A satisfaction survey of current medicines used for migraine therapy in China: is Chinese patent medicine effective compared with Western medicine for the acute treatment of migraine?

OBJECTIVE: To investigate the patient satisfaction with medications commonly used for migraine therapy in patients seen in headache clinic in China with emphasis on the evaluation of Chinese patent medicine (CPM) in relieving acute migraine attack. METHODS: Patients admitted at headache clinics in the neurological departments of four hospitals during April to October 2011 were enrolled in the investigation. The questionnaire was designed based on the validation of a diagnostic questionnaire for a population-based survey in China in 2009. RESULTS: Among 219 eligible patients, 58% had used CPM at the acute attack of migraine while the guideline-recommended treatments were seldom used. However, patients using CPMs were less satisfied than those using Western Medicines (WMs) in either single medication groups or mixed medication groups (P < 0.05). CONCLUSION: Fifty-eight percent of the eligible respondents in Guangdong and Guangxi Province had used CPM at the acute attack of migraine, but based on our data, the effect of CPM on treating migraine attack was poor with low satisfaction compared with WMs. However, many factors may bias or explain our findings. This suggests the need for accelerated research in understanding patient choice, treatment availability, and use of medications.

A randomized, one-year clinical trial comparing the efficacy of topiramate, flunarizine, and a combination of flunarizine and topiramate in migraine prophylaxis.

OBJECTIVES: The objective of this study was to observe the efficacy, safety, and side effects of a combination of flunarizine plus topiramate compared with either flunarizine and or toparamate alone for migraine prophylaxis. METHODS: Out of 150 patients with migraine recruited into the study and randomly assigned to one of three conditions, 126 completed the trial in their group: flunarizine (39), topiramate (44), and flunarizine plus topiramate (43). Patient information was assessed at enrollment and at follow-up visits at the end of months 1-3, 6, 9, and 12. The primary measure of efficacy reduction in mean monthly migraine frequency of at least 50% as compared with baseline. Secondary efficacy parameters included reduction in mean monthly migraine days and severity of headache. Side effects were compared in the three groups by recording adverse reactions and weight changes. RESULTS: The proportion whose monthly headache frequency decreased more than 50% was 66.7% (26/39) in the flunarizine group, 72.7% (32/44) in the topiramate group and 76.7% (33/43) in the combination group, respectively (P=0.593). The mean monthly days and severity of headache in the three groups also declined and was more significant in the flunarizine plus topiramate group than in the flunarizine group and the topiramate group (P<0.05). In the flunarizine group, the average weight change was 0.6kg. Topiramate was associated with a mean weight loss was of -0.9kg in the topiramate group and -0.2kg in the flunarizine plus topiramate group. CONCLUSION: Flunarizine, topiramate, and the combination of flunarizine with topiramate are all effective and have good tolerability in migraine prophylaxis. Adding topiramate to flunarizine may reduce the latter's impact on body weight.

Neurosteroids and self-reported pain in veterans who served in the U.S. Military after September 11, 2001.

OBJECTIVE: Nearly half of Operation Enduring Freedom/Operation Iraqi Freedom veterans experience continued pain post-deployment. Several investigations report analgesic effects of allopregnanolone and other neurosteroids in animal models, but few data are currently available focusing on neurosteroids in clinical populations. Allopregnanolone positively modulates GABA(A) receptors and demonstrates pronounced analgesic and anxiolytic effects in rodents, yet studies examining the relationship between pain and allopregnanolone in humans are limited. We thus hypothesized that endogenous allopregnanolone and other neurosteroid levels may be negatively correlated with self-reported pain symptoms in humans. DESIGN: We determined serum neurosteroid levels by gas chromatography/mass spectrometry (allopregnanolone, pregnenolone) or radioimmunoassay (dehydroepiandrosterone [DHEA], progesterone, DHEA sulfate [DHEAS]) in 90 male veterans who served in the U.S. military after September 11, 2001. Self-reported pain symptoms were assessed in four areas (low back pain, chest pain, muscle soreness, headache). Stepwise linear regression analyses were conducted to investigate the relationship between pain assessments and neurosteroids, with the inclusion of smoking, alcohol use, age, and history of traumatic brain injury as covariates. SETTING: Durham VA Medical Center. RESULTS: Allopregnanolone levels were inversely associated with low back pain (P=0.044) and chest pain (P=0.013), and DHEA levels were inversely associated with muscle soreness (P=0.024). DHEAS levels were positively associated with chest pain (P=0.001). Additionally, there was a positive association between traumatic brain injury and muscle soreness (P=0.002). CONCLUSIONS: Neurosteroids may be relevant to the pathophysiology of self-reported pain symptoms in this veteran cohort, and could represent future pharmacological targets for pain disorders.

Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer's disease compared to cognitively intact control subjects.

The neurosteroid allopregnanolone has pronounced neuroprotective actions, increases myelination, and enhances neurogenesis. Evidence suggests that allopregnanolone dysregulation may play a role in the pathophysiology of Alzheimer's disease (AD) and other neurodegenerative disorders. Our prior data demonstrate that allopregnanolone is reduced in prefrontal cortex in male patients with AD compared to male cognitively intact control subjects, and inversely correlated with neuropathological disease stage (Braak and Braak). We therefore determined if allopregnanolone levels are also reduced in AD patients compared to control subjects in temporal cortex, utilizing a larger set of samples from both male and female patients. In addition, we investigated if neurosteroids are altered in subjects who are APOE4 allele carriers. Allopregnanolone, dehydroepiandrosterone (DHEA), and pregnenolone levels were determined in temporal cortex postmortem samples by gas chromatography/mass spectrometry, preceded by high performance liquid chromatography (40 subjects with AD/41 cognitively intact control subjects). Allopregnanolone levels are reduced in temporal cortex in patients with AD (median 2.68 ng/g, n=40) compared to control subjects (median 5.64 ng/g, n=41), Mann-Whitney p=0.0002, and inversely correlated with Braak and Braak neuropathological disease stage (Spearman r=-0.38, p=0.0004). DHEA and pregnenolone are increased in patients with AD compared to control subjects. Patients carrying an APOE4 allele demonstrate reduced allopregnanolone levels in temporal cortex (Mann-Whitney p=0.04). In summary, our findings indicate that neurosteroids are altered in temporal cortex in patients with AD and related to neuropathological disease stage. In addition, the APOE4 allele is associated with reduced allopregnanolone levels. Neurosteroids may be relevant to the neurobiology and therapeutics of AD.

Premature ventricular complexes and the risk of incident stroke: the Atherosclerosis Risk In Communities (ARIC) Study.

BACKGROUND AND PURPOSE: Premature ventricular complexes (PVCs) on a 2-minute electrocardiogram are a common, largely asymptomatic finding associated with increased risk of coronary heart disease and death. They may reflect atherosclerosis or other pathogenic pathways that predispose to arrhythmias and stroke. METHODS: We conducted a prospective evaluation of the Atherosclerosis Risk In Communities Study cohort (n=14,783) of middle-aged men and women to assess whether the presence of PVCs at study baseline (1987 to 1989) influenced the risk of incident stroke through December 31, 2004. RESULTS: PVCs were seen in 6.1% of the participants at baseline, and 729 (4.9%) had incident stroke. The unadjusted cumulative proportion of incident stroke in individuals with any PVC was 6.6% compared with 4.1% in those without PVC. The unadjusted hazard ratio of incident stroke in individuals with any PVC compared with those without any PVCs was 1.71 (95% CI, 1.33 to 2.20). Among individuals without hypertension and diabetes at baseline, PVCs were independently associated with incident stroke (hazard ratio: 1.72; 95% CI: 1.14 to 2.59). Among those with either diabetes or hypertension, the presence of any PVCs did not increase the risk of stroke. The association was stronger for noncarotid embolic stroke than for thrombotic stroke and its magnitude increased with higher frequency of PVCs. CONCLUSIONS: Frequent PVCs are associated with risk of incident stroke in participants free of hypertension and diabetes. This suggests that PVCs may contribute to atrioventricular remodeling or may be a risk marker for incident stroke, particularly embolic stroke.

