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The authors sought to determine whether symptoms experienced by formerly depressed patients after at least 8 weeks of remission can be used to identify their risk for relapse during the next 6 months.The study included 188 patients with major depressive disorder from the National Institute of Mental Health Collaborative Depression Study who had at least one Symptom Checklist-90 (SCL-90) assessment after at least 8 weeks of full remission from a depressive episode (defined as a value of 1 on the weekly psychiatric rating scale for all depressive conditions, recorded on Longitudinal Follow-Up Evaluation interviews). Mixed logistic regression was used to identify a set of SCL-90 items that were most predictive of relapse compared with nonrelapse within the next 6 months.Of 514 SCL-90 assessments completed after remission, 73 (14.2%) were followed by depressive relapse within 6 months. Seventeen SCL-90 items (including symptoms of depression, anxiety, and psychological vulnerability) significantly distinguished relapse from nonrelapse. Of these, a set of 12 symptoms maximally separated relapse from nonrelapse. Experiencing one or more of these symptoms had a sensitivity of 80.8% and a specificity of 51.2% for identifying a period in which a relapse occurred, with a positive predictive value of 21.5% and a negative predictive value of 94.2%. The relapse rate was 5.8% when none of the 12 symptoms were present, 16.4% when one to five symptoms were present, 34.1% when six to nine symptoms were present, and 72.7% when 10 or more symptoms were present.A brief symptom scale can be used to identify patients who, despite full remission from a depressive episode, are at substantial risk of relapse within the next 6 months, and this can be used to provide a basis for personalizing the intensity of follow-up visits.

OBJECTIVE To provide the first head-to-head test of the predictive validity of 2 resolution levels included in the current consensus definition of major depressive episode (MDE) recovery and provide an empirically based, clinically useful definition of the end of an MDE. METHOD 322 participants entering the National Institute of Mental Health Collaborative Depression Study with MDE (diagnosed by Research Diagnostic Criteria) in 1978-1981, and followed thereafter for up to 31 years, were divided into those with 8 consecutive weeks of asymptomatic MDE recovery or residual subsyndromal depressive symptom (SSD) resolution of their index MDE. These 2 levels of recovery were defined based on weekly symptom status on all depressive conditions, assessed by Longitudinal Interval Follow-Up Evaluation (LIFE) interviews conducted every 6 months. Primary measures of validity of these 2 alternative definitions were first well interval duration and long-term depressive illness burden. Groups were also compared on clinical variables, antidepressant treatment, and psychosocial function. RESULTS 61.2% of subjects recovered asymptomatically from their index MDE. By survival analysis, they remained free of a depressive episode relapse or recurrence 4.2 times longer than those with SSD resolution (median = 135 vs 32 weeks; χ² = 70.65; P < .0001). This was not attributable to a difference in intensity of antidepressant medication. Compared to asymptomatic recovery, SSD resolution was associated with significantly longer and more severe index MDEs, with more miscellaneous psychopathology as well as increased long-term psychosocial dysfunction and a greater depressive illness burden during the ensuing 10 or 20 years. Asymptomatic MDE resolution was a stronger predictor of time well than any of 18 other predictors, singly or combined. Eight consecutive weeks of asymptomatic recovery had 93% overlap with a 4-week definition and conferred little benefit over 4 weeks. CONCLUSIONS Four consecutive weeks of asymptomatic recovery defines the end of an MDE and the beginning of a stable well state with improved psychosocial function. Residual symptom resolution is a continuation of an active state of the episode, not the end of an MDE.

Objective Some reports suggest an increase in suicide ideations and behaviors in patients treated with antidepressants. This is an analysis of the impact of fluoxetine on suicide ideations in outpatients with minor depressive disorder. Methods Research subjects were adult outpatients with minor depressive disorder ( N = 162), who received fluoxetine or placebo in a prospective, 12-week, double-blind randomized trial. The research participants were evaluated weekly with standard rating scales that included four suicide-related items: item 3 of the Hamilton Rating Scale for Depression (HRSD), item 18 of Inventory of Depressive Symptomatology (IDS-C), and items 15 and 59 of the Hopkins Symptom Checklist (SCL-90). Clinically significant intensification of suicide ideation was defined as an increase of ≥2 points on any of these items. Results Overall 60/162 subjects (37%) had an increase of ≥1 point during treatment and 17/162 (10.5%) of ≥2 points on at least one suicide item, with 12/81 (14.8%) placebo and 5/81 (6.2%) fluoxetine-treated subjects having a ≥2 point gain. Of the study participants with baseline suicide ideation, 9/22 (40.9%) placebo and 3/24 (12.5%) fluoxetine treated had ≥2 point increase ( p = 0.04). Survival analysis revealed that subjects on placebo were significantly more likely ( p = 0.050) to experience a ≥2 point increase on one or more item, a difference that emerged early and continued throughout the 12-week trial. Conclusions Compared to placebo, fluoxetine was not associated with a clinically significant increase in suicide ideation among adults with minor depressive disorder during 12 weeks of treatment.

The discovery of glucocorticoids and their enormous therapeutic benefits led to the use of these compounds as valuable medications for a wide variety of diseases. In 1950 this effort was ushered in by a landmark event—the awarding of the 1950 Nobel Prize in Physiology and Medicine to Drs. Phillip Hench, Edward Kendall, and Tadeus Reichstein. It was Hench who described and researched the successful use of the glucocorticoid, cortisone, and pituitary adrenocorticotrophic hormones to treat rheumatoid arthritis. Significant scientific discovery preceded Hench and colleagues’ efforts, but the revolutionary accumulation of discovery in glucocorticoids since then is one of the unique scientific stories in the history of medicine. The scientific conference upon which this volume is based represents an attempt to convene a state-of-the-science meeting on the current understanding and scientific status of this fascinating, far-reaching, and fast-moving field. This last chapter will summarize the exciting presentations of this 2-day conference.

