Middle Insomnia Research Articles

Gender differences in bipolar disorder: age of onset, course, comorbidity, and symptom presentation

To determine whether men and women with bipolar disorder differ in age of onset, course of illness, number of suicide attempts, comorbidity rates and symptom presentation. Data were collected from 211 (121 women; 90 men) adults using the Diagnostic Interview for Genetic Studies, medical records, and additional information gathered from relatives. Most gender comparisons showed no evidence of differences. Nonetheless, more men than women reported mania at the onset of bipolar I disorder. Men also had higher rates of comorbid alcohol abuse/dependence, cannabis abuse/dependence, pathological gambling and conduct disorder. Men were more likely to report 'behavioural problems' and 'being unable to hold a conversation' during mania. Women reported higher rates of comorbid eating disorders, and weight change, appetite change and middle insomnia during depression. Men and women were generally similar in their symptom presentation, age of onset of bipolar disorder, and in the total number of mood episodes. However, they differed in the type of episode at onset and comorbidity patterns.

Assessing insomnia severity in depression: comparison of depression rating scales and sleep diaries

Depression and sleep researchers typically assess insomnia severity differently. Whereas depression researchers usually assess insomnia with items on depression symptom inventories, sleep researchers usually assess the subjective experience of insomnia with sleep diaries. The present manuscript utilizes baseline data from 397 participants in a large multi-site chronic depression study to assess agreement between these two methodologies. The results indicate that the early, middle, and late insomnia items of the Hamilton Rating Scale for Depression (HRSD 24) and the Inventory of Depression Symptoms – Self Report (IDS-SR 30) are highly correlated with the weekly mean values of time to sleep onset, time awake after sleep onset, and time awake prior to the planned wake-up obtained from prospective sleep diaries. Results also reveal significant correspondence between the weekly-mean of daily sleep efficiency, an accepted measure of sleep continuity (the ratio between reported time asleep and time in bed), and the insomnia scale scores of the HRSD 24 and the IDS-SR 30 (the mean score on the three insomnia items of each depression measure). Unit increments in HRSD 24 scores for early, middle and late insomnia were associated with significant increases in unwanted minutes awake for corresponding periods on sleep diaries. Similar relationships were found for early insomnia on the IDS-SR 30 but not for middle and late insomnia. Overall, with few exceptions, findings revealed substantial agreement between the HRSD 24, IDS-SR 30 and prospective sleep diary data. The study supports the validity of the sleep items and sleep subscales of the HRSD 24 and the IDS-SR 30 as global measures of insomnia severity in depression. Conventional sleep assessment procedures can complement depression scales by providing additional information about specific aspects of sleep in depression.

Time course of depression-symptom improvement during treatment with duloxetine

The aim of this study was to examine the longitudinal response for overall and individual symptoms during the treatment of major depressive disorder. Data were pooled from two 9-week trials, which compared duloxetine 60-mg QD (n=251) with placebo (n=261) in the treatment of MDD. Changes from baseline in the 17-item Hamilton Depression Rating Scale (HAMD17) and in the Visual Analog Scales for pain were analyzed. Compared to placebo-treated patients, duloxetine-treated patients experienced greater improvement (P<.05) in the HAMD17 total score at Week 2. The individual symptoms showing the most rapid improvements (Week 1) were depressed mood, guilt, suicidal ideation, work/activities, and psychic anxiety as well as VAS back pain and shoulder pain. At subsequent visits, significant improvements were observed in retardation (Week 2); hypochondriasis (Week 3); general somatic symptoms (Week 5); middle and late insomnia (Week 7); and gastrointestinal (GI) symptoms, genital symptoms (level of sexual interest or ease of sexual arousal), insight, and early insomnia (Week 9). Significant advantages for duloxetine were not achieved at any visit for agitation, somatic anxiety, or weight loss. At Weeks 1 and 2, placebo-treated patients had significantly lower GI symptoms and reported less weight loss compared with duloxetine-treated patients; however, differences were not significant at subsequent visits. Furthermore, duloxetine was superior to placebo on GI symptoms at endpoint compared to placebo-treated patients; duloxetine-treated patients had a significantly higher response rate at Week 2 and a higher remission rate at Week 5. These results may help clinicians establish more accurate expectations regarding treatment with duloxetine.

