EEG sleep of young adults with major depression: a controlled study

The EEG sleep of 75 subjects aged 16-25 years was studied. Thirty-eight were in an episode of RDC major depression, and 37 were normal controls. Only one sleep continuity measure differed between the two groups: sleep latency was significantly longer in the depressive group. REM period latencies and other sleep variables did not differ between the groups. Subgroup analyses, within the depressed group with respect to inpatient status, revealed significantly higher REM density (P less than 0.03) and a marginally shortened REM period latency (P less than 0.07) among the inpatient depressives. Subgroup analysis across suicidal ratings revealed a significantly higher REM density (P less than 0.04) among suicidal depressives. Severity estimates of depression did not correlate with sleep findings. These results parallel another recent report on adolescent depressed subjects, suggesting that inpatient and/or suicidal status is an important variable in the expression of EEG sleep abnormalities in the adolescent/young adult age group.     

Neurovegetative symptoms in chronic pain and depression

The pattern and frequency of neurovegetative symptoms was studied in 57 patients with chronic pain. Seventy-nine percent of these patients had a diagnosable depressive illness, but endogenous depression was rare (5%). Patients with chronic pain were divided into major depressives, minor/intermittent depressives and patients with no depression. A control group of nonendogenous major depressives without pain was also utilized. Major depressives differed from the other two chronic pain groups in that there was more frequent or severe early waking, weight loss, anorexia, diminished libido and initial insomnia. Diurnal variation of mood was not a characteristic of major depression with chronic pain, and did not differ in frequency from the other two chronic pain groups. Major depressives exhibited a profile of neurovegetative symptoms very similar to that found in the control group of major depressives. Over one-third of minor/intermittent depressed patients with chronic pain exhibited atypical (reversed) vegetative symptoms of hyperphagia and weight gain. This finding, together with our review of the literature, suggests an important and previously unrecognized link between atypical depression and chronic pain.     

EEG sleep in primary depression. A longitudinal placebo study.

Characteristic EEG sleep changes in depression are highlighted by a sleep continuity disturbance, delta sleep reduction, and a shortened REM latency. Since these findings have been derived primarily from only a few baseline recordings, questions regarding their persistence and/or variability have not been previously addressed. As part of an extensive set of investigations of EEG sleep in depression, we examined nightly the sleep of 12 hospitalized, non-delusional, primary depressives who were involved in a program of active psychosocial treatment intervention and received only placebo during a 5-week study period. EEG sleep findings revealed a relative lack of change across time, particularly in those parameters reported to be associated with a primary or 'biologic' depressive episode. While some degree of clinical improvement was noted, the group failed to achieve a state of remission or even partial remission as determined by the Hamilton Rating Scale. It appears that the major sleep alterations associated with such disorders persist for up to at least 5 weeks in the absence of pharmacologic or other somatic intervention.     

Heterogeneity in EEG sleep findings in adolescent depression: unipolar versus bipolar clinical course

Background: EEG sleep measures in child and adolescent subjects with depression have shown considerable variability regarding group differences between depressed and control subjects. This investigation was designed to assess whether some of the observed variability is related to undifferentiated unipolar and bipolar disorders in a sample that was reported previously. Methods: Twenty-eight adolescents who met criteria for unipolar major depression and 35 controls with no lifetime psychiatric disorder participated in a cross-sectional sleep polysomnography study. Approximately 7 years later, follow-up clinical evaluations were conducted in 94% of the original cohort. Clinical course during the interval period was assessed without knowledge of subjects’ initial diagnostic and psychobiological status. Re-analysis of the original sleep data were performed with the added information of longitudinal clinical course. Results: Depressed subjects who had a unipolar course showed reduced REM latency, higher REM density, and more REM sleep (specifically in the early part of the night) compared with depressed adolescents who converted to bipolar disorder and controls who remained free from psychopathology at follow-up. In contrast to the unipolar group, depressed subjects who would later switch to bipolar disorder had demonstrated more stage 1 sleep and diminished stage 4 sleep. Conclusions: These preliminary results indicate that some of the observed variability in EEG sleep measures in adolescent depression appear to be confounded by latent bipolar illness. The findings also suggest that sleep regulatory changes associated with unipolar versus bipolar mood disorders may be different.     