After the collaborative is over: what sustains quality improvement initiatives in primary care practices?

BACKGROUND: Multisite quality improvement (QI) initiatives, often known as collaboratives, involving primary care practices such as community health centers, academic practices, and managed care groups have been reported. Yet relatively little is known about the sustainability of these QI initiatives after the initial project, and frequently its funding, has ended. A series of practice characteristics that constitute critical elements for QI sustainability activities, as described in a Sustainability Pyramid Model, were proposed. METHODS: Approximately five months after the cessation of formalized activities of the final collaborative, 25 in-person interviews were conducted in 13 primary care practices that had participated in the three North Carolina Chronic Disease Management collaboratives, which initially involved 33 practices. Clinical outcomes were not considered. FINDINGS: Twelve of the 13 practices stated that the collaborative work resulted in improvement in one or more process and/or outcome clinical measures and those improvements have been continued. Five of the 13 practices reported that sustaining improvements had been a challenge since the collaboratives ended. Content analysis of the interviews indicated that the practices variously cited the practice characteristics, as included in the Sustainability Pyramid Model: regular meetings to study practice population data, leadership commitment, availability of infrastructure/staff support, pursuit of additional funding, publicity, and strategic partnerships. DISCUSSION: Although the improvement activities initiated during the collaborative were sustained, the process of developing and implementing new QI activities appeared to be more challenging for almost half of the practices. The practices that could accomplish this ongoing new QI process had "institutionalized" their QI strategies--a finding with important implications for sustainability.

Novel relationship of serum cholesterol with asthma and wheeze in the United States.

BACKGROUND: Cholesterol exerts complex effects on inflammation. There has been little investigation of whether serum cholesterol is associated with asthma, an inflammatory airways disease with great public health impact. OBJECTIVE: To determine relationships between levels of 3 serum cholesterol measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], and non-HDL-C) and asthma/wheeze in a sample representative of the US population. METHODS: Cross-sectional study of 7005 participants age >or=6 years from the 2005 to 2006 National Health and Nutrition Examination Survey. RESULTS: Serum TC and non-HDL-C were lower in patients with current asthma than in subjects without current asthma in the overall population (TC, 188.5 vs 192.2 mg/dL; non-HDL-C, 133.9 vs 137.7 mg/dL; P < .05 for both), whereas HDL-C was not different. Adjusted odds ratios (ORs) from multivariate logistic regression per 1-SD increase of TC and non-HDL-C for current asthma were 0.92 (95% CI, 0.86-0.98) and 0.91 (95% CI, 0.85-0.98), respectively. On racial/ethnic stratification, these relationships reflect marked reductions unique to Mexican Americans (MAs; TC, 171.4 vs 189.3 mg/dL; P < .001; OR, 0.62; 95% CI, 0.48-0.80; non-HDL-C, 119.8 vs 137.9 mg/dL; P < .001; OR, 0.62; 95% CI, 0.48-0.79). Among MAs, the adjusted OR for wheeze requiring medical attention was 0.57 (95% CI, 0.43-0.75) for TC and 0.53 (95% CI, 0.33-0.85) for non-HDL-C. Relationships between cholesterol and asthma/wheeze were independent of body mass index and serum C-reactive protein, and similar between atopic and nonatopic participants. CONCLUSION: Serum TC and non-HDL-C are inversely related to asthma in the US population, chiefly reflecting a relationship among MAs.

Cerebrospinal fluid dehydroepiandrosterone levels are correlated with brain dehydroepiandrosterone levels, elevated in Alzheimer's disease, and related to neuropathological disease stage.

