Biomedical subjects

Ellen Frank

Publications and source records attributed to Ellen Frank.

At least 55 records · Page 3Linked to original sources

PubMed2004

Reduced left anterior cingulate volumes in untreated bipolar patients.

BACKGROUND: Functional and morphologic abnormalities of the cingulate cortex have been reported in mood disorder patients. To examine the involvement of anatomic abnormalities of the cingulate in bipolar disorder, we measured the volumes of this structure in untreated and lithium-treated bipolar patients and healthy control subjects, using magnetic resonance imaging (MRI). METHODS: The volumes of gray matter at the right and left anterior and posterior cingulate cortices were measured in 11 bipolar patients not taking any psychotropic medications (aged 38 +/- 11 years, 5 women), 16 bipolar patients treated with lithium monotherapy (aged 33 +/- 11 years, 7 women), and 39 healthy control subjects (aged 37 +/- 10 years, 14 women). Volumetric measurements were made with T1-weighted coronal MRI images, with 1.5-mm-thick slices, at 1.5T, and were done blindly. RESULTS: Using analysis of covariance with age and intracranial volume as covariates, we found that untreated bipolar patients had decreased left anterior cingulate volumes compared with healthy control subjects [2.4 +/-.3 cm3 and 2.9 +/-.6 cm3, respectively; F(1,58) = 6.4, p =.042] and compared with lithium-treated patients [3.3 +/-.5 cm3; F(1,58) = 11.7, p =.003]. The cingulate volumes in lithium-treated patients were not significantly different from those of healthy control subjects. CONCLUSIONS: Our findings indicate that anatomic abnormalities in left anterior cingulate are present in bipolar patients. Furthermore, our results suggest that lithium treatment might influence cingulate volumes in bipolar patients, which could possibly reflect postulated neuroprotective effects of lithium.

Adult↗

PubMed2004

Computerized adaptive measurement of depression: a simulation study.

BACKGROUND: Efficient, accurate instruments for measuring depression are increasingly important in clinical practice. We developed a computerized adaptive version of the Beck Depression Inventory (BDI). We examined its efficiency and its usefulness in identifying Major Depressive Episodes (MDE) and in measuring depression severity. METHODS: Subjects were 744 participants in research studies in which each subject completed both the BDI and the SCID. In addition, 285 patients completed the Hamilton Depression Rating Scale. RESULTS: The adaptive BDI had an AUC as an indicator of a SCID diagnosis of MDE of 88%, equivalent to the full BDI. The adaptive BDI asked fewer questions than the full BDI (5.6 versus 21 items). The adaptive latent depression score correlated r =.92 with the BDI total score and the latent depression score correlated more highly with the Hamilton (r =.74) than the BDI total score did (r =.70). CONCLUSIONS: Adaptive testing for depression may provide greatly increased efficiency without loss of accuracy in identifying MDE or in measuring depression severity.

Adult↗

PubMed2004

Anatomic evaluation of the orbitofrontal cortex in major depressive disorder.

BACKGROUND: The orbitofrontal cortex (OFC) plays a major role in neuropsychologic functioning including exteroceptive and interoceptive information coding, reward-guided behavior, impulse control, and mood regulation. This study examined the OFC and its subdivisions in patients with MDD and matched healthy control subjects. METHODS: Magnetic resonance imaging (MRI) was performed on 31 unmedicated MDD and 34 control subjects matched for age, gender, and race. Gray matter volumes of the OFC and its lateral and medial subdivisions were measured blindly. RESULTS: The MDD patients had smaller gray matter volumes in right medial [two-way analysis of covariance F(1,60) = 4.285; p =.043] and left lateral OFC [F(1,60) = 4.252; p =.044]. Left lateral OFC volume correlated negatively with age in patients but not in control subjects. Male, but not female patients exhibited smaller left and right medial OFC volumes compared with healthy control subjects of the same gender. CONCLUSIONS: These findings suggest that patients with MDD have reduced OFC gray matter volumes. Although this reduction might be important in understanding the pathophysiology of MDD, its functional and psychopathologic consequences are as yet unclear. Future studies examining the relationship between specific symptomatic dimensions of MDD and OFC volumes could be especially informative.

