Biomedical subjects

M A Frye

Publications and source records attributed to M A Frye.

At least 19 recordsLinked to original sources

PubMed2006

Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline.

BACKGROUND: Few studies have examined the relative risks of switching into hypomania or mania associated with second-generation antidepressant drugs in bipolar depression. AIMS: To examine the relative acute effects of bupropion, sertraline and venlafaxine as adjuncts to mood stabilisers. METHOD: In a 10-week trial, participants receiving out-patient treatment for bipolar disorder (stratified for rapid cycling) were randomly treated with a flexible dose of one of the antidepressants, or their respective matching placebos, as adjuncts to mood stabilisers. RESULTS: A total of 174 adults with bipolar disorder I, II or not otherwise specified, currently in the depressed phase, were included. All three antidepressants were associated with a similar range of acute response (49-53%) and remission (34-41%). There was a significantly increased risk of switches into hypomania or mania in participants treated with venlafaxine compared with bupropion or sertraline. CONCLUSIONS: More caution appears indicated in the use of venlafaxine rather than bupropion or sertraline in the adjunctive treatment of bipolar depression, especially if there is a prior history of rapid cycling.

Adjuvants, Pharmaceutic↗

PubMed2005

Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in bipolar depression.

Supplementation of standard treatment with high-dose levothyroxine (L-T(4)) is a novel approach for treatment-refractory bipolar disorders. This study tested for effects on brain function associated with mood alterations in bipolar depressed patients receiving high-dose L-T(4) treatment adjunctive to ongoing medication (antidepressants and mood stabilizers). Regional activity and whole-brain analyses were assessed with positron emission tomography and [(18)F]fluorodeoxyglucose in 10 euthyroid depressed women with bipolar disorder, before and after 7 weeks of open-label adjunctive treatment with supraphysiological doses of L-T(4) (mean dose 320 microg/day). Corresponding measurements were acquired in an age-matched comparison group of 10 healthy women without L-T(4) treatment. The primary biological measures were relative regional activity (with relative brain radioactivity taken as a surrogate index of glucose metabolism) in preselected brain regions and neuroendocrine markers of thyroid function. Treatment-associated changes in regional activity (relative to global activity) were tested against clinical response. Before L-T(4) treatment, the patients exhibited significantly higher activity in the right subgenual cingulate cortex, left thalamus, medial temporal lobe (right amygdala, right hippocampus), right ventral striatum, and cerebellar vermis; and had lower relative activity in the middle frontal gyri bilaterally. Significant behavioral and cerebral metabolic effects accompanied changes in thyroid hormone status. L-T(4) improved mood (remission in seven patients; partial response in three); and decreased relative activity in the right subgenual cingulate cortex, left thalamus, right amygdala, right hippocampus, right dorsal and ventral striatum, and cerebellar vermis. The decrease in relative activity of the left thalamus, left amygdala, left hippocampus, and left ventral striatum was significantly correlated with reduction in depression scores. Results of the whole-brain analyses were generally consistent with the volume of interest results. We conclude that bipolar depressed patients have abnormal function in prefrontal and limbic brain areas. L-T(4) may improve mood by affecting circuits involving these areas, which have been previously implicated in affective disorders.

Adult↗

PubMed2004

Use of quetiapine in bipolar disorder: a case series with prospective evaluation.

Quetiapine, a new atypical antipsychotic, was added to ongoing treatment of bipolar I outpatients (n=15) for symptoms of illness (mood lability, irritability, psychosis and/or difficulty sleeping). All evaluations were prospectively obtained, with the majority of patients (n=9) showing much or very much improvement on the Clinical Global Impression for Bipolar Disorder (CGI-BP). Somatic complaints were limited. Mean (SD) duration before changes in medication regimens was 134 (100) days. Studies of the use of quetiapine in maintenance treatment of bipolar disorder are warranted.

Antipsychotic Agents↗

PubMed2001

Fly flight: a model for the neural control of complex behavior.

