In this multicenter trial, conducted at 19 sites, patients aged 18-65 years with a DSM-IV/ICD-10 diagnosis of unipolar, nonpsychotic major depressive disorder (confirmed by the Mini-International Neuropsychiatric Interview) who had failed at least 1 adequate trial of an antidepressant (N = 183) were first treated for 8 weeks with open-label paroxetine or paroxetine controlled-release in dosages up to 50 mg/d or 62.5 mg/d, respectively. Individuals with a 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 15 (n = 96) were then randomized on a double-blind basis to receive either placebo or lamotrigine in dosages titrated upward to a maximum of 400 mg/d for 10 weeks. Sixty-five patients completed the study. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS), and the main secondary outcome measures were the HDRS-17 and Clinical Global Impressions-Severity of Illness (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) ratings. Data were collected from 2003 to 2006. RESULTS: Results of the primary efficacy analysis of the randomized patients using the MADRS, HDRS-17, CGI-S, and CGI-I did not demonstrate a statistically significant difference between lamotrigine and placebo groups, although some secondary analyses were suggestive of efficacy, particularly in those patients who completed the study (completer analysis) and in more severely ill patients (HDRS-17 ≥ 25). CONCLUSIONS: This add-on study of patients with treatment-resistant depression failed to detect a statistically significant difference between lamotrigine and placebo given for 10 weeks. However, post hoc analyses suggest that future studies of lamotrigine's efficacy might focus on specific subgroups with depression. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00901407.

The melanocortin 3 receptor: a novel mediator of exercise-induced inflammation reduction in postmenopausal women?

The purpose of this study was to determine whether resistance exercise training-induced reductions in inflammation are mediated via melanocortin 3 receptor expression in obese (BMI 32.7 ± 3.7) women (65.6 ± 2.8 yrs) randomized to either a control (N = 11) or resistance training group (N = 12). The resistance trained group performed resistance training 3 days/week for 12 weeks. Resting blood samples were collected before and after the training intervention in both resistance trained and control groups. Resistance training upregulated melanocortin 3 receptor mRNA by 16-fold (P = .035) and decreased monocyte count, without changing leukocyte number, body composition, or body weight. Resistance trained individuals exhibited increased sensitivity to inflammatory stimuli, whereas control individuals exhibited no change. While there was no change in whole blood tumor necrosis factor alpha mRNA between the groups, whole blood interleukin 10 mRNA was higher in the resistance trained group following the intervention period. In summary, it appears that resistance training may modulate melanocortin 3 receptor expression, providing a possible mechanism for the anti-inflammatory effects of exercise training.

Exercise-associated hyponatremia: the influence of pre-exercise carbohydrate status combined with high volume fluid intake on sodium concentrations and fluid balance.

To evaluate the effect of hydration and carbohydrate (CHO) status on plasma sodium, fluid balance, and regulatory factors (IL-6 & ADH) during and after exercise; 10 males completed the following conditions: low CHO, euhydrated (fluid intake = sweat loss) (LCEH); low CHO, dehydrated (no fluid) (LCDH); high CHO, euhydrated (HCEH); and high CHO, dehydrated (HCDH). Each trial consisted of 90-min cycling at 60% VO(2) max in a 35°C environment followed by 3-h rehydration (RH). During RH, subjects received either 150% of sweat loss (LCDH & HCDH) or an additional 50% of sweat loss (LCEH and HCEH). Blood was analyzed for glucose, IL-6, ADH, and Na(+). Post-exercise Na(+) was greater (p < 0.001) for LCDH and HCDH (141.7 + 0.72 and 141.6 + 0.4 mM) versus LCEH and HCEH (136.4 + 0.6 and 135.9 + 0.3 mM). Post-exercise IL-6 was similar in all conditions, and post-exercise ADH was greater (p = 0.01) in dehydrated versus euhydrated conditions. The rate of urine production was greater in HCEH (7.59 + 3.0 mL/min) compared to all other conditions (3.86 + 2.2, 5.29 + 3.1, and 2.96 + 1.1 mL/min for LCDH, LCEH, and HCDH, respectively). Despite CHO and hydration manipulations, no regulatory effects of IL-6 and ADH on plasma [Na(+)] were observed. With euhydration during exercise and additional fluid consumed during recovery, a high-CHO status increased urinary output during recovery, and it decreased the frequency of hyponatremia (Na(+) < 135 mM). Therefore, a high-CHO status may provide some protection against exercise-associated hyponatremia.

Effect of prior exercise on postprandial triglycerides in overweight young women after ingesting a high-carbohydrate meal.

