Glycemic control and major depression in patients with type 1 and type 2 diabetes mellitus.

The current study evaluated the association of glycemic control and major depression in 33 type 1 and 39 type 2 diabetes mellitus patients. Type 1 patients with a lifetime history of major depression showed significantly worse glycemic control than patients without a history of psychiatric illness (t = 2.09; df = 31, p < 0.05). Type 2 diabetes patients with a lifetime history of major depression did not have significantly worse control than those with no history of psychiatric illness. Findings from this study indicate different relationships between lifetime major depression and glycemic control for patients with type 1 and type 2 diabetes. Treatment implications for glycemic control in type 1 and type 2 diabetes patients are discussed.

Hypothalamic-pituitary-adrenal axis effects on plasma homovanillic acid in man.

BACKGROUND: Effects of the hypothalamic-pituitary-adrenal (HPA) axis on central dopaminergic systems have been proposed to underlie the development of psychotic symptoms in depression. This study examined HPA axis hormone effects on plasma levels of homovanillic acid (HVA), the dopamine metabolite, in healthy volunteers, using a placebo-controlled, double-blind, random-assignment, crossover design. On the basis of preliminary studies, we hypothesized that HPA axis hormones would produce delayed effects on plasma HVA levels measured in the afternoon. METHODS: Ten healthy subjects underwent a standard protocol on four occasions and each time received ovine corticotropin-releasing hormone, synthetic adrenocorticotropic hormone (ACTH), cortisol, or placebo. Plasma HVA was measured at 9 AM and 4 PM on Day 1, immediately prior to administration of the test substance at 7 PM, then at 30-60-min intervals until 11 PM. Plasma HVA levels were subsequently obtained at 9 AM and 4 PM on Days 2 and 3. RESULTS: As predicted, there were significant differences between test substances in delayed effects on afternoon HVA levels measured on Days 2 and 3, with cortisol and ACTH producing greater increases in HVA than placebo. Acute effects of HPA axis hormones on HVA were not found, while differences between test substances in delayed effects on morning HVA levels approached significance. CONCLUSIONS: HPA axis hormones exert delayed effects on plasma HVA levels in healthy humans.

McLean Hospital depression research facility: early-onset phobic disorders and adult-onset major depression.

BACKGROUND: This study explores the temporal relationship between anxiety and major depressive disorders in a cohort of patients with current major depression. METHOD: Current prevalence and lifetime history of specific anxiety disorders were assessed using the Structured Clinical Interview for DSM-III-R Diagnosis (SCID-P) in 85 patients with DSM-III-R major depression. Consensus DSM-III-R diagnoses were assigned by at least two psychiatrists or psychologists. RESULTS: Twenty-nine per cent met criteria for at least one current anxiety disorder and 34% had at least one anxiety disorder at some point in their lives. The mean (s.d.) age of onset of anxiety disorder in the depressed patients with comorbid social or simple phobia (15 (9) years) was significantly younger than was that of their major depression (25 (9) years). In contrast, the mean (s.d.) age of onset of anxiety in patients with comorbid panic or OCD (20 (8) years) was similar to that seen for their major depression (21 (9) years). In patients with major depression with comorbid anxiety disorders, both the social phobia (10 of 13) and simple phobia (4 of 4) were more commonly reported to start at least two years prior to their major depression in contrast to depressives with comorbid panic (3 of 10 subjects)-Fisher's exact test, P = 0.01. CONCLUSIONS: Early-onset social and simple phobias appear to be risk factors for later onset of major depression.

Signal transduction by platelet adenylate cyclase: alterations in depressed patients may reflect impairment in the coordinated integration of cellular signals (coincidence detection).