Adult↗

PubMed2004

Pharmacotherapy for bipolar disorder and comorbid conditions: baseline data from STEP-BD.

Relatively absent from previous studies of the pharmacotherapy for bipolar disorder is examination of the impact of comorbidity on treatment choices. This has occurred despite the presence of high levels of comorbid anxiety and substance use disorders, and the association of these disorders with severity and course markers of bipolar disorder. In this study, we examined comorbid disorders, identified by structured interviews, and the pharmacotherapy reported at study entry by the first 1000 patients entered into a large, multicenter study of bipolar disorder (Systematic Treatment Enhancement Program for Bipolar Disorder). Our study focused on the degree to which comorbid conditions are linked to the reported use of mood stabilizers deemed "minimally adequate" and the association between specific comorbidities and pharmacotherapy treatment, such as the use of anxiolytics in patients with anxiety disorders. Despite the presence of high levels of comorbidity, the presence of these disorders was only minimally associated with pharmacotherapy. Of the sample of bipolar outpatients, only 59% reported pharmacotherapy use meeting criteria for "minimally adequate" mood stabilizer, regardless of comorbid diagnoses, rapid cycling, or bipolar I or II status. Moreover, the cross-sectional use of "comorbidity-specific" pharmacotherapy for anxiety disorders, substance use disorders, and attention deficit disorder in this outpatient sample of patients with bipolar disorders was limited, suggesting that comorbid conditions in patients with bipolar disorder may be undertreated. Our findings highlight the need for greater clinical guidance and treatment options for patients with bipolar disorder and comorbidity.

Adult↗

PubMed2004

Randomized, placebo-controlled trial of fluoxetine for acute treatment of minor depressive disorder.

OBJECTIVE: Minor depressive disorder is both common and associated with significant psychosocial impairment. This study examined antidepressant treatment efficacy in a large group of patients with minor depressive disorder. METHOD: One hundred sixty-two patients with minor depressive disorder were randomly assigned to receive fluoxetine or placebo in a 12-week, double-blind study; 73% (59 of 81) of the patients in each treatment group completed the study. Patients were evaluated weekly with standard depression rating instruments and measures of psychosocial impairment. Hypotheses were tested by last-observation-carried-forward analysis of variance (ANOVA) and confirmed by mixed (random-effects) regression analysis. RESULTS: At baseline, minor depressive disorder patients were mildly to moderately depressed, with a corresponding degree of functional impairment. Over 12 weeks of treatment, both ANOVA and mixed regression showed fluoxetine to be superior to placebo as indicated by significantly greater improvement of fluoxetine-treated patients in scores on the 30-item clinician-rated Inventory of Depressive Symptomatology, the 17-item and 21-item Hamilton Depression Rating Scale, the Beck Depression Inventory, and the Clinical Global Impression severity scale. Improvement in Global Assessment of Functioning Scale score was significantly greater for the fluoxetine group in mixed regression analysis only. Patients in both treatment groups reported a similar number and severity of adverse events during the 12-week treatment period. CONCLUSIONS: Clinicians frequently encounter minor depressive disorder either as a prodromal or residual phase of illness in major depressive disorder or as de novo minor depressive disorder episodes. Fluoxetine is significantly superior to placebo in reducing minor depressive disorder symptoms within a 12-week period. Improvement in psychosocial function with fluoxetine may take longer than 12 weeks.

Adaptation, Psychological↗

PubMed2004

Relationship of variability in residual symptoms with recurrence of major depressive disorder during maintenance treatment.