Antidepressant-associated chronic irritable dysphoria (acid) in bipolar disorder: a case series

Background Antidepressants administered to bipolar subjects may induce manias, mixed states, or rapid cycling. More recently, we have noted that long-term use of antidepressants may induce a chronic dysphoric, irritable state. Method A case series is presented in which six type I bipolar subjects receiving antidepressants continuously for several years developed chronic irritable dysphoria. Results A triad of dysphoric mood, irritability, and middle insomnia that is frequently associated with occupational and social dysfunction can occur in some bipolar patients receiving antidepressants for at least 3 years. Typically, initial treatments with antidepressants for the index episode were effective. Over time, depressive symptoms returned and would transiently improve with dose increase or change of agents. Ultimately, the dysphoria and associated symptoms became chronic and resulted in dysfunction. Concomitant mood stabilizer did not appear to alter this pattern. Discontinuation of antidepressants was associated with a slow and gradual improvement in these symptoms over the ensuing year. Conclusion Additional studies are required to investigate safety of long-term use of antidepressants in bipolar illness.

Predictors of improved mood over time in clinical trials for major depression

The objective of this exploratory analysis was to use a repeated measures modeling approach to identify potential predictors of improved mood over time in patients with major depression. Fifty-one subjects with major depressive disorder (MDD) were enrolled in a 1-week single blind placebo lead-in, followed by an 8-week, double-blind placebo-controlled treatment with either fluoxetine or venlafaxine. Hierarchical linear regression models were used to identify baseline and placebo lead-in predictors of change in repeated measures of the Hamilton Depression Rating Scale (HDRS) during treatment. Non-specific predictors of improved mood included decreased prefrontal activity during placebo lead-in as measured by quantitative electroencephalographic cordance, lower pretreatment depressed mood on the HDRS, shorter duration of current episode, increased verbalization of suicidal thoughts, no family history of mood disorders, less severe middle insomnia, higher guilt, lower somatic anxiety, and younger age. Moderators of improved mood included somatization, paranoid ideation, and self-reported depressed mood. We also found that change in prefrontal cordance after randomization mediated the effects of middle insomnia, suicidal thoughts, and family history of mood disorders. We recommend the use of repeated measures modeling, and the exploration of relationships among biological and psychological factors, for future analyses of clinical trial data.

P.1.117 Morning light therapy as an augmenting strategy of antidepressant treatment

Unhelpful sleep-related cognitions play an important role in insomnia and major depressive disorder, but their role in seasonal affective disorder has not yet been explored. Therefore, the purpose of this study was to determine if individuals with seasonal affective disorder (SAD) have sleep-related cognitions similar to those with primary insomnia, and those with insomnia related to comorbid nonseasonal depression.Participants (n=147) completed the Dysfunctional Beliefs and Attitudes about Sleep 16-item scale (DBAS-16) and the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version (SIGH-SAD), which assesses self reported sleep problems including early, middle, or late insomnia, and hypersomnia in the previous week. All participants were assessed in winter, and during an episode for those with a depressive disorder.Individuals with SAD were more likely to report hypersomnia on the SIGH-SAD, as well as a combined presentation of hypersomnia and insomnia on the Pittsburgh Sleep Quality Index (PSQI). The SAD group reported DBAS-16 scores in the range associated with clinical sleep disturbance, and DBAS-16 scores were most strongly associated with reports of early insomnia, suggesting circadian misalignment.Limitations include the self-report nature of the SIGH-SAD instrument on which insomnia and hypersomnia reports were based.Future work could employ sleep- or chronobiological-focused interventions to improve clinical response in SAD.

Genetic dissection of psychopathological symptoms: insomnia in mood disorders and CLOCK gene polymorphism.