Vasoactive intestinal polypeptide decreased in cerebrospinal fluid (CSF) in atypical depression. Vasoactive intestinal polypeptide, cholecystokinin and gastrin in CSF in psychiatric disorders

Vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and gastrin in the cerebrospinal fluid (CSF) were studied in patients with endogenous depression, non-endogenous depression, mania, schizophrenia and a control group. All patients were classified according to ICD-9 and the group of depressions was further classified according to the Newcastle Rating Scales for depression (Carney et al. 1965) (N-I). In the group of non-endogenously depressed patients, CSF-VIP levels (median 16 pmol/l) were found to be significantly lower than those of controls (median = 32 pmol/l) and endogenous depressives (36 pmol/l). In the non-endogenous group, it appeared that the low CSF-VIP was due to a group of patients who, during a past or present depressive episode, had been diagnosed as suffering from endogenous depression. Moreover, this group was clinically characterized by 'dysphoric/hysterical features', 'reversed diurnal variation' (i.e. worse in the evening), and 'lack of clearly circumscribed episodes'. In many aspects this group seems similar to the atypical depressives described as monoamine oxidase inhibitor responders. Concerning CSF-CCK and CSF-gastrin, no significant differences between the examined groups were demonstrated.     

The validity of diagnosis of melancholic depression according to different diagnostic systems.

BACKGROUND: Melancholic versus nonmelancholic depression dichotomy is perhaps the most widely accepted distinction in categorization of depression. This research aims to compare RDC, DSM-III, DSM-III-R, DSM-IV and ICD-10 melancholic/endogenous/somatic and nomelancholic/nonendogenous/nonsomatic depressive patients with regards to biological variables thyroid stimulating hormone (TSH), basal and post dexamethasone cortisol levels, age, age of onset of depression, psychosocial stressors, and severity of depression. METHODS: Sixty-five patients who had been diagnosed as having major depression according to DSM III-R, using SCID were included in this study. Patients were divided into melancholic and nonmelancholic subtypes using RDC, DSM-III, DSM III-R, DSM-IV and ICD-10 criteria and groups were compared on the basis of biological variables, as well as age, psychosocial stressors and the severity of depression. RESULTS: RDC endogenous depressives were older, more severely depressed and had higher cortisol levels then RDC nonendogenous depressives. DSM III-R melancholics were older, more severely depressed, reported fewer numbers of psychosocial stressors and had lower levels of TSH than nonmelancholics. DSM-IV melancholics were more severely depressed, had higher basal and post dexamethasone cortisol levels and lower TSH levels. The ICD 10 somatic depression group contained more severe, older depressives with lower TSH levels. CONCLUSION: The results of this research show that different criteria may identify different groups of patients as having melancholic depression. They also partly support the hypothesis that endogenous or melancholic depression have a biological basis. LIMITATIONS OF STUDY: The study involved a relatively small sample size from a single centre and the results are based on this relatively small sample.     

The role of cyclothymia in atypical depression: toward a data-based reconceptualization of the borderline-bipolar II connection