OBJECTIVE: To investigate how residual symptoms from an index episode of major depressive disorder may be associated with recurrence, the authors conducted a trial involving four maintenance treatment approaches and examined 1) whether the level and variability of residual symptoms differed among the maintenance treatment conditions and 2) whether greater symptom variability is associated with a higher likelihood of recurrence and more rapid recurrence. METHOD: Patients enrolled in a maintenance treatment study (N=114) were randomly assigned to one of four maintenance treatment conditions: imipramine plus interpersonal psychotherapy, imipramine alone, interpersonal psychotherapy alone, or no active treatment. Residual symptoms were characterized both as continuous variables (mean values and coefficients of variation for Hamilton Depression Rating Scale and Global Assessment Scale [GAS] scores) and as a categorical variable, the percentage of maintenance evaluations with a Hamilton depression scale score > or =8 (e.g., with a symptom peak). RESULTS: Analysis of variance revealed no differences among the four treatment conditions in patients' levels of residual symptoms or symptom variability assessed as a continuous variable, but patients in the combined treatment group had fewer symptom peaks, compared to those in the placebo and interpersonal psychotherapy groups. Cox proportional hazards modeling showed that higher coefficients of variation for both the Hamilton depression scale and the GAS scores and a greater percentage of evaluations with symptom peaks were associated with shorter survival times. CONCLUSIONS: A higher level of symptom variability during maintenance treatment is associated with higher risk for recurrence of depression and may provide a specific target for maintenance treatments.

Adult↗

PubMed2004

Anxiety disorder comorbidity in bipolar disorder patients: data from the first 500 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

OBJECTIVE: The authors provide a detailed perspective on the correlates of comorbid anxiety in a large, well-characterized sample of bipolar disorder patients. METHOD: Anxiety and its correlates were examined in a cross-sectional sample from the first 500 patients with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder, a multicenter project funded by the National Institute of Mental Health designed to evaluate the longitudinal outcome of patients with bipolar disorder. RESULTS: Lifetime comorbid anxiety disorders were common, occurring in over one-half of the sample, and were associated with younger age at onset, decreased likelihood of recovery, poorer role functioning and quality of life, less time euthymic, and greater likelihood of suicide attempts. Although substance abuse disorders were particularly prevalent among patients with anxiety disorders, comorbid anxiety appeared to exert an independent, deleterious effect on functioning, including history of suicide attempts (odds ratio=2.45, 95% CI=1.4-4.2). CONCLUSIONS: An independent association of comorbid anxiety with greater severity and impairment in bipolar disorder patients was demonstrated, highlighting the need for greater clinical attention to anxiety in this population, particularly for enhanced clinical monitoring of suicidality. In addition, it is important to determine whether effective treatment of anxiety symptoms can lessen bipolar disorder severity, improve response to treatment of manic or depressive symptoms, or reduce suicidality.

Adolescent↗

PubMed2004

The mood spectrum in unipolar and bipolar disorder: arguments for a unitary approach.

OBJECTIVE: This study examined the extent to which individuals with a lifetime diagnosis of recurrent unipolar disorder endorse experiencing manic/hypomanic symptoms over their lifetimes and compared their reports with those of patients with bipolar I disorder. METHOD: The study group included 117 patients with remitted recurrent unipolar depression and 106 with bipolar I. Subjects had their clinical diagnosis confirmed by the Mini International Neuropsychiatric Interview and were administered the Structured Clinical Interview for the Mood Spectrum, which assesses lifetime symptoms, traits, and lifestyles that characterize threshold and subthreshold mood episodes as well as "temperamental" features related to mood dysregulation. RESULTS: The patients with recurrent unipolar depression endorsed experiencing a substantial number of manic/hypomanic symptoms over their lifetimes. In both patients with recurrent unipolar depression and patients with bipolar I disorder, the number of manic/hypomanic items endorsed was related to the number of depressive items endorsed. In the group with recurrent unipolar depression, the number of manic/hypomanic items was related to an increased likelihood of endorsing paranoid and delusional thoughts and suicidal ideation. In the bipolar I group, the number of lifetime manic/hypomanic items was related to suicidal ideation and just one indicator of psychosis. CONCLUSIONS: The presence of a significant number of manic/hypomanic items in patients with recurrent unipolar depression seems to challenge the traditional unipolar-bipolar dichotomy and bridge the gap between these two categories of mood disorders. The authors argue that their mood spectrum approach is useful in making a more accurate diagnostic evaluation in patients with mood disorders.

Adult↗

PubMed2004

A pilot study of brief interpersonal psychotherapy for depression among women.

A matched-case-control study compared eight-week outcomes between a group of 16 depressed women who received brief (eight-session) interpersonal psychotherapy and a group of 16 who received a selective serotonin reuptake inhibitor (sertraline). Women who met DSM-IV criteria for major depression and who had a score above 15 on the Hamilton Rating Scale for Depression were treated openly with brief interpersonal psychotherapy and were matched on key variables with women being treated with sertraline. Linear mixed-effects regression models were used to compare groups on measures of symptoms and functioning during eight weeks of treatment. Both groups improved significantly over time, with large effect sizes. However, contrary to expectations, the women who received psychotherapy improved more quickly than those who received sertraline.