BACKGROUND: Adenylate cyclase (AC) responds to distinct but coincident signals from the agonist-stimulated G-protein Gs and the inhibitory G-protein Gi by generating a greater output signal-to-noise ratio--i.e., agonist-stimulated to basal ratio (fold-stimulation)--through coincidence detection than that generated by a single input (Gs) alone. Such coincidence detection by murine brain AC was found to be enhanced during chronic antidepressant treatment with imipramine. METHODS: We examined and compared the basal, agonist-stimulated, and guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) or AlF4 ion postreceptor-stimulated AC activities in mononuclear leukocytes and platelets from the same blood specimens obtained from depressed patients (n = 27) and control subjects (n = 19). RESULTS: In all subjects, the differences (delta GTP gamma S or delta AlF4) between postreceptor measures of AC in mononuclear leukocytes (where AC is regulated by Gs but not by Gi) and platelets (where AC is regulated by both Gs and Gi) were highly significant. In controls, the relationships between delta GTP gamma S or delta AlF4 and basal, agonist-stimulated, and the fold-stimulation of agonist-stimulated platelet AC resembled the regulation of AC by Gi in model-membrane systems. Comparable relationships between delta GTP gamma S or delta AlF4 and basal, agonist-stimulated, and the fold-stimulation of agonist-stimulated platelet AC activities were not observed in depressed patients. CONCLUSIONS: Our results suggest that in controls, platelet AC enzyme activity is determined (in part) by the coordinated integration of signals from Gs and Gi through coincidence detection, while such coincidence detection by platelet AC may be impaired in patients with depressive disorders.

Revisiting the factor structure for positive and negative symptoms: evidence from a large heterogeneous group of psychiatric patients.

OBJECTIVE: The factor structures of individual positive and negative symptoms as well as global ratings were examined in a diagnostically heterogeneous group of subjects. METHOD: Subjects were identified through a clinical and family study of patients with major psychoses at a VA medical center and evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. For the examination of global-level factor structures (N = 630), both principal-component analysis and factor analysis with orthogonal rotation were used. Factor analysis was used for the examination of item-level factor structures as well (N = 549). RESULTS: The principal-component analysis of global ratings revealed three factors: negative symptoms, positive symptoms, and disorganization. The factor analysis of global ratings revealed a negative symptom factor and a positive symptom factor. The item-level factor analysis revealed two negative symptom factors (diminished expression and disordered relating), two positive symptom factors (bizarre delusions and auditory hallucinations), and a disorganization factor. CONCLUSIONS: The generation of additional meaningful factors at the item level suggests that important information about symptoms is lost when only global ratings are viewed. Future work should explore clinical and pathological correlates of the more differentiated item-level symptom dimensions.

The effects of psychiatric disorders and symptoms on quality of life in patients with type I and type II diabetes mellitus.

The purpose of this study was to evaluate the influence of psychiatric symptoms and illness status on the health-related quality of life (HRQOL) of out-patients with Type I and Type II diabetes mellitus. Using a two-stage design, all patients were assessed by two measures of quality of life (Diabetes Quality of Life Measure; Medical Outcome Study Health Survey) and a psychiatric symptoms checklist (SCL-90R). Patients scoring 63 or greater on the global severity index of the SCL-90R and 30% below this cutoff were then evaluated using the Structured Clinical Interview for the DSM-III-R (SCID). Quality of life in both Type I and Type II diabetes was influenced by the level of current psychiatric symptoms and presence of co-morbid psychiatric disorder, after controlling for number of diabetic complications (e.g. effect of lifetime psychiatric illness on diabetes-related HRQOL; F = 46.8; df = 3, 135; p < 0.005). These effects were found consistently across specific domains. Both recent and past psychiatric disorders influenced HRQOL. Separate analyses comparing patients with and without depression showed similar effects. No interaction effects between diabetes type, number of complications, and psychiatric status were found in analyses. Finally, increased severity of psychiatric symptoms was correlated with decreased HRQOL in patients without current, recent, or past psychiatric diagnosis. This study shows the consistent, independent contribution of psychiatric symptoms and illness to the HRQOL of patients with a co-existing medical illness. Thus, psychiatric interventions addressing common conditions, such as depression, could improve the HRQOL of patients without changing medical status.

Diurnal variation of plasma cortisol and homovanillic acid in healthy subjects.

We investigated the relationship between plasma levels of cortisol, the dopamine metabolite homovanillic acid (HVA) and norepinephrine in healthy human subjects. Plasma cortisol and HVA levels were measured at 0800h, and in an integrated sampling procedure involving samples every 15 min between 1300 and 1600h. Plasma norepinephrine was measured at 0800 and 1300h. Cortisol, HVA and norepinephrine indices did not show significant correlations with each other. Both cortisol and HVA showed significant decreases over time. Longitudinal Random Effects (LRE) models were used to test whether individual cortisol and HVA curves over time were correlated; significant correlations were not found with this procedure. While significant correlations between cortisol and catecholamine indices have been reported in depressed patients, our results do not suggest such correlations in healthy subjects.