Data since 1980 demonstrate that the DSM-III model requires revisions in its assumptions and format. Problems inherent in the DSM-III model are considered and a paradigm shift toward a mixed categorical-dimensional classification system for DSM-V is recommended. This will reduce comorbidity, allow symptom weighting, introduce noncriterion symptoms, eliminate NOS categories, and provide new directions to biological researchers. We suggest reevaluating the threshold concept and use of quality-of-life assessment. A framework for such a revision is presented. Drawbacks to change include retraining of clinicians, administrative and policy changes, and possible reinterpretation of data collected under the DSM-III model. Nevertheless, clinicians and clinical researchers are ready for a diagnostic system that more accurately reflects the patients that they treat and study. © 2009 American Psychological Association.

Weekly affective symptom severity and polarity were compared in 135 bipolar I (BP I) and 71 bipolar II (BP II) patients during up to 20 yr of prospective symptomatic follow-up. The course of BP I and BP II was chronic; patients were symptomatic approximately half of all follow-up weeks (BP I 46.6% and BP II 55.8% of weeks). Most bipolar disorder research has concentrated on episodes of MDD and mania and yet minor and subsyndromal symptoms are three times more common during the long-term course. Weeks with depressive symptoms predominated over manichypomanic symptoms in both disorders (31) in BP I and BP II at 371 in a largely depressive course (depressive symptoms=59.1% of weeks vs. hypomanic=1.9% of weeks). BP I patients had more weeks of cyclingmixed polarity, hypomanic and subsyndromal hypomanic symptoms. Weekly symptom severity and polarity fluctuated frequently within the same bipolar patient, in which the longitudinal symptomatic expression of BP I and BP II is dimensional in nature involving all levels of affective symptom severity of mania and depression. Although BP I is more severe, BP II with its intensely chronic depressive features is not simply the lesser of the bipolar disorders; it is also a serious illness, more so than previously thought (for instance, as described in DSM-IV and ICP-10). It is likely that this conventional view is the reason why BP II patients were prescribed pharmacological treatments significantly less often when acutely symptomatic and during intervals between episodes. Taken together with previous research by us on the long-term structure of unipolar depression, we submit that the thrust of our work during the past decade supports classic notions of a broader affective disorder spectrum, bringing bipolarity and recurrent unipolarity closer together. However the genetic variation underlying such a putative spectrum remains to be clarified.

Background: Despite emerging international consensus on the high prevalence of the bipolar spectrum in both clinical and community samples, many skeptics contend that narrowly defined bipolar disorder with a lifetime rate of about 1% represents a more accurate estimate of prevalence. This may in part be due to the fact that higher figures proposed for the bipolar spectrum (5–8%) have not been based on national data and have not included all levels of manic symptom severity. In the present secondary analyses of the US National Epidemiological Catchment Area (ECA) database, we provide further clarification on this fundamental public health issue. Methods: All respondents in the first wave (first interview) of the ECA household five site sample (n=18,252) were classified on the basis of DSM-III criteria into lifetime manic and hypomanic episodes, as well as those with at least two lifetime manic/hypomanic symptoms below the threshold for at least 1 week duration (subsyndromal manic symptoms [SSM] group). Odds ratios were calculated on lifetime service utilization for mental health problems, measures of adverse psychosocial outcome, and suicidal behavior compared to subjects with no mental disorders or manic symptoms. Results: As originally reported nearly two decades ago by the primary investigators of the ECA, the lifetime prevalence for manic episode was 0.8%, and for hypomania, 0.5%. What is new here is the inclusion of subthreshold SSM subjects, which accounted for 5.1%, yielding a total of 6.4% lifetime prevalence for the bipolar spectrum. All three (manic, hypomanic and SSM) groups had greater marital disruption. There were significant increases in lifetime health service utilization, need for welfare and disability benefits and suicidal behavior when the SSM, hypomanic and manic subjects were compared to the no mental disorder group. Suicidal behavior was non-significantly highest in the hypomanic (bipolar II) group. Otherwise, hypomanic and manic groups had comparable level of service utilization and social disruption. Limitations: Comorbid disorders, which might influence functioning, were not included in the present analyses. Conclusion: These secondary analyses of the US National ECA database provide convincing evidence for the high prevalence of a spectrum of bipolarity in the community at 6.4%, and indicate that subthreshold cases are at least five times more prevalent than DSM-based core syndromal diagnoses at about 1%. These SSM subjects, who met the criteria of “caseness” from the point of view of harmful dysfunction, are of great theoretical and public health significance.

Background: The present analyses were designed to compare the clinical characteristics and long-term episode course of Bipolar-I and Bipolar-II patients in order to help clarify the relationship between these disorders and to test the bipolar spectrum hypothesis. Methods: The patient sample consisted of 135 definite RDC Bipolar-I (BP-I) and 71 definite RDC Bipolar-II patients who entered the NIMH Collaborative Depression Study (CDS) between 1978 and 1981; and were followed systematically for up to 20 years. Groups were compared on demographic and clinical characteristics at intake, and lifetime comorbidity of anxiety and substance use disorders. Subsets of patients were compared on the number and type of affective episodes and the duration of inter-episode well intervals observed during a 10-year period following their resolution of the intake affective episode. Results: BP-I and BP-II had similar demographic characteristics and ages of onset of their first affective episode. Both disorders had more lifetime comorbid substance abuse disorders than the general population. BP-II had a significantly higher lifetime prevalence of anxiety disorders in general, and social and simple phobias in particular, compared to BP-I. Intake episodes of BP-I were significantly more acutely severe. BP-II patietns had a substantially more chronic course, with significantly more major and minor depressive episodes and shorter inter-episode well intervals. BP-II patients were prescribed somatic treatment a substantially lower percentage of time during and between affective episodes. Limitations: BP-I patients with severe manic course are less likely to be retained in long-term follow-up, whereas the reverse might be true for BP-II patients who are significantly more prone to depression (i.e., patients with less inclination to depression and with good prognosis may have dropped out in greater proportions); this could increase the gap in long term course characteristics between the two samples. The greater chronicity of BP-II may be due, in part, to the fact that the patients were prescribed somatic treatments substantially less often both during and between affective episodes. Conclusions: The variety in severity of the affective episodes shows that bipolar disorders, similar to unipolar disorders, are expressed longitudinally during their course as a dimensional illness. The similarities of the clinical phenotypes of BP-I and BP-II, suggest that BP-I and BP-II are likely to exist in a disease spectrum. They are, however, sufficiently distinct in terms of long-term course (i.e., BP-I with more severe episodes, and BP-II more chronic with a predominantly depressive course), that they are best classified as two separate subtypes in the official classification systems.