Case-Control Studies↗

PubMed2004

Suicide attempts and ideation in patients with bipolar I disorder.

BACKGROUND: Suicidal thinking and behavior are common in individuals with bipolar disorder. METHOD: Suicidal ideation and suicide attempts were examined in 175 patients with bipolar I disorder (diagnosis confirmed with the Schedule for Affective Disorders and Schizophrenia or the Structured Clinical Interview for DSM-IV) participating in the Pittsburgh Study of Maintenance Therapies in Bipolar Disorder. Patients who attempted suicide before entering the study were compared with those who did not attempt suicide with respect to clinical and demographic characteristics. RESULTS: Twenty-nine percent of the patients had attempted suicide prior to entering the study. Suicide attempts happened at a relatively young age and in the first period of the illness. Greater severity of bipolar disorder, as indicated by a greater number of previous depressive episodes (p =.0009) and higher HAM-D-25 scores (p =.04), and higher body mass index (p =.03) were significantly correlated with a history of suicide attempts. None of the patients with a history of suicide attempt attempted suicide again. However, 5 patients without a history of suicide attempt did attempt suicide. Four of these patients did not display severe suicidal ideation at the assessment that preceded the suicide attempt. No subject completed suicide during the 11 years of the study. CONCLUSION: Greater severity of bipolar disorder and higher body mass index are significantly correlated with a history of suicide attempts. However, a treatment program in a maximally supportive clinical environment can reduce suicidal behavior in high-risk patients. In some cases, suicide risk is transient and may be preceded by a period of severe suicidal ideation that lasts only a few minutes or hours. In such cases, mental health professionals are unable to predict suicide attempts.

Adult↗

PubMed2003

Magnetic resonance imaging study of corpus callosum abnormalities in patients with bipolar disorder.

BACKGROUND: This study was conducted to further examine the hypothesis of abnormalities in size of corpus callosum in subjects with bipolar disorder. METHODS: Sixteen right-handed DSM-IV bipolar I patients and 27 right-handed healthy control subjects were studied. A 1.5-T GE Signa magnet was used, and three-dimensional gradient echo imaging (spoiled gradient recall acquisition) was conducted. Area measurements of corpus callosum were obtained blindly, with a semi-automated software, by a well-trained rater. RESULTS: Right-handed bipolar I patients had significantly smaller total corpus callosum, genu, posterior body, and isthmus areas compared with right-handed healthy control subjects (analysis of covariance with age, gender, and intracranial volume as covariates, p <.05). Partial correlation analyses, controlled for intracranial volumes, found a significant inverse relationship between age and total callosal, genu, anterior body, isthmus, and circularity in healthy control subjects (p <.05) but not in bipolar patients (p >.05). CONCLUSIONS: Smaller callosal areas may lead to altered inter-hemispheric communication and be involved in the pathophysiology and cognitive impairment found in bipolar disorder.

Adult↗

PubMed2003

Anatomical MRI study of basal ganglia in major depressive disorder.

The basal ganglia form a part of the brain neuroanatomic circuits that may be involved in mood regulation. Decreases in basal ganglia volumes have been previously reported in major depressive disorder patients in comparison to healthy controls. In this study, we measured caudate, putamen, and globus pallidus volumes in 25 patients with major depressive disorder (4 M; age+/-S.D.=41+/-11 years) and 48 healthy controls (29 M; age+/-S.D.=35+/-10 years), using high-resolution magnetic resonance imaging (MRI), in an attempt to replicate prior findings. Unlike most previous studies, we did not find significant differences between patient and control groups in basal ganglia volumetric measures. Nonetheless, there was a significant interaction between diagnosis and cerebral hemisphere, with MDD patients showing decreased asymmetry in globus pallidus volumes in comparison with healthy controls. Furthermore, in the patient group, left putamen volumes correlated inversely with length of illness, and left globus pallidus volume correlated directly with number of prior depressive episodes. These findings suggest that abnormalities in lateralization and possibly neurodegenerative changes in basal ganglia structures participate in the pathophysiology of major depressive disorder.

