International journal of medical and biological frontiers最新文献

The default mode network (DMN) supports self-referential thought processes important for successful socialization including: theory-of-mind, episodic memory, and prospection. Connectivity between DMN's nodes, which are distributed between the frontal, temporal, and parietal lobes, change with age and may continue changing into adulthood. We have previously explored the maturation of functional connections in the DMN as they relate to autism spectrum disorder (ASD) in children 6 to 18 years of age. In this chapter, we refine our earlier study of DMN functional maturation by focusing on the development of inter-nodal connectivity in a larger pool of typically developing people 6 to 25 years of age (mean = 13.22 years ± 5.36 s.d.; N = 36; 42% female). Correlations in BOLD activity (Fisher's Z) between ROIs revealed varying strengths of functional connectivity between regions, the strongest of which was between the left and right inferior parietal lobules or IPLs (Z = 0.62 ± 0.25 s.d.) and the weakest of which was between the posterior cingulate cortex (PCC) and right middle temporal gyrus or MTG (Z = 0.06 ± 0.22 s.d.). Further, connectivity between two pairs of DMN nodes significantly increased as a quadratic function of age (p < 0.05), specifically the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and PCC nodes and the left IPL and right MTG nodes. The correlation between ACC/mPFC ↔ PCC connectivity and age was more significant than the correlation between left IPL ↔ right MTG connectivity and age by more than an order of magnitude. We suggest that these changes in functional connectivity in part underlie the introspective mental changes known to commonly occur between the preadolescent and adult years. A range of neurological and psychological conditions that hamper social interactions, from ASD to psychopathy, may be marked by deviations from this maturational trajectory.

The results of some studies suggest that the serotonin transporter-linked polymorphic region (5-HTTLPR) short (S) allele, relative to the long (L) allele, is associated with risk for Major Depressive Disorder (MDD) and for Alcohol Use Disorder (AUD), and thus serves as biomarker for those disorders, while results from other studies do not support that conclusion. Persons with an S allele demonstrate a 2- to 2.5 fold decrease in serotonin transcription rate compared to the L-allele, which may increase their risk for MDD. Differences in study populations may help explain the differences in findings between those meta-analyses. To date, there have been no published reports which have addressed the possible association between the S allele and MDD among military veterans. This manuscript describes a first study to assess the possible association of the S allele with MDD or with AUD among a study population of veterans in treatment for a substance use disorder. We hypothesized that the S allele would be associated with MDD in our study sample. Subjects signing informed consent were 101 Veterans recruited from VA behavioral health and substance use treatment clinics in the VA Pittsburgh Healthcare System, and 91 of those subjects were genotyped for 5-HTTLPR polymorphisms. The study sample from whom genetic material was collected included 82 males and 9 females, of whom 53 were white, 38 were black, and one was "other". Fifty-four members of the study sample (59%) met DSM-IV criteria for an MDD on the SCID. Forty-five of the subjects demonstrated one or two S alleles, while 46 did not do so. The presence of the S allele of the serotonin transporter was not found to be significantly associated with the diagnosis of major depressive disorder or with alcohol use disorders in our sample. Those findings, in combination with other recent negative findings from other researchers involving non-veterans, raise questions regarding the clinical utility of utilizing genetics tests involving the assessment of the alleles of the serotonin transporter as a possible biomarker for MDD or for AUD.

Cognitive Behavioral Therapy (CBT) is a commonly used therapy among persons with major depressive disorder (MDD) and also among those with alcohol use disorders (AUD). However, less is known regarding the efficacy of CBT for treating persons with co-occurring disorders involving both MDD and an AUD. Studies assessing the efficacy of CBT in adolescent populations with co-occurring disorders are particularly sparse, especially studies designed to assess the potential longer-term efficacy of an acute phase trial of CBT therapy in that youthful comorbid population. We recently conducted a first acute phase treatment study involving comorbid AUD/MDD adolescents, which involved the medication fluoxetine as well as manualized CBT therapy. The results of that acute phase study suggested efficacy for CBT therapy but not for fluoxetine for treating the depressive symptoms and the excessive alcohol use of study subjects (Cornelius et al., 2009). The current chapter provides an assessment of the long-term efficacy of CBT for treating comorbid AUD/MDD adolescents, based on results from our own long-term (four-year) follow-up study, which was conducted following the completion of our recent acute phase treatment study. The results of the study suggest long-term efficacy for acute phase CBT/MET therapy for treating both the depressive symptoms and the excessive alcohol use of comorbid AUD/MDD adolescents, but demonstrate no evidence of long-term efficacy for fluoxetine for treating either the depressive symptoms or the excessive alcohol use of that population.

Background: Interleukin-17 (IL-17A) expression is increased in prostate cancer. This study investigated the expression of IL-17A receptor C (IL-17RC) in prostatic intraepithelial neoplasia (PIN) lesions and the effects of IL-17A on prostatic epithelial cells in in-vitro studies.

Methods: IL-17RC expression in human and rodent prostate tissues was detected by immunohistochemistry. Quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot analyses were used to determine mRNA and protein expression in human and mouse prostatic epithelial cell lines.

