International Journal of Methods in Psychiatric Research, 1999
We evaluated the internal consistency, discriminant validity, inter‐rater reliability and test–re... more We evaluated the internal consistency, discriminant validity, inter‐rater reliability and test–retest reliability of a new instrument for the assessment of lifetime symptoms related to mood spectrum disorders: the Structured Clinical Interview for Mood Spectrum (SCI‐MOODS). We report on results obtained from 491 subjects assessed across eight psychiatric centres in Italy who were given the SCI‐MOODS and the Mini International Neuropsychiatric Interview (MINI). The study sample consisted of four groups: 141 students, 116 gastrointestinal (GI) patients, 112 bipolar patients and 122 patients with recurrent depression. To evaluate the inter‐rater reliability and the test–retest reliability, an additional group of 30 subjects (10 non‐psychiatric patients enrolled in an orthopaedic clinic, 10 unipolar patients and 10 bipolar patients) was given the SCI‐MOODS at a baseline assessment and six to eight days later. At the baseline assessment, these subjects were also interviewed using the Str...
International Journal of Methods in Psychiatric Research, 2000
In this study we evaluated the psychometric properties of the Structured Clinical Interview for t... more In this study we evaluated the psychometric properties of the Structured Clinical Interview for the Anorexic‐Bulimic Spectrum (SCI‐ABS), including internal consistency, concurrent validity, discriminant validity and test–retest reliability. We also determine acceptability and feasibility of administration of the interview. The SCI‐ABS was designed to assess typical and atypical symptoms, behaviours and temperament traits pertaining to eating disorders. The interview included 134 items grouped into nine domains, four of which were divided into subdomains.Data were collected from 372 subjects: 55 psychiatric patients with any eating disorder according to DSM‐IV criteria, 118 university students, 141 subjects working out in a gym, and 65 obstetrical patients. Concurrent validity of the instrument was assessed against the Eating Attitude Test (EAT) and the Eating Disorder Inventory (EDI). Thirty‐five subjects were also recruited to study the test–retest reliability and 25 women with any...
This report presents data on normative nocturnal penile tumescence (NPT), based on a study of 48 ... more This report presents data on normative nocturnal penile tumescence (NPT), based on a study of 48 healthy men aged 20-59 years, without complaints of erectile dysfunction. In general, the current measures show good concordance with those reported by Karacan and colleagues in 1976. The effect of "pathology-free" aging (from age 20 to 59) on electrographic measures of NPT is relatively modest, accounting for 8.4-14.4% of the variance. Furthermore, no age effect on visual estimates of erectile fullness or on buckling force estimates of penile rigidity were present. Maximum buckling force and maximum erectile fullness showed stability across the four decades of the Pittsburgh sample.
Objective-Oxytocin is a hypothalamic neuropeptide that plays a key role in mammalian female repro... more Objective-Oxytocin is a hypothalamic neuropeptide that plays a key role in mammalian female reproductive function. Animal research indicates that central oxytocin facilitates adaptive social attachments and modulates stress and anxiety responses. Major depression is prevalent among postpubertal females, and is associated with perturbations in social attachments, dysregulation of the hypothalamic-pituitary-adrenal stress axis, and elevated levels of anxiety. Thus, depressed women may be at risk to display oxytocin dysregulation. The current study was developed to compare patterns of peripheral oxytocin release exhibited by depressed and nondepressed women. Methods-Currently depressed (N = 17) and never-depressed (N = 17) women participated in a laboratory protocol designed to stimulate, measure, and compare peripheral oxytocin release in response to two tasks: an affiliation-focused Guided Imagery task and a Speech Stress task. Intermittent blood samples were drawn over the course of two, 1-hour sessions including 20minute baseline, 10-minute task, and 30-minute recovery periods. Results-The 10-minute laboratory tasks did not induce identifiable, acute changes in peripheral oxytocin. However, as compared with nondepressed controls, depressed women displayed greater variability in pulsatile oxytocin release over the course of both 1-hour sessions, and greater oxytocin concentrations during the 1-hour affiliation-focused imagery session. Oxytocin concentrations obtained during the imagery session were also associated with greater symptoms of depression, anxiety, and interpersonal dysfunction. Conclusions-Depressed women are more likely than controls to display a dysregulated pattern of peripheral oxytocin release. Further research is warranted to elucidate the clinical significance of peripheral oxytocin release in both depressed and nondepressed women.