Platelet monoamine oxidase activity and deficit syndrome schizophrenia.

Measures of affective flattening that combine self-reported emotional experience with observed affect may identify deficit syndrome patients better than ratings based on observed affect alone. In this study, we examined 23 clinically stable but chronically ill schizophrenic patients, 15 of whom were found to have a deficit syndrome. After exclusion of patients with self-reported depressed mood from the deficit syndrome group, the remaining patients with a deficit syndrome not accompanied by self-reported depressed mood showed a strikingly homogeneous distribution of platelet monoamine oxidase activity. Results suggest that inclusion of self-reported emotional experience in clinical definitions of the deficit syndrome will increase the specificity of diagnosis.

Ten-year outcome of tardive dyskinesia.

OBJECTIVE: The purpose of this study was to assess the long-term outcome of patients with tardive dyskinesia. METHOD: A group of 122 neuroleptic-treated Hungarian outpatients were assessed for tardive dyskinesia on the Abnormal Involuntary Movement Scale and the Tardive Dyskinesia Rating Scale by the same rater over a 10-year period. RESULTS: Sixty-three of the patients received both 5- and 10-year follow-up assessments and are the subjects of this report. The overall prevalence of tardive dyskinesia in this group changed little over time; it was 30.2% at baseline, 36.5% at 5 years, and 31.7% at 10 years. However, there were changes in the tardive dyskinesia status of individual patients; 11 patients had remissions, and 12 who did not have tardive dyskinesia at the baseline assessment had developed it by the 10-year assessment. These two subgroups did not differ significantly on demographic and drug history variables. Outcome of tardive dyskinesia was not significantly related to neuroleptic treatment or to age. CONCLUSIONS: The data of this 10-year follow-up study provide evidence for the long-term stability of tardive dyskinesia and for the feasibility of maintenance neuroleptic therapy for chronic psychotic patients who have tardive dyskinesia.

The evaluation of two measures of quality of life in patients with type I and type II diabetes.

OBJECTIVE: To examine the effects of type I and type II diabetes on patient perceptions of their quality of life and compare the psychometric properties of a generic versus a diabetes-specific quality of life measure. RESEARCH DESIGN AND METHODS: Consecutive outpatients (n = 240) from a large multispecialty diabetes clinic were studied on a single occasion using two measures of quality of life--Diabetes Quality of Life Measure (DQOL) and the Medical Outcome Study Health Survey 36-Item Short Form (SF-36). No interventions were performed. This study examines three issues: 1) the reliability (internal consistency) of the two measures; 2) the relationship between the DQOL and SF-36 scales; and 3) the influence of clinical patient characteristics, such as number and severity of diabetes complications, on quality of life. Examination of this issue provides information about the construct validity of the two quality of life measures. RESULTS: The estimates of internal consistency (Cronbach's alpha) for the DQOL and SF-36 subscales ranged from 0.47 to 0.97. These values were very similar to the published findings from previous studies. The subscales of the two measures were variably correlated with one another (range of correlations: -0.003 to 0.60), indicating that the areas of functioning addressed by the DQOL and SF-36 overlapped only to a modest degree. Examination of the relationship of demographic factors to the DQOL measures suggests that they are not generally confounded by factors such as education, sex, or duration of diabetes. Health-related quality of life is affected by the marital status of both type I and type II diabetic patients, with separated and divorced individuals generally experiencing lower levels of quality of life. The quality of life measures were sensitive to clinical characteristics, such as frequency and severity of complications. Even after factors such as marital status and, among type II diabetic patients, type of treatment, patients' severity of diabetes complications was a significant predictor of both the diabetes-related and the more broad-based measure of quality of life. For type II diabetic patients, insulin treatment was associated with lower levels of satisfaction with diabetes and greater impact of diabetes on quality of life. CONCLUSIONS: This study provides evidence for the reliability and validity of two measures of quality of life. The two measures examine quality of life from different but complimentary perspectives. The DQOL seems more sensitive to lifestyle issues and contains special questions and worry scales oriented toward younger patients, whereas the SF-36 provides more information about functional health status. Thus, the measures may be used usefully in combination in studies of both type I and type II diabetic patients.