Results: IL-17RC protein was increased in human and rodent PIN lesions, compared to the normal human and rodent prostatic epithelium. IL-17A treatment activated the Nuclear Factor-κB (NF-κB) and/or Extracellular signal-Regulated Kinase (ERK) pathways in human PIN and LNCaP cell lines as well as mouse prostate cancer cell line TRAMP-C1. IL-17A treatment did not affect cell growth of the cell lines studied. However, IL-17A induced expression of CXCL1, CXCL2, CCL2, CCL5, and IL-6 in human and mouse prostatic epithelial cell lines. When the full-length IL-17RC was over-expressed in human PIN and LNCaP cell lines, activation of NF-κB and/or ERK pathways and expression of CXCL1, CXCL2, and CCL5 chemokines were significantly enhanced upon IL-17A treatment.

Conclusion: These findings suggest that the prostatic epithelial cells in PIN lesions may respond to IL-17A stimuli with augmented synthesis of chemokines, due to increased IL-17RC expression.

Objective: This study compared the acute phase (12-week) and the long-term (1 year) efficacy of fluoxetine versus placebo for the treatment of the depressive symptoms and the cannabis use of youth with comorbid major depressive disorder (MDD) and an cannabis use disorder (CUD)(cannabis dependence or cannabis abuse). We hypothesized that fluoxetine would demonstrate efficacy in the acute phase trial and at the 1-year follow-up evaluation. Data is also provided regarding the prevalence of risky sexual behaviors in our study sample.

Methods: We recently completed the first double-blind placebo-controlled study of fluoxetine in adolescents and young adults with comorbid MDD/CUD. A total of 70 persons participated in the acute phase trial, and 68 of those persons (97%) also participated in the 1-year follow-up evaluation. Results of the acute phase study have already been presented (Cornelius, Bukstein, et al., 2010), but the results of the 1 year follow-up assessment have not been published previously. All participants in both treatment groups also received manual-based cognitive behavioral therapy (CBT) and motivation enhancement therapy (MET) during the 12-week course of the study. The 1-year follow-up evaluation was conducted to assess whether the clinical improvements noted during the acute phase trial persisted long term.

Results: During the acute phase trial, subjects in both the fluoxetine group and the placebo group showed significant within-group improvement in depressive symptoms and in cannabis-related symptoms. However, no significant difference was noted between the floxetine group and the placebo group on any treatment outcome variable during the acute phase trial. End of study levels of depressive symptoms were low in both the fluoxetine group and the placebo group. Most of the clinical improvements in depressive symptoms and for cannabis-related symptoms persisted at the 1-year follow-up evaluation.

Conclusions: Fluoxetine did not demonstrate greater efficacy than placebo for treating either the depressive symptoms or the cannabis-related symptoms of our study sample during the acute phase study or at the 1-year follow-up assessment. The lack of a significant treatment effect for fluoxetine may at least in part reflect efficacy of the CBT/MET psychotherapy. A persistence of the efficacy of the acute phase treatment was noted at the 1-year follow-up evaluation, suggesting long-term effectiveness for the CBT/MET psychotherapy.

This manuscript begins by reviewing the literature concerning the use of the SCID versus the PCL for diagnosing PTSD, and by reviewing the literature regarding the presence of suicidal ideation as a clinical correlate of PTSD. This manuscript then describes our recent study involving PTSD among Veterans, which assessed the presence of suicidal ideation as a clinical correlate of PTSD, as diagnosed by the SCID versus as diagnosed by the PCL. We hypothesized that the presence of suicidal ideation would be associated with a diagnosis of PTSD. Subjects were 101 Veterans recruited from VA behavioral health and substance use treatment clinics in the VA Pittsburgh Healthcare System. The study compared correlations of suicidal ideation with PTSD as determined with the PTSD Checklist versus the Structured Clinical Interview for DSM-IV, and utilized question 9 of the Beck Depression Inventory for assessing presence of SI. PTSD was diagnosed in 15 subjects using the SCID, and in 15 subjects using the PTSD Checklist. SI were reported by 16 subjects. The presence of SI was significantly associated with the diagnosis of PTSD on the PCL (chi-square=5.73, df=1, p=0.017) but not on the SCID (chi-square=0.08, df=1, p=0.773). These findings suggest that SI associated with the diagnosis of PTSD among Veterans are better ascertained by the PCL as compared to the more elaborate diagnostic algorithm used in the SCID. The current study finding raises the possibility that a less complicated diagnostic assessment instrument such as the PCL may be superior to the SCID, a more complicated instrument for diagnosing PTSD, at least in some populations.

Background: Previous cross-sectional studies involving adults suggest that sexually transmitted diseases (STD) such as cocaine use disorders and opioid use disorders are associated with the development of sexually transmitted diseases (STD). However, it is less clear whether cannabis use disorders (CUD) are associated with the development of STDs, or whether those associations extend to adolescent populations. Longitudinal studies examining those associations are particularly scarce. The current report provides findings from a longitudinal study that examined the relationship between STD and CUD among youth transitioning to young adulthood.

Method: The subjects in this longitudinal study were initially recruited when the index sons of these fathers were 10-12 years of age, and subsequent assessments were conducted at age 12-14, 16, 19, and 22. Multivariate logistic regression and path analyses were conducted.

Results: At age 22, of the 345 subjects, 30 subjects were diagnosed with one or more STD, and 105 were diagnosed with a CUD. STDs were almost four times as common among those with a CUD as among those without a CUD, which was a significant difference. Path analyses demonstrated that peer deviance mediated the association between a measure of risk for SUD knows as the TLI and CUD, and that peer deviance mediated the association between TLI and STD. Risky sexual behaviors were common.

Conclusions: These finding suggest that cannabis use disorders (CUD) predispose to the development of sexually transmitted disorders (STD) among youth. These findings also suggest that peer deviance mediates the development of STD and of CUD among teenagers making the transition to young adulthood.