OBJECTIVE This report compares response to cognitive-behavioral therapy (CBT) and pharmacotherapy... more OBJECTIVE This report compares response to cognitive-behavioral therapy (CBT) and pharmacotherapy in sequential cohorts of men with DSM-III-R major depression. METHOD Patients were enrolled in consecutive standardized 16-week treatment protocols conducted in the same research clinic. The first group (N = 52) was treated with Beck's model of CBT, whereas the second group (N = 23) received randomized but open-label treatment with either fluoxetine (N = 10) or bupropion (N = 13). Crossover to the alternate medication was permitted after 8 weeks of treatment for antidepressant nonresponders. The patient groups were well matched prior to treatment. Outcomes included remission and nonresponse rates, as well as both independent clinical evaluations and self-reported measures of depressive symptoms. RESULTS Despite limited statistical power to detect differences between treatments, depressed men treated with pharmacotherapy had significantly greater improvements on 4 of 6 continuous dependent measures and a significantly lower rate of nonresponse (i.e., 13% vs. 46%). The difference favoring pharmacotherapy was late-emerging and partially explained by crossing over nonresponders to the alternate medication. The advantage of pharmacotherapy over CBT also tended to be larger among the subgroup of patients with chronic depression. CONCLUSION Results of prior research comparing pharmacotherapy and CBT may have been influenced by the composition of study groups, particularly the gender composition, the choice of antidepressant comparators, or an interaction of these factors. Prospective studies utilizing flexible dosing of modern antidepressants and, if necessary, sequential trials of dissimilar medications are needed to confirm these findings.
To the Editor: As indicated in the recent review by Maurer, 1(p139) "depression has an estimated ... more To the Editor: As indicated in the recent review by Maurer, 1(p139) "depression has an estimated prevalence of 5.4 to 8.9 percent in the US general population 2 and affects 5 to 13 percent of patients in primary care settings. 3 " The condition accounts for more than $43 billion in medical care costs and $17 billion in lost productivity annually. 4 Depression is projected to become the second largest cause of worldwide disability by 2020. 5 The most frequently used tools for screening of depression in primary care are the Patient Health Questionnaire-2 (PHQ-2) and PHQ-9; however, both suffer from poor sensitivity: 61% and 74%, respectively, 6 in primary care settings and much lower in cardiology settings (eg, 39% for the PHQ-2 in cardiology settings 7). The development of new statistical tools with higher sensitivity for screening depression in primary care is critical. The Computerized Adaptive Diagnostic Test for Major Depressive Disorder (CAD-MDD) 8 is clearly such a tool. In the mental health settings in which we have studied the CAD-MDD (a mixture of academic medical center and community mental health settings), it dramatically increases sensitivity to 0.95 with comparable specificity to existing methods. Assuming the CAD-MDD is comparably sensitive in primary care settings, for every 100 cases of major depressive disorder the PHQ-2 will miss 39, the PHQ-9 will miss 26, but the CAD-MDD will miss only 5. As we have shown in our article, all of this can be achieved using an average of only 4 items in less than 1 minute anywhere on the planet via the Internet or in a kiosk in a health care provider's office. We think that this is a good thing and will continue to study the properties of the CAD-MDD in different populations in which, as we noted in our article, variation in case mix and prevalence may well affect sensitivity. The use of this new statistical approach to develop screening instruments for other disorders should remain a high priority on our nation's mental health agenda. Dr Carroll raises the conjecture that "specificity was probably no better than 0.50 in the clinical subsample and close to 1.0 in the 'scrubbed' control subsample. " In fact, for the clinical subsample (Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania), both sensitivity and specificity remained high at 0.92 and 0.85, respectively, and did not degrade as Dr Carroll suggests. In the community mental health clinic (DuBois Community Mental Health Center, DuBois, Pennsylvania), sensitivity was 1.00 and specificity was 0.88. These findings reveal that the CAD-MDD is robust to both psychiatric comorbidity and the overall incidence of depression. We note that the incidence was 30% in the "clinical" sample and 15% in the community mental health center. The community mental health center has an incidence that is not dissimilar to what is typically found in primary care settings. 3 Nevertheless, sensitivity was perfect and specificity remained high.