Flies exhibit a repertoire of aerial acrobatics unmatched in robustness and aerodynamic sophistication. The exquisite control of this complex behavior emerges from encoding intricate patterns of optic flow, and the translation of these visual signals into the mechanical language of the motor system. Recent advances in experimental design toward more naturalistic visual and mechanosensory stimuli have served to reinforce fly flight as a key model system for understanding how feedback from multiple sensory modalities is integrated to control complex and robust motor behaviors across taxa.

Animals↗

PubMed2001

Putative uremic encephalopathy in horses: five cases (1978-1998).

OBJECTIVE: To determine historical, physical examination, clinicopathologic, and postmortem findings in horses with putative uremic encephalopathy. Design-Retrospective study. Animals-5 horses with renal failure and neurologic disease not attributable to abnormalities in any other organ system. PROCEDURE: Medical records from 1978 to 1998 were examined for horses with renal disease and neurologic signs not attributable to primary neurologic, hepatic, or other diseases. Signalment, history, physical examination findings, clinicopathologic data, renal ultrasonographic findings, and postmortem data were reviewed. RESULTS: Of 332 horses with renal disease, 5 met selection criteria. Historical findings, physical examination findings, clinicopathologic data, ultrasonographic data, and postmortem findings were consistent with chronic renal failure. Swollen astrocytes were detected in all 4 horses examined at necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: A single criterion was not determined to be pathognomonic for uremic encephalopathy in horses. Uremic encephalopathy should be considered as a differential diagnosis in horses with evidence of chronic renal failure and encephalopathic neurologic sign not attributable to other causes. Astrocyte swelling, which was common to all 4 horses examined at necropsy, may serve as a microscopic indicator of uremic encephalopathy in horses.

Animals↗

PubMed2001

Effects of mood and subtype on cerebral glucose metabolism in treatment-resistant bipolar disorder.

BACKGROUND: Functional brain imaging studies in unipolar and secondary depression have generally found decreased prefrontal cortical activity, but in bipolar disorders findings have been more variable. METHODS: Forty-three medication-free, treatment-resistant, predominantly rapid-cycling bipolar disorder patients and 43 age- and gender-matched healthy control subjects had cerebral glucose metabolism assessed using positron emission tomography and fluorine-18-deoxyglucose. RESULTS: Depressed bipolar disorder patients compared to control subjects had decreased global, absolute prefrontal and anterior paralimbic cortical, and increased normalized subcortical (ventral striatum, thalamus, right amygdala) metabolism. Degree of depression correlated negatively with absolute prefrontal and paralimbic cortical, and positively with normalized anterior paralimbic subcortical metabolism. Increased normalized cerebello-posterior cortical metabolism was seen in all patient subgroups compared to control subjects, independent of mood state, disorder subtype, or cycle frequency. CONCLUSIONS: In bipolar depression, we observed a pattern of prefrontal hypometabolism, consistent with observations in primary unipolar and secondary depression, suggesting this is part of a common neural substrate for depression independent of etiology. In contrast, the cerebello-posterior cortical normalized hypermetabolism seen in all bipolar subgroups (including euthymic) suggests a possible congenital or acquired trait abnormality. The degree to which these findings in treatment-resistant, predominantly rapid-cycling patients pertain to community samples remains to be established.

Acoustic Stimulation↗

PubMed2001

The Stanley Foundation Bipolar Treatment Outcome Network. II. Demographics and illness characteristics of the first 261 patients.

