The balance of positive and negative affects in major depression: a further test of the States of Mind model.

The States of Mind (SOM) model provided a framework for assessing the balance between self-reported positive and negative affects in a sample of 39 outpatients with major depression and 43 healthy control subjects. The SOM model proposes that healthy functioning is characterized by an optimal balance of positive (P) and negative (N) cognitions or affects (P/(P + N) approximately 0.63), and that psychopathology is marked by deviations from the optimal balance. Research thus far has focused on the functional significance of cognitive rather than affective balance. Within this framework, we hypothesized that patients in untreated episodes of major depression would balance their positive and negative affects at the same level where depressed patients in other studies have balanced their positive and negative cognitions--namely, at P/(P + N) approximately 0.37. Points and confidence interval (CI) estimation procedures yielded results (mean = 0.35, 95% CI = 0.30 - 0.40) consistent with this hypothesis in a sample of 39 depressed male outpatients. Correlational analysis indicated that affect balance is inversely related to symptom severity as measured by self-report (Beck) and clinician-rating (Hamilton) scales.     

Rumination: One Construct, Many Features in Healthy Individuals, Depressed Individuals, and Individuals with Lupus

Rumination has been associated with depression and negative health effects. Yet measures of rumination appear to index multiple constructs that may be differentially related to clinical phenomena. To clarify this literature, we explored convergence and divergence among self-report measures of rumination in 349 undergraduates, 59 depressed adults, 81 healthy adults, and 15 never-depressed adults with Systemic Lupus Erythematosis (SLE). Results suggested there are separate constructs labeled rumination with different relationships to depression. Yet, aggregate measures index a central construct. Depressed individuals ruminated more, across measures, than individuals with SLE, who ruminated more than healthy individuals; this relationship was mediated by dysphoria. Thus, administering multiple rumination measures and attending to constructs assessed by rumination measures appears important in clinical studies.     

Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness.

BACKGROUND: Partial response, no response, or residual symptoms following antidepressant therapy is common in clinical psychiatry. This study evaluated modafinil in patients with major depressive disorder (MDD) who were partial responders to adequate selective serotonin reuptake inhibitor (SSRI) therapy and excessive sleepiness and fatigue. METHODS: This retrospective analysis pooled the data of patients (18-65 yrs) who participated in two randomized, double-blind, placebo-controlled studies of modafinil (6-week, flexible-dose study of 100-400 mg/day or 8-week, fixed-dose study of 200 mg/day) plus SSRI therapy. Patients (n=348) met criteria for several residual symptoms (Epworth Sleepiness Scale [ESS] score>or=10; 17-item Hamilton Depression Scale [HAM-D] score between 4 and 25; and Fatigue Severity Scale [FSS] score>or=4). RESULTS: Compared to placebo, modafinil augmentation rapidly (within 1 week) and significantly improved overall clinical condition (Clinical Global Impression-Improvement), wakefulness (ESS), depressive symptoms (17-item HAM-D), and fatigue (FSS) (p<.01 for all). At final visit, patients receiving modafinil augmentation experienced statistically significant improvements in overall clinical condition, wakefulness, and depressive symptoms. Modafinil was well tolerated in combination with SSRI. CONCLUSIONS: Results of this pooled analysis provide further evidence suggesting that modafinil is an effective and well-tolerated augmentation therapy for partial responders to SSRI therapy, particularly when patients continue to experience fatigue and excessive sleepiness.     

Diagnostic performance of nocturnal penile tumescence studies in healthy, dysfunctional (impotent), and depressed men

Nocturnal penile tumescence (NPT) studies were evaluated in 17 men with a clinical diagnosis of organic erectile dysfunction in comparison to age-matched healthy controls (n = 17) and depressed men (n = 17). The dysfunctional group had significantly fewer NPT episodes and reduced maximal penile tip changes when compared to healthy controls and depressed patients. Further, the dysfunctional group had significantly diminished erectile fullness and reduced penile rigidity. Diagnostic performance of polygraphic (night 1) and visual inspection (nights 2 or 3) components of the NPT protocol were examined in these criterion groups. A diagnostic classification based on polygraphic measures successfully discriminated 73.5% of dysfunctional and healthy control subjects, but classified 47% of depressives in the dysfunctional range. Use of visual inspection indices correctly identified 88% of the dysfunctional sample and 94% of normal controls, and reduced the "false-positive" rate in depression to only 18%. Results support the diagnostic utility of NPT studies, particularly when enhanced by visual inspection procedures. Nevertheless, the presence of major depression may confound interpretation of such studies.     