OBJECTIVE: It is currently unknown whether cerebrospinal fluid (CSF) neurosteroid levels are related to brain neurosteroid levels in humans. CSF and brain dehydroepiandrosterone (DHEA) levels are elevated in patients with Alzheimer's disease (AD), but it is unclear whether CSF DHEA levels are correlated with brain DHEA levels within the same subject cohort. We therefore determined DHEA and pregnenolone levels in AD patients (n = 25) and cognitively intact control subjects (n = 16) in both CSF and temporal cortex. DESIGN: DHEA and pregnenolone levels were determined by gas chromatography/mass spectrometry preceded by HPLC. Frozen CSF and temporal cortex specimens were provided by the Alzheimer's Disease Research Center at Duke University Medical Center. Data were analyzed by Mann-Whitney U test statistic and Spearman correlational analyses. RESULTS: CSF DHEA levels are positively correlated with temporal cortex DHEA levels (r = 0.59, P < 0.0001) and neuropathological disease stage (Braak and Braak) (r = 0.42, P = 0.007). CSF pregnenolone levels are also positively correlated with temporal cortex pregnenolone levels (r = 0.57, P < 0.0001) and tend to be correlated with neuropathological disease stage (Braak) (r = 0.30, P = 0.06). CSF DHEA levels are elevated (P = 0.032), and pregnenolone levels tend to be elevated (P = 0.10) in patients with AD, compared with cognitively intact control subjects. CONCLUSIONS: These findings indicate that CSF DHEA and pregnenolone levels are correlated with temporal cortex brain levels of these neurosteroids and that CSF DHEA is elevated in AD and related to neuropathological disease stage. Neurosteroids may thus be relevant to the pathophysiology of AD.

Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting: Intervention in Older Persons with Acute Coronary Syndrome-Part I.

This is Part I of a two-part article on treatment of acute coronary syndrome in the older population. Part I analyzes the differential utilization of invasive therapies with respect to age and heart disease. Part II (to be published in the next issue of Clinical Geriatrics) will summarize information from the literature on acute coronary syndrome outcomes from invasive treatments (percutaneous coronary interventions or coronary artery bypass grafting) among older persons.

Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting: Intervention in Older Persons with Acute Coronary Syndrome-Part II.

This is Part II of a two-part article on treatment of acute coronary syndrome in the older population. Part I (published in the October issue of Clinical Geriatrics) analyzed the differential utilization of invasive therapies with respect to age and heart disease. Part II summarizes information from the literature on acute coronary syndrome outcomes from invasive treatments (percutaneous coronary interventions or coronary artery bypass grafting) among older persons.

Trends in emergency Medicaid expenditures for recent and undocumented immigrants.

CONTEXT: Undocumented immigrants and legal immigrants who have been in the United States less than 5 years are excluded from Medicaid eligibility, with the exception of limited coverage for emergency conditions (Emergency Medicaid). New immigrant population growth has been rapid in recent years, but little is known about use of health services by this group or the conditions for which Emergency Medicaid coverage has been applied. OBJECTIVE: To describe Emergency Medicaid use by recent and undocumented immigrants including patient characteristics, diagnoses, and recent spending trends in North Carolina, a state with a rapidly increasing population of undocumented immigrants. DESIGN, SETTING, AND PATIENTS: Descriptive analysis of North Carolina Medicaid administrative data for all claims reimbursed under Emergency Medicaid eligibility criteria 2001 through 2004 in North Carolina, a state with high immigration from Mexico and Latin America. Patients are recent and undocumented immigrants who meet categorical and income criteria for Medicaid coverage, but are excluded from full coverage due to legal status. MAIN OUTCOME MEASURES: Patient characteristics, hospitalizations, diagnoses, and Medicaid spending for emergency care. RESULTS: A total of 48,391 individuals received services reimbursed under Emergency Medicaid during the 4-year period of this study. The patient population was 99% undocumented, 93% Hispanic, 95% female, and 89% in the 18- to 40-year age group. Total spending increased by 28% from 2001 through 2004, with more rapid spending increases among elderly (98%) and disabled (82%) patients. In 2004, childbirth and complications of pregnancy accounted for 82% of spending and 91% of hospitalizations. Injury, renal failure, gastrointestinal disease, and cardiovascular conditions were also prevalent. CONCLUSIONS: Childbirth and complications of pregnancy account for the majority of Emergency Medicaid spending for undocumented immigrants in North Carolina. Spending for elderly and disabled patients, however, is increasing at a faster rate. Among nonpregnant immigrants, injuries, other acute emergencies, and severe complications of chronic disease are major contributors to Emergency Medicaid use.