BACKGROUND: Since recent NIMH Bipolar Disorder Workshops highlighted the dearth of longitudinal and controlled studies of bipolar illness, the Stanley Foundation Bipolar Network (SFBN) has recruited a large cohort of patients with bipolar disorder to begin to address these issues. This report describes the demographics and course of illness characteristics of this study population. METHODS: The first 261 outpatients to be diagnosed by the Structured Clinical Interview for DSM-IV (SCID) and complete a detailed patient and a brief clinician questionnaire are described. All patients met DSM-IV criteria for bipolar I (n=211), bipolar II (n=42), or NOS (n=5) or schizoaffective (n=3), bipolar type. Chi-square and t-tests were used to examine statistically significant associations among important demographic and descriptive items. RESULTS: The general demographic and illness characteristics were similar to those in many bipolar clinical samples and not dissimilar from those reported in epidemiological surveys. The majority of patients had been hospitalized, with almost half reporting a worsening of illness over time, and two-thirds were not asymptomatic between episodes. First treatment for patients had been delayed by an average of 10 years from illness onset (by SCID). Almost a third of patients had attempted suicide at least once, and 30% reported current suicidal ideation at study entry. A total of 62% reported moderate to severe impact of the illness on occupational functioning. Early onset bipolar illness (< or =17 years old) was associated with increased frequency of mood switches, worsening course of illness, and history of early abuse (physical, verbal, or sexual). CONCLUSION: The SFBN represents a sample of predominantly BP I patients largely recruited from the community who will be followed in detail longitudinally, participate in clinical trials, and thus help advance our understanding and treatment of this life-threatening medical disorder. While there is a broad range of illness characteristics and severity, the majority of patients have been severely impacted by their illness despite the availability of multiple conventional treatment approaches in the community. These data further underscore the need for development of new and earlier treatment interventions. LIMITATION: The SFBN population is limited by the lack of random selection and represents a cohort willing to be treated and followed intensively in academic tertiary referral centers. While its characteristics are similar to many clinical study populations, the generalizability to non-clinic populations remains uncertain.

Activities of Daily Living↗

PubMed2001

Post-dexamethasone cortisol correlates with severity of depression before and during carbamazepine treatment in women but not men.

OBJECTIVE: Previous studies show a state-dependent relationship between depression and post-dexamethasone suppression test (DST) cortisol level, as well as differences in DST response with age and gender. METHOD: In this study, 74 research in-patients with affective disorders were given the DST on placebo and in a subgroup following treatment with carbamazepine. Depression was evaluated twice daily with the Bunney-Hamburg (BH) rating scale. Data were examined for the total subject population, by gender and by menopausal status in women. RESULTS: A robust positive correlation was observed between depression severity and post-DST cortisol in pre- and postmenopausal females, but not in males. This relationship persisted in women when restudied on a stable dose of carbamazepine (n=42). CONCLUSION: The pathophysiological implications of this selective positive relationship between severity of depression and post-DST cortisol in women, but not men, should be explored further.

Adult↗

PubMed2001

Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature.

OBJECTIVE: The delayed onset of therapeutic response to antidepressants remains a major problem in the treatment of depression. Among the strategies to accelerate response to treatment, the early addition of thyroid hormone to antidepressants has been suggested as a viable method. The authors performed a meta-analysis of the literature on the use of thyroid hormone supplementation to accelerate the treatment of depression to determine whether there is sufficient evidence to support the clinical efficacy of this strategy. METHOD: Both a computer-aided search of the National Library of Medicine MEDLINE and an intensive search by hand were conducted to identify all double-blind, placebo-controlled studies assessing the concomitant administration of thyroid hormone and antidepressant to accelerate clinical response in patients with nonrefractory depression. RESULTS: Six studies were identified. All were conducted with triiodothyronine (T(3)) and a tricyclic antidepressant. Five of the six studies found T(3) to be significantly more effective than placebo in accelerating clinical response. The pooled, weighted effect size index was 0.58, and the average effect was highly significant. Further, the effects of T(3) acceleration were greater as the percentage of women participating in the study increased. CONCLUSIONS: This meta-analysis supports the efficacy of T(3) in accelerating clinical response to tricyclic antidepressants in patients with nonrefractory depression. Furthermore, women may be more likely than men to benefit from this intervention.

Amitriptyline↗

PubMed2001

Axis I psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar disorder.