Failure to recognize subthreshold expressions of mania contributes to the frequent under-diagnosi... more Failure to recognize subthreshold expressions of mania contributes to the frequent under-diagnosis of bipolar disorder. There are several reasons for the lower rate of recognition of subthreshold manic symptoms, when compared to the analogous pure depressive ones. These include the lack of subjective suffering, enhanced productivity, ego-syntonicity, and diurnal and seasonal rhythmicity associated with many of the manic and hypomanic symptoms, and the psychiatrists' tendency to subsume persistent or even alternating symptoms among personality disorders. Furthermore, the central diagnostic importance placed on alterations in mood distracts clinicians from paying attention to other more subtle but clinically meaningful symptoms, such as changes in energy, neurovegetative symptoms and distorted cognitions. Although officially accepted in both ICD-10 and DSM-IV, we believe bipolar II disorder is underdiagnosed because of inattention to symptoms of hypomania. Moreover, by requiring the presence of both full-blown hypomanic and major depressive episodes, current nosology fails to include symptoms or signs which are mild and do not meet threshold criteria. There is already agreement in the field that such symptoms are important for depression. We now propose that attention should also be devoted to mild symptomatic manifestations of a manic diathesis, even if such manifestations may sometimes enhance quality of life. The term 'spectrum' is used to refer to the broad range of such manifestations of a disorder from core symptoms to temperamental traits. Spectrum manifestations may be present during, between, or even in the absence of, an episode of full-blown disorder. We have developed a structured clinical interview to assess the mood spectrum (SCI-MOODS) to evaluate the whole range of depressive and manic symptoms. This instrument is currently undergoing psychometric testing procedures. Similar to the SCID interview, the SCI-MOODS interview provides a separate rating for TM each of the major DSM-IV symptoms, but the latter also identifies and rates subthreshold and atypical manifestations. This paper presents the concept of a subthreshold bipolar disorder and discusses the potential epidemiological, diagnostic and therapeutic relevance of such a spectrum conditions. We also describe the SCI-MOODS interview used reliably to identify the occurrence of a bipolar spectrum condition. Obviously a great deal of systematic research needs to be conducted to ascertain the reliability and validity of subthreshold bipolarity as summarized in this paper and embodied in our instrument.
Recent epidemiologic studies have found that most patients with mental illness are seen exclusive... more Recent epidemiologic studies have found that most patients with mental illness are seen exclusively in primary care medicine. These patients often present with medically unexplained somatic symptoms and utilize at least twice as many health care visits as controls. There has been an exponential growth in studies in this interface between primary care and psychiatry in the last 10 years. This special section, edited by Wayne J. Katon, M.D., will publish informative research articles that address primary care-psychiatric issues.
Background: To date, no cross-national RCT has addressed the mechanisms underlying the relative s... more Background: To date, no cross-national RCT has addressed the mechanisms underlying the relative success of pharmacological and psychotherapeutic interventions for depression. A multi-site clinical trial that includes psychotherapy as one of the treatments presents numerous challenges related to cross-site consistency and communication. Purpose: This report describes how those challenges were met in the study ``Depression: The Search for Treatment Relevant Phenotypes'', being carried out at the University of Pittsburgh and the University of Pisa, Italy. Methods: Implementing the study required the investigators to address methodological and practical challenges related to the different requirements of the two Institutional Review Boards (IRBs), psychotherapy training, independent evaluator training, patient recruitment, development of common tools for data entry, quality control and generation of weekly reports of patient progress as well as establishing a similar clinical an...
Sixteen male outpatients with major depression and 20 age-equated healthy controls were awakened ... more Sixteen male outpatients with major depression and 20 age-equated healthy controls were awakened from rapid eye movement (REM) sleep between 1:30 and 3:30 AM, and the rapidity of return to REM sleep was determined. The time it took to return to REM sleep was reduced in depressives compared with controls: 6•.6 (17.9 SD) min versus 80.6 (24.9 SD) rain, respectively (p = 0.01). The time elapsed until the return to REM sleep was significantly correlated with baseline REM latency in controls (but not depressives). In contrast, return to REM time was significantly correlated with depression severity scores in depressives (but not controls). There was no evidence to support the hypothesis that the more rapid return to REId sleep in depression was caused by a slow wave sleep deficit. The mechanism underlying the rapid return of REM sleep in depression thus may be related to a severity-linked disturbance, such as a proposed increase in REM "pressure."
