Nonpsychotic Depressed Patients Research Articles

Platelet 5-HT concentrations and suicidal behaviour in recurrent major depression

Platelet 5-HT concentrations were determined in 84 male and 82 female psychotic and non-psychotic depressed inpatients with various degrees of suicidal behaviour, and in 175 healthy controls. Psychotic patients had higher platelet 5-HT concentrations than non-psychotic depressed patients and healthy controls. A sex difference, i.e., lower platelet 5-HT concentrations in females was found in healthy controls, depressed patients, non-psychotic patients and non-suicidal depressed patients. A negative relationship was shown between platelet 5-HT concentrations and suicidal behaviour. The lowest platelet 5-HT concentrations were associated with the most pronounced suicidal behaviour (with suicidal attempts and with the acts of suicide). The results suggest that the differences in platelet 5-HT concentrations found in depressed patients might be used as a biological marker for suicidal behaviour.

Psychosis and vulnerability to ECT-induced seizures

Medical records of patients with major depressive disorders who had received electroconvulsive therapy (ECT) for the first time were studied to test the hypothesis that psychotic patients are more vulnerable to seizures than nonpsychotic patients. This hypothesis was based on studies suggesting a putative purinergic deficiency in psychosis. Results showed that the duration of ECT-induced seizures as a measure of seizure vulnerability was significantly longer in psychotic than in nonpsychotic depressive patients. The association applied for the first ECT as well as for the course of eight ECTs. These findings were still present when covariates such as age, electrical energy applied, dosage of methohexital and succinylcholine, and psychotropic medications such as neuroleptics, benzodiazepines, and tricyclics were included in the statistical analysis. The results are discussed in the context of the role of neurotransmitters such as glutamate, γ-aminobutyric acid, adenosine, and dopamine on seizure vulnerability and psychosis.

An analysis of memory dysfunction in major depression

15 patients suffering from DSM-III-R major depression were compared with 15 age-, sex-and intelligence-matched controls on a battery of memory tests, aimed at fractionating memory dysfunction in depression. Patients were unimpaired relative to controls on measures of short-term memory, recognition, semantic memory and implicit memory. There was no evidence of a hedonic bias in recall of positive vs. negatively valenced stimuli, nor was there any correlation between depression severity and level of memory impairment. Psychotic patients did not demonstrate greater memory impairment relative to nonpsychotic depressed patients. As a group, however, depressed patients demonstrated deficits in psychomotor speed and in free recall of material (both immediate and delayed). The selective recall deficit suggests that material has been encoded but that patients are particularly impaired with regard to search and retrieval processes.

Vulnerability to psychosis in unipolar major depression: is premorbid functioning involved?

This research examined whether deficits in premorbid functioning are associated with a vulnerability to psychosis in unipolar major depressive disorder. A group of 92 inpatients with unipolar major depression were assessed for premorbid functioning and psychotic symptoms during an index hospitalization. They were prospectively assessed for psychotic symptoms 2.0 and 4.5 years after hospital discharge. The psychotic depressed patients had significantly poorer premorbid functioning--particularly, adolescent social functioning--than the nonpsychotic depressed patients. Longitudinal analyses indicated that poor premorbid social adaptation was significantly associated with the emergence of psychosis during the follow-up period in depressed patients who had not been psychotic as inpatients. Factors related to a vulnerability to psychosis among patients with major depression are present even years before the onset of overt psychotic symptoms. The data could support the view that impaired premorbid functioning is one manifestation of prepsychotic processes that constitute an underlying diathesis for psychotic episodes during the longitudinal course of unipolar major depression. These findings are consistent with other emerging findings pointing to early developmental deficits in patients who subsequently develop psychotic disorders.

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.