OBJECTIVE: Bipolar disorder often co-occurs with other axis I disorders, but little is known about the relationships between the clinical features of bipolar illness and these comorbid conditions. Therefore, the authors assessed comorbid lifetime and current axis I disorders in 288 patients with bipolar disorder and the relationships of these comorbid disorders to selected demographic and historical illness variables. METHOD: They evaluated 288 outpatients with bipolar I or II disorder, using structured diagnostic interviews and clinician-administered and self-rated questionnaires to determine the diagnosis of bipolar disorder, comorbid axis I disorder diagnoses, and demographic and historical illness characteristics. RESULTS: One hundred eighty-seven (65%) of the patients with bipolar disorder also met DSM-IV criteria for at least one comorbid lifetime axis I disorder. More patients had comorbid anxiety disorders (N=78, 42%) and substance use disorders (N=78, 42%) than had eating disorders (N=9, 5%). There were no differences in comorbidity between patients with bipolar I and bipolar II disorder. Both lifetime axis I comorbidity and current axis I comorbidity were associated with earlier age at onset of affective symptoms and syndromal bipolar disorder. Current axis I comorbidity was associated with a history of development of both cycle acceleration and more severe episodes over time. CONCLUSIONS: Patients with bipolar disorder often have comorbid anxiety, substance use, and, to a lesser extent, eating disorders. Moreover, axis I comorbidity, especially current comorbidity, may be associated with an earlier age at onset and worsening course of bipolar illness. Further research into the prognostic and treatment response implications of axis I comorbidity in bipolar disorder is important and is in progress.

Adult↗

PubMed2001

The Stanley Foundation Bipolar Network. I. Rationale and methods.

BACKGROUND: The Stanley Foundation Bipolar Network (SFBN) was created to address the paucity of help studies in bipolar illness. AIMS: To describe the rationale and methods of the SFBN. METHOD: The SFBN includes five core sites and a number of affiliated sites that have adopted consistent methodology for continuous longitudinal monitoring of patients. Open and controlled studies are performed as patients' symptomatology dictates. RESULTS: The reliability of SFBN raters and the validity of the rating instruments have been established. More than 500 patients are in continuous daily longitudinal follow-up. More than 125 have been randomised to one of three of the newer antidepressants (bupropion, sertraline and venlafaxine) as adjuncts in a study of mood stabilizers and 93 to omega-3 fatty acids. A number of open clinical case series have been published. CONCLUSIONS: Well-characterised patients are followed in a detailed continuous longitudinal fashion in both opportunistic case series and double-blind, randomised controlled trials with reliable and validated measures.

Antimanic Agents↗

PubMed2001

Effects of stretch receptor ablation on the optomotor control of lift in the hawkmoth Manduca sexta.

In insects, fast sensory feedback from specialized mechanoreceptors is integrated with guidance cues descending from the visual system to control flight behavior. A proprioceptive sensory organ found in both locusts and moths, the wing hinge stretch receptor, has been extensively studied in locusts for its powerful influence on the activity of flight muscle motoneurons and interneurons. The stretch receptor fires a high-frequency burst of action potentials near the top of each wingstroke and encodes kinematic variables such as amplitude and timing. Here, I describe the effects of stretch receptor ablation on the visual control of lift during flight in the hawkmoth Manduca sexta. Using a combination of extracellular muscle recordings, force and position measurements and high-speed video recording, I tracked power muscle activity, net vertical flight force (lift), abdomen deflection and wing kinematics in response to image motions of varying velocity during tethered flight in a wind tunnel. As a result of bilateral ablation of the wing hinge stretch receptors, visually evoked lift decreased to nearly one-third of that exhibited by intact animals. The phase and frequency of indirect power muscle action potentials and the patterns of abdominal deflection were unaffected; however, wingstroke amplitude was clearly reduced after ablation. Collectively, these results suggest that stretch receptor feedback is integrated with descending visual cues to control wing kinematics and the resultant aerodynamic force production during flight.

Animals↗

PubMed2001

Encoding properties of the wing hinge stretch receptor in the hawkmoth Manduca sexta.