OBJECTIVE: Recent data, including our own, indicate significant overlap between atypical depression and bipolar II. Furthermore, the affective fluctuations of patients with these disorders are difficult to separate, on clinical grounds, from cyclothymic temperamental and borderline personality disorders. The present analyses are part of an ongoing Pisa-San Diego investigation to examine whether interpersonal sensitivity, mood reactivity and cyclothymic mood swings constitute a common diathesis underlying the atypical depression-bipolar II-borderline personality constructs. METHOD: We examined in a semi-structured format 107 consecutive patients who met criteria for major depressive episode with DSM-IV atypical features. Patients were further evaluated on the basis of the Atypical Depression Diagnostic Scale (ADDS), the Hopkins Symptoms Check-list (HSCL-90), and the Hamilton Rating Scale for Depression (HRSD), coupled with its modified form for reverse vegetative features as well as Axis I and SCID-II evaluated Axis II comorbidity, and cyclothymic dispositions ('APA Review', American Psychiatric Press, Washington DC, 1992). RESULTS: Seventy-eight percent of atypical depressives met criteria for bipolar spectrum-principally bipolar II-disorder. Forty-five patients who met the criteria for cyclothymic temperament, compared with the 62 who did not, were indistinguishable on demographic, familial and clinical features, but were significantly higher in lifetime comorbidity for panic disorder with agoraphobia, alcohol abuse, bulimia nervosa, as well as borderline and dependent personality disorders. Cyclothymic atypical depressives also scored higher on the ADDS items of maximum reactivity of mood, interpersonal sensitivity, functional impairment, avoidance of relationships, other rejection avoidance, and on the interpersonal sensitivity, phobic anxiety, paranoid ideation and psychoticism of the HSCL-90 factors. The total number of cyclothymic traits was significantly correlated with 'maximum' reactivity of mood and interpersonal sensitivity. A significant correlation was also found between interpersonal sensitivity and 'usual' and 'maximum' reactivity of mood. LIMITATION: Correlational study. CONCLUSIONS: Mood lability and interpersonal sensitivity traits appear to be related by a cyclothymic temperamental diathesis which, in turn, appears to underlie the complex pattern of anxiety, mood and impulsive disorders which atypical depressive, bipolar II and borderline patients display clinically. We submit that conceptualizing these constructs as being related will make patients in this realm more accessible to pharmacological and psychological interventions geared to their common temperamental attributes. More generally, we submit that the construct of borderline personality disorder is better covered by more conventional diagnostic entities.     

Symposium: Normal and abnormal REM sleep regulation: REM sleep in depression-an overview

Abnormalities of REM sleep, i.e. shortening of REM latency, lengthening of the duration of the first REM period and heightening of REM density, which are frequently observed in patients with a major depressive disorder (MDD), have attracted considerable interest. Initial hopes that these aberrant patterns of sleep constitute specific markers for the primary/endogenous sub-type of depression have not been fulfilled. The specificity of REM sleep disinhibition for depression in comparison with other psychopathological groups is challenged as well. Demographic variables like age and sex exert strong influences on sleep physiology and must be controlled when searching for specific markers of depressed sleep. It is still an open question whether abnormalities of sleep are state- or trait-markers of depression. Beyond baseline studies, the cholinergic REM induction test (CRIT) indicated a heightened responsitivity of the REM sleep system to cholinergic challenge in depression compared with healthy controls and other psychopathological groups, with the exception of schizophrenia. A special role for REM sleep in depression is supported by the well-known REM sleep suppressing effect of most antidepressants. The antidepressant effect of selective REM deprivation by awakenings stresses the importance of mechanisms involved in REM sleep regulation for the understanding of the pathophysiology of depressive disorders. The positive effect of total sleep deprivation on depressive mood which can be reversed by daytime naps, furthermore emphasizes relationships between sleep and depression. Experimental evidence as described above instigated several theories like the REM deprivation hypothesis, the 2-process model and the reciprocal interaction model of nonREM-REM sleep regulation to explain the deviant sleep pattern of depression. The different models will be discussed with reference to empirical data gathered in the field.     

Neuroendocrine aspects of primary endogenous depression. III. Cortisol secretion in relation to diagnosis and symptom patterns

In order to ascertain the extent of hypothalamo-pituitary-adrenal cortical (HPA) hyperactivity in endogenous depression, we determined circadian serum cortisol patterns, cortisol responses to dexamethasone (DEX) administration, and urine free cortisol excretion before and after DEX administration in 40 definite endogenous depressives diagnosed with the Research Diagnostic Criteria. The cortisol measures ranged from normal to clearly elevated. To elucidate the clinical correlates of these hormone measures in the patients, we examined the relationships of the pre- and post-DEX cortisol measures to the diagnosis of endogenous/melancholic depression by different systems and to the overall severity and specific dimensions of depressive symptomatology. In this group of endogenous depressives, none of the diagnostic schemes for endogenous/melancholic depression which we studied was significantly related to the pre- or post-DEX cortisol measures. Of the other subject and symptom variables, only age and the agitation/anxiety factor of the Hamilton depression scale shown consistent relationships with the cortisol measures. Both were positively correlated, to a moderate degree, with the hormone measures, and they were not correlated with each other. Together they explained approximately 20% of the variance in the cortisol measures. Thus, within a group of moderately to severely ill endogenous depressives, the older and the more agitated anxious patients have a significantly greater likelihood of showing increased HPA activity. These findings indicate that age should be controlled in studies of the HPA axis and that the subjective experience of anxiety may contribute to HPA hyperactivity in endogenous depression.     