The generation of life events in recurrent and non-recurrent depression

BACKGROUND: The stress generation hypothesis proposed by Hammen (1991) holds that depressed individuals generate stressful conditions for themselves, which lead to recurrence. The original test of this hypothesis compared dependent life events in women with recurrent depression to medical and normal controls. Two further research questions emerged from this work: (a) do individuals with a history of many depressive episodes generate more dependent life events than depressives with fewer episodes?; and (b) what is the aetiological relevance of any stress that may be generated? METHODS: The present research tested differences in dependent and independent events between depressed individuals who had experienced: (a) no previous major depressive episodes; (b) one previous episode; and (c) two or more previous episodes. We predicted that, based on the stress generation hypothesis, recurrent depressives would show more dependent events than people without a depression history, and that these generated stressors would be of aetiological importance for precipitating recurrence (i.e. severe events in the 3 months preceding recurrence). RESULTS: Recurrent depressives experienced significantly more total dependent events than first-onset depressives in the 12 months, but not the 3 months, preceding their episode. CONCLUSIONS: Although the findings supported the general premise of stress generation, the aetiological relevance of the generated stress for recurrence requires further study.     

Gender differences in treatment response to sertraline versus imipramine in chronic depression

OBJECTIVE: The authors examined gender differences in treatment response to sertraline, a selective serotonin reuptake inhibitor (SSRI), and to imipramine, a tricyclic antidepressant, in chronic depression. METHOD: A total of 235 male and 400 female outpatients with DSM-III-R chronic major depression or double depression (i.e., major depression superimposed on dysthymia) were randomly assigned to 12 weeks of double-blind treatment with sertraline or with imipramine after placebo washout. RESULTS: Women were significantly more likely to show a favorable response to sertraline than to imipramine, and men were significantly more likely to show a favorable response to imipramine than to sertraline. Gender and type of medication were also significantly related to dropout rates; women who were taking imipramine and men who were taking sertraline were more likely to withdraw from the study. Gender differences in time to response were seen with imipramine, with women responding significantly more slowly than men. Comparison of treatment response rates by menopausal status showed that premenopausal women responded significantly better to sertraline than to imipramine and that postmenopausal women had similar rates of response to the two medications. CONCLUSIONS: Men and women with chronic depression show differential responsivity to and tolerability of SSRIs and tricyclic antidepressants. The differing response rates between the drug classes in women was observed primarily in premenopausal women. Thus, female sex hormones may enhance response to SSRIs or inhibit response to tricyclics. Both gender and menopausal status should be considered when choosing an appropriate antidepressant for a depressed patient.     

Response to placebo among bipolar I disorder patients experiencing their first manic episode

Background: The first episode of an illness may respond differently to any treatment compared to multiple episodes of the same illness. This study details the treatment response of six first-episode manic patients who participated in a previously reported study of 139 subjects comparing olanzapine to placebo in bipolar I mania (Tohen M, Sanger TM, McElroy SL, Tollefson GD, Chengappa KNR, Daniel DG. Olanzapine versus placebo in the treatment of acute mania. Am J Psychiatry 1999; 156: 702–709).

Methods: Six first-episode subjects participated in a 3-week double-blind, random assignment, parallel group, placebo-controlled study of olanzapine for bipolar mania. The Young Mania Rating Scale (Y-MRS), Clinical Global Impression, and Hamilton Depression ratings were administered weekly. Lorazepam as rescue medication was permitted for the first 10 days.