Serotonin function and depression: neuroendocrine and mood responses to intravenous L-tryptophan in depressed patients and healthy comparison subjects

This study was designed to compare central serotonergic function in depressed patients and healthy comparison subjects by examining neuroendocrine and mood responses to intravenous L-tryptophan. One hundred twenty-six drug-free patients with DSM-III-R major depression (109 unipolar, 17 bipolar; 68 melancholic, 58 nonmelancholic; 28 psychotic, and 98 nonpsychotic patients) and 58 healthy comparison subjects participated. After an overnight fast, subjects received an intravenous infusion of L-tryptophan, 7 g. Blood was obtained for determination of serum prolactin, serum growth hormone (GH), and plasma tryptophan levels. Visual analogue scales were used to assess mood. Prolactin responses were blunted in nonmelancholic and higher in melancholic and psychotic depressed patients, while GH responses were blunted in combined unipolar, nonmelancholic, and nonpsychotic depressed patients. Controlling for baseline biological, clinical, and demographic factors eliminated the higher prolactin response in the melancholic and psychotic patients, attenuated the blunted GH response in the unipolar patients, and revealed a blunted GH response in the melancholic patients. Patients and comparison subjects differed on five of 13 mood responses, primarily because of baseline differences. These findings are consistent with previous studies demonstrating blunted neuroendocrine responses to intravenous L-tryptophan in depression. Restriction of these findings to specific subtypes of depression may reflect a differential role of serotonergic abnormalities in these subtypes.

Risk for Suicide in Schizophrenia and Other Psychotic and Nonpsychotic Disorders

To determine the rate of suicide in young, early phase schizophrenics and other psychotic disorders, and to analyze risk factors for suicide, a large sample of patients was prospectively assessed at index hospitalization and then followed up systematically after discharge. Thirty-six patients committed suicide and these patients were compared with those who did not commit suicide for major diagnostic and prognostic factors. Results indicated the following: a) During early years, schizophrenics and other types of psychotic patients were more likely to commit suicide than nonpsychotic patients. b) Similarly, among depressives, psychotic depressed patients were more likely to commit suicide than nonpsychotic depressed patients. c) Schizophrenics and other psychotic patients were especially vulnerable to suicide within the first 6 years of their first hospitalization. d) Among the combined sample of psychotic patients (schizophrenic and other psychotic patients), those at greater risk for suicide were unmarried, white, high IQ, male patients with a more gradual onset of disorder and were of "chronic" Research Diagnostic Criteria subtypes.

Relationships between brain ct scan findings and cortisol in psychotic and nonpsychotic depressed patients

In this report, data are presented on pre- and postdexamethasone cortisol levels, neuropsychological testing, and computed tomography (CT) scan findings in 30 depressed patients (15 psychotic and 15 nonpsychotic). Particularly significant findings were observed when data from the unipolar subgroup ( n = 22) were analyzed separately. Unipolar psychotic depressed patients had significantly larger ( p < 0.05) anterior pole and cella media ventricle-to-brain ratios (VBRs) and significantly greater ( p < 0.05) left and right inferior parietal brain “atrophy” than nonpsychotic depressed patients. Higher rates of Dexamethasone Suppression Test (DST) nonsuppression were observed in psychotic depressed patients and in patients with larger cella VBRs. Inferior parietal brain atrophv and large VBRs were also associated with greater cognitive impairment on psychometric testing. Implications of these findings are discussed.

Placebo response rates in psychotic and nonpsychotic depression

The authors reanalyzed data from two earlier studies that used double-blind placebo-controlled formats to study the efficacy of amitriptyline. Using a 14-day drug-free ‘wash-out’ period, they found that the placebo response rates were 0% for psychotic depressives and 13.3% for nonpsychotic depressives. Amitriptyline was significantly superior to placebo for both psychotic ( P ⩽ 0.05) and nonpsychotic ( P ⩽ 0.05) depressed patients.

The prognostic relevance of delusions in depression: a follow-up study.

To determine whether delusional depression has a different clinical course from other types of depression, the authors followed up 31 unipolar delusional depressed patients, 28 unipolar nonpsychotic depressed patients, and 51 schizophrenic patients 14 months after hospital discharge. Patients were assessed on 1) overall outcome, 2) psychotic, anxiety-neurotic, and depressive symptoms, 3) social and work functioning, and 4) rehospitalization. The delusional depressed patients showed significantly more mood-incongruent delusions at follow-up. Surprisingly, the nonpsychotic depressed patients exhibited more depressed mood and significantly more anxiety at follow-up. The findings suggest that the diagnostic distinction between delusional and nonpsychotic depression is relevant to the clinical course of major depression.

Raised plasma cortisol concentrations a feature of drug-free psychotics and not specific for depression.