A descriptive study was conducted in a new sample of 51 men with DSM-III-R research diagnostic cr... more A descriptive study was conducted in a new sample of 51 men with DSM-III-R research diagnostic criteria (RDC) major depression in order to replicate earlier observations that measure~ of nocturnal penile tumescence (NPT) and penile rigidity are disturbed in depressive s:~ztes. When compared to both the age-equated patient (n = 34) and normal control (n = 28) groups reported in our 1988 study, the new sample manifested significant abnormalities ~,f NPT and diminished penile rigidity. Such distuP bances were not, however, significantly correlated with psychobiological indicators oJ severe or endogenous depression.
Circadian clocks are temporal interfaces that organize biological systems and behavior to dynamic... more Circadian clocks are temporal interfaces that organize biological systems and behavior to dynamic external environments. Components of the molecular clock are expressed throughout the brain and are centrally poised to play an important role in brain function. This paper focuses on key issues concerning the relationship among circadian clocks, brain function, and development, and discusses three topic areas: (1) sleep and its relationship to the circadian system; (2) systems development and psychopathology (spanning the prenatal period through late life); and (3) circadian factors and their application to neuropsychiatric disorders. We also explore circadian genetics and psychopathology and the selective pressures on the evolution of clocks. Last, a lively debate is presented on whether circadian factors are central to mood disorders. Emerging from research on circadian rhythms is a model of the interaction among genes, sleep, and the environment that converges on the circadian clock to influence susceptibility to developing psychopathology. This model may lend insight into effective treatments for mood disorders and inform development of new interventions.
Objective-Little is known about predictors of recovery from bipolar depression or moderators of t... more Objective-Little is known about predictors of recovery from bipolar depression or moderators of treatment response. In the present study we investigated attributional style (a cognitive pattern of explaining the causes of life events) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychotherapy for bipolar depression. Method-106 depressed outpatients with DSM-IV bipolar I or II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were randomized to intensive psychotherapy for depression (n=62), or collaborative care (n=44), a minimal psychoeducational intervention. The primary outcome was recovery status at each study visit as measured by the Clinical Monitoring Form. Attributional style was measured at baseline using the Attributional Style Questionnaire. Data were collected between 1998 and 2005. Results-All analyses were by intention to treat. Extreme attributions predicted a lower likelihood of recovery (p=.01, OR=0.93, 95% CI=.88-.98) and longer time until recovery (p<.01, OR=0.96, 95% CI=.93-.99), independent of the effects of initial depression severity. Among individuals with more pessimistic attributional styles, initial depression severity predicted a lower likelihood of recovery (p=.01, OR=0.64, 95% CI=.45-.91) and longer time until recovery (p<.001, OR=0.76, 95% CI=.66-.88). There was no difference in recovery rates between intensive psychotherapy and collaborative care (OR=0.90, 95% CI=0.40-2.01) in the full sample.
Treatment guidelines for major depressive disorders suggest that combined treatment of pharmacoth... more Treatment guidelines for major depressive disorders suggest that combined treatment of pharmacotherapy and psychotherapy may be helpful in the acute phase of severe major depression. 1 However, combined treatment is not strongly recommended in mild to moderate depression. In these cases, either pharmacotherapy or psychotherapy can be used, depending on the preference of the patient, the treatment history, and other clinical factors. However, is this recommendation still supported by the current state of knowledge? In this Viewpoint, I will discuss recent evidence suggesting that combined treatment could be a first-line treatment in the acute phase of mild to moderate depressive disorders and whether this evidence is strong enough to reconsider the recommendations in treatment guidelines.
This study evaluates the validity and the reliability of a new instrument developed to assess the... more This study evaluates the validity and the reliability of a new instrument developed to assess the psychotic spectrum: the Structured Clinical Interview for the Psychotic Spectrum (SCI-PSY). The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising the clinical and subsyndromal psychotic manifestations. The items of the interview include, in addition to a subset of the DSM-IV criteria for psychotic syndromes, a number of features derived from clinical experience and from a review of the phenomenological descriptions of psychoses. Study participants were enrolled at 11 Italian Departments of Psychiatry located at 9 sites and included 77 consecutive patients with schizophrenia or schizoaffective disorder, 66 with borderline personality disorder, 59 with psychotic mood disorders, 98 with non-psychotic mood disorders and 57 with panic disorder. A comparison group of 102 unselected controls was enrolled at the same sites. The SCI-PSY significantly discriminated subjects with any psychiatric diagnosis from controls and subjects with from those without psychotic disorders. The hypothesized structure of the instrument was confirmed empirically.
