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Objectives: To prospectively characterize and compare daytime symptoms in primary insomnia (PI) and good sleeper control (GSC) subjects using ecological momentary assessment; to examine relationships between daytime symptom factors, retrospective psychological and sleep reports, and concurrent sleep diary reports., Methods: Subjects included 47 PI and 18 GSC. Retrospective self-reports of daytime and sleep symptoms were collected. Daytime symptoms and sleep diary information were then collected for 1 week on hand-held computers. The Daytime Insomnia Symptom Scale (DISS) consisted of 19 visual analog scales completed four times per day. Factors for the DISS were derived using functional principal components analysis. Nonparametric tests were used to contrast DISS, retrospective symptom ratings, and sleep diary results in PI and GSC subjects, and to examine relationships among them., Results: Four principal components were identified for the DISS: Alert Cognition, Negative Mood, Positive Mood, and Sleepiness/Fatigue. PI scored significantly worse than GSC on all four factors (p<0.0003 for each). Among PI subjects DISS scales and retrospective psychological symptoms were related to each other in plausible ways. DISS factors were also related to self-report measures of sleep, whereas retrospective psychological symptom measures were not., Conclusions: Daytime symptom factors of alertness, positive and negative mood, and sleepiness/fatigue, collected with ecological momentary assessment, showed impairment in PI versus GSC. DISS factors showed stronger relationships to retrospective sleep symptoms and concurrent sleep diary reports than retrospective psychological symptoms. The diurnal pattern of symptoms may inform studies of the pathophysiology and treatment outcome of insomnia.

Objective: The authors describe a junior faculty scholars program in a large academic department of psychiatry, designed to reduce attrition during the high-risk period of transition from post-doctoral fellowship to receipt of the first extramural research award., Method: Scholars receive 25% salary support for two years to enable their participation in a research survival skills practicum, mentored collection of pilot data, preparation of manuscripts for peer-reviewed publication, and submission of K23 and K01 proposals., Results: Of 22 junior faculty scholars appointed during the period of 1999-2004, 17 have submitted K award proposals. All were funded on either the first or second submission, Conclusions: A program for junior faculty scholars can provide support for successfully navigating the critical and often difficult transition from post-doctoral fellowship to junior faculty. The program is expanding its efforts to assist K awardees in moving successfully along the developmental continuum (e.g., successful submission of R01, development of mentoring skills).

Objective: The authors report on the relationship between cognitive functioning and instrumental activities of daily living (IADLs) in elderly, clinically euthymic adults with bipolar disorder., Methods: Twenty patients with bipolar disorder (age range: 61-86 years) were administered comprehensive neuropsychologic testing. Structured in-home performance-based assessments of IADLs were performed in 19 of these patients., Results: Relative to age-equated comparators, bipolar subjects performed worse in information-processing speed and executive functioning. IADL performance was strongly correlated with these cognitive domains., Conclusions: In euthymic elderly patients with bipolar disorder, decrements in information processing speed and executive functioning characterize cognitive function and are associated with poorer IADL performance.

Objective: To study how early father involvement and children's biobehavioral sensitivity to social contexts interactively predict mental health symptoms in middle childhood., Method: Fathers' involvement in infant care and maternal symptoms of depression were prospectively ascertained in a community-based study of child health and development in Madison and Milwaukee, WI. In a subsample of 120 children, behavioral, autonomic, and adrenocortical reactivity to standardized challenges were measured as indicators of biobehavioral sensitivity to social context during a 4-hour home assessment in 1998, when the children were 7 years of age. Mental health symptoms were evaluated at age 9 years using parent, child, and teacher reports., Results: Early father involvement and children's biobehavioral sensitivity to context significantly and interactively predicted symptom severity. Among children experiencing low father involvement in infancy, behavioral, autonomic, and adrenocortical reactivity became risk factors for later mental health symptoms. The highest symptom severity scores were found for children with high autonomic reactivity that, as infants, had experienced low father involvement and mothers with symptoms of depression., Conclusions: Among children experiencing minimal paternal caretaking in infancy, heightened biobehavioral sensitivity to social contexts may be an important predisposing factor for the emergence of mental health symptoms in middle childhood. Such predispositions may be exacerbated by the presence of maternal depression.

Context: Exploratory studies that generate testable models of how risk factors for childhood mental health problems work together over time are critical for developing effective prevention and treatment strategies., Objective: To build models addressing the following 2 questions: (1) How early can we identify children at risk for mental health problems in third grade? (2) How do the risk factors work together over time?, Design and Participants: We assessed a Wisconsin community sample 8 times, beginning during pregnancy. Three hundred seventy-nine families completed multi-informant reports (mothers, teachers, and children) of children's mental health symptoms in third grade., Main Outcome Measures: Symptom severity and directionality (externalizing vs internalizing)., Results: The hypothesis was generated that family socioeconomic status (SES) defined different pathways to symptom severity. In low/middle SES families, children were at risk if their mothers were distressed during the infancy period, which was then associated with more generalized maternal and child distress and dysregulation during the preschool period. In high SES families, the picture was more complex, beginning with parental histories of depression and family psychopathology, which then led to greater family stress in the infancy period and maternal and child distress and dysregulation during the preschool period. For all children, social and academic impairment during the school transition was an important mediator. Two pathways to later symptom directionality consisted of one beginning with child sex and the other with child temperament., Conclusions: Most risk factors predicted symptom severity and not directionality. The risk factors for internalizing and externalizing problems may be much the same, and the same preventive interventions might be effective for both classes of problems. Furthermore, at-risk children from high SES families might be identifiable as early as infancy, whereas those from lower SES families may be identifiable only as preschoolers.

This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed.

In randomized clinical trails (RCTs), effect sizes seen in earlier studies guide both the choice of the effect size that sets the appropriate threshold of clinical significance and the rationale to believe that the true effect size is above that threshold worth pursuing in an RCT. That threshold is used to determine the necessary sample size for the proposed RCT. Once the RCT is done, the data generated are used to estimate the true effect size and its confidence interval. Clinical significance is assessed by comparing the true effect size to the threshold effect size. In subsequent meta-analysis, this effect size is combined with others, ultimately to determine whether treatment (T) is clinically significantly better than control (C). Thus, effect sizes play an important role both in designing RCTs and in interpreting their results; but specifically which effect size? We review the principles of statistical significance, power, and meta-analysis, and commonly used effect sizes. The commonly used effect sizes are limited in conveying clinical significance. We recommend three equivalent effect sizes: number needed to treat, area under the receiver operating characteristic curve comparing T and C responses, and success rate difference, chosen specifically to convey clinical significance.