Scientific evidence has accumulated during the last 15 years establishing that SD symptoms have a high prevalence in the general population and in clinically depressed patient cohorts studied cross-sectionally or followed longitudinally. The clinical relevance and public health importance of SD symptoms were confirmed when various investigators, including the authors' group at University of California, San Diego, found that SD symptoms are associated with a significant and pervasive impairment of psychosocial function when compared to no depressive symptoms. There is strong evidence that all levels of depressive symptom severity of unipolar MDD are associated with significant psychosocial impairment, which increases significantly and linearly with each increment in level of symptom severity. It is only when MDD patients are completely symptom free that psychosocial function returns to good or very good levels. The disability associated with depression is state dependent, and disability returns to good or normal levels only when all of the depressed patients' symptoms abate, because disability is present when even a few symptoms (i.e., SD symptoms) are detected. There is strong evidence during the long-term course of illness that major, minor, dysthymic, and subsyndromal symptoms wax and wane within the same patient and that these symptomatic periods are interspersed in the overall course with times when patients are remitted and symptom free. The modal longitudinal symptom status of MDD patients involves primarily subthreshold depressive symptoms, which are much more common than symptoms at the syndromal MDE level. The longitudinal systematic examination of the clinical relevance and high prevalence of SD symptoms helped establish the fact that the long-term symptomatic expression of MDD is dimensional, not categorical, in nature. Abatement of SD symptoms is of fundamental importance in defining full remission or recovery of MDEs. Ongoing residual SD symptoms during the recovery periods after an MDE are associated with psychosocial disability, more rapid MDE relapse, and a more severe chronic future course of illness, all of which indicate that when residual SD symptoms are present the MDE has not fully remitted and the disease is still active. When all depressive symptoms of an MDE abate for a minimum of 8 weeks, then full remission has been achieved. MDE remission defined in this way is associated with significant delay or even prevention of future episode relapse and a less severe, relapsing, and chronic future course. The authors submit that the research reviewed in this article heralds a new paradigm in understanding the progression of clinical depression through various overlapping stages of severity, which begin at the seemingly "subclinical" level of depressive symptoms. This conceptualization in turn dictates a public health approach, which emphasizes that treatment of MDD even at the deceptively mild levels of symptoms should be initiated or maintained.

The authors provide a detailed clinical description of minor depression: its symptoms, level of disability, stability, and relationship to patient and family history of major depressive disorder.Rigorous criteria for minor depression, including functional disability, were used to identify 226 individuals for a three-phase treatment study. This report presents data obtained on that study group during the first study phase, a 4-week placebo lead-in period.One hundred sixty-two subjects (72% of the initial study group) remained in the study for 4 weeks and continued to meet criteria for minor depression. Minor depression in these subjects was primarily characterized by mood and cognitive symptoms, not the classical neurovegetative signs and symptoms of depression. Approximately one-third of the subjects with minor depression had a past history of major depressive disorder, and nearly half had a family history of unipolar depressive disorder; however, neither factor affected the severity or quality of minor depressive symptoms.These data suggest that 1) minor depression is not evanescent; 2) minor depression is characterized by mood and cognitive symptoms rather than neurovegetative symptoms; 3) minor depression may occur either independently of a lifetime history of major depressive disorder or as a stage of illness in the course of recurrent unipolar depressive disorder; and 4) depressive disorders should be conceptualized as a continuum of severity.

Item does not contain fulltext Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as ways to prevent and treat these disturbances. An illustrative case vignette is presented describing a patient's experience of cycles of manic-like behavior and depression while on high-dosage prednisone, with long-term cognitive disorganization, vulnerability to stress, and personality changes. Severe neuropsychiatric consequences (including suicide, suicide attempt, psychosis, mania, depression, panic disorder, and delirium, confusion, or disorientation) have been reported to occur in 15.7 per 100 person-years at risk for all glucocorticoid courses, and 22.2 per 100 person-years at risk for first courses. The majority of patients experience less severe but distressing and possibly persistent changes in mood, cognition, memory, or behavior during glucocorticoid treatment or withdrawal. Although prediction of such effects is difficult, risks vary with age, gender, dosage, prior psychiatric history, and several biological markers. Key mechanisms thought to underlie these risk factors are briefly described. Recommendations are given for identifying individual risk factors and for monitoring and managing adverse neuropsychiatric effects of glucocorticoids.

Studies to date on the effects of benzodiazepines on neuropsychologic function have yielded conflicting data with respect to the type, severity, and duration of deficits that may be induced by these agents. As part of a placebo-controlled trial of alprazolam-XR (extended release) administered in combination with cognitive-behavioral therapy in patients with panic disorder, a battery of tests was used to measure neuropsychologic function. Thirty-eight outpatients were randomly assigned to receive either alprazolam-XR or placebo. Dosages were titrated up so that the alprazolam group (N = 18) received a mean dose of 4 mg/day (reduced in two patients because of sedative side effects). Neuropsychologic function after 6 weeks of therapy at the target dosage was compared with baseline assessments in each group. Both groups showed a statistically significant improvement from baseline to repeated assessments on measures of attention, executive functioning, psychomotor speed, and visual memory (p < 0.001); these gains were attributed to a practice effect. No significant changes were noted in measures of learning, verbal memory, or reaction time, and neither group showed any deterioration from baseline to retesting in any aspect of neuropsychologic function. These findings call into question the assumption that long-term benzodiazepine therapy produces significant neuropsychologic deficit in patients with diagnosed anxiety disorders.