International Journal of Methods in Psychiatric Research, 1999
We evaluated the internal consistency, discriminant validity, inter‐rater reliability and test–re... more We evaluated the internal consistency, discriminant validity, inter‐rater reliability and test–retest reliability of a new instrument for the assessment of lifetime symptoms related to mood spectrum disorders: the Structured Clinical Interview for Mood Spectrum (SCI‐MOODS). We report on results obtained from 491 subjects assessed across eight psychiatric centres in Italy who were given the SCI‐MOODS and the Mini International Neuropsychiatric Interview (MINI). The study sample consisted of four groups: 141 students, 116 gastrointestinal (GI) patients, 112 bipolar patients and 122 patients with recurrent depression. To evaluate the inter‐rater reliability and the test–retest reliability, an additional group of 30 subjects (10 non‐psychiatric patients enrolled in an orthopaedic clinic, 10 unipolar patients and 10 bipolar patients) was given the SCI‐MOODS at a baseline assessment and six to eight days later. At the baseline assessment, these subjects were also interviewed using the Str...
International Journal of Methods in Psychiatric Research, 2000
In this study we evaluated the psychometric properties of the Structured Clinical Interview for t... more In this study we evaluated the psychometric properties of the Structured Clinical Interview for the Anorexic‐Bulimic Spectrum (SCI‐ABS), including internal consistency, concurrent validity, discriminant validity and test–retest reliability. We also determine acceptability and feasibility of administration of the interview. The SCI‐ABS was designed to assess typical and atypical symptoms, behaviours and temperament traits pertaining to eating disorders. The interview included 134 items grouped into nine domains, four of which were divided into subdomains.Data were collected from 372 subjects: 55 psychiatric patients with any eating disorder according to DSM‐IV criteria, 118 university students, 141 subjects working out in a gym, and 65 obstetrical patients. Concurrent validity of the instrument was assessed against the Eating Attitude Test (EAT) and the Eating Disorder Inventory (EDI). Thirty‐five subjects were also recruited to study the test–retest reliability and 25 women with any...
This report presents data on normative nocturnal penile tumescence (NPT), based on a study of 48 ... more This report presents data on normative nocturnal penile tumescence (NPT), based on a study of 48 healthy men aged 20-59 years, without complaints of erectile dysfunction. In general, the current measures show good concordance with those reported by Karacan and colleagues in 1976. The effect of "pathology-free" aging (from age 20 to 59) on electrographic measures of NPT is relatively modest, accounting for 8.4-14.4% of the variance. Furthermore, no age effect on visual estimates of erectile fullness or on buckling force estimates of penile rigidity were present. Maximum buckling force and maximum erectile fullness showed stability across the four decades of the Pittsburgh sample.
Objective-Oxytocin is a hypothalamic neuropeptide that plays a key role in mammalian female repro... more Objective-Oxytocin is a hypothalamic neuropeptide that plays a key role in mammalian female reproductive function. Animal research indicates that central oxytocin facilitates adaptive social attachments and modulates stress and anxiety responses. Major depression is prevalent among postpubertal females, and is associated with perturbations in social attachments, dysregulation of the hypothalamic-pituitary-adrenal stress axis, and elevated levels of anxiety. Thus, depressed women may be at risk to display oxytocin dysregulation. The current study was developed to compare patterns of peripheral oxytocin release exhibited by depressed and nondepressed women. Methods-Currently depressed (N = 17) and never-depressed (N = 17) women participated in a laboratory protocol designed to stimulate, measure, and compare peripheral oxytocin release in response to two tasks: an affiliation-focused Guided Imagery task and a Speech Stress task. Intermittent blood samples were drawn over the course of two, 1-hour sessions including 20minute baseline, 10-minute task, and 30-minute recovery periods. Results-The 10-minute laboratory tasks did not induce identifiable, acute changes in peripheral oxytocin. However, as compared with nondepressed controls, depressed women displayed greater variability in pulsatile oxytocin release over the course of both 1-hour sessions, and greater oxytocin concentrations during the 1-hour affiliation-focused imagery session. Oxytocin concentrations obtained during the imagery session were also associated with greater symptoms of depression, anxiety, and interpersonal dysfunction. Conclusions-Depressed women are more likely than controls to display a dysregulated pattern of peripheral oxytocin release. Further research is warranted to elucidate the clinical significance of peripheral oxytocin release in both depressed and nondepressed women.