Chronic depressions. Part 2. Sleep EEG differentiation of primary dysthymic disorders from anxious depressions

In this clinical, psychometric and polysomnographic study, primary dysthymics (N = 20) were compared with anxious depressives (N = 22), and non-psychiatric controls (N = 11). Beck and MMPI depression scores were similar in the two affective groups. Prominent insomnia occurred in 82% of the anxious group; hypersomnia was more characteristic of the dysthymic group. On night 1, the anxious group had the poorest sleep efficiency (P less than 0.001), while dysthymics had the highest REM% (P less than 0.05) and shortest REM latency (P less than 0.01). On night 2, differences tended to be minimized, although the number of awakenings was still high (P less than 0.05) in the anxious group, and REM% was highest (P less than 0.01) and REM latency shortest (P less than 0.01) in the dysthymics. These findings suggest that patients with primary anxiety disorders experience greater sleep continuity difficulties on the adaptation night. Despite significant clinical overlap in depressive symptomatology between the two groups, REM% and REM latency appear as sturdy psychophysiological markers in differentiating primary dysthymics and anxious depressives on both nights. These data suggest that distinct anxious depressive and subaffective dysthymic subtypes can be distinguished within the universe of the atypical depressions.     

Platelet 5-HT uptake in delusional and nondelusional depressions

Platelet 5-hydroxytryptamine (5-HT) uptake was measured in a group of 28 endogenously depressed patients, at three points during the day, before, during and after treatment. It was also measured in 20 controls at the same three times. Uptake rates varied in control subjects in a manner consistent with the presence of a circadian rhythm in uptake. This variation was absent in depressed subjects. Deluded and nondeluded depressives showed a similar absence of variation but differed in the absolute values for their uptake rates. In particular deluded depressives did not show the lowering of platelet uptake rates, which has been widely reported for endogenous depression. This difference between the two groups was maintained after treatment was started but was not present after clinical recovery, suggesting a state-rather than trait-dependent marker. These differences between deluded and nondeluded depressives have implications for the investigation of platelet 5-HT uptake in other psychiatric illnesses.     

Plasma tyrosine/neutral amino acid ratio correlated with clinical response to nortriptyline in endogenously depressed patients

Ratios in plasma of tryptophan (Trp) and tyrosine (Tyr) to other large neutral amino acids were determined in 26 endogenous depressives before and after treatment with nortriptyline in doses adequate to achieve a steady-state serum level between 70 and 130 ng/ml, i.e., within the recommended therapeutic range. Pretreatment plasma Trp ratio and Tyr ratio were normal and did not change significantly during treatment. The plasma Trp and Tyr concentrations and the plasma Trp ratio showed no significant association with the therapeutic response. However, the pretreatment plasma Tyr ratio correlated significantly and directly with the final Hamilton rating score, and inversely with the per cent reduction of Hamilton rating score. Moreover, depressives with plasma Tyr ratio below the normal mean showed significantly greater clinical improvement than patients with higher plasma Tyr ratio with comparable serum nortriptyline levels. Evidence has been presented that biochemical variables in depressed patients are important determinants of clinical improvement following pharmacotherapeutic treatment. Moreover, the results suggest that the plasma Tyr ratio may be a guideline for antidepressant response to nortriptyline.     