The diagnosis of psychopathology among geriatric acute inpatients requires comprehensive evaluation. To our knowledge, no recently published papers in the geriatric psychiatry literature have systematically examined diagnostic changes during single admissions. We reviewed the charts of 159 patients consecutively admitted to an acute geriatric psychiatry unit over 18 months. We recorded admission diagnoses from initial treatment plans, and discharge diagnoses from discharge summaries. Mean patient age was 80 years and average length of stay was 17 days. The most common primary diagnoses were psychotic and depressive disorders. The most common secondary diagnoses were dementias and depressive disorders. Primary diagnoses changed from admission to discharge in 31 patients (20%), and secondary diagnoses changed in 76 patients (48%). There was a significant change involving the diagnosis of dementia, but not that of depressive or psychotic disorders. A large proportion of inpatients had their diagnoses altered, especially those involving dementias, during hospitalization. Inpatient admission may be valuable for clarifying the diagnoses of elderly psychiatric patients.

An interview designed to assess a respondent's experience with erotic material in photographs, films, and books, during adolescence and adulthood, was administered to convicted male rapists, pedophiles, homosexuals, transsexuals, heavy pornography users, and two nondeviant contrast groups. One nondeviant group was composed of whites matched for the sex offender group; the other was composed of ghetto and middle-class blacks. Adolescent exposure to erotica was significantly less for all deviant and offender groups compared to the nondeviants. During adulthood, the sex offenders and transsexuals continued to report less exposure to erotic stimuli than controls. The homosexuals and users, however, both report greater exposure during adulthood. As adolescents, the control group, rapists, and heavy users were excited to masturbate by the erotic materials more than the other groups. As adults, the controls and rapists showed a sharp decrease in being excited to masturbate to erotica while the users' rate remained high and the homosexuals' rate rose. Less than a quarter of the respondents in any group imitated sexual behavior seen in the erotic material immediately or shortly after its viewing. The hypothesis that extent of exposure during adolescence to erotica is positively associated with the later emergence of sexual pathology is not borne out by this study. The nondeviant, non-sex-offender groups sampled had had significantly greater exposure to erotic materials during adolescence than the deviants, convicted sex offenders, or heavy adult users of pornography.

Those afflicted with bipolar disorder often suffer from substantial functional impairment both when in episode and when in remission. This study examined the psychometric properties of a brief assessment of psychosocial functioning, the Range of Impaired Functioning Tool (LIFE-RIFT), among subjects with bipolar I disorder. The study sample consisted of 163 subjects who presented with bipolar I disorder at intake into the NIMH Collaborative Depression Study (CDS). All LIFE-RIFT items come from the Longitudinal Interval Follow-up Evaluation (LIFE). Follow-up data that were used to examine the reliability and validity of the scale come from assessments of psychosocial functioning that were conducted 6, 12, 18, and 24 months after intake into the CDS. The results of factor analyses indicate that the scale items are measures of one construct, psychosocial functioning. The interrater agreement on the scale score was very good with an intraclass correlation coefficient was 0.94. The internal consistency reliability among the scale items was uniformly satisfactory over the four assessment periods, with coefficient alpha ranging from 0.78 to 0.84. Mixed-effect regression analyses showed that during mood episodes subjects were significantly more impaired than those in recovery. In conclusion, the psychometric properties of the LIFE-RIFT were examined in subjects with bipolar I disorder. The analyses from this longitudinal, observational study provide empirical support for the reliability and validity of the scale. The LIFE-RIFT provides a brief, inexpensive alternative to scales currently used to assess psychosocial functioning and can be easily added to semistructured assessments that are used in clinical and treatment outcome studies.

Through the use of polysomnographic, epidemiologic, and prospective clinical follow-up studies, the authors document that the course of major depressive disorder (MDD) is expressed by fluctuating symptoms in which depressive subtypes included in official diagnostic systems do not represent discrete disorders, but are stages along a dimensional continuum of symptomatic severity. Depressive symptoms at the major, minor, dysthymic or otherwise sub-threshold levels are all integral components of the longitudinal clinical structure of MDD with each symptom level representing a different phase of illness intensity, activity and severity. Detailed analyses indicate that patients are symptomatic 60 % of the time, much of it at the minor, dysthymic or subthreshold level. The symptomatic phases of illness activity are interspersed sporadically with inactive phases, when patients are asymptomatic. These findings are pertinent to both clinical cohorts and community-based epidemiologic samples. Each level of depressive symptom severity is associated with significant psychosocial impairment; such impairment increases progressively with each stepwise increment in symptom severity. When patients are asymptomatic their psychosocial functioning returns to good or very good levels. Residual subthreshold symptoms in the course of MDD are associated with high risk for early episode relapse and a significantly more chronic course of illness. Asymptomatic recovery from MDD is associated with significant delays in episode relapse and recurrence and a more benign course of illness. We submit that, as in the case of chronic medical conditions, the goal of treating unipolar depressive illness should optimally be to return the patient to as asymptomatic a level as is feasible by all available therapeutic means.