OBJECTIVE This report compares response to cognitive-behavioral therapy (CBT) and pharmacotherapy... more OBJECTIVE This report compares response to cognitive-behavioral therapy (CBT) and pharmacotherapy in sequential cohorts of men with DSM-III-R major depression. METHOD Patients were enrolled in consecutive standardized 16-week treatment protocols conducted in the same research clinic. The first group (N = 52) was treated with Beck's model of CBT, whereas the second group (N = 23) received randomized but open-label treatment with either fluoxetine (N = 10) or bupropion (N = 13). Crossover to the alternate medication was permitted after 8 weeks of treatment for antidepressant nonresponders. The patient groups were well matched prior to treatment. Outcomes included remission and nonresponse rates, as well as both independent clinical evaluations and self-reported measures of depressive symptoms. RESULTS Despite limited statistical power to detect differences between treatments, depressed men treated with pharmacotherapy had significantly greater improvements on 4 of 6 continuous dependent measures and a significantly lower rate of nonresponse (i.e., 13% vs. 46%). The difference favoring pharmacotherapy was late-emerging and partially explained by crossing over nonresponders to the alternate medication. The advantage of pharmacotherapy over CBT also tended to be larger among the subgroup of patients with chronic depression. CONCLUSION Results of prior research comparing pharmacotherapy and CBT may have been influenced by the composition of study groups, particularly the gender composition, the choice of antidepressant comparators, or an interaction of these factors. Prospective studies utilizing flexible dosing of modern antidepressants and, if necessary, sequential trials of dissimilar medications are needed to confirm these findings.
To the Editor: As indicated in the recent review by Maurer, 1(p139) "depression has an estimated ... more To the Editor: As indicated in the recent review by Maurer, 1(p139) "depression has an estimated prevalence of 5.4 to 8.9 percent in the US general population 2 and affects 5 to 13 percent of patients in primary care settings. 3 " The condition accounts for more than $43 billion in medical care costs and $17 billion in lost productivity annually. 4 Depression is projected to become the second largest cause of worldwide disability by 2020. 5 The most frequently used tools for screening of depression in primary care are the Patient Health Questionnaire-2 (PHQ-2) and PHQ-9; however, both suffer from poor sensitivity: 61% and 74%, respectively, 6 in primary care settings and much lower in cardiology settings (eg, 39% for the PHQ-2 in cardiology settings 7). The development of new statistical tools with higher sensitivity for screening depression in primary care is critical. The Computerized Adaptive Diagnostic Test for Major Depressive Disorder (CAD-MDD) 8 is clearly such a tool. In the mental health settings in which we have studied the CAD-MDD (a mixture of academic medical center and community mental health settings), it dramatically increases sensitivity to 0.95 with comparable specificity to existing methods. Assuming the CAD-MDD is comparably sensitive in primary care settings, for every 100 cases of major depressive disorder the PHQ-2 will miss 39, the PHQ-9 will miss 26, but the CAD-MDD will miss only 5. As we have shown in our article, all of this can be achieved using an average of only 4 items in less than 1 minute anywhere on the planet via the Internet or in a kiosk in a health care provider's office. We think that this is a good thing and will continue to study the properties of the CAD-MDD in different populations in which, as we noted in our article, variation in case mix and prevalence may well affect sensitivity. The use of this new statistical approach to develop screening instruments for other disorders should remain a high priority on our nation's mental health agenda. Dr Carroll raises the conjecture that "specificity was probably no better than 0.50 in the clinical subsample and close to 1.0 in the 'scrubbed' control subsample. " In fact, for the clinical subsample (Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania), both sensitivity and specificity remained high at 0.92 and 0.85, respectively, and did not degrade as Dr Carroll suggests. In the community mental health clinic (DuBois Community Mental Health Center, DuBois, Pennsylvania), sensitivity was 1.00 and specificity was 0.88. These findings reveal that the CAD-MDD is robust to both psychiatric comorbidity and the overall incidence of depression. We note that the incidence was 30% in the "clinical" sample and 15% in the community mental health center. The community mental health center has an incidence that is not dissimilar to what is typically found in primary care settings. 3 Nevertheless, sensitivity was perfect and specificity remained high.