To determine whether high plasma cortisol concentrations are a distinctive feature of depression or whether plasma cortisol is also elevated in other forms of psychosis, cortisol concentrations were measured in 59 patients with acute functional psychoses, six non-psychotic depressed patients and 37 control subjects, all free of antidepressant and neuroleptic drugs for at least three months. Patients with schizo-affective disorder, manic type, had the highest concentrations throughout the day and those with major depressive disorder, psychotic sub-type had higher concentrations than controls in the afternoon and evening. Manic and schizophrenic patients had cortisol concentrations above controls in the afternoon only. Elevated concentrations were not related to the presence of depressed mood or to duration of stay in hospital, and a return to normal occurred irrespective of the type of treatment used. Thus raised plasma cortisol concentrations are a feature of psychotic illness, but in drug-free patients are not specific for severe depression.

Information-processing abnormalities: trait- and state-dependent components.

Schizophrenics were compared to schizoaffective, bipolar, and nonpsychotic depressed patients in a visual masking paradigm in which an informational target stimulus was followed at varying intervals by a noninformational masking stimulus. In limiting the availability of the sensory signal provided by the target stimulus, the mask was used to probe how information from the environment enters and is processed by the central nervous system. The use of the masking paradigm was originally based on the hypothesis that thought disorder is a result of a more primary dysfunction in the processes that precede and result in thought. Results confirmed previous findings of a performance deficit in the schizophrenics when compared to nonpsychotic controls. Schizoaffective and bipolar patients also showed evidence of impaired processing, however. Results were interpreted in terms of a trait/state formulation in which impaired information processing is seen as a fundamental trait of schizophrenia spectrum disorders and as a state that can covary with psychotic illness in general. A unifying concept centers on the effects of psychopathological conditions on an individual's processing resources that results in either underprovision or overprovision of information from sensory input to complex cognitive operations dependent on the cerebral cortex. Findings from a variety of paradigms are consistent with those of the masking paradigm in revealing that the processing deficits of schizophrenics are time dependent and occur in the 500 ms following stimulus input.

Postdexamethasone Cortisol Levels and Subgroups of Affective Illness-Reply

<h3>In Reply.—</h3> We thank Rothschild and Schatzberg for calling our attention to their earlier results showing a unipolar-bipolar difference in the plasma cortisol level after administration of dexamethasone.^1,2The clinical significance of this finding is moot; other authors have not found the difference^3,4and we found that much of the difference can be accounted for by confounding variables.⁵ They point out that we found a higher incidence of nonsuppression in psychotic than in nonpsychotic unipolar depressed patients,⁶and asked if psychosis might have influenced our more recent results.⁵This is not likely, since only three of 107 unipolar and none of 69 bipolar patients were psychotic. This low incidence of psychosis may reflect our requiring valid, complete symptom ratings for patients included in this study.

Individual variations in the sleep of depression.

Variations in the intensity or severity of affective disorders were evaluated relative to perturbations in nocturnal sleep physiology. Individual variations in polygraphic features of the sleep cycle based upon psychopathologic scale ratings were investigated in two constituencies (Ns = 6) for 8 hr during 1-3 consecutive nights. The constituencies consisted of twelve young adult (18-25 years) nonpsychotic unipolar depressed psychiatric patients with a primary affective illness and an age-matched normal healthy control group (N = 8). The severely versus mildly depressed patient subgroups scored significantly higher on the Hamilton, Beck and Zung psychopathologic rating scales, indicating a larger magnitude of depressive symptomatology. The average value for total time asleep was 6.1 hr in severely versus 7.8 hr among the mildly depressed patients and controls. EEG-sleep of the severely versus mildly depressed patients and controls contained significantly less stages 2 and 3. Although total time asleep was almost identical in the mildly depressed constituency compared with controls, patients accumulated significantly more of stages 2 and 3. Both patient subgroups exhibited a significantly shorter REM latency than controls. REM latency was reduced to a significantly lower level in the severely versus mildly depressed patients. A significant decrease of REM cycle duration occurred in the polygraphic sleep recordings of severely depressed patients compared with the age-matched controls. The shortened REM latencies indicate a disinhibition of neural processes that would normally delay appearance of the initial REM episodes during nocturnal sleep. The present study generally extends and confirms finding on nocturnal EEG-sleep disturbances in depression associated with the severity of affective illness, particularly the disrupted REM cycle and shorter REM latency.