Joiner (this issue) outlines an organizational framework of dysfunctional psychological processes observed in unipolar major depressive disorder (MDD) patients, which he hypothesizes makes substantial contributions to the chronicity of this common and disabling disorder. Rather than concentrating on the clinical characteristics, past history, biological markers, or genetic variables as risk factors for chronicity, Joiner references the scarring effects of repeated episodes and a set of destructive interpersonal processes present in depressed patients that he feels promotes depressive chronicity. This extends observations reported in prior studies on psychosocial disability in depression, which have concentrated primarily on such issues as employment status, estimates of well-being, and so on, whereas Joiner emphasizes psychological disability and disrupted interpersonal relationships. This commentary introduces a new dimension of chronicity of unipolar MDD that involves the long-term, chronic manifestation of depressive symptomatology, in addition to the frequent major depressive episode relapse. Further, the long-term symptomatic structure of unipolar MDD is described as a dimensional continuum of symptom severity and illness activity and then highlighted as to the relevance of both of these newer concepts to Joiner's proposals. A number of interesting research questions are outlined in by Joiner that need empirical validation but, if answered, could make a contribution to the understanding and reduction of depression chronicity.

Recent studies of patients with affective disorders have found that there are biological differences between inpatients and outpatients. Concerned by these findings, we compared individuals admitted to our inpatient and outpatient affective disorders clinical research center who met criteria for major depression. We hypothesized that inpatients would be more severely ill, more suicidal, more functionally impaired, and have more co-morbid disorders and higher ratings of depression and mood state dysfunction. The demographic profiles, lifetime co-morbid Axis I diagnoses, consumption histories, symptom profiles, global assessment of functioning, and severity of current stressors (Axis IV) were compared and contrasted for the two groups. Inpatients had more severe current psychosocial stressors, lower current levels of functioning, increased lifetime co-morbid Axis I diagnoses, and increased rates of psychiatric hospitalizations, however, they did not have higher depression symptom ratings. In conclusion, inpatients and outpatients differed significantly in the severity of their stressors, coping abilities and history of previous hospitalizations, but not in most demographic variables or their current symptoms of depression.

Background: Gray, 1982 proposed that the septo-hippocampal system, which plays an important role in learning and memory, may partially mediate anxiety. Thus, patients with anxiety disorders may manifest neurocognitive performance deficits. We hypothesized that patients with panic disorder would demonstrate learning and memory deficits relative to normal comparison subjects. Method: Comprehensive neuropsychological batteries were administered to 69 panic disorder subjects and 19 normal volunteers. Results: There were no significant group differences in any neuropsychological performance domain including learning, memory, attention, visuospatial functioning, and psychomotor speed. Multiple regression conducted to evaluate the contribution of clinical symptoms to neuropsychological impairment within the panic disorder sample revealed that anxiety severity did not affect neuropsychological test performance. Limitations: Most patients had mild or moderate, rather than severe, panic disorder. Conclusion: Neuropsychological dysfunction was not associated with panic disorder.

Background: This study quantifies functional impairment and depressive symptomatology in patients with minor depressive disorder (MinD) and subsyndromal depressive symptomatology (SSD) before and after 8 weeks of treatment with fluvoxamine. Study patients were compared and contrasted with archival data from a sample of the general population measured by the Medical Outcome Survey Short Form 36. Method: Fifteen patients with MinD and 15 patients with SSD were identified from primary care clinics, referrals and newspaper advertisements. Patients signed informed consent and were offered open label treatment with fluvoxamine 25–100 mg/day. Patients were seen biweekly and measures of functional impairment and depressive symptomatology were gathered systematically. Results: MinD and SSD were associated with dysfunction and disability when compared to archival normative data from the general population. Eight week treatment with fluvoxamine was associated with a substantial decrease in depressive symptomatology and a normalization of psychosocial functioning. Conclusion: This is the first study to quantify functional impairment and the severity of depressive symptomatology in a clinical sample of patients with MinD and SSD, and to demonstrate that treatment with a selective serotonin reuptake inhibitor decreases depressive symptomatology and improves psychosocial functioning. Placebo-controlled double-blind confirmation of these preliminary observations seems warranted.

While it is becoming increasingly clear that mood disorders tend to be chronic, intermittent and/or recurrent conditions with different manifestations over time, little is known of the variability or course of mood disorders that are associated with severe psychosocial stress. This paper reports on the prevalence and course of major, minor, and subsyndromal depressions in 328 widows and widowers followed prospectively from 2 to 25 months following one of the most disruptive of all naturally occurring stressors, spousal bereavement. The results are consistent with the following conclusions: (1) past major depression (prior to the death) predicts an increased risk for major depression following bereavement; (2) membership in any of the unipolar subgroups, in turn, predicts future depression throughout the unipolar depressive spectrum; (3) subsyndromal and minor depression stand between major depression, on the one hand, and no depression, on the other, in terms of their effects on overall adjustment to widowhood. Thus, the results support the validity of subsyndromal depression, and that the three subgroups (major, minor and subsyndromal depression) are pleiomorphic manifestations of the same unipolar depression disorder.

Data presented during the 1996 CINP President's Workshop supported the conclusion that unipolar major depressive disorder (MDD) is a pleomorphic mood disorder consisting of a cluster of depressive subtypes existing in a relatively homogeneous symptomatic clinical continuum, extending from subsyndromal depressive symptomatology (SSD) through minor depressive episode, dysthymic disorder, major depressive episode and double depression. This indicates that common unipolar depressive subtypes can be conceptualized as alternate forms or different symptomatic phases of the same parent illness. Although there appears to be great overlap across time in the symptomatological expressions of these clinical depressive subtypes, they may be derived from different etiological and genetic factors. The one exception may be major depressive episode with psychotic features, which exists on a severity continuum with other subtypes of unipolar MDD, but does not appear to be on a symptomatic continuum with dysthymic, subsyndromal or minor depressions. By contrast, SSD and minor depressive disorder represent clinically significant depressive subtypes, which are commonly observed during the course of illness of patients with unipolar major depressive illness. Compared to no depressive symptoms, SSD is associated with harmful dysfunction, as evidenced by significant increases in psychosocial impairment, signifying that SSD is an active, inter-episode disease state of unipolar major depressive disorder. Finally, SSD, possibly jointly with subthreshold anxiety symptoms, may also represent potent risk factors for rapid depressive episode relapse. In the aggregate, these findings and conclusions have broad and important implications for diagnostic and treatment strategies of unipolar MDD.