Objective: We studied the relationship between number of medical comorbidities in patients with bipolar I disorder and their demographic and clinical characteristics., Method: Data were from 174 patients in the acute phase of the Pittsburgh Maintenance Therapies in Bipolar Disorder (MTBD) study, a randomized controlled trial comparing Interpersonal and Social Rhythm Therapy to an intensive clinical management approach for individuals with a lifetime diagnosis of bipolar I disorder or schizoaffective disorder, manic type, according to Research Diagnostic Criteria, who were receiving adjunctive protocol-driven pharmacotherapy. Patients entered the MTBD study from 1991 to 2000. We examined the acute-phase Hamilton Rating Scale for Depression (HAM-D) and Bech-Rafaelsen Mania Scale scores, demographics, clinical history, and medical comorbidities., Results: Patients with a high number of medical comorbidities had longer duration of both lifetime depression (p = .02) and lifetime inpatient depression treatment (p = .04), had higher baseline HAM-D score (p = .01), and were more likely to be treated for a depressed clinical state during the acute phase of the MTBD study (p = .05). Moreover, higher severity of baseline medical comorbidities predicted slower decreases in HAM-D score among depressed (p = .004) and mixed/cycling (p = .003) patients even after controlling for baseline HAM-D score., Conclusions: Medical illness is correlated with several indicators of poorer prognosis and outcome in bipolar I disorder. Not only do preventing and treating medical comorbidities in bipolar patients decrease the morbidity and mortality related to physical illness, but they could also enhance psychological well-being and possibly improve the course of bipolar illness. Identification of characteristics in bipolar I patients that are correlated to increased risk for medical comorbidities is a fundamental step in understanding the nature of the relationship between bipolar disorder and medical illness.

Background: The anterior cingulate cortex is a key structure in brain networks involved in mood regulation. Abnormalities in this brain region are possibly implicated in the pathophysiology of depression. This anatomical magnetic resonance imaging (MRI) study compared cingulate cortex volumes in unipolar depressed patients and age- and gender-matched healthy control subjects., Methods: Thirty-one unmedicated DSM-IV unipolar patients (24 female, aged 39.2 +/- 11.9 years [mean +/- SD]) and 31 healthy control subjects (24 female, aged 36.7 +/- 10.7 years) were studied in a 1.5-T GE Signa magnet (General Electric Medical Systems, Milwaukee, Wisconsin). Cingulate volumes were compared by analysis of covariance with intracranial volume as the covariate., Results: The unipolar patients had significantly smaller anterior and posterior cingulate volumes bilaterally compared with healthy control subjects. When patients were divided into currently depressed (n = 21) and remitted (n = 10) subgroups, currently depressed patients had significantly smaller anterior and posterior cingulate volumes bilaterally compared with healthy control subjects, whereas remitted patients had significantly smaller left anterior cingulate volumes compared with healthy individuals., Conclusions: Gray matter abnormalities in the cingulate cortex are implicated in the pathophysiology of unipolar depression. Smaller cingulate volumes in currently depressed patients support the hypothesis that cingulate cortex abnormalities are state dependent, whereas changes in left anterior cingulate might be trait related.

Aims: This study evaluated the frequency and clinical significance of abnormal Thyroid Stimulating Hormone (TSH) and Free Thyroxine Index (FTI) in patients with bipolar I disorder treated primarily with lithium., Method: We evaluated the medical records of 143 participants in the Pittsburgh study of Maintenance Therapies in Bipolar Disorder who did not have a thyroid abnormality at entry., Results: Thirty-six percent of the 143 patients developed abnormal TSH and/or FTI values. Thirty-eight percent of the 135 patients who received lithium developed abnormal TSH and/or FTI, spent significantly longer time in the acute treatment phase (t = -3.6, df = 133, p = .0004), and had significantly higher mean Hamilton Scale for Depression scores over the course of the maintenance phase (t = -2.3, df = 71.6, p = .03). Time on lithium and development of abnormal TSH and/or FTI were positively correlated (r = .25, p = .004)., Conclusions: Thyroid dysfunction can be frequent in patients exposed to lithium treatment for bipolar I disorder; it also appears to be correlated with a slower response to acute treatment, and may be related to poorer quality of long-term remission. A prospective study is needed to confirm our findings and determine whether more aggressive thyroid replacement can optimize thyroid function to facilitate clinical recovery., Declaration of Interest: Supported in part by National Institute of Mental Health Grants MH 029618 (Drs. Frank and Fagiolini) and MH 030915 (Drs. Kupfer and Fagiolini), and the Bosin Memorial Fund of The Pittsburgh Foundation (Drs. Fagiolini, Kupfer, Cook, Scott, Novick and Frank). Dr. Fagiolini is on the advisory board and a consultant to Pfizer Inc, and Bristol Myers Squibb, and is on the speaker bureau of Bristol Myers Squibb, Eli Lilly Italy, Pfizer Inc, and Shire. Dr. Frank is on the advisory board of Pfizer Inc. and Eli Lilly & Company, and is a consultant to Pfizer Italia and Servier Amerique. Dr. Kupfer is on the advisory board of Pfizer, Inc., Forest Pharmaceuticals, Inc., and Solvay-Wyeth Pharmaceuticals, and is a consultant to Servier Amerique.

We hypothesize that circadian dysfunction could underlie, at least partially, the liability for bipolar 1 disorder (BD1). Our hypothesis motivated tests for the association between the polymorphisms of genes that mediate circadian function and liability for BD1. The US Caucasian patients with BD1 (DSM-IV criteria) and available parents were recruited from Pittsburgh and surrounding areas (n = 138 cases, 196 parents) and also selected from the NIMH Genetics Collaborative Initiative (n = 96 cases, 192 parents). We assayed 44 informative single-nucleotide polymorphisms (SNPs) from eight circadian genes in the BD1 samples. A population-based sample, specifically cord blood samples from local live births, served as community-based controls (n = 180). It was used as a contrast for genotype and haplotype distributions with those of patients. US patients with schizophrenia/schizoaffective disorder (SZ/SZA, n = 331) and available parents from Pittsburgh (n = 344) were assayed for a smaller set of SNPs based on the results from the BD1 samples. Modest associations with SNPs at ARNTL (BmaL1) and TIMELESS genes were observed in the BD1 samples. The associations were detected using family-based and case-control analyses, albeit with different SNPs. Associations with TIMELESS and PERIOD3 were also detected in the Pittsburgh SZ/SZA group. Thus far, evidence for association between specific SNPs at the circadian gene loci and BD1 is tentative. Additional studies using larger samples are required to evaluate the associations reported here.