Adolescent↗

PubMed2003

Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD).

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was conceived in response to a National Institute of Mental Health initiative seeking a public health intervention model that could generate externally valid answers to treatment effectiveness questions related to bipolar disorder. STEP-BD, like all effectiveness research, faces many design challenges, including how to do the following: recruit a representative sample of patients for studies of readily available treatments; implement a common intervention strategy across diverse settings; determine outcomes for patients in multiple phases of illness; make provisions for testing as yet undetermined new treatments; integrate adjunctive psychosocial interventions; and avoid biases due to subject drop-out and last-observation-carried-forward data analyses. To meet these challenges, STEP-BD uses a hybrid design to collect longitudinal data as patients make transitions between naturalistic studies and randomized clinical trials. Bipolar patients of every subtype with age >/= 15 years are accessioned into a study registry. All patients receive a systematic assessment battery at entry and are treated by a psychiatrist (trained to deliver care and measure outcomes in patients with bipolar disorder) using a series of model practice procedures consistent with expert recommendations. At every follow-up visit, the treating psychiatrist completes a standardized assessment and assigns an operationalized clinical status based on DSM-IV criteria. Patients have independent evaluations at regular intervals throughout the study and remain under the care of the same treating psychiatrist while making transitions between randomized care studies and the standard care treatment pathways. This article reviews the methodology used for the selection and certification of the clinical treatment centers, training study personnel, the general approach to clinical management, and the sequential treatment strategies offered in the STEP-BD standard and randomized care pathways for bipolar depression and relapse prevention.

Bipolar Disorder↗

PubMed2003

Beyond the question of placebo controls: ethical issues in psychopharmacological drug studies.

RATIONALE: There is a broad range of complex ethical issues in the conduct of psychopharmacological drug studies that go beyond the question of the ethics of placebo controls. However, our empirical knowledge with respect to these issues is very limited. This review, although not exhaustive, highlights an array of ethical issues that arose from discussions within the NIMH Human Subjects Research Council Workgroup. OBJECTIVES: To delineate issues in psychopharmacological drug studies that require debate and would benefit from research leading to the development of empirically-supported guidelines. METHODS: Information included in this report was drawn from the first author's participation as chair of the NIMH Human Subjects Research Council Workgroup, guidelines for the ethical conduct of research proposed by professional organizations to which the first and third author belong, and relevant research literature. RESULTS: We have focused on general issues relating to informed consent, research with special populations, and long-term treatment studies. Additionally, we raise issues relevant to large research-oriented institutions. CONCLUSIONS: The essential ethical challenge in psychopharmacological trials is to balance risks and benefits in the context of the needs and capacities of individual research subjects. The IRB system must become evidence-based and not rely on unproven assumptions. Specific research studies should be undertaken to address many of the issues of informed consent and research ethics postulated in this paper.

Adolescent↗

PubMed2003

Difficult-to-treat depression: the role of contexts and comorbidities.

In this review, we examine several special psychosocial contexts, including pregnancy and motherhood, that may seriously interfere with depressed patients' ability or willingness to engage and remain in treatment for their depression. We also explore the kinds of often-unrecognized subsyndromal comorbidities, such as panic-agoraphobic spectrum, that may complicate conventional treatments for depression or prevent depressed patients from remaining engaged long enough to fully benefit from treatment. We argue that psychotherapy can play a crucial role in addressing the special psychosocial contexts and the kinds of comorbidities experienced by the patient with difficult-to-treat depression. For difficult-to-treat depression during pregnancy and motherhood, preliminary data from several studies suggest that 8-24 sessions of weekly interpersonal psychotherapy (IPT), often followed by monthly maintenance IPT, is a promising long-term treatment for both middle- and low-income women. For difficult-to-treat depression with panic-agoraphobic subsyndromal features, preliminary results suggest that an integrated treatment approach, combining IPT for depression and cognitive-behavioral treatment for coexisting symptoms of panic, leads to higher depression response rates. These data imply that tailoring treatments to patients' specific needs and circumstances may be the real key to making depression less difficult to treat.