Urinary MHPG and clinical symptoms in patients with unipolar depression.

The relationship between levels of urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) and symptom scores on the Hamilton Rating Scale for Depression was examined in 31 patients with unipolar depression. Patients with either low MHPG or high MHPG showed significant sleep disturbance in the form of early morning awakening. Patients with mid-range or high MHPG showed decreased work and activities. Endogenomorphy factor scores represented a blend of these findings.

Fluoxetine and desipramine in major depressive disorder.

The efficacy and safety of fluoxetine and desipramine were compared in a 6-week double-blind, parallel group study of patients with major depression. Twenty-five were studied while hospitalized for treatment, and 33 were studied as outpatients. Improvement on the Hamilton Rating Scale for Depression was significant for both treatments from week 1 through the end of the study and did not differ between the two treatments at any week. Overall, 64% of fluoxetine-treated patients and 68% of desipramine-treated patients had at least a 50% reduction in Hamilton Depression score. We assessed whether improvement relatively early in treatment was predictive of categorical response at 6 weeks. Among fluoxetine-treated patients, but not desipramine-treated patients, the week 3 change in the Hamilton Depression mood item was significantly predictive of the response at 6 weeks. Patients treated with fluoxetine had significantly fewer side effects than those treated with desipramine. Desipramine, but not fluoxetine, caused a persistent increase in heart rate. The results suggest that early signs of response to fluoxetine are not dependent on achieving steady-state levels of the drug.

Efficacy of the combination of fluoxetine and perphenazine in the treatment of psychotic depression.

BACKGROUND: The aim of this study was to examine the efficacy of the combination of fluoxetine plus perphenazine in the treatment of psychotic depression. METHOD: Thirty patients who met DSM-III-R criteria for major depression with psychotic features were treated with fluoxetine plus perphenazine for 5 weeks. Patients were assessed at baseline and weekly using the Hamilton Rating Scale for Depression (HAM-D), Brief Psychiatric Rating Scale (BPRS), and a side-effect checklist that included specific extrapyramidal and anticholinergic side effects. RESULTS: Twenty-two (73%) of the 30 patients had a 50% or greater reduction in total HAM-D by Week 5. There was a significant improvement in HAM-D and BPRS scores at each week compared with baseline scores. Side effects reported by the patients included dry mouth (40%), blurry vision (40%), constipation (40%), tremor or rigidity (40%), and orthostatic hypotension or dizziness (27%). CONCLUSION: Fluoxetine when used in combination with perphenazine for the treatment of patients with psychotic depression has a response rate similar to the reported rates of response for tricyclic antidepressants (TCAs) plus antipsychotics, amoxapine, and electroconvulsive therapy. The side effects produced by the fluoxetine plus perphenazine combination were less than what has been reported for TCA plus antipsychotic treatment of psychotic depression and similar to the side effects reported with amoxapine. These data suggest that the combination of fluoxetine and perphenazine is effective for the treatment of psychotic depression and may be easier for patients to tolerate than a TCA plus antipsychotic.

Hypothalamic-pituitary-adrenal axis activity and 1-year outcome in depression.

The relationships of longitudinal biological measures to longer-term outcome in depressed patients have not been well explored. This study was designed to investigate whether in a sample of depressed patients: (a) symptomatic and functional outcome at 1 year was significantly different in psychotic major depressed (PMD) patients as compared with nonpsychotic major depressed (NPMD) patients and (b) high urinary or plasma cortisol levels at baseline or 1 year were associated with poorer outcomes at 1 year. Forty-two depressed patients (9 psychotic, 33 nonpsychotic) were evaluated at baseline and at 1 year using a battery of clinical ratings and measures of cortisol. A group of normal, healthy control subjects were similarly evaluated at baseline. At 1-year follow-up, PMD patients did not differ from NPMD patients in their Hamilton Depression Rating Scale (HDRS) and Brief Psychiatric Rating Scale scores (BPRS), but PMD patients demonstrated significantly poorer social and occupational functioning. Significant correlations were observed (n = 18) between higher levels of urinary and plasma cortisol at 1 year and poorer social and occupational functioning at 1 year, independent of the degree of residual depression. In contrast, baseline measures of urinary and plasma cortisol did not predict social and occupational functioning at 1 year.