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has focused scientific attention on the necessary tools to understand the human brain and mind. Here, we outline our collective vision for what we can achieve within a decade with properly targeted efforts, and discuss likely technological deliverables and neuroscience progress.

Objective: The authors’ goal was to evaluate the association between impairment in daily f unction and subsyndromal depressive symptoms as well as major depression to determine the economic and societal significance of these conditions. Method: Using 12-month prevalence data gathered by the National Institute of Mental Health (NIMH) Epidemiologic Catchment Area Program (ECA), based on responses to the NIMH Diagnostic Interview Schedule, the authors divided the 2,393 subjects from the Los Angeles ECA site into three groups: subjects with subsyndromal depressive symptoms (N=2 70), major depression (N= I 02), and no depressive disorder or symptoms (N=2,02 1). The groups were compared on I 0 domains of functional outcome and well-being. Results: Significantly more subjects with depressive symptoms than subjects who had no disorder reported high levels ofhousehold strain, social irritability, and f inancial strain as well as limitations in physical or job functioning, restricted activity days, bed days, and poor health status. Significantly more subjects with major depression than subjects with no disorder reported major financial losses, bed days, high levels of financial strain, limitations in physical or job functioning, and poor health status. Except for lower self-ratings of health status, no significant differences were found between subjects with subsyndromal symptoms and those with major depression. Conclusions: Significantly more people with subsyndromal depressive symptoms or major depression reported impairment in eight of I 0 functional domains than did subjects with no disorder. The high 1-year prevalence of subsyndromal depressive symptoms, combined with the associated functional impairment, emphasizes the clinical and public health importance and need for additional investigations iiito these symptoms. (AmJ Psychiatry 1996; 153:1411-1417)

Uncertainty about the generalizability of results from clinical trials is a nagging issue plaguing psychiatric research. The possible bias introduced by the use of subjects recruited from advertisements is one source of concern. Investigators question whether these subjects are representative of the types of individuals who seek treatment in clinical practice. This article compares and contrasts demographic characteristics, functional disabilities, symptomatologies, and the health beliefs and expectations of a cohort seeking treatment at a university outpatient clinic with a cohort of symptomatic volunteers recruited by advertisements. These two groups were alike in most variables ; however, the clinical subjects reported more recent exposure to psychotropic medications and were more likely to indicate that they wanted psychotherapy. The symptomatic volunteers were slightly older, endorsed more psychiatric symptoms, drank more alcohol, and believed that combined pharmacology and psychotherapy would most help them. These findings suggest that the two cohorts were remarkably similar on most variables.

Objective : The authors compared the health-related quality of life of patients with panic disorder to that of patients with other major chronic medical and psychiatric conditions. Method : The physical and mental health of a group of 433 patients with current panic disorder and 9,839 outpatients with psychiatric or medical disorders were assessed with the 20- and 36-item short-form surveys of the Medical Outcomes Study. After controlling for other disease conditions, demographics, and study site, the authors used multiple regression methods to estimate health-related quality of life levels for panic disorder patients and patients with hypertension, diabetes, heart disease, arthritis, chronic lung problems, and major depression. Results : Patients with panic disorder had levels of mental health and role functioning that were substantially lower than those of patients with other major chronic medical illnesses but were higher than or comparable to those of patients with depression. However, their physical functioning levels and perceptions of current health were more like those of patients with hypertension and were similar to general population norms. Conclusions : Panic disorder is a serious societal health problem with large consequences, and it affects primarily psychological and role domains.

Worry about the generalizability of findings derived from clinical trials is a nagging problem. Because most clinical trials use individuals recruited by advertisements rather than patients solicited from clinical practice, bias in subject recruitment is a major concern. This paper compares and contrasts the demographic characteristics, symptomatologies, functional disabilities, health beliefs, and health expectations of clinical outpatients to those of subjects recruited from the media (symptomatic volunteers) for pharmacologic trials. Clinical patients were slightly younger, better educated, wealthier, and were more likely to be married. They had more recent exposure to benzodiazepines and antidepressants and were more likely to view their current condition as amenable to psychotherapy. They were more likely to feel that their symptoms would get worse without some type of treatment and to believe that treatment would cure them. The symptomatic volunteers had more presenting symptoms than the clinical patients. The two groups had similar Sheehan Disability Scale scores. These results suggest that further study is warranted of the characteristics of clinical patients and symptomatic volunteers.

This paper is a review of the diagnosis and treatment of major depression for health professionals and the public. It is designed to help non-mental health professionals understand the important health and societal consequences of major depression. And, it serves as a guide to help health professionals make the diagnosis of major depression and explore treatment options with patients. Depression 3:108–120 (1995). © 1995 Wiley-Liss, Inc.

Serotonin receptors - from genes to pathology relapse, recurrence and chronicity in depression nicotine and major depression - a genetically based association with clinical implications the treatment of depression in primary care a double-blind study with Fluvoxamine versus Desipramine combined with placebo or Haloperidol in delusional depression - preliminary results methodological issues in collaborative multicentre placebo-controlled studies in the treatment of depression efficacy and safety of anti-depressants in the elderly. (Part contents).