Results: Five subjects were randomized to placebo and one to olanzapine. Two subjects (40%) with psychotic mania (who also had their first-illness episode) were assigned to placebo and responded with greater than 50% reduction in the Y-MRS score and also remitted in 3 weeks. Another placebo-assigned subject had a 46% reduction in the Y-MRS scores, and two placebo-assigned subjects worsened. The olanzapine-assigned subject had a 44% reduction in the Y-MRS score. In contrast, 34 of 69 (48.6%) multiple-episode olanzapine subjects responded and 14 of 61 (23.0%) of placebo-treated subjects did.

Conclusions: This preliminary data set suggest there may be differences in treatment response between first-illness episode versus multi-episode bipolar manic subjects. Larger numbers of subjects with these illness characteristics are needed to either confirm or refute this suggestion.     

Common and Dissociable Dysfunction of the Reward System in Bipolar and Unipolar Depression

Unipolar and bipolar depressive episodes have a similar clinical presentation that suggests common dysfunction of the brain’s reward system. Here, we evaluated the relationship of both dimensional depression severity and diagnostic category to reward system function in both bipolar and unipolar depression. In total, 89 adults were included, including 27 with bipolar depression, 25 with unipolar depression, and 37 healthy comparison subjects. Subjects completed both a monetary reward task and a resting-state acquisition during 3T BOLD fMRI. Across disorders, depression severity was significantly associated with reduced activation for wins compared with losses in bilateral ventral striatum, anterior cingulate cortex, posterior cingulate cortex, and right anterior insula. Resting-state connectivity within this reward network was also diminished in proportion to depression severity, most notably connectivity strength in the left ventral striatum. In addition, there were categorical differences between patient groups: resting-state connectivity at multiple reward network nodes was higher in bipolar than in unipolar depression. Reduced reward system task activation and resting-state connectivity therefore appear to be a brain phenotype that is dimensionally related to depression severity in both bipolar and unipolar depression. In contrast, categorical differences in reward system resting connectivity between unipolar and bipolar depression may reflect differential risk of mania. Reward system dysfunction thus represents a common brain mechanism with relevance that spans categories of psychiatric diagnosis.     

Patterns of Suicidality and Alcohol Use in Alcoholics with Major Depression

The aims of this study were (1) to comprehensively characterize a population of alcoholics with major depression in a psychiatric hospital, (2) to determine the prevalence of suicidal behavior in this sample, and (3) to determine whether quantity of alcohol ingested was associated with level of suicidality. Ratings of drinking, depression, and suicidality were obtained using both self-rated and observer-rated instruments. The prevalence of suicide attempts in the week before hospitalization was remarkably high, approaching 40%, whereas 70% had made a suicide attempt at some point in their lifetime. These suicide attempts were typically impulsive in nature, involving little if any premeditation. Most subjects reported drinking more heavily than usual on the day of their suicide attempt. Recent suicidal behavior was significantly associated with recent very heavy drinking (<70 drinks per week) and with number of drinks per drinking day. Quantity of drinking per drinking day was also significantly higher in those making a recent suicide attempt. However, no association was found between quantity of alcohol consumption and suicidal ideation. These findings suggest that recent heavy alcohol use primarily affects suicidality by increasing the likelihood of acting on suicidal ideation rather than by inducing suicidal ideation.     

HIV Prevalence Among Hospitalized Patients at the Main Psychiatric Referral Hospital in Botswana

We examined HIV prevalence among patients 18–49 year olds admitted to a psychiatric hospital in Botswana in 2011 and 2012. The retrospective study analyzed females (F) and males (M) separately, comparing proportions with Chi square test and continuous variables with Wilcoxon rank-sum test, assessing significance at the 5% level. HIV seroprevalence among hospitalized psychiatric patients was much more common among females (53%) compared with males (19%) (p < 0.001). These women also appeared more vulnerable to infection compared with females in the general population (29%) (p < 0.017). Among both women and men, HIV-infection appeared most common among patients with organic mental disorders (F:68%, M:41%) and neurotic, stress related and somatoform disorders (F:68%, M:42%). The largest proportion of HIV infections co-occurred among patients diagnosed with schizophrenia, schizotypal and other psychotic disorders (F:48%; M:55%), mood (affective) disorders (F:21%; M:16%) and neurotic, stress-related and somatoform disorders (F:16%; M:20%). Interventions addressing both mental health and HIV among women and men require development.