To examine the effect of prior exercise on the postprandial lipid response to a high-carbohydrate meal in normal-weight (NW=BMI <25) and overweight (OW=BMI >or= 25) women (age 18-25), 10 NW and 10 OW participants completed 2 conditions separated by 1 month. In the morning, the day after control (CT=no exercise) or exercise conditions (EX=60 min cycling at 60% VO(2peak)), participants consumed a high-carbohydrate meal (80% CHO, 15% protein, 5% fat; 75 kJ/kg BM) followed by 6 hr of hourly blood sampling. Blood was analyzed for triglycerides (TG), blood glucose (BG), and insulin (IN). TG levels over the 6-hr period were lower in NW than OW (p= .021) and lower in EX than in CT (p= .006). Area under the curve (AUC) for TG was lower in NW than OW (p= .016) and EX than CT (p= .003). There were nonsignificant tendencies for reduced BG over time (p= .053) and AUC (p= .083), and IN AUC was lower in EX than in CT (p= .040) for both groups and lower in NW than in OW (p= .039). Prior exercise improved TG levels after a high-carbohydrate meal in both groups, and OW women demonstrated a greater postprandial lipemic response than NW regardless of condition. There were tendencies for improved glucose removal with prior exercise in NW vs. OW. Acute exercise can improve postprandial TG responses and might also improve postprandial BG and IN after a large meal in NW and OW young women.

Cyclic AMP-independent activation of CYP3A4 gene expression by forskolin.

Forskolin and cAMP have been shown to have paradoxical effects in the regulation of expression levels of mRNA of cytochrome P450 3A (CYP3A) family members. We demonstrate in this study that forskolin upregulated the promoter for CYP3A4 independent of its ability to increase cAMP levels. This activity was explained showing forskolin directly activated the pregnane-X-receptor, a known regulator of CYP3A genes.

The effectiveness of olanzapine, risperidone, quetiapine, and ziprasidone as augmentation agents in treatment-resistant major depressive disorder.

BACKGROUND: Many questions remain regarding the use of atypical neuroleptics as antidepressant augmentation agents. To date, there have been no reports in the literature regarding the effectiveness of these drugs when trials of one or more of them have failed previously as antidepressant augmentation. METHOD: This retrospective chart review was conducted to determine the effectiveness of olanzapine, risperidone, quetiapine, and ziprasidone when given in a fee-for-service setting as anti-depressant augmentation agents to patients with treatment-resistant, nonpsychotic major depressive disorder (DSM-IV). Prospective (Global Assessment of Functioning [GAF]) along with retrospective (Clinical Global Impressions-Improvement [CGI-I] and -Severity of Illness scales) ratings were completed for each patient. Analyses were conducted in an attempt to identify factors that appeared to correlate with response, including order of administration and Thase-Rush staging of treatment resistance. RESULTS: In this study of 76 medication trials in 49 patients, the overall response rate based on the CGI-I ratings was 65% (32/49). Individual rates of response were 57% (21/37) for olanzapine, 50% (7/14) for risperidone, 33% (6/18) for quetiapine, and 10% (1/10) for ziprasidone. None of the differences between neuroleptics in rates of response were significant. The difference between baseline and final GAF scores was statistically significant only in the olanzapine (p <.001) and risperidone (p =.047) groups. Rates of discontinuation did not vary significantly between agents, though trends were present. Crossover trials from one atypical neuroleptic to another in the event of nonresponse appeared to be effective. CONCLUSIONS: Although limited by its design, this study suggests atypical neuroleptic augmentation of antidepressants may be a viable option in treatment-resistant major depressive disorder.

Aripiprazole augmentation in treatment-resistant depression.

BACKGROUND: Evidence is accumulating to support the use of atypical neuroleptics as adjunctive treatment for refractory mood disorders, although there are currently no published data on the efficacy of an atypical neuroleptic in treatment-resistant depression when a previous trial of drug from the same class has failed. The authors hypothesized that aripiprazole would be efficacious in augmenting antidepressant treatment in resistant patients with non-psychotic unipolar depression who had previously failed a trial of another atypical neuroleptic. METHODS: This study was a retrospective chart review of the efficacy of aripiprazole augmentation in 30 treatment-resistant unipolar depression patients who had failed multiple previous antidepressant trials and had also failed augmentation with at least one other atypical neuroleptic. Prospective Global Assessment of Functioning and Clinical Global Impressions-Improvement scores were completed on each patient throughout treatment. RESULTS: Utilizing an intent-to-treat analysis (including 9 patients who dropped out prior to completion of 6 weeks), 46.7% (14/30) patients were rated much improved or very much improved with treatment. This improvement negatively correlated with Thase-Rush staging of treatment resistance. GAF scores also showed a significant improvement. Six of the 14 patients who initially improved subsequently relapsed (yielding a long-term net response rate of 26.7%). CONCLUSION: Aripiprazole may be effective as an antidepressant augmentation agent in highly treatment resistant patients who had failed a prior trial of another atypical neuroleptic.