The family drawing depression scale

Described the development of a standardized rating scale for scoring Kinetic Family Drawings of depressed patients. The Zung Self Rating Depression Scale (SDS) and a Kinetic Family Drawing (KFD) task were administered to hospitalized depressives who met the DSM-III criteria for Major Depression. Using the Family Drawing Depression Scale (FDDS), family drawings were analyzed in the depressed patients, pre- and posttreatment, and in a group of normal control Ss (N = 71). It is concluded that the FDDS is a useful and reliable measure of depression. Potential clinical and research applications are discussed.     

Residual symptoms at remission from depression: impact on long-term outcome

Background: Although residual symptoms after remission from depression are common and predict early relapse, little is known about the impact of residual symptoms on longer-term clinical course of depression or social functioning. Methods: Sixty severe recurrent depressives, who remitted from an index episode of depression with residual symptoms or below residual symptomatology, were followed-up at 8–10 years. Subjects underwent detailed longitudinal interviewing on course of depression, treatment and socioecomonic functioning over follow-up. Results: Long-term follow-up data was obtained on all living subjects and 55 (95%) were interviewed. The residual symptoms group spent more time with depressive symptoms over follow-up but not at full criteria for major depression and showed greater impairment in longitudinal and follow-up social adjustment. No significant differences were found between the two groups in percentage recurring long-term, mean number of recurrences, readmissions, chronic episodes or clinical global outcome criteria. Limitations: Long-term clinical and social outcomes were assessed by a single retrospective longitudinal interview. Conclusions: Patients who remit from depression with residual symptomatology continue to have more depressive symptoms and impaired social functioning long-term and may need more aggressive treatment.     

Study of the diagnostic value of the dexamethasone suppression test in endogenous depression

The diagnostic value of the dexamethasone suppression test (DST) in "endogenous" depression was evaluated in 209 psychiatric inpatients. A high incidence of abnormal DST results was observed in "endogenous" depressives (52%), schizo-affective (69%) and borderline patients (38%). However, 25% of the patients with other psychiatric disease also failed to suppress on the DST. Diagnostic criteria, previous history of alcoholism, psychiatric drug treatment, age and sex did not significantly affect DST performance. The present data do not indicate that the DST represents a highly specific marker of "endogenous" depression.     

Contrasts between symptoms of summer depression and winter depression.

Epidemiological studies and studies of clinical populations suggest that there are primarily two opposite patterns of seasonally recurring depressions: summer depression and winter depression. In addition, there is preliminary evidence that the two seasonal types of depression may have opposite types of vegetative symptoms. In the present study, we prospectively monitored symptoms of depression in 30 patients with recurrent summer depression and 30 sex-matched patients with recurrent winter depression and compared the symptom profiles of the two groups. Consistent with predictions based on the earlier reports, we found that winter depressives were more likely to have atypical vegetative symptoms, with increased appetite, carbohydrate craving, weight gain and hypersomnia, and that summer depressives were more likely to have endogenous vegetative symptoms, with decreased appetite and insomnia. A cluster analysis performed on the patients' symptom profiles without reference to season of occurrence of their episodes separated 78% of the summer depressives and winter depressives from each other on the basis of their symptoms (chi 2 = 19.29, P less than 0.001).     

The DSM IV diagnoses of melancholic and atypical depression in pregnancy

Atypical and melancholic subtypes of depression based on the Diagnostic and Statistical Manual (DSM) IV are important concepts, especially for biological psychiatry. The aim of this study was to determine whether the symptoms used for the diagnoses of atypical and melancholic depression can distinguish these subtypes during pregnancy. A modified version of the Structured Clinical Interview for DSM IV (SCID interview) was used that allowed assessment of all DSM IV symptoms of melancholic and atypical depression with depressed and non-depressed women in pregnancy. A Swiss cohort of 449 women was interviewed. Four diagnostic groups were compared: women with melancholic, atypical or non specified depression, and those without depression. Seventeen per cent of the cohort met SCID criteria for a depressive episode of depression at least once in pregnancy, with melancholic depression 2.4%, atypical depression 4.4% and non specified depression 10.2%. Many of the symptoms used to distinguish atypical and melancholic depression did not discriminate between these groups during pregnancy. However some, such as mood reactivity, distinct quality of mood and sleep pattern, did discriminate. Differential diagnosis between melancholic and atypical depression in pregnancy needs to be based on pregnancy specific definitions. The possible therapeutic consequences and the neurobiological basis for these findings warrant further research.     