Objective To explore which symptoms are common in patients who experience a range of symptom severity that spans minor depression and major depressive disorder (MDD). Method A post hoc analysis of subjects entering outpatient, pharmacologic treatment studies for minor depression or MDD who provided baseline data on the Inventory for Depressive Symptomatology-Clinician Rated (IDS-C) was performed in November 2000. The minor depression sample included 161 patients diagnosed according to the National Institute of Mental Health Diagnostic Interview Schedule, while the MDD subjects included 969 subjects diagnosed according to the Structured Clinical Interview for DSM-III-R. Descriptive statistics were calculated for the total IDS-C score and for each item-rating score for both groups. The percentages of patients within the low, medium, and high severity groups of minor depression and MDD endorsing each IDS-C item were calculated and used to identify specific patterns of prevalence across the 6 groups: symptoms with high prevalence in all groups (core symptoms), those with increasing prevalence across groups (continuum symptoms), and those that become prominent only at a certain threshold of illness severity. Results The mean (SD) IDS-C score was 21.18 (5.37) for minor depression patients, while it was 37.14 (7.27) for the MDD patients (P = .0001). Ten items pertaining mostly to mood state and cognition were identified as "core" symptoms of depression based on their high prevalence in all groups. Fourteen items consisting mostly of neurovegetative and somatic symptoms were identified as "continuum" symptoms based on their general pattern of increasing prevalence across the 6 severity groups. Four "threshold" symptoms, including suicidal ideation, psychomotor slowing, gastrointestinal symptoms, and panic/phobic symptoms, were prevalent in only the most severely depressed groups. Conclusions The presence of core, continuum, and threshold depressive symptoms indicates central features of both minor depression and MDD as well as symptoms that increase or emerge with depressive illness severity. Some of the core symptoms of minor depression and MDD are not included in DSM depressive criteria or traditional assessment rating scales.

There is very strong evidence in the literature indicating that the presence of subthreshold depressive symptoms is not a benign clinical condition. At least 5 separate investigational groups, including our own, have confirmed that the presence of depressive symptomology not reaching the diagnostic threshold for a DSM-III-R mood disorder diagnosis is correlated with social dysfunction, work impairment and absenteeism, and the potential risk of future episodes of major depression.

Suicide has become an important public health issue. It is the eighth leading cause of death among adults and varies between the second and third leading cause of death for youth under the age of 24 years. Suicidal ideation is a common symptom of psychiatric disorders; over 55% of individuals with mental disorders report suicidal ideation at some point in their lives. Fully 25% of individuals with mental disorders make at least one lifetime suicide attempt and over 12% make multiple suicide attempts. Suicidal ideation and suicidal acts are most prevalent in individuals with mood disorders. Almost 17% of individuals with either major depression or dysthymia make at least one suicide attempt while over 28% of individuals with bipolar disorders attempt suicide. Intensification of suicidal thoughts and behavior can occur in depressed patients undergoing active treatment, including antidepressant pharmacotherapy, and the risk may persist until remission occurs. Within this context, it is likely that reports linking the SSRI fluoxetine (and other antidepressants) with intensification of suicidal ideation represent random occurrences rather than causation. Although it is possible that some type of aberration in CNS serotonergic function in rare individuals might be associated with an idiosyncratic response to serotonin-specific medications, the retrospective meta-analyses of a number of databases indicate there is no causal relationship between SSRI or other antidepressant medication treatment and the emergence of suicidal ideation or behavior. Rather, the available data support the conclusion that antidepressant pharmacotherapy diminishes suicidal ideation and acts. Depression 2:169–172 (1994/1995). © 1995 Wiley-Liss, Inc.

The social and economic impact of depression on society at large has only recently been elucidated. The U.S. National Institute of Mental Health (NIMH) Epidemiology Catchment Area (ECA) Program demonstrated that the 1 year prevalence of DSM-III mood disorders was almost 10% in the adult population of the United States—or that in any year over 17 million adults suffer from a major mood disorder. Moreover, data gathered by the Cross-National Collaborative Group suggest further that the incidence of depression is increasing, not only in the United States, but in many countries all over the world. And results from the Medical Outcomes Study, which assessed the level of disability associated with depression compared with other common medical disorders, suggested that patients with major depression and dysthymia suffer greater levels of impairment than patients with hypertension, diabetes, arthritis, lung disease, and GI disorders. A number of recent investigations have sought to quantify the costs of depression in the United States and the United Kingdom, and found that depression has remarkably high direct and indirect economic costs, comparable to those associated with other major public health problems. This paper reviews depression within this larger framework and evaluates the impact of treatment advances on the costs of depression. Both pharmaceutical-sponsored and non-sponsored cost-benefit analyses reveal that while the classical anti-depressants cost less on a per-pill basis, ultimately treatment may be less expensive with the newer SSRIs because of improved compliance leading to better outcomes. Depression 2:173–177 (1994/1995). © 1995 Wiley-Liss, Inc.

Background There is increasing evidence that subsyndromal manic symptoms occur frequently during bipolar major depressive episodes (MDEs) and may be a subtle form of ‘depressive mixed state.’ This paper examines the prevalence and clinical characteristics of MDEs with subsyndromal manic symptoms. The specific effects of overt irritability and psychomotor agitation are examined. Methods Bipolar (type I or II) patients with an MDE at intake (N = 142) were compared based on the presence or absence of concurrent subsyndromal manic symptoms. The groups were further subdivided by the presence of symptoms of overt irritability and/or psychomotor agitation. Results Subsyndromal manic symptoms during bipolar MDEs were highly prevalent (76.1%), and were associated with significantly increased severity of depression/dysphoria in the intake episode, longer episode duration, and more suicidal ideation and behavior (past, current, and during long-term follow-up). Overt irritability and psychomotor agitation were the most prevalent subsyndromal manic symptoms (co-occurring in 57% and 39% of MDEs, respectively), and accounted for most of the negative effects associated with subsyndromal manic symptoms. Limitations The findings need to be confirmed in larger samples, which also examine the relationship to adequate antidepressant and/or mood stabilizing treatment. Conclusions The presence of one or more subsyndromal manic symptoms appears to be the modal presentation of bipolar MDEs and a marker for a subtle form of bipolar mixed depressive state. In particular, patients with symptoms of overt irritability and/or psychomotor agitation should be monitored closely to avoid serious clinical outcomes such as longer affective episodes, exacerbation of manic symptoms syndromal mania, and heightened suicidality.