To characterize the in vivo responses of the wing hinge stretch receptor of Manduca sexta, I recorded its activity and simultaneously tracked the up-and-down motion of the wing while the hawkmoth flew tethered in a wind tunnel. The stretch receptor fires a high-frequency burst of spikes near each dorsal stroke reversal. The onset of the burst is tightly tuned to a set-point in wing elevation, and the number of spikes contained within the burst encodes the maximal degree of wing elevation during the stroke. In an effort to characterize its mechanical encoding properties, I constructed an actuator that delivered deformations to the wing hinge and simultaneously recorded the resultant stretch and tension and the activity of the stretch receptor. Stimuli included stepwise changes in length as well as more natural dynamic deformation that was measured in vivo. Step changes in length reveal that the stretch receptor encodes the static amplitude of stretch with both phasic and tonic firing dynamics. In vivo sinusoidal deformation revealed (i) that the timing of stretch receptor activity is tightly phase-locked within the oscillation cycle, (ii) that the number of spikes per burst is inversely related to oscillation frequency and (iii) that the instantaneous frequency of the burst increases with oscillation rate. At all oscillation rates tested, the instantaneous frequency of the burst increases with amplitude.

Action Potentials↗

PubMed2001

The Stanley Foundation Bipolar Network. 2. Preliminary summary of demographics, course of illness and response to novel treatments.

BACKGROUND: The Stanley Foundation Bipolar Network (SFBN) evaluates treatments, course and clinical and neurobiological markers of response in bipolar illness. AIMS: To give a preliminary summary of emerging findings in these areas. METHOD: Studies with established and potentially antimanic, antidepressant and mood-stabilising agents range from open case series to double-blind randomised clinical trials, and use the same core assessment methodology, thereby optimising the comparability of the outcomes. The National Institute of Mental Health Life Chart Method is the core instrument for retrospective and prospective longitudinal illness description. RESULTS: The first groups of patients enrolled show a considerable degree of past and present symptomatology, psychiatric comorbidity and functional impairment. There are associations of both genetic and early environmental factors with more severe courses of illness. Open case series with add-on olanzapine, lamotrigine, gabapentin or topiramate show a differential spectrum of effectiveness in refractory patients. CONCLUSIONS: The SFBN provides important new data for the understanding and treatment of bipolar disorder.

Adult↗

PubMed2001

Rate of switch in bipolar patients prospectively treated with second-generation antidepressants as augmentation to mood stabilizers.

INTRODUCTION: Bipolar patients with breakthrough major depressive episodes despite ongoing adequately-dosed mood stabilizer medication were randomized in a double-blind manner to one of three antidepressants with different mechanisms of action: bupropion, sertraline, or venlafaxine. Preliminary data are presented on the switch rates into hypomania or mania for the antidepressants as a group prior to unblinding the specific individual drug efficacy and tolerability data in this ongoing clinical trial. METHODS: Subjects included 64 bipolar patients who participated at five sites in a 10-week double-blind trial for depression and a 1-year blinded continuation maintenance phase for responders. Nonresponders were re-randomized such that there were 95 acute treatment phases. In the acute phase, doses were titrated to clinical response, side effects, or maximum dose of bupropion (450 mg/day), sertraline (200 mg/day), or venlafaxine (375 mg/day). Daily ratings on the National Institute of Mental Health-Life Chart Methodology (NIMH-LCM) were inspected for the degree of improvement on the Clinical Global Impressions scale as revised for bipolar illness (CGI-BP) and the occurrence of hypomania or mania. RESULTS: Thirty-five (37%) of the 95 acute treatment phases were associated with a much or very much improved rating in depression on the CGI-BP. Thirteen (14%) of these 95 acute trials of antidepressants as adjuncts to mood stabilizers were associated with switches, seven into hypomania and six into mania. Forty-two patients elected to go into the continuation phase in 48 instances. Sixteen (33%) of the continuation phase trials were associated with mood switches, 10 into hypomania and six into mania. CONCLUSIONS: In this randomized double-blind prospective study of three second-generation antidepressants (bupropion, sertraline, and venlafaxine) in bipolar patients whose depression broke through ongoing treatment with mood stabilizers, switches into hypomania or mania occurred in 14% of the acute phases and 33% of the continuation phases. Individual data on each drug will be assessed in the next phase of the study after more subjects are recruited and the blind is broken.

Adult↗

PubMed2000

Open-label adjunctive topiramate in the treatment of bipolar disorders.