Topiramate in the treatment of severe bulimia nervosa with comorbid mood disorders: a case series.

OBJECTIVE: To report observations on the efficacy and tolerability of topiramate in a sample of five patients with severe symptoms of bulimia nervosa and comorbid mood and/or anxiety disorders. METHOD: Topiramate was added to other psychotropic medication under open-label conditions up to the maximum tolerated dose or until remission of the eating disorder was achieved. RESULTS: Topiramate almost completely eliminated binging and purging behavior in three of the five patients. Improvement was maintained throughout the period of follow-up for up to 18 months. One patient showed a partial, temporary response, and the fifth was intolerant of the drug and unable to complete an adequate trial. DISCUSSION: These results suggest strongly that the efficacy of topiramate in patients with bulimia nervosa with and without comorbid mood and anxiety disorders should be investigated more fully.

A follow-up study of DSM-III-R generalized anxiety disorder with syndromal and subsyndromal major depression.

OBJECTIVE: The authors examined the long-term outcome of generalized anxiety disorder with depressive symptoms utilizing both categorical and dimensional analyses. METHOD: Thirty-nine out-patients with a DSM-III-R diagnosis of generalized anxiety disorder (GAD) with depressive symptoms, both with (n=23) and without (n=16) syndromal major depression (MD) participated in an 11-week clinical trial. Approximately 18 months after initial screening, these individuals were once again evaluated using a structured diagnostic interview and a battery of rating scales. RESULTS: Three distinct groups were discernible at follow-up. Twenty-three (60%) of the patients remained syndromal for GAD; 10 patients (43%) were in partial remission from GAD; six (15%) were asymptomatic. Of the 23 patients who were syndromal for MD at baseline, 13 (56%) remained syndromal for MD at follow-up. All of the patients who were syndromal for MD at follow-up remained syndromal for GAD as well. CONCLUSIONS: Outcomes in this study were quite divergent, though they support the concept of GAD as a chronic illness in most patients, with or without MD. The presence or absence of MD versus subsyndromal depression at baseline appeared to have relatively little impact upon the outcome. Patients with subsyndromal anxiety and depressive symptoms may be at special risk for syndromal disorders over time.

Stability of worry content in GAD patients: a descriptive study.

The stability of worry content was investigated in a sample of 27 individuals diagnosed with Generalized Anxiety Disorder. During an initial evaluation, participants were asked to describe the content of their current worries, and the examining psychiatrist rated the frequency and intensity of these topics. During the following year, the investigators interviewed the participants on a monthly basis assessing the intensity and frequency of original worries, intensity and frequency of new worries, overall worry level, and general anxiety level. Analysis of this longitudinal data indicated level of overall worry and anxiety remained fairly stable over a 12-month period. Although the intensity and frequency of original worries decreased over time, few original worry topics completely remitted. In fact, at the end of the 12-month monitoring period, worry content identified at baseline continued to account for over 65% of the overall worry variance. Most participants did identify new worry topics during the course of the 12-month period, and the frequency and intensity of the new worries were comparable to the decrease in frequency and intensity of the original worries.

Lamotrigine as an augmentation agent in treatment-resistant depression.

BACKGROUND: The anticonvulsant lamotrigine has been reported to be efficacious and well tolerated as monotherapy in the treatment of bipolar patients as well as in treatment-refractory bipolar disorder. However, there is a paucity of research on the use of lamotrigine as an augmentation agent in treatment-refractory unipolar major depressive disorder. METHOD: This study was a retrospective chart review on the efficacy of lamotrigine augmentation in 37 individuals diagnosed with chronic or recurrent major depressive disorder (DSM-IV) who had failed to respond adequately to at least 2 previous trials of antidepressants. Thirty-one patients who were on lamotrigine treatment for at least 6 weeks (6 discontinued prematurely due to adverse events) took a mean dose of 112.90 mg/day for a mean of 41.80 weeks. The primary efficacy parameter for this study was the Clinical Global Impressions scale, which was retrospectively applied. In addition, these data were supplemented by an analysis of prospectively rated Global Assessment of Functioning scores. RESULTS: On the basis of intent-to-treat analysis, response rates were as follows: 40.5% (15/37) much improved or very much improved, 21.6% (8/37) mildly improved, and 37.8% (14/37) unchanged. The percentage of patients who were rated much or very much improved and completed 6 weeks on the drug was 48.4% (15/31). No differences were found in the doses of lamotrigine given to responders and nonresponders. CONCLUSION: Analyses revealed that lamotrigine treatment was most effective for patients who had been depressed for shorter periods of time and had failed fewer previous trials of antidepressants. Data also suggested a trend toward increased response for patients with comorbid anxiety disorders and/or chronic pain syndromes.