Usefulness of ventricular premature complexes to predict coronary heart disease events and mortality (from the Atherosclerosis Risk In Communities cohort).

The clinical relevance of ventricular premature complexes (VPCs) in apparently healthy patients is not clear and is typically not considered when evaluating risk. We conducted a prospective longitudinal study of the population-based Atherosclerosis Risk In Communities (ARIC) study of 15,070 Caucasians and African-Americans, 45 to 64 years of age, to assess the risks of coronary heart disease (CHD) events and mortality associated with VPCs among participants with and without prevalent CHD at baseline. VPCs on a single 2-minute electrocardiogram were identified in 940 participants (6.2%). After a follow-up of >10 years, 1,762 participants died, with 366 deaths related to CHD, and 1,736 had cardiac events. The percentage of participants with CHD mortality was >3 times greater for those with VPCs compared with those without VPCs. After controlling for cardiovascular risk factors and therapy with proportional hazards regression, participants with VPCs were >2 times as likely to die due to CHD than were those without VPCs. Increased risk was found for participants with and without baseline CHD. In conclusion, a clinical finding of VPCs on electrocardiography of even apparently healthy patients may warrant a heightened awareness of and attention to cardiovascular risk assessment and management.

Feasibility of a primary care intervention to decrease oral antibiotics for acute upper respiratory tract infections: A pilot study.

BACKGROUND: Antimicrobial resistance in common respiratory tract pathogens is a growing public health threat, especially in the southeastern United States. The excessive use of antibiotics for common infections is a major contributing factor in the emergence of antibiotic resistance. We report results from a multi-site outpatient pilot project in North Carolina to reduce antibiotic prescriptions for acute nonbacterial upper respiratory tract infections (URIs). METHODS: Primary care practices were provided education and symptom therapy kits for patients with URIs, as an alternative to antibiotics, in a project to reduce the overuse of antimicrobial therapy The feasibility of this approach was evaluated with interviews and surveys. A methodology for claims-based evaluation of intervention efficacy in reduction of antibiotics use was developed as part of this project. RESULTS: Of eight contacted practices, four agreed to participate and three participated fully. Physicians reported that symptom therapy kits were useful for patients with URIs and resulted in a meaningful change in antibiotic prescribing behaviors. A claims-based approach is a feasible and promising method to evaluate efficacy in subsequent post-pilot large-scale implementations. LIMITATIONS: Due to the small number of outpatient practices and the lack of controls in this pilot study, the efficacy of the intervention in reducing antibiotic use could not be determined. CONCLUSIONS: Education combined with symptom therapy kits as an alternative to oral antibiotics is a feasible intervention that warrants additional studies to evaluate the efficacy of this approach in the reduction of antibiotic use for URIs.

Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions.