Objectives: Recurrent depression predicts risk for subsequent episodes, but it is unclear how it relates to demographic features, course of illness, and clinical presentation., Methods: We report on the baseline data for the first 1500 patients enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org). Patients were required to have a DSM-IV diagnosis of nonpsychotic major depression and to score > or = 14 on the 17-item Hamilton rating scale for depression. Status with respect to recurrent depression and other aspects of illness course and demographic features were ascertained at intake, along with measures of depression and concurrent general medical illness., Results: Patients with recurrent depression were older, had an earlier age of onset, and were more likely to have a positive family history of depression than first episode patients. However, recurrent patients were less likely to be chronic and reported shorter current episodes than first episode patients, something that was largely confined to females. Recurrent patients were more likely than first episode patients to report non-essential aspects of mood, cognition, and somatic symptoms, although largely as a consequence of greater overall depressive symptom severity., Conclusions: As compared to single episode depressions, recurrent depression was associated with greater symptom severity and illness characteristics suggestive of greater underlying risk, but not other demographic characteristics than age. Risk for recurrence appeared to be distinct from chronic depression. A subset of chronic first episode patients may lack the capacity to remit and may therefore be distinct from those with recurrent episodes.

Objective: The authors describe a developmental model for enhancing residency research training for careers in academic psychiatry. Over the past 10 years, the University of Pittsburgh Department of Psychiatry has developed a research track (RT) for its residents. While the Department's plan has been to address the critical need of training physician-scientists in psychiatry, the RT continues to evolve as a structured extension of the University's residency-training program. Recently, the University's departmental leadership has taken several steps that address regulatory, institutional, and personal barriers to residency research training put forth by the 2003 Institute of Medicine (IOM) report., Methods: The authors outline a model of residency research training, elements of which should be exportable to the majority of U.S. psychiatry residency programs., Results: For residents in the RT, up to 50% of time in PGY-3 and up to 75% of time in PGY-4 can be devoted to research-related activities. The authors currently have 13 residents and fellows in their track. Over the past 10 years, 15 of 33 RT residents have become research postdocs or full-time grant-funded researchers in academic positions., Conclusion: The authors' experience suggests that it is possible to organize and implement an RT during psychiatry residency within the parameters presented by the Psychiatry Residency Review Committee (RRC).

This commentary focuses on the current dilemma regarding the application of dimensional models for research and diagnosis. Four articles are used to review the positive contributions of dimensional approaches. Although categorical approaches are integral in deciding the characteristics of the group to be studied (i.e., development of inclusion/exclusion criteria), the generation of cutpoints for categorical classification is, in reality, working with dimensional data. Ultimately, new methodological strategies need to be incorporated that address both categorical and dimensional aspects of the overall diagnostic framework. These refinements will be vital in determining the extent and reality of co-occurrence of disorder and the determination of boundaries across specific disorders., (Copyright (c) 2005 APA, all rights reserved.)

Objective: This study sought to evaluate the presence of the metabolic syndrome in a group of 171 patients with bipolar disorder who were consecutively recruited in the Bipolar Disorder Center for Pennsylvanians., Methods: Data were collected from participants entering the Bipolar Disorder Center for Pennsylvanians protocol between 2003 and 2004. The study focused on the presence of the metabolic syndrome, as defined by the National Cholesterol Education Program Expert Panel on Detection, Evaluation And Treatment of High Blood Cholesterol in Adults (NCEP ATP III)., Results: Thirty percent of the sample met the NCEP ATP III criterion for the metabolic syndrome, 49% met the criterion for abdominal obesity, 41% met the criterion for hypertriglyceridemia, 48% met the criterion for hypertriglyceridemia or were on a cholesterol-lowering medication, 23% met the criterion for low high-density lipoprotein cholesterol, 39% met the criterion for hypertension and 8% met the criterion for high fasting glucose or antidiabetic medication use. Patients with the metabolic syndrome and patients endorsing the obesity criterion were more likely (p = 0.05 and p = 0.004, respectively) to report a lifetime history of suicide attempt/s., Conclusions: The prevalence of the metabolic syndrome in patients with bipolar disorder is alarmingly high, as it is for the general population. The prevalence of obesity is even higher than the already very high prevalence that has been estimated for the US general population. Our findings are a reason for concern, considering the difficulty in implementing prevention and treatment programs in the bipolar population. We strongly support the development and testing of interventions specifically designed for preventing and treating the metabolic syndrome and its components in patients with bipolar disorder.

Context: Numerous studies have pointed to the failure of prophylaxis with pharmacotherapy alone in the treatment of bipolar I disorder. Recent investigations have demonstrated benefits from the addition of psychoeducation or psychotherapy to pharmacotherapy in this population., Objective: To compare 2 psychosocial interventions: interpersonal and social rhythm therapy (IPSRT) and an intensive clinical management (ICM) approach in the treatment of bipolar I disorder., Design: Randomized controlled trial involving 4 treatment strategies: acute and maintenance IPSRT (IPSRT/IPSRT), acute and maintenance ICM (ICM/ICM), acute IPSRT followed by maintenance ICM (IPSRT/ICM), or acute ICM followed by maintenance IPSRT (ICM/IPSRT). The preventive maintenance phase lasted 2 years., Setting: Research clinic in a university medical center., Participants: One hundred seventy-five acutely ill individuals with bipolar I disorder recruited from inpatient and outpatient settings, clinical referral, public presentations about bipolar disorder, and other public information activities., Interventions: Interpersonal and social rhythm therapy, an adaptation of Klerman and Weissman's interpersonal psychotherapy to which a social rhythm regulation component has been added, and ICM., Main Outcome Measures: Time to stabilization in the acute phase and time to recurrence in the maintenance phase., Results: We observed no difference between the treatment strategies in time to stabilization. After controlling for covariates of survival time, we found that participants assigned to IPSRT in the acute treatment phase survived longer without a new affective episode (P = .01), irrespective of maintenance treatment assignment. Participants in the IPSRT group had higher regularity of social rhythms at the end of acute treatment (P<.001). Ability to increase regularity of social rhythms during acute treatment was associated with reduced likelihood of recurrence during the maintenance phase (P = .05)., Conclusion: Interpersonal and social rhythm therapy appears to add to the clinical armamentarium for the management of bipolar I disorder, particularly with respect to prophylaxis of new episodes.