Psychotic features in major depression: Is mood congruence important?

We studied outcome and family history in 203 patients with psychotic depression. Patients whose psychotic features were mood-incongruent were significantly younger and had a slightly poorer outcome. Morbid risks for affective disorder and schizophrenia among relatives distinguished these mood-incongruent patients from patients with non-psychotic depression but not from patients with schizophrenia. In contrast, depressive probands with mood-congruent psychotic features resembled probands with non-psychotic depression and differed significantly from schizophrenia probands in terms of family history. While depressed patients with mood-congruent psychotic features experienced poorer short-term outcome relative to nonpsychotic depressed patients, a 40-year follow-up has shown that these differences disappear over time. Moreover, these two groups are quite similar according to family history data. Both family history and short-term outcome data suggest that major depression with mood-incongruent psychotic features cannot be classified altogether with either effective disorders or schizophrenia. More definite conclusions must await the results of long-term outcome and family studies of these patients presently underway.

Recent developments in the psychotherapy of depression

The effectiveness of several types of psychotherapy for ambulatory, nonpsychotic depressed patients has been demonstrated in controlled clinical studies. Psychotherapy combined with antidepressant drug treatment appears to be the most effective form of treatment for most outpatients with major depression, although either treatment alone can be effective for patients who will not accept both. There is no evidence for negative interactions between psychotherapy and drug treatment. Interpersonal psychotherapy, cognitive therapy, and intensive psychodynamic cognitive therapy are types of individual psychotherapy that appear to have particular relevance for depression.

Variations in Self-Assessment of Personality Characteristics in Depressed Patients, with Special Reference to Aspects of Aggression

30 in-patients, 14 male and 16 female, aged 24-69 years (mean age 47.1 +/- 2.7) suffering from a moderately severe or severe depressive syndrome completed a new personality inventory, the KSP, on two separate occasions. The first-when they were depressed and had just been admitted to the hospital, the second when they were at home and in their customary situation. On the same test occasions the severity of their psychopathology was rated by means of the CPRS. A significant improvement in CPRS rating was ascertained on the second test occasion. In contrast only small changes occurred in the subscales of the KSP. The score referring to 'psychic anxiety' and to 'somatic anxiety' decreased slightly but significantly (p less than 0.05). The scores referring to 'social desirability' also showed a significant (p less than 0.01) slight decrease. Of particular note is that no significant differences were found in the 6 KSP subscales concerned with aspects of aggression, or in the factors which can be obtained from these subscales. Our findings amongst this population of non-psychotic depressed patients do not support the assumption that changes in the direction of aggression occur during depression.

Electrographic analysis of the sleep cycle in young depressed patients

Electrographic (EEG) patterns df nocturnal sleep were investigated in young psychiatric patients during unipolar depressive episodes. EEG-sleep data was recorded in 20 non-psychotic depressed patients all under 26 years old individually matched with a normal control group. All 20 subjects slept in the laboratory for 1–3 consecutive baseline nights from 12–8:00 a.m. During a subsequent extended condition 14 in each group were allowed to sleep ad-lib. Although the mean total time asleep on baseline nights was about the same between groups (> 7.1 hr), the depressives had a statistically significant reduction in REM time, increased transitions into stage 1, but most especially averaged: (a) less stage 4; and (b) more stage 1. Compared with the prior eight-hour night 27 28 subjects among both groups exhibited elevated time asleep during the extended condition, but the patients' mean total 10.3 hr sleep was significantly greater by 1.5 hr than the controls ( X =8.8 hr) . Sleep exceeding 9 hr on the ad-lib night was a consistent phenomenon which occurred in significantly more ( 11 14 ) young depressed patients contrasted to 4 14 control subjects. These findings indicate that young persons with primary affective disorders do not exhibit nocturnal EEG disturbances of comparable severity to most older depressed patients such as reduced time asleep, increased wakefulnees or lowered slow-wave (stages 3 and 4) sleep. Although no direct evidence of symptomatic ‘hypersomnia’ in these patients was provided, the present results demonstrated that some young persons with clinical depression have the capacity to sleep for sustained periods.