Changes in norepinephrine output following light therapy for fall/winter seasonal depression.

Recurrent fall/winter depressions that remit during spring and summer have been called Seasonal Affective Disorders (SAD) (Wehr and Rosenthal 1989). The pathophysiology of SAD, its relationship to nonseasonal affective disorders, and the mechanism of action of light therapy, which is effective in treating SAD, remain to be elucidated (Depue et al 1989; Jacobsen et al 1987; James et al 1986; Joseph-Vanderpool et al 1991; Skwerer et al 1988, Terman et al 1989). Norepinephrine (NE) may play a role in the mechanisms of action of many antidepressant treatments (Schildkraut 1965) that alter NE metabolism (Schildkraut et al 1964 and 1965) and decrease the urinary output of NE and its metabolites, i.e., "whole-body NE turnover" (WBNET) (Golden et al 1988; Potter et al 1988). The present study explored whether light therapy also reduces the urinary output of NE and its metabolites.

Learned helplessness and urinary MHPG levels in unipolar depression.

OBJECTIVE: Studies of the learned helplessness paradigm in laboratory animals show increased central noradrenergic activity following exposure to uncontrollable stressors. In clinical studies, depressed patients as a group report higher perceptions of helplessness and powerlessness. The authors examined the relationship between perceptions of powerlessness and noradrenergic activity in depressed patients. METHOD: Twenty drug-free patients (12 women and 8 men) meeting DSM-III criteria for major depressive disorder were given the Kobasa Hardiness Questionnaire, which contains subscales measuring feelings of powerlessness, security, and alientation. Concurrently, 24-hour urine samples were collected for measurement of urinary MHPG. RESULTS: Significant correlations were found between MHPG levels and total hardiness scores as well as between MHPG levels and total powerlessness scores but not between MHPG levels and total security or total alientation scores. CONCLUSIONS: These results suggest that depressed patients with high urinary output of MHPG are more likely to show the cognitive features of learned helplessness.

Urinary 3-methoxy-4-hydroxyphenylglycol and the depression-type score as predictors of differential responses to antidepressants.

Pretreatment 24 hr urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and the Depression-type (D-type) scores (derived from a multivariate discriminant function equation based on levels of urinary catecholamines and metabolites) were examined as possible predictors of antidepressant responses to either imipramine or alprazolam. In the case of imipramine, the responders had significantly lower pretreatment urinary MHPG levels (p = 0.002) and D-type scores (p less than 0.001) than did nonresponders. In contrast, responders to the antidepressant effects of alprazolam had significantly higher pretreatment urinary MHPG levels (p less than 0.05) and D-type scores (p = 0.02) than did nonresponders. For each antidepressant treatment, D-type scores appeared to provide a better separation of responders from nonresponders than did urinary MHPG levels. For each drug, the effect size for the difference in mean log-transformed D-type scores between responders and nonresponders was greater than the effect size for the difference in mean log-transformed MHPG levels. The difference between the effect sizes was statistically significant for imipramine (p = 0.02) and tended toward significance for alprazolam using two-tailed tests. These results suggest that the D-type equation, which was initially derived to separate bipolar manic-depressive depressions from other subgroups of depressive disorders, can also be used to predict differential responses to certain antidepressant drugs in patients with unipolar depressions.

Depression secondary to anxiety: findings from the McLean Hospital Depression Research Facility.

Methodologic issues pertinent to the study of depression secondary to anxiety are reviewed. Data on the frequency and temporal sequence of comorbid DSM-III-R anxiety and depressive disorders in a sample from the McLean Hospital Depression Research Facility are presented. Patients with major depression secondary to anxiety are compared with major depressed patients without anxiety on a variety of demographic and clinical variables. Conceptual and practical frameworks are developed for assessing and understanding comorbidity and secondary depression.