In the management of late-life depression, a major set of issues concerns the terms or language used to describe the course of illness and response to treatment. There appear to be considerable advantages in the application of standardized remission criteria. If one is primarily concerned with symptomatic remission and the resolution of a single or initial episode of depression, then a moderately strict criterion is sufficient, for example, Hamilton Rating Scale for Depression (HRSD) < or = 10. However, as the goal of treatment is to achieve complete recovery, which may reduce the risk for either relapse or recurrence, then there may be a strong advantage in applying a more stringent remission criterion such as HRSD < or = 6 or 7. The characteristics of the response pattern (ie, trajectory of clinical course) also can provide important prognostic information. Such pattern characteristics can be modeled with newer statistical methods, which in turn can better inform the course of future treatment. Finally, there is growing recognition that standardized remission criteria can be valuable for establishing treatment guidelines for late-life depression, as well as for educating clinicians and consumers.

Previous studies have suggested abnormal cerebral lateralization in major depressive disorder (MDD). Few controlled MRI studies have investigated the corpus callosum (CC), the largest commissura connecting the two cerebral hemispheres, in MDD. This study investigated anatomical abnormalities in the CC and its subdivisions in MDD patients. Twenty-two unmedicated MDD patients and 39 healthy subjects underwent brain magnetic resonance imaging (MRI). Measurements of the CC and its sub-regions were performed with a semi-automated software (NIH Image, version 1.62). ANCOVA with age, gender, and intra-cranial volume (ICV) as covariates showed no significant differences in CC measurements between patients and controls (df=1,56; p>0.05). However, patients with familial MDD had a significantly larger middle genu area (F(1,45)=4.252; p=0.045) compared to healthy controls, and significantly larger middle genu (F(1,13)=5.366; p=0.037), anterior splenium (F(1,13)=6.27; p=0.026), and middle splenium areas (F(1,13)=4.706; p=0.049) compared to patients with non-familial MDD. Although preliminary, our findings suggest that anatomical abnormalities in CC may be restricted to patients with familial MDD, with possible enlargement of CC in this particular sub-group. The possible role of callosal abnormalities in the pathogenesis of mood disorders should be further examined.

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.

Objectives: The purpose of this study was to evaluate functional impairment in a group of patients with bipolar disorder in remission and to determine the extent of relationships between overall functioning and current depressive, manic and panic spectrum symptoms., Method: A subset of the patient population at the Pittsburgh site of the Systematic Treatment Enhancement Program in Bipolar Disorder (STEP-BD) study was evaluated in this study. The subsample comprises 103 male and female subjects with bipolar I disorder (n = 70), bipolar II disorder (n = 24), schizoaffective disorder - bipolar type (n = 4), or bipolar disorder NOS (n = 5). Subjects were evaluated in a period of remission (at least 4 weeks with no more than two depressive or manic symptoms). Subjects were assessed for overall functional status using the Work and Social Adjustment Scale (WSAS) and for current bipolar and panic spectrum symptoms using the Mood Spectrum Self-Report questionnaire (MOODS-SR) and Panic-Agoraphobic Spectrum Self-Report questionnaire (PAS-SR)., Results: The median WSAS total score in these remitted subjects was 14, indicating significant functional impairment. Regressing WSAS on current depressive, manic, and panic spectrum total scores, we observed a highly significant depressive spectrum effect (t = 4.9, df = 94, p < 0.0001), but non-significant panic and manic spectrum effects (t = 1.3, df = 94, p = 0.19 and t = -1.8, df = 94, p = 0.07, respectively)., Conclusion: Bipolar disorder is associated with functional deficits even during periods of sustained and substantial remission. The degree of functional impairment is correlated with the degree of depressive spectrum symptoms.

Introduction: Pain and depression are mutually exacerbating. We know that both of these syndromes predict the future occurrence of the other. It has not been shown, however, whether the presence of pain slows the effect of treatment for depression. We hypothesized that greater pain and somatic scores prior to treatment with imipramine and interpersonal psychotherapy would predict a slowed time to remission from depression., Method: We performed secondary data analyses of an archived study. Subjects (N = 230) were between 21 and 65 years of age and were enrolled in a study of maintenance treatment for recurrent unipolar depression. Patients had to meet Research Diagnostic Criteria (RDC) for a major depressive episode and historical requirements for at least 3 prior episodes and clear remissions (according to RDC). Patients were also required to have a minimum Hamilton Rating Scale for Depression score of 15 and a minimum score of 7 on the Raskin Severity of Depression Scale. This report describes the acute treatment phase, during which all subjects received combination therapy consisting of imipramine hydrochloride (150 to 300 mg) and interpersonal psychotherapy. Pain and somatization were measured with the Hopkins Symptom Checklist., Results: Higher levels of both pain and somatization predicted a longer time to remission. After controlling for baseline severity of depression, only pain was still significant in predicting a longer time to remission. Headache and muscle soreness were the 2 variables from the pain index whose presence independently predicted a slower remission. Both pain and somatization improved during acute treatment. Subjects with more pain and somatization, after controlling for severity of depression, reported more suicidality. Women reported more pain than men., Conclusions: Pain, but not somatization, predicted a longer time to remission and may be a marker of a more difficult-to-treat depression. Adults with recurrent depression should be screened for the presence of pain prior to treatment, as the presence of these symptoms may require more aggressive treatment or may be a marker for suicidality or the use of dual-mechanism antidepressants.

The objective of this study was to investigate anatomical brain abnormalities in adult bipolar patients using a deformation field morphometry technique. Our sample consisted of 32 right-handed bipolar I patients (men/women=16/16) and 32 right-handed, age and gender matched healthy controls. Deformation field morphometry analysis was performed on three-dimensional spoiled gradient recalled acquisition images. We found gender-specific structural differences between bipolar patients and healthy individuals. Bipolar men had significantly larger lateral ventricles (especially pronounced in the left hemisphere) and smaller left dorsolateral prefrontal cortex than healthy male controls. Our results are complementary to the findings of functional imaging and post-mortem studies that demonstrate abnormalities in the dorsolateral prefrontal cortex in bipolar patients.