Bipolar outcome in the course of depressive illness: Phenomenologic,familial, and pharmacologic predictors

Twenty percent of a cohort of 206 outpatient depressives with no past bipolar history switched during prospective observation. These 41 probands developed manic periods on the average of 6.4 years (median 4, range 1–25) after their first depressive episode. The change in polarity occurred throughout the life span, but was most common in adolescence and early adulthood. The following variables were found useful in predicting this outcome: onset ≤ 25 years, bipolar family history, loaded pedigrees, precipitation by childbirth, hypersomnic-retarded phenomenology, and pharmacologically-mobilized hypomania. Although the respective sensitivities of these findings were relatively low (32–71%), their specificities ranged from 69% to 100% for bipolar outcome; the diagnostic specificity of any 3 of these variables when combined was 98%. When compared with nonbipolar depression, bipolar disorder was seldom chronologically secondary to nonaffective psychiatric disorders. These findings suggest that many young depressives with lethargy and oversleeping are not manifesting a “neurotic” disorder, but rather a precursor of primary bipolar affective disorder. Finally, a psychotically depressed adolescent or young adult with positive bipolar family history should be observed for eventual bipolar outcome, especially when the clinical presentation is that of stupor.     

Sleep in the laboratory and sleep at home II: comparisons of middle-aged insomnia sufferers and normal sleepers.

STUDY OBJECTIVES: The study compared adaptation responses and sleep pattern differences shown by normal sleepers and insomnia sufferers during lab (LPSG) and home (HPSG) polysomnography. DESIGN: A counter-balanced, matched-group design was used. Participants underwent 3 consecutive nocturnal LPSG's and 3 consecutive nocturnal PSG's in their homes (HPSG's). SETTING: The sleep disorders laboratories at affiliated VA and university medical centers. PARTICIPANTS: Thirty-five (18 women) middle-aged (40 to 59 years) noncomplaining normal sleepers and an age-matched sample of 33 (17 women) individuals who met structured interview criteria for persistent primary insomnia were the study participants. MEASUREMENTS AND RESULTS: A series of multivariate and univariate analyses were conducted with 9 common sleep parameters to address study objectives. Bed partner influences were controlled by conducting separate sets of analyses for those with and without routine home bed partners. The interaction of participant type (normal vs. insomnia), sleep setting, and PSG sequence (HPSG 1st vs. LPSG 1st) affected first night values of sleep efficiency and stage 2 sleep among those without routine bed partners, and REM latency and sleep efficiency among those with routine bed partners. Analyses which controlled for first night and sequencing effects showed a significant participant type x sleep setting interaction among those with bed partners. These latter analyses suggested that LPSG's may underestimate the home sleep time of insomnia sufferers and overestimate the sleep continuity of normal sleepers, at least among those who routinely sleep with a bed partner. CONCLUSIONS: The nocturnal recording site may influence adaptation effects and sleep pattern differences noted between insomnia sufferers and normal sleepers.     

Primary non-endogenous depression and features attributed to reactive depression

Primary non-endogenous depression was examined with respect to preceding life stress and instability of personality. A sample of 146 hospitalized patients suffering from primary endogenous depression, primary non-endogenous depression or depression secondary to a neurosis was interviewed for preceding personal loss and completed the Eysenck Personality Inventory after recovery. Presence of a preceding personal loss did not discriminate between the three types of depression. Only in personality patterns did primary non-endogenous depressives show features that have been attributed to reactive depression. The primary non-endogenous depressives were significantly more introverted and neurotic than the endogenous depressives, but had lower neuroticism scores than patients with depression secondary to neuroses. Two-thirds of all depressives were found to dissimulate on the Lie scale. Depressives secondary to neuroses showed significantly lower Lie scores than primary endogenous and non-endogenous depressives. High Lie scores were interpreted as expressions of denial or conformity.