Failure to recognize subthreshold expressions of mania contributes to the frequent under-diagnosi... more Failure to recognize subthreshold expressions of mania contributes to the frequent under-diagnosis of bipolar disorder. There are several reasons for the lower rate of recognition of subthreshold manic symptoms, when compared to the analogous pure depressive ones. These include the lack of subjective suffering, enhanced productivity, ego-syntonicity, and diurnal and seasonal rhythmicity associated with many of the manic and hypomanic symptoms, and the psychiatrists' tendency to subsume persistent or even alternating symptoms among personality disorders. Furthermore, the central diagnostic importance placed on alterations in mood distracts clinicians from paying attention to other more subtle but clinically meaningful symptoms, such as changes in energy, neurovegetative symptoms and distorted cognitions. Although officially accepted in both ICD-10 and DSM-IV, we believe bipolar II disorder is underdiagnosed because of inattention to symptoms of hypomania. Moreover, by requiring the presence of both full-blown hypomanic and major depressive episodes, current nosology fails to include symptoms or signs which are mild and do not meet threshold criteria. There is already agreement in the field that such symptoms are important for depression. We now propose that attention should also be devoted to mild symptomatic manifestations of a manic diathesis, even if such manifestations may sometimes enhance quality of life. The term 'spectrum' is used to refer to the broad range of such manifestations of a disorder from core symptoms to temperamental traits. Spectrum manifestations may be present during, between, or even in the absence of, an episode of full-blown disorder. We have developed a structured clinical interview to assess the mood spectrum (SCI-MOODS) to evaluate the whole range of depressive and manic symptoms. This instrument is currently undergoing psychometric testing procedures. Similar to the SCID interview, the SCI-MOODS interview provides a separate rating for TM each of the major DSM-IV symptoms, but the latter also identifies and rates subthreshold and atypical manifestations. This paper presents the concept of a subthreshold bipolar disorder and discusses the potential epidemiological, diagnostic and therapeutic relevance of such a spectrum conditions. We also describe the SCI-MOODS interview used reliably to identify the occurrence of a bipolar spectrum condition. Obviously a great deal of systematic research needs to be conducted to ascertain the reliability and validity of subthreshold bipolarity as summarized in this paper and embodied in our instrument.
Recent epidemiologic studies have found that most patients with mental illness are seen exclusive... more Recent epidemiologic studies have found that most patients with mental illness are seen exclusively in primary care medicine. These patients often present with medically unexplained somatic symptoms and utilize at least twice as many health care visits as controls. There has been an exponential growth in studies in this interface between primary care and psychiatry in the last 10 years. This special section, edited by Wayne J. Katon, M.D., will publish informative research articles that address primary care-psychiatric issues.
Background: To date, no cross-national RCT has addressed the mechanisms underlying the relative s... more Background: To date, no cross-national RCT has addressed the mechanisms underlying the relative success of pharmacological and psychotherapeutic interventions for depression. A multi-site clinical trial that includes psychotherapy as one of the treatments presents numerous challenges related to cross-site consistency and communication. Purpose: This report describes how those challenges were met in the study ``Depression: The Search for Treatment Relevant Phenotypes'', being carried out at the University of Pittsburgh and the University of Pisa, Italy. Methods: Implementing the study required the investigators to address methodological and practical challenges related to the different requirements of the two Institutional Review Boards (IRBs), psychotherapy training, independent evaluator training, patient recruitment, development of common tools for data entry, quality control and generation of weekly reports of patient progress as well as establishing a similar clinical an...
Sixteen male outpatients with major depression and 20 age-equated healthy controls were awakened ... more Sixteen male outpatients with major depression and 20 age-equated healthy controls were awakened from rapid eye movement (REM) sleep between 1:30 and 3:30 AM, and the rapidity of return to REM sleep was determined. The time it took to return to REM sleep was reduced in depressives compared with controls: 6•.6 (17.9 SD) min versus 80.6 (24.9 SD) rain, respectively (p = 0.01). The time elapsed until the return to REM sleep was significantly correlated with baseline REM latency in controls (but not depressives). In contrast, return to REM time was significantly correlated with depression severity scores in depressives (but not controls). There was no evidence to support the hypothesis that the more rapid return to REId sleep in depression was caused by a slow wave sleep deficit. The mechanism underlying the rapid return of REM sleep in depression thus may be related to a severity-linked disturbance, such as a proposed increase in REM "pressure."
