Marian I. Butterfield

Efficacy of Dialectical Behavior Therapy in Women Veterans With Borderline Personality Disorder

Twenty women veterans who met criteria for borderline personality disorder (BPD) were randomly assigned to Dialectical Behavior Therapy (DBT) or to treatment as usual (TAU) for 6 months. Compared with patients in TAU, those in DBT reported significantly greater decreases in suicidal ideation, hopelessness, depression, and anger expression. In addition, only patients in DBT demonstrated significant decreases in number of parasuicidal acts, anger experienced but not expressed, and dissociation, and a strong trend on number of hospitalizations, although treatment group differences were not statistically significant on these variables. Patients in both conditions reported significant decreases in depressive symptoms and in number of BPD criterion behavior patterns, but no decrease in anxiety. Results of this pilot study suggest that DBT can be provided effectively independent of the treatments developer, and that larger efficacy and effectiveness studies are warranted.

Recent Victimization in Women and Men With Severe Mental Illness: Prevalence and Correlates

The problem of violence against individuals with severe mental illness (SMI) has received relatively little notice, despite several studies suggesting an exceptionally high prevalence of victimization in this population. This paper describes the results of an investigation of the prevalence and correlates of past year physical and sexual assault among a large sample of women and men with SMI drawn from inpatient and outpatient settings across 4 states. Results confirmed preliminary findings of a high prevalence of victimization in this population (with sexual abuse more prevalent for women and physical abuse more prevalent for men), and indicated the existence of a range of correlates of recent victimization, including demographic factors and living circumstances, history of childhood abuse, and psychiatric illness severity and substance abuse. The research and clinical implications of these findings are discussed.

A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder

BACKGROUND The anticonvulsant, lamotrigine, may be useful for symptom management in PTSD. METHODS Subjects enrolled in a 12-week double-blind evaluation of lamotrigine and placebo. Patients were randomized 2:1 to either lamotrigine or placebo. Lamotrigine was initiated at 25 mg/day and slowly titrated every 1 to 2 weeks over 8 weeks to a maximum dosage of 500 mg/day if tolerated. RESULTS Fifteen subjects entered treatment, fourteen of whom returned for subsequent visits. Of 10 patients who received lamotrigine, 5 (50%) responded according to the DGRP, compared to 1 of 4 (25%) who received placebo. Lamotrigine patients showed improvement on reexperiencing and avoidance/numbing symptoms compared to placebo patients. Treatments were generally well tolerated. CONCLUSIONS Lamotrigine may be effective as a primary psychopharmacologic treatment in both combat and civilian PTSD and could also be considered as an adjunct to antidepressant therapy used in the treatment of PTSD. These promising results warrant further large sample double-blind, placebo-controlled trials.

Mirtazapine vs. placebo in posttraumatic stress disorder: a pilot trial

BACKGROUND Based on an earlier pilot study, as well as a theoretical consideration of its mechanism of action, we undertook a placebo-controlled, double-blind trial of mirtazapine in posttraumatic stress disorder. METHODS Twenty-nine patients were randomized to receive drug up to 45 mg/day or placebo double-blind on a 2:1 ratio for 8 weeks, with data being available for analysis in 26. Primary outcome measures comprised the Short Posttraumatic Stress Disorder Rating Interview (SPRINT) Global Improvement item and total score. Secondary measures comprised the Davidson Trauma Scale, Structured Interview for Posttraumatic Stress Disorder and Hospital Anxiety Depression Scale. Adverse events were also measured. RESULTS On the Short Posttraumatic Stress Disorder Rating Interview Global Improvement measure, rates of response were 64.7% and 20.0% for mirtazapine and placebo. Treatment effects in favor of mirtazapine were noted on the Short Posttraumatic Stress Disorder Rating Interview global, Structured Interview for Posttraumatic Stress Disorder, and Hospital Anxiety Depression Scale anxiety subscale scores. The drug was well tolerated. CONCLUSIONS Mirtazapine was more effective than placebo on some measures in posttraumatic stress disorder and general anxiety symptoms.

Olanzapine in the treatment of post-traumatic stress disorder: a pilot study

Because the atypical antipsychotic olanzapine may be efficacious in treating post-traumatic stress disorder (PTSD) symptoms, we conducted a 10-week, double-blind, placebo-controlled evaluation in which 15 patients were randomized 2: 1 to either olanzapine or placebo. The initial dosage was 5 mg/day and was titrated to a maximum of 20 mg/day. Eleven patients completed the study. Patients in both groups showed improvement in PTSD symptoms, but no between-group differences in treatment response were observed and a high placebo response rate was found. Both treatments were tolerated well, although the olanzapine treatment group had more weight gain. Olanzapine fared no better than placebo in this preliminary study in the treatment of PTSD. The lack of difference between olanzapine and placebo may in part be due to olanzapines not being effective in PTSD or, alternatively, a small sample size, a high placebo response in certain forms of PTSD and the chronicity of PTSD symptoms in some patients.

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 GABAA 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.

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

BACKGROUND Few data are currently available investigating neurosteroids (NS) in Alzheimers 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.

Access to Medical Care Among Persons With Psychotic and Major Affective Disorders

OBJECTIVE People with serious mental illness have higher mortality rates than the general population, and this difference is not explained by such causes as suicide or accidents. This study therefore examined access and barriers to medical care among persons with serious mental illness. METHODS Using a nationally representative sample, the authors examined access and barriers to medical care among individuals reporting psychotic and mood disorders. The National Health Interview Survey (NHIS) and NHIS-Disability Component for 1994 and 1995 were merged to provide a sample of 156,475 people over age 18. Individuals with psychotic disorders, bipolar disorder, or major depression were compared with persons without mental disorders on the following outcomes: having a primary care physician, being unable to get needed medical care, being unable to get a needed prescription medication, and delaying medical care because of cost. RESULTS Persons with psychotic disorders (odds ratio [OR]=.55, 95% confidence interval [CI]=.44-.69) and bipolar disorder (OR=.74, CI=.56-.98) had significantly reduced odds of having a primary care physician compared with people without mental disorders. For any barriers to care, persons with psychotic disorders, bipolar disorder, or major depressive disorder had greatly increased odds (ORs=2.5-7.0) of reporting difficulties in accessing care. CONCLUSIONS Persons with psychotic disorders and bipolar disorder reported markedly more difficulty in obtaining a primary care physician and greater barriers to care than the general population. Interventions are needed to improve provision of primary medical care to this population.

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.

Hostility and functional health status in women veterans with and without posttraumatic stress disorder: A preliminary study

This study investigated hostility and functional health status in 90 women veterans with and without PTSD. Compared to women without PTSD, women veterans with PTSD reported significantly higher levels of hostility. Minority status was associated with increased hostility. Compared to a national sample, hostility scores for women with PTSD were greater by a factor of 1.5. PTSD diagnosis was also associated with poorer functioning on all SF-36 Health Survey scales. Controlling for age and education, hostility was related to all SF-36 Health Survey scales in the women with PTSD.