Olanzapine and fluoxetine elevate the GABAergic neuroactive steroid allopregnanolone to physiologically relevant concentrations in rodent cerebral cortex. It is unknown if these agents also alter pregnenolone or deoxycorticosterone. Since olanzapine and fluoxetine in combination have clinical utility and may demonstrate synergistic effects, we investigated neuroactive steroid alterations following olanzapine, fluoxetine or coadministration. Male rats received IP vehicle, olanzapine, fluoxetine or the combination of both agents in higher-dose (0, 10, 20 or 10/20 mg/kg, respectively) and lower-dose (0, 5, 10 or 5/10 mg/kg, respectively) experiments. Pregnenolone and allopregnanolone levels in hippocampus were determined by gas chromatography/mass spectrometry. Peripheral deoxycorticosterone and other steroid levels were determined by radioimmunoassay. Olanzapine, fluoxetine or the combination increased hippocampal pregnenolone and serum deoxycorticosterone in both higher- and lower-dose experiments, and elevated hippocampal allopregnanolone in higher-dose conditions. No synergistic effects on pregnenolone or allopregnanolone were observed following olanzapine and fluoxetine coadministration compared to either compound alone. Pregnenolone and its sulfate enhance learning and memory in rodent models, and therefore pregnenolone elevations may be relevant to cognitive changes in psychotic and affective disorders. Since pregnenolone decreases have been linked to depression, it is possible that olanzapine- and fluoxetine-induced pregnenolone elevations may contribute to the antidepressant actions of these agents.

The neurosteroid allopregnanolone is reduced in prefrontal cortex in Alzheimer's disease.

BACKGROUND: Few data are currently available investigating neurosteroids (NS) in Alzheimer's disease (AD). The NS allopregnanolone may be decreased in serum and plasma in patients with AD, but it is unclear if allopregnanolone is also reduced in brain. Because a number of NS exhibit neuroprotective effects and impact cognitive performance in rodent models, these molecules may be relevant to the pathophysiology of neurodegenerative disorders. We therefore investigated prefrontal cortex (PFC) NS levels in AD. METHODS: Neurosteroid levels (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined in postmortem PFC in 14 male subjects with AD and 15 cognitively intact male control subjects by gas chromatography/mass spectrometry preceded by high-performance liquid chromatography purification. RESULTS: Subjects with AD exhibit significant reductions in allopregnanolone compared with cognitively intact control subjects (median levels = 2.50 ng/g vs. 5.59 ng/g, respectively; p = .02). Allopregnanolone levels are inversely correlated with neuropathological disease stage (Braak), r = -.49, p = .007. Median DHEA levels are elevated in subjects with AD (p = .01). CONCLUSIONS: Subjects with AD demonstrate significant reductions in PFC allopregnanolone levels, a finding that may be relevant to neuropathological disease stage severity. Neurosteroids may have utility as candidate biomarkers in AD.

Clozapine markedly elevates pregnenolone in rat hippocampus, cerebral cortex, and serum: candidate mechanism for superior efficacy?

Clozapine demonstrates superior efficacy in patients with schizophrenia, but the precise mechanisms contributing to this clinical advantage are not clear. Clozapine and olanzapine increase the GABAergic neuroactive steroid (NS) allopregnanolone, and it has been hypothesized that NS induction may contribute to the therapeutic actions of these agents. Pregnenolone administration improves learning and memory in rodent models, and decreases in this NS have been associated with depressive symptoms in humans. These pregnenolone characteristics may be relevant to the actions of antipsychotics. We therefore investigated potential pregnenolone alterations in rat hippocampus and cerebral cortex following clozapine, olanzapine, and other second generation agents as a candidate NS mechanism contributing to antipsychotic efficacy. In the first set of experiments, intact, adrenalectomized, and sham-operated male rats received vehicle or clozapine (20 mg/kg) IP. In the second set, male rats received vehicle, olanzapine (5 mg/kg), quetiapine (20 mg/kg), ziprasidone (10 mg/kg) or aripiprazole (5 mg/kg) IP. Pregnenolone levels were determined by gas chromatography/mass spectrometry. Clozapine markedly elevates pregnenolone in rat hippocampus, cerebral cortex, and serum; hippocampal levels were strongly correlated with serum levels (r=0.987). Olanzapine also elevates pregnenolone levels, but to a lesser degree than clozapine. Pregnenolone induction may contribute to the clinical actions of clozapine and olanzapine.