Adult↗

PubMed2003

Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review.

BACKGROUND: Antidepressant drugs can promote remission from acute depressive episodes. Our aim was to establish how long such treatments should be continued to prevent relapse. METHOD: We did a systematic overview of evidence from randomised trials of continuing treatment with antidepressants in patients with depressive disorders who have responded to acute treatment. Medline, Embase, Cinahl, PsycLIT, Psyndex, and Lilacs were searched. FINDINGS: Data were pooled from 31 randomised trials (4410 participants). Continuing treatment with antidepressants reduced the odds of relapse by 70% (95% CI 62-78; 2p<0.00001) compared with treatment discontinuation. The average rate of relapse on placebo was 41% compared with 18% on active treatment. The treatment effect seemed to persist for up to 36 months, although most trials were of 12 months' duration, and so the evidence on longer-term treatment requires confirmation. Significantly more participants allocated antidepressants withdrew from the trials than did those allocated to placebo (18% vs 15%, respectively; odds ratio 1.30, 95% CI 1.07-1.59): the treatment effect could be even greater in adherent patients. The two-thirds reduction in risk of depressive relapse seemed to be largely independent of the underlying risk of relapse, the duration of treatment before randomisation, or the duration of the randomly allocated therapy. INTERPRETATION: Antidepressants reduce the risk of relapse in depressive disorder, and continued treatment with antidepressants would benefit many patients with recurrent depressive disorder. The treatment benefit for an individual patient will depend on their absolute risk of relapse with greater absolute benefits in those at higher risk. Further trials are needed to establish the optimum length of therapy and should include patients who were not well represented in these trials, including those at low risk of relapse.

Antidepressive Agents↗

PubMed2003

Development and preliminary testing of the General 5-Spectrum Measure (GSM-V).

The Collaborative Spectrum Project has developed structured interviews and self-report instruments to assess the spectrum of symptomatology related to panic-agoraphobia, mood, social phobia, and obsessive-compulsive and eating disorders. In order to obtain a rapid pre-test on all five of these spectrum conditions, the authors sought to develop a brief instrument that would tap these conditions. This paper reports on 1) the procedures to derive this composite instrument, the General 5-Spectrum Measure (GSM-V), by selecting items from five existing spectrum instruments, and 2) preliminary testing of the internal consistency and test-retest reliability of the GSM-V. The GSM-V consists of 54 items grouped into scales that explore the five spectra described above. It was derived from existing data on five Structured Clinical Interviews that were designed to assess spectrum features by using multiple regression models. The GSM-V was administered as a stand-alone instrument along with the self-report versions of the spectrum interviews to a sample of 56 psychiatric patients in order to determine the internal consistency of its scales and the correlation with the parent spectrum measures. Moreover, to determine whether subjects would respond consistently to the same items on two different occasions (test-retest reliability), the GSM-V was re-administered within 1 month from the baseline. From each of the five spectrum interviews, items were selected that accounted for a significant proportion of variance of the total score of the parent instrument. The five sets of items so selected constitute separate scales. The scales of the GSM-V had a good to excellent internal consistency, excellent test-retest reliability, and proved to reproduce adequately the long-form measures. The GSM-V appears to provide a reliable alternative to the five longer spectrum interviews. It is envisaged that the instrument will be most useful as a pre-test to identify subjects with spectrum features that should be explored in greater detail. Additionally, it could provide a better characterization of patients with a syndromal level Axis-I disorder, who might require specific treatment strategies targeted to co-occurring subsyndromal conditions.

Adolescent↗

PubMed2003

Microstructure of sleep in depressed patients according to the cyclic alternating pattern.

BACKGROUND: The aim of this study was to evaluate the microstructure of the EEG sleep of depressed subjects by cyclic alternating pattern (CAP) analysis. METHODS: 78 patients affected by major depression and 18 control subjects matched for age and sex underwent a full night polysomnographic study. RESULTS: A significant increase in CAP rate (60 versus 35%) was found in the patients group compared to controls while no significant difference was found with the traditional analysis. CONCLUSION: In depressed subjects CAP analysis is able to show a microstructural sleep impairment, which is not evident at the macrostructural level, providing an objective measure of sleep disturbance in those patients.

Adolescent↗