Objective: The authors sought to determine the feasibility of treating elderly adults with bipolar disorder under standardized-treatment conditions., Methods: Thirty-one patients age 60 and older with bipolar disorder were treated in standardized pathways. Mood state was checked at each study visit with the Hamilton Rating Scale for Depression-17 item (Ham-D-17) and the Young Mania Rating Scale (YMRS)., Results: Defining "well days" as both Ham-D and YMRS scores of

Background: Depression is associated with sleep disturbances, including alterations in non-rapid eye movement (NREM) sleep. Non-rapid eye movement sleep is associated with decreases in frontal, parietal, and temporal cortex metabolic activity compared with wakefulness., Objective: To show that depressed patients would have less of a decrease than controls in frontal metabolism between waking and NREM sleep and to show that during NREM sleep, they would have increased activity in structures that promote arousal., Design: Subjects completed electroencephalographic sleep and regional cerebral glucose metabolism assessments during both waking and NREM sleep using [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography., Setting: General clinical research center., Patients: The study included 29 unmedicated patients who met the Structured Clinical Interview for DSM-IV criteria for current major depression and who had a score of 15 or greater on a 17-item Hamilton Rating Scale for Depression and 28 medically healthy subjects of comparable age and sex who were free of mental disorders., Main Outcome Measures: Electroencephalographic sleep and regional cerebral metabolism during waking and NREM sleep., Results: Depressed patients showed smaller decreases than healthy subjects in relative metabolism in broad regions of the frontal, parietal, and temporal cortex from waking to NREM sleep. Depressed patients showed larger decreases than healthy subjects in relative metabolism in the left amygdala, anterior cingulate cortex, cerebellum, parahippocampal cortex, fusiform gyrus, and occipital cortex. However, in post hoc analyses, depressed patients showed hypermetabolism in these areas during both waking and NREM sleep., Conclusions: The smaller decrease in frontal metabolism from waking to NREM sleep in depressed patients is further evidence for a dynamic sleep-wake alteration in prefrontal cortex function in depression. Hypermetabolism in a ventral emotional neural system during waking in depressed patients persists into NREM sleep.

Background: We sought to develop a series of assessment measures of psychiatric spectrum conditions associated with major DSM-IV mood and anxiety disorders that might capture the true phenotypes underlying these disorders. The specific objective of this report was to describe the methods we employed to create instruments that could cross linguistic and national boundaries and to evaluate the comparability of results obtained when one of these instruments, the Structured Clinical Interview for Panic-Agoraphobic Spectrum (SCI-PAS), was administered in the United States and in Italy., Method: After developing, in parallel, the English and the Italian versions of the SCI-PAS, identical protocols were conducted in patients and control samples at the University of Pittsburgh and the University of Pisa to examine the reliability and validity of the interview., Results: Total and domain scores on the SCI-PAS were strikingly similar in the US and Italian patient groups and in controls. In addition, similarly high levels of inter-rater and test-retest reliability were found at the two sites. Finally, virtually identical patterns of relationships were found between the domains of the SCI-PAS and established measures of the same constructs., Conclusions: The SCI-PAS displays similar reliability and validity properties in the two versions. This suggests that the instrument taps a phenotype that is consistent in American and Italian patient and control populations.

Objective: The authors investigated the influence of body pain on 1) time to treatment response and 2) suicidal ideation, in late-life depression. They hypothesized that higher levels of body pain would predict a longer time to and lower likelihood of response, and increased levels of suicidal ideation., Methods: Subjects (N=187) were older adult outpatients (age > or =69 years), with current episodes of major depression, who were openly treated with paroxetine up to 40 mg daily and weekly interpersonal psychotherapy. Response was defined as 3 consecutive weeks of Hamilton Rating Scale for Depression at < or =10. Body pain was measured with the Bodily Pain Index of the SF-36 quality-of-life assessment. Authors used survival-analysis models on the responder sample to test the effect of body pain on response, after controlling for severity of depression., Results: Overall response rate was 75.4%. Nonresponders reported more severe pain at baseline. After covarying for severity of baseline depression, no effect was found for physical pain on time-to-response or degree of suicidality. Bodily pain remained stable during acute treatment for responders, independent of depression response to combination psychotherapy and antidepressant treatment., Conclusions: Older adult patients with higher levels of physical pain can still respond to antidepressant treatment; however, reported bodily pain may be associated with a more difficult-to-treat depression.

Neuroimaging and postmortem studies have suggested the involvement of the dorsolateral prefrontal cortex (DLPFC) in the pathophysioloy of unipolar disorder. We examined with in vivo 1H magnetic resonance spectroscopy (MRS) the levels of specific metabolites in the DLPFC of adult unipolar patients and the role of illness chronicity on DLPFC abnormalities. Nineteen unmedicated unipolar mood disorder patients and 19 age- and gender-matched healthy controls underwent a short echo-time 1H MRS examination localized to an 8-cm3 single voxel placed in the left DLPFC. There were no significant differences in metabolite levels, including N-acetylaspartate (NAA), phosphocreatine plus creatine (PCr+Cr) and choline-containing-compounds (GPC+PC), between the two groups. However, NAA/PCr+Cr ratios were significantly lower in the chronic than in the less chronically ill patients and healthy controls. The low levels of NAA/PCr+Cr ratios in the left DLPFC of unipolar patients who had been more chronically ill suggest a potential role for illness chronicity in neuronal abnormalities in the DLPFC in unipolar disorder. This could possibly be accounted for by neurodegenerative processes arising with the progression of the illness. Future 1H MRS investigations should longitudinally examine the role of illness chronicity on DLPFC abnormalities and their relationship with the symptoms of unipolar disorder.