A descriptive study was conducted in a new sample of 51 men with DSM-III-R research diagnostic cr... more A descriptive study was conducted in a new sample of 51 men with DSM-III-R research diagnostic criteria (RDC) major depression in order to replicate earlier observations that measure~ of nocturnal penile tumescence (NPT) and penile rigidity are disturbed in depressive s:~ztes. When compared to both the age-equated patient (n = 34) and normal control (n = 28) groups reported in our 1988 study, the new sample manifested significant abnormalities ~,f NPT and diminished penile rigidity. Such distuP bances were not, however, significantly correlated with psychobiological indicators oJ severe or endogenous depression.
Circadian clocks are temporal interfaces that organize biological systems and behavior to dynamic... more Circadian clocks are temporal interfaces that organize biological systems and behavior to dynamic external environments. Components of the molecular clock are expressed throughout the brain and are centrally poised to play an important role in brain function. This paper focuses on key issues concerning the relationship among circadian clocks, brain function, and development, and discusses three topic areas: (1) sleep and its relationship to the circadian system; (2) systems development and psychopathology (spanning the prenatal period through late life); and (3) circadian factors and their application to neuropsychiatric disorders. We also explore circadian genetics and psychopathology and the selective pressures on the evolution of clocks. Last, a lively debate is presented on whether circadian factors are central to mood disorders. Emerging from research on circadian rhythms is a model of the interaction among genes, sleep, and the environment that converges on the circadian clock to influence susceptibility to developing psychopathology. This model may lend insight into effective treatments for mood disorders and inform development of new interventions.
Objective-Little is known about predictors of recovery from bipolar depression or moderators of t... more Objective-Little is known about predictors of recovery from bipolar depression or moderators of treatment response. In the present study we investigated attributional style (a cognitive pattern of explaining the causes of life events) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychotherapy for bipolar depression. Method-106 depressed outpatients with DSM-IV bipolar I or II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were randomized to intensive psychotherapy for depression (n=62), or collaborative care (n=44), a minimal psychoeducational intervention. The primary outcome was recovery status at each study visit as measured by the Clinical Monitoring Form. Attributional style was measured at baseline using the Attributional Style Questionnaire. Data were collected between 1998 and 2005. Results-All analyses were by intention to treat. Extreme attributions predicted a lower likelihood of recovery (p=.01, OR=0.93, 95% CI=.88-.98) and longer time until recovery (p<.01, OR=0.96, 95% CI=.93-.99), independent of the effects of initial depression severity. Among individuals with more pessimistic attributional styles, initial depression severity predicted a lower likelihood of recovery (p=.01, OR=0.64, 95% CI=.45-.91) and longer time until recovery (p<.001, OR=0.76, 95% CI=.66-.88). There was no difference in recovery rates between intensive psychotherapy and collaborative care (OR=0.90, 95% CI=0.40-2.01) in the full sample.
Treatment guidelines for major depressive disorders suggest that combined treatment of pharmacoth... more Treatment guidelines for major depressive disorders suggest that combined treatment of pharmacotherapy and psychotherapy may be helpful in the acute phase of severe major depression. 1 However, combined treatment is not strongly recommended in mild to moderate depression. In these cases, either pharmacotherapy or psychotherapy can be used, depending on the preference of the patient, the treatment history, and other clinical factors. However, is this recommendation still supported by the current state of knowledge? In this Viewpoint, I will discuss recent evidence suggesting that combined treatment could be a first-line treatment in the acute phase of mild to moderate depressive disorders and whether this evidence is strong enough to reconsider the recommendations in treatment guidelines.
This study evaluates the validity and the reliability of a new instrument developed to assess the... more This study evaluates the validity and the reliability of a new instrument developed to assess the psychotic spectrum: the Structured Clinical Interview for the Psychotic Spectrum (SCI-PSY). The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising the clinical and subsyndromal psychotic manifestations. The items of the interview include, in addition to a subset of the DSM-IV criteria for psychotic syndromes, a number of features derived from clinical experience and from a review of the phenomenological descriptions of psychoses. Study participants were enrolled at 11 Italian Departments of Psychiatry located at 9 sites and included 77 consecutive patients with schizophrenia or schizoaffective disorder, 66 with borderline personality disorder, 59 with psychotic mood disorders, 98 with non-psychotic mood disorders and 57 with panic disorder. A comparison group of 102 unselected controls was enrolled at the same sites. The SCI-PSY significantly discriminated subjects with any psychiatric diagnosis from controls and subjects with from those without psychotic disorders. The hypothesized structure of the instrument was confirmed empirically.
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Papers by E. Frank