Neuroactive steroids, negative affect, and nicotine dependence severity in male smokers.

RATIONALE: Nicotine administration alters neuroactive steroids in rodent models, and serum levels of the neuroactive steroid DHEAS (dehydroepiandrosterone sulfate) appear to be higher in smokers. These molecules may be relevant to tobacco addiction and affective symptoms. OBJECTIVES: This study aims to investigate DHEAS, allopregnanolone, pregnenolone, and other steroids in male smokers to determine potential associations with nicotine dependence severity and negative affect. MATERIALS AND METHODS: Allopregnanolone and pregnenolone serum levels were determined by gas chromatography/mass spectrometry, while DHEAS and other steroid levels were determined by radioimmunoassay in 28 male smokers. Correlational analyses were performed to determine potential associations with rating measures, including the Fagerstrom Test for Nicotine Dependence (FTND), the addiction subscale of the Ikard Smoking Motivation Questionnaire (ISMQ), the craving item on the Reasons to Smoke (RTS) Questionnaire, and the negative affect and craving subscales of the Shiffman-Jarvik Withdrawal Questionnaire. RESULTS: DHEAS levels were inversely correlated with the negative affect subscale of the Shiffman-Jarvik Withdrawal Questionnaire (r=-0.60, p=0.002) and the RTS craving item (r=-0.43, p=0.03), and tended to be inversely correlated with the FTND scores (r=-0.38, p=0.067) and the ISMQ addiction subscale (r=-0.38, p=0.059), adjusting for age. Allopregnanolone levels were positively correlated with cotinine levels (r=0.57, p=0.006); pregnenolone levels tended to be positively correlated with cotinine levels (r=0.40, p=0.066). CONCLUSIONS: DHEAS levels were inversely correlated with negative affect and craving measures, and may predict nicotine dependence severity. Allopregnanolone levels were positively correlated with cotinine levels, suggesting that this neuroactive steroid may be upregulated in smokers. Neuroactive steroids may represent novel smoking cessation agents.

Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics.

Evidence suggests that neuroactive steroids may be candidate modulators of schizophrenia pathophysiology and therapeutics. We therefore investigated neuroactive steroid levels in post-mortem brain tissue from subjects with schizophrenia, bipolar disorder, nonpsychotic depression, and control subjects to determine if neuroactive steroids are altered in these disorders. Posterior cingulate and parietal cortex tissue from the Stanley Foundation Neuropathology Consortium collection was analyzed for neuroactive steroids by negative ion chemical ionization gas chromatography/mass spectrometry preceded by high-performance liquid chromatography. Subjects with schizophrenia, bipolar disorder, nonpsychotic depression, and control subjects were group matched for age, sex, ethnicity, brain pH, and post-mortem interval (n = 14-15 per group, 59-60 subjects total). Statistical analyses were performed by ANOVA with post-hoc Dunnett tests on log transformed neuroactive steroid levels. Pregnenolone and allopregnanolone were present in human post-mortem brain tissue at considerably higher concentrations than typically observed in serum or plasma. Pregnenolone and dehydroepiandrosterone levels were higher in subjects with schizophrenia and bipolar disorder compared to control subjects in both posterior cingulate and parietal cortex. Allopregnanolone levels tended to be decreased in parietal cortex in subjects with schizophrenia compared to control subjects. Neuroactive steroids are present in human post-mortem brain tissue at physiologically relevant concentrations and altered in subjects with schizophrenia and bipolar disorder. A number of neuroactive steroids act at inhibitory GABA(A) and excitatory NMDA receptors and demonstrate neuroprotective and neurotrophic effects. Neuroactive steroids may therefore be candidate modulators of the pathophysiology of schizophrenia and bipolar disorder, and relevant to the treatment of these disorders.