This report presents a brief overview of the current National Institute of Mental Health (NIMH) research program in panic disorder and examines some exciting new directions for panic disorder research in the future

Objectives Subthreshold depression (StD) is common in older adults and is associated with poor self-rated health. However, the impact of StD on broader indicators of successful aging, such as positive psychological constructs, cognitive functioning, or quality of well-being, has not been assessed. The authors compared persons with scores above and below a predetermined threshold on the Center for Epidemiological Studies Scale for Depression (CES-D) with nondepressed (ND) persons on measures of multiple domains associated with successful aging. Design Cross-sectional survey-based psychological assessments. Participants A total of 1,979 community-dwelling older women participating in the Women's Health Initiative study. Measurements ND was defined as a CES-D score below 8, StD as a score between 8 and 15, and CES-D Depression (CD) as a score of 16 or above. The study questionnaire consisted of multiple self-reported measures of positive psychological functioning (e.g., optimism and resilience), cognitive functioning and complaints, and quality of well-being. The authors also obtained a history of diagnosis, treatment, and hospitalization related to mental health problems. Results Overall 20.2% of women met CES-D criteria for StD and 7% for CD. Women with StD had worse self-rated successful aging, worse physical and emotional functioning, lower optimism, more negative attitudes toward aging, lower personal mastery and self-efficacy, and greater anxiety and hostility than ND women but scored better on all these measures than women with CD. Subjects with StD also had higher self-reported rates of previous diagnosis, treatment, and hospitalization for mental health problems than the ND group. Subjects with StD with depressed mood and/or anhedonia were largely similar to those without these symptoms. Conclusions Mild-moderate levels of depressive symptoms that likely fall under a general category of StD were common and were associated with worse functioning on virtually every component of successful aging that the authors examined. StD represents a clinical entity that may affect the longitudinal course of successful aging for large numbers of persons and is a potential target for clinical intervention.

Objective: It has been widely hypothesized that sensory gating failures and sensory overload occur in schizophrenic patients compared to normal subjects. The authors ofthis study sought to confirm and extend results ofearlier studies that showed specific sensory gating deficits in schizophrenic patients. Method: Age- and sex-matched schizophrenic patients (N=20) and normal subjects (N=20) were tested using electrophysiologically recorded P50 event-related potentials to assess the overall competence ofthe subjects’ central sensory inhibitory capacity by measuring sensory filtering or gating. P50 area responses to two 75-dB (conditioning and test) click stimuli of O.04-msec duration, averaged over 60 trials, were recorded for each subject. Normally, the first (conditioning) click stimulus induces gating mechanisms that result in diminished or gated P50 event-related potentials in response to the second click stimulus. Results: The schizophrenic subjects manifested a significant sensory gating deficit at frontal, central, and parietal electrode placement sites, with a nonsignificant tendency for the deficit to be most prominent in the frontal areas of the brain. Conclusions: These data reflect a regionally diffuse loss of normal sensory gating in schizophrenic patients. (Am J Psychiatry 1992; 149:488-493)

Background The authors used results from a 20-year, high-intensity follow-up to measure the influence of ageing, and of age at onset, on the long-term persistence of symptoms in major depressive disorder (MDD). Method Subjects who completed a 20-year series of semi-annual and then annual assessments with a stable diagnosis of MDD or schizo-affective disorder other than mainly schizophrenic (n=220) were divided according to their ages at intake into youngest (18-29 years), middle (30-44 years) and oldest (>45 years) groups. Depressive morbidity was quantified as the proportion of weeks spent in major depressive or schizo-affective episodes. General linear models then tested for effects of time and time x group interactions on these measures. Regression analyses compared the influence of age of onset and of current age. Results Analyses revealed no significant time or group x time effects on the proportions of weeks in major depressive episodes in any of the three age groups. Earlier ages of onset were associated with greater symptom persistence, particularly in the youngest group. The proportions of weeks ill showed intra-individual stability over time that was most evident in the oldest group. Conclusions These results indicate that the persistence of depressive symptoms in MDD does not change as individuals move from their third to their fifth decade, from their fourth to their sixth decade, or from their sixth to their eighth decade. An early age of onset, rather than youth per se, is associated with greater morbidity over two decades.

Studies of the longitudinal natural history of the longterm course of illness (up to 20 years) of patients with bipolar I (BP-I) and bipolar II (BP-II) have found that both disorders are highly chronic. BP-l patients were symptomatic from their illness only 47% of the weeks and BP-II patients were symptomatic 54% of the weeks. All levels of depressive and manic symptom severity ranging from the subsyndromal to syndromal level fluctuated frequently within the same bipolar patient over time, indicating that both BP-I and BP-II disorders are symptomatically expressed across time as dimensional illnesses. Minor and subsyndromal manic and depressive symptoms were 3 times more common than syndromal level symptoms of mania and major depression. Depressive symptoms were three times more common than manic during the course of BP-I patients, and BP-II is overwhelmingly a depressive illness in which depressive symptoms are over 30 times more common than symptoms in the manic spectrum. Examination of hypomanic episodes in BP-II revealed that hypomanias of short duration (2-6 days) compared to long duration (more than 6 days) are not clinically significantly different and appear to be part of the same disease process. Detailed analyses of psychosocial impairment during the course of bipolar illness show that affective symptom severity and psychosocial disability increase and decrease in parallel. Depressive symptoms are equally disabling in BP-I and BP-II, often more disabling than manic/hypomanic symptoms. When asymptomatic, BP-I and BP-II patients' psychosocial function normalizes and no disability is present. Recovery from episodes in BP-I and BP-II with ongoing residual subsyndromal affective symptoms is associated with risk for very rapid relapse. Thus, all levels of affective symptom severity, including subsyndromal, are legitimate targets for therapeutic intervention to reduce risk of relapse and disability. The predominance of depressive symptoms indicates that more emphasis should be placed on the identification and management of depressive symptoms that present in patients with bipolar I and II disorders.