Background: Typical experimental categorizations of treatment responses in bipolar disorder (BPD) patients may have limited relationship to clinical recovery or functional status, and there is inadequate research on such clinically important outcomes., Methods: We analyzed data from a study of open continuation of olanzapine treatment following a 3-week placebo-controlled trial involving initially hospitalized adult subjects with DSM-IV BP-I mania to estimate rates and times to symptomatic remission (low scores on standardized symptomatic assessments) and clinical recovery (remission sustained>or=8 weeks), associated clinical factors, and functional outcomes., Results: During treatment with olanzapine for 27.9+/-20.1 weeks, symptomatic remission was attained by 70% of subjects, half by 8 weeks (95% CI 6-10) weeks, and later lost by 82% of remitted subjects; remitted (versus non-remitted) subjects had slightly lower baseline clinical global impression scores and greater trial-completion. Sustained clinical recovery was attained by only 40 of 113 (35%) of subjects, half by 36 (95% CI 20-40) weeks, and later lost by 45%. Subjects with above-median (>12) initial Hamilton-Depression rating scale depression scores were half as likely to recover (p=0.016) and did so much later (36 versus 12 weeks) than those with lower scores. At final assessment, self-rated well being (SF-36 psychosocial functioning scores) improved substantially more among recovered versus non-recovered subjects (mean changes: 87% versus 23%), and two-thirds of recovered subjects remained unemployed-for-pay while half received disability-compensation., Conclusions: Clinically meaningful symptomatic remission and recovery in relatively severely ill adult bipolar I manic patients were achieved slowly and sustained by only some patients within an average of 7 months of continuous treatment. These clinically relevant outcomes were worse with relatively high initial dysphoria ratings. Well-being was rated higher by recovered subjects, but their ability to work and live independently were markedly impaired. These findings underscore the emerging view that BPD can often be severe, slow to remit, and disabling, particularly in association with prominent depression-dysphoria symptoms. Improved treatments for BPD are needed, guided by longitudinal assessments of clinically meaningful measures of symptomatic recovery and functional outcome., (Copyright (c) 2005, Blackwell Munksgaard.)

Objectives: The goal of this paper was to compare clinical characteristics and treatment history of African-American and Caucasian participants in a bipolar disorder registry., Methods: The Western Pennsylvania Bipolar Disorder Registry used several recruitment methods to reach individuals self-identified as having bipolar disorder. Individuals who contacted and joined the registry completed an interviewer-administered questionnaire on clinical characteristics and treatment history. A sample of 2,718 registry participants was analyzed in order to compare these characteristics and history by race., Results: African-Americans in the registry reported a greater number of inpatient hospitalizations (9.8 versus 4.4) than Caucasians, as well as a higher suicide attempt rate (64% versus 49%). African-American participants were more likely to report a family member with schizophrenia. With respect to psychotropic medication, African-Americans were less likely to report taking antimanic medication or benzodiazepines, but more likely to report taking antipsychotics than Caucasians., Conclusions: The present findings reinforce previous reports regarding the chronicity and severity of bipolar disorder among African-Americans. They also support previous studies that found high rates of attempted suicide among African-Americans with bipolar disorder. These findings provide further impetus for specific community and mental health services delivery efforts to reduce barriers to early accurate diagnosis and to appropriate ambulatory treatment for bipolar disorder., (Copyright (c) 2005, Blackwell Munksgaard.)

Abnormalities in circadian rhythms are prominent features of bipolar I disorder (BD1). To investigate circadian variation in BD1, we evaluated morningness-eveningness (M/E), a stable trait reflecting circadian phase, using the composite scale (CS) among BD1 patients (DSM IV criteria; n = 75), unscreened controls (n = 349), and patients with schizophrenia (SZ) or schizoaffective disorder (SZA) (n = 81). Our analyses showed that CS scores correlated significantly with age but did not differ by gender among the controls. BD1 patients differed significantly from controls and from SZ/SZA patients when age was considered. CS scores were distributed bi-modally among BD1 cases. There are several possible reasons for the observed heterogeneity. Younger BD1 patients, and those with rapid mood swings, were significantly more likely to have lower CS scores (i.e., to score in the 'evening' range and to have later circadian phase). CS scores were also positively correlated with the age at onset and the duration of the most severe depressive episodes. These relationships were not observed among the SZ/SZA groups. Thus, distinct patterns of M/E were noted among BD1 patients and among BD1 subgroups. The impact of medication, mood state, and chronicity on CS scores needs to be considered.

This review focuses on information concerning antidepressants and psychotherapy in the treatment of both acute and chronic forms of unipolar depression in the English language literature. In it, we address the use of combination therapy, both from the outset of treatment and in a variety of sequences, ie, we examine the potential advantages of adding a targeted psychotherapy to an incompletely effective pharmacotherapy and the potential advantages of adding pharmacotherapy to an incompletely effective psychotherapy. The number of research reports available to address these questions is small relative to their importance for clinical practice. There is a clear need for more information about the relative efficacy of pharmacotherapy-psychotherapy combinations or sequences versus either pharmacotherapy or psychotherapy provided as monotherapies.

The pathogenesis of bipolar disorder may involve, at least in part, aberrations in serotonergic neurotransmission. Hence, serotonergic genes are attractive targets for association studies of bipolar disorder. We have reviewed the literature in this field. It is difficult to synthesize results as only one polymorphism per gene was typically investigated in relatively small samples. Nevertheless, suggestive associations are available for the 5HT2A receptor and the serotonin transporter genes. With the availability of extensive polymorphism data and high throughput genotyping techniques, comprehensive evaluation of these genes using adequately powered samples is warranted. We also report on our investigations of the serotonin transporter, SLC6A4 (17q11.1-q12). An insertion/deletion polymorphism (5HTTLPR) in the promoter region of this gene has been investigated intensively. However, the results have been inconsistent. We reasoned that other polymorphism/s may contribute to the associations and the inconsistencies may be due to variations in linkage disequilibrium (LD) patterns between samples. Therefore, we conducted LD analyses, as well as association and linkage using 12 polymorphisms, including 5HTTLPR. We evaluated two samples. The first sample consisted of 135 US Caucasian nuclear families having a proband with bipolar I disorder (BDI, DSM IV criteria) and available parents. For case-control analyses, the patients from these families were compared with cord blood samples from local Caucasian live births (n = 182). Our second, independent sample was recruited through the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD, 545 cases, 548 controls). No significant associations were detected at the individual polymorphism or haplotype level using the case-control or family-based analyses. Our analyses do not support association between SLC6A4 and BDI families. Further studies using sub-groups of BDI are worthwhile.

Patients whose depression is complicated by a lifetime history of panic symptoms display a poorer treatment response to both psychotherapeutic and pharmacologic interventions. A newly adapted psychosocial treatment for depression with lifetime panic spectrum symptoms was evaluated in an open pilot study., (Copyright (c) 2005 Wiley-Liss, Inc.)