BACKGROUND: To preliminarily explore the spectrum of effectiveness and tolerability of the new antiepileptic drug topiramate in bipolar disorder, we evaluated the response of 56 bipolar outpatients in the Stanley Foundation Bipolar Outcome Network (SFBN) who had been treated with adjunctive topiramate in an open-label, naturalistic fashion. METHODS: In this case series, response to topiramate was assessed every 2 weeks for the first 3 months according to standard ratings in the SFBN, and monthly thereafter while patients remained on topiramate. Patients' weights, body mass indices (BMIs), and side effects were also assessed. RESULTS: Of the 54 patients who completed at least 2 weeks of open-label, add-on topiramate treatment, 30 had manic, mixed, or cycling symptoms, 11 had depressed symptoms, and 13 were relatively euthymic at the time topiramate was begun. Patients who had been initially treated for manic symptoms displayed significant reductions in standard ratings scores after 4 weeks, after 10 weeks, and at the last evaluation. Those patients who were initially depressed or treated while euthymic showed no significant changes. Patients as a group displayed significant decreases in weight and BMI from topiramate initiation to week 4, to week 10, and to the last evaluation. The most common adverse side effects were neurologic and gastrointestinal. CONCLUSIONS: These preliminary open observations of adjunctive topiramate treatment suggest that it may have antimanic or anticycling effects in some patients with bipolar disorder, and may be associated with appetite suppression and weight loss that is often viewed as beneficial by the patient and clinician. Controlled studies of topiramate's acute and long-term efficacy and side effects in bipolar disorder appear warranted.

Adult↗

PubMed2000

Validation of the prospective NIMH-Life-Chart Method (NIMH-LCM-p) for longitudinal assessment of bipolar illness.

BACKGROUND: Systematic and accurate depiction of a patient's course of illness is crucial for assessing the efficacy of maintenance treatments for bipolar disorder. This need to rate the long-term prospective course of illness led to the development of the National Institute of Mental Health prospective Life Chart Methodology (NIMH-LCM-p or LCM). The NIMH-LCM-p allows for the daily assessment of mood and episode severity based on the degree of mood associated functional impairment. We have previously presented preliminary evidence of the reliability and validity of the LCM, and its utility in clinical trials. This study is a further and more extensive validation of the clinician rated NIMH-LCM-p. METHODS: Subjects included 270 bipolar patients from the five sites participating in the Stanley Foundation Bipolar Network. Daily prospective LCM ratings on the clinician form were initiated upon entry, in addition to at least monthly ratings with the Inventory of Depressive Symptomatology-clinician rated (IDS-C), the Young Mania Rating Scale (YMRS) and the Global Assessment of Functioning (GAF). We correlated appropriate measures and time domains of the LCM with the IDS-C, YMRS and GAF. RESULTS: Severity of depression on the LCM and on the IDS-C were highly correlated in 270 patients (r = -0.785, P < 0.001). Similarly, a strong correlation was found between LCM mania and the YMRS (r = 0.656, P < 0.001) and between the LCM average severity of illness and the GAF (r = -0.732, P < 0.001). CONCLUSIONS: These data further demonstrate the validity and potential utility of the NIMH-LCM-p for the detailed daily longitudinal assessment of manic and depressive severity and course, and response to treatment.

Adult↗

PubMed2000

Emerging trends in the treatment of rapid cycling bipolar disorder: a selected review.

Recent evidence suggests that lithium therapy (even as supplemented by antidepressants and neuroleptics) is inadequate for the majority of patients with bipolar illness, and particularly those with rapid cycling. Valproate and carbamazepine have emerged as adjuncts and alternatives, but they, too, often require additional approaches with lithium, thyroid hormones, and other putative mood stabilizers, including nimodipine (and related dihydropyridine calcium channel blockers), lamotrigine, gabapentin, topiramate, and the atypical neuroleptics. Evaluating how these agents and the unimodal antidepressants are optimally applied and sequenced in the treatment of bipolar illness with its multiple subtypes, patterns and comorbidities will require much future investigation and the development of new methodological clinical trial approaches.

Algorithms↗