Depressive disorders are common, recurrent, and chronic, and require treatment A review of the symptom picture and current drug targets demonstrates the need for accurate assessment of depression severity, including suicidality. The initial focus of treatment is rapid resolution of symptoms during an acute phase, followed by continuation. Maintenance treatment is indicated if the risk of recurrence is high. The range of available medications is considerable and the benefit/risk ratio is acceptable. Depression is diagnosable across the life span and treatable at every age (although recent disagreement has arisen with regard to young patients). Comorbidity, both psychiatric and medical, need to be assessed, as does the possible presence of two subtypes of depression (psychotic and bipolar) often requiring different interventions. It is expected that the next generation of antidepressants would be associated with more specific disease and outcome biomarkers.

Morphometric MRI studies suggest decreased hippocampal volumes in currently depressed patients, with conflicting findings for the amygdala. We studied these temporal lobe structures and superior temporal gyrus (STG) in patients with current and remitted major depression. We scanned 31 unmedicated depressed patients (21 currently depressed, 10 remitted) and 31 matched healthy controls with a 3D SPGR sequence in a 1.5 Tesla GE Signa Imaging System. There was a trend towards smaller left amygdala volumes in all depressed patients compared with healthy controls. We found significantly smaller hippocampal volumes bilaterally in currently depressed patients than in remitted patients. Furthermore, we found a statistically significant inverse correlation between length of illness and left hippocampus volumes and right superior temporal gyrus volumes. Our finding of smaller hippocampi in currently depressed patients is consistent with the hypothesis that hypercortisolism could result in hippocampal neurotoxicity in major depression. A smaller hippocampal size may be more characteristic of the depressive state and not be present in remitted patients.

Objective: The authors investigated the neurobiological basis of poor sleep and daytime fatigue in insomnia., Method: [(18)F]Fluorodeoxyglucose positron emission tomography was used to assess regional cerebral glucose metabolism of seven patients with insomnia and 20 healthy subjects., Results: Compared with healthy subjects, patients with insomnia showed greater global cerebral glucose metabolism during sleep and while awake, a smaller decline in relative metabolism from waking to sleep states in wake-promoting regions, and reduced relative metabolism in the prefrontal cortex while awake., Conclusions: Subjectively disturbed sleep in patients with insomnia is associated with greater brain metabolism. The inability to fall asleep may be related to a failure of arousal mechanisms to decline in activity from waking to sleep states. Further, daytime fatigue may reflect decreased activity in the prefrontal cortex resulting from inefficient sleep.

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.

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.

Objective: Sleep disturbances characterize depression and may reflect the abnormal persistence of brain activity from wakefulness into non-REM sleep. The goal of this study was to investigate the functional neuroanatomical correlates of non-REM sleep relative to presleep wakefulness in depressed patients and healthy subjects., Method: Twelve medication-free depressed patients and 13 healthy subjects underwent polysomnography and [(18)F]fluorodeoxyglucose positron emission tomography scans during presleep wakefulness and non-REM sleep. Statistical parametric mapping contrasts were performed to detect differences in relative regional cerebral glucose metabolism between presleep wakefulness and non-REM sleep in each group as well as interactions across states and between groups., Results: Relative to healthy subjects, depressed patients showed less of a decrease in relative regional cerebral glucose metabolism from presleep wakefulness to non-REM sleep in the left and right laterodorsal frontal gyri, right medial prefrontal cortex, right superior and middle temporal gyri, insula, right posterior cingulate cortex, lingual gyrus, striate cortex, cerebellar vermis, and left thalamus., Conclusions: Patterns of relative regional cerebral glucose metabolism changes from presleep wakefulness to non-REM sleep differ in healthy subjects and depressed patients. Specifically, the transition from wakefulness to non-REM sleep was characterized by the relative persistence of elevated metabolic activity in frontoparietal regions and thalamus in depressed patients compared with healthy subjects. These findings suggest that abnormal thalamocortical network function may underlie sleep anomalies and complaints of nonrestorative sleep in depressed patients.

Objectives: To evaluate the point prevalence of the metabolic syndrome in patients with schizoaffective disorder--bipolar type., Methods: Consenting patients who were participants in an ongoing clinical trial of adjunctive topiramate treatment for schizoaffective disorder, bipolar type were evaluated at baseline for the point prevalence of the metabolic syndrome. The criteria for the metabolic syndrome included: (a) waist circumference > 102 cm (40 inches) in males, or > 88 cm (35 inches) in females; (b) fasting serum triglyceride levels > or = 150 mg/dL; (c) fasting high density lipoproteins (HDL) cholesterol <40 mg/dL in men or <50 mg/dL in women; (d) blood pressure > or = 130/85 mmHg; and (e) fasting glucose > or = 110 mg/dL. Subjects who had at least three of these five criteria were defined as meeting criteria for the metabolic syndrome., Results: Thirty-six subjects (males = 15, females = 21) were evaluated, and three were excluded for missing data. Among those 33 subjects with complete data, 14 subjects (42.4%, males = 7, females = 7, African Americans = 6, Caucasians = 8) met criteria for the metabolic syndrome. Not unexpectedly, those with the metabolic syndrome were significantly more likely to be obese, and have significantly higher mean systolic and diastolic blood pressure, mean fasting triglyceride levels and larger mean waist circumferences, and significantly lower HDL cholesterol levels; and a trend toward higher fasting blood glucose levels. Furthermore, the fasting mean total cholesterol in those with the metabolic syndrome was 217 mg/dL (+/-46)., Conclusions: This preliminary report suggests that the point prevalence of the metabolic syndrome in patients with schizoaffective disorder appears to be higher than that reported in the general population of the USA. Targeted weight reduction and life style change strategies (increased exercise, smoking cessation, stress reduction) may provide useful interventions to decrease the morbidity and mortality that accompanies the presence of the metabolic syndrome in patients with psychiatric illnesses.

Background: Depression is associated with sleep disturbances, including alterations in rapid eye movement (REM) sleep, that may relate to the neurobiology of the disorder. Given that REM sleep activates limbic and anterior paralimbic cortex and that depressed patients demonstrate increases in electroencephalographic sleep measures of REM, we hypothesized greater activation of these structures during waking to REM sleep in depressed patients., Design: Subjects completed electroencephalographic sleep and regional cerebral glucose metabolism assessments during both waking and REM sleep using [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography., Setting: Patients and healthy subjects recruited from the general community to participate in a research study of depression at an academic medical center. Patients Twenty-four unmedicated patients who met the Structured Clinical Interview for DSM-IV criteria for current major depression and who had a score of 15 or higher on a 17-item Hamilton Rating Scale for Depression; 14 medically healthy subjects of comparable age and sex who were free of mental disorders., Main Outcome Measures: Electroencephalographic sleep, semiquantitative and relative regional cerebral metabolism during waking and REM sleep., Results: Depressed patients showed greater REM sleep percentages. While both healthy and depressed patients activated anterior paralimbic structures from waking to REM sleep, the spatial extent of this activation was greater in the depressed patients. Additionally, depressed patients showed greater activation in bilateral dorsolateral prefrontal, left premotor, primary sensorimotor, and left parietal cortices, as well as in the midbrain reticular formation., Conclusions: Increased anterior paralimbic activation from waking to REM sleep may be related to affective dysregulation in depressed patients. Increased activation of executive cortex may be related to a cognitive dysregulation. These results suggest that altered function of limbic/anterior paralimbic and prefrontal circuits in depression is accentuated during the REM sleep state. The characteristic sleep disturbances of depression may reflect this dysregulation.

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.

Although multiple factors may influence the sexual function of depressed women over the course of treatment, the independent contributions of these factors are poorly understood. The current study examined the effects of depression, SSRI treatment, and sexual partner availability on women's sexual function. The sexual function of 68 recurrently depressed women was assessed at 3-month intervals over a 1-year course of treatment with interpersonal psychotherapy with or without adjunctive SSRI treatment. Random regression models assessing changes in sexual function were conducted to test the effects of three time-dependent covariates: depression symptom scores, sexual partner availability, and SSRI medication status. Controlling for the other variables, depressive symptoms were associated with decrements in sexual desire, sexual cognition/fantasy, sexual arousal, orgasmic function, and global evaluations of sexual function. SSRI treatment was associated with orgasmic difficulty only. The availability of a sexual partner was associated with increased sexual arousal, orgasmic function, and sexual behavior. Among treatment remitters, patient reports of severe sexual dysfunction did not change over the course of treatment, although mild improvement was observed in patients' global assessment of the quality of their sexual function. This report illustrates the prevalence and persistence of sexual dysfunction in this sample, and highlights the importance of monitoring both pharmacologic and psychosocial variables that can affect the sexual function of recurrently depressed women throughout the course of treatment.

The relation between morningness (M) - eveningness (E) and lifestyle regularity was studied in a convenience sample of 100 healthy subjects aged between 20 and 59 yrs (47 males and 53 females; mean age 33.6 yrs). Morningness-eveningness was measured by a single administration of the 13-item Composite Scale for Morningness (CSM). Lifestyle regularity was measured by requiring subjects to complete a five-item Social Rhythm Metric diary (SRM-5) each evening for two weeks. Each week of SRM-5 was analyzed separately and the two SRM scores averaged to yield the lifestyle regularity measure for the subject. Subjects were categorized by morningness into top and bottom quartiles of CSM score (denoted M-types and E-types, respectively), with the remaining 50% of subjects denoted as intermediate (I-types). Mean SRM scores significantly differed between the three morningness groups (p <0.001) in the order E-types (SRM = 3.6), then I-types (SRM=4.0), then M-types (SRM=4.9), with higher scores indicating greater daily lifestyle regularity. The effect size of the E-type versus M-type difference was approximately 1.3. The relationship between the CSM and SRM scores was also confirmed using a correlational analysis (rho = 0.428; p < 0.001). This correlational finding was substantially weaker when age was partialed out (r=0.186; p=0.065), although there was still a trend toward a significan relationship. Thus it appears that morning types appear to be more regular in their daily lifestyle than are evening types, suggesting a relationship between these two aspects of human circadian behavior.

Background: Of the 2 reports in the literature on anger attacks in bipolar depression, one found them to be uncommon (12%) compared with the rate in bipolar mixed states and unipolar depression (40%-60%), whereas the other found them to be common (62%). We examined anger attacks among participants in an 8-week trial of open-label citalopram added to mood stabilizer for the treatment of bipolar depression. We also examined trait anger, hypomanic symptoms, and depressive symptoms as predictors of anger attacks. We hypothesized that if anger attacks were related to hypomanic symptoms they would respond unfavorably to citalopram, whereas if they were related to trait anger or depressive symptoms they would respond favorably., Method: In 45 participants with a DSM-IV diagnosis of bipolar I or II depression, anger attacks, hypomanic symptoms, and depressive symptoms were assessed using a modified Anger Attacks Questionnaire, Young Mania Rating Scale, and Hamilton Rating Scale for Depression, respectively. Trait anger was measured using the State-Trait Anger Inventory. Posttreatment data were collected at the end of 8 weeks of treatment with citalopram or at dropout from the trial. The first participant study visit was in November 1998, and the final participant study visit was in December 2000., Results: Before treatment with citalopram, 17 (38.6%) of 44 participants reported anger attacks (data on anger attacks were missing for 1 participant before treatment and 4 after treatment). Significantly fewer participants reported anger attacks after treatment (6 of 41, 14.6%; McNemar test, p <.05, 2-tailed). At pretreatment and post-treatment, trait anger was the only significant predictor of anger attacks (p <.05)., Conclusions: These findings suggest that in bipolar depression anger attacks are common, may respond favorably to acute treatment with citalopram added to mood stabilizer, and are better predicted by trait anger than hypomanic or depressive symptoms. Further studies are needed to clarify the diagnostic and treatment implications of anger attacks in bipolar depression.

Objective: This study characterized cognitive functioning in elderly patients with bipolar disorder., Method: The cognitive functioning of 18 euthymic patients with a history of bipolar disorder I or II, ages 60 years and older, was tested with the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale, and the Executive Interview. Cognitive functioning in these subjects was compared with that of an age- and education-matched group of 45 comparison subjects without mood disorders., Results: Approximately half of the bipolar subjects scored one or more standard deviations below the mean of the comparison subjects on the MMSE (N=8, 44%) and the Mattis Dementia Rating Scale total (N=10, 56%). On the Executive Interview, three subjects (17%) scored between one and two standard deviations below the mean of the comparison subjects., Conclusions: A significant proportion of older bipolar subjects exhibited neuropsychological deficits when they were clinically euthymic.

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.