We investigated the possible effect of the 3111T/C CLOCK gene polymorphism on sleep disorders in a sample of 620 patients affected by major depressive disorder (MDD) and bipolar disorder (BP). We detected a significantly higher recurrence of initial (P = 0.0001), middle (P = 0.0009), and early (P = 0.0008) insomnia in homozygotes for the C variant and a similar trend concerning decreased need of sleep in BP (P = 0.0074). Other demographic and clinical features were found not related with CLOCK polymorphisms. This preliminary observation leads to hypothesize a possible involvement of the CLOCK gene polymorphism in the sleep disregulations in MDD and BP.

Evaluating the continuity of symptomatology between depressed and nondepressed individuals.

Debate is contentious concerning whether depression should be viewed as a distinct category or as a continuum including overlapping normal and clinical phenomena. A nonparametric item response model was used to evaluate whether the probability of expressing individual symptoms differed between nondepressed and clinically depressed adults experiencing similar levels of overall severity. Even though depressed and nondepressed individuals were equated in terms of overall severity, differences on specific symptoms emerged. Depressed mood, anhedonia, and suicidality were more likely to be expressed in depressed than in nondepressed individuals, whereas hypochondriasis and middle insomnia were more likely to be expressed in nondepressed individuals at similar levels of severity. Such differences are inconsistent with the view of depression as a simple continuum.

Posttraumatic stress disorder in co-workers following exposure to a fatal construction accident in China.

To assess the mental disturbances induced by accidents at work, 41 male workers who had witnessed a fatal work accident were evaluated utilizing the criteria for posttraumatic stress disorder (PTSD) from the ICD-10 Classification of Mental and Behavioral Disorders. The Hamilton Depression Rating Scale (HDRS) was also administered to the exposed workers, as well as to 47 non-exposed construction-worker controls. The two groups were well matched with respect to age, years of employment, and years of education. They were all of Han sect; and lifestyles, incomes, and living conditions were similar. The exposed workers had a high rate of PTSD: 11 of 41 (26.8%) at one month and five of 39 (12.9%) four months after the fatal accident. The exposed groups' scores for depressive symptoms were significantly higher than those of the controls, including: 1) depressed mood, 2) guilt, 3) initial insomnia, 4) middle insomnia, 5) delayed insomnia, 6) decreased interest in work and other activities, 7) anxiety, 8) somatization, and 9) gastrointestinal symptoms (p < 0.05, p < 0.01, p < 0.001). Fatal work accidents, a major hazard in the construction industry, affect not only the victims but also the mental health of other workers. PTSD and associated emotional disorders related to exposure to serious work accidents deserve more attention for clinical and research purposes.

Nonorganic insomnia in panic Disorder: comparative sleep laboratory studies with normal controls and placebo-controlled trials with alprazolam.

Objective and subjective sleep and awakening quality was investigated in 11 drug-free patients (4 females, 7 males) aged 30-55 (mean: 44+/-9) years with nonorganic insomnia (F 51.0) related to panic disorder (F 41.0) as compared with 11 age- and sex-matched normal controls aged 30-58 (mean: 44+/-9) years, utilising polysomnography (PSG) and psychometry. PSG demonstrated decreased sleep efficiency (primary target variable), total sleep time (TST) and S2 as well as increased middle and late insomnia, S1, S3+S4, snoring and PLM in patients. There were no intergroup differences in REM variables. Subjective sleep quality deteriorated, as did drive and fine motor activity in the morning, while concentration increased. Blood pressure in the evening and morning and pulse rate in the evening were elevated. These differences as compared with normals were distinct from those observed in other sleep disorders. In a subsequent acute, placebo-controlled cross-over design study, patients received alprazolam 0.5 mg (Xanor((R));) and placebo. As compared with placebo, alprazolam induced an increase in sleep efficiency (primary target variable), TST and S2, a decrease in wakefulness during the total sleep period, S3+S4 and the oxygen desaturation and PLM indices, and improved subjective sleep quality, somatic complaints, drive, affectivity and drowsiness in the morning. There were no changes in REM variables. Thus, alprazolam induced changes that were opposite to the differences observed between patients and controls before treatment, thereby normalizing sleep and awakening quality. As observed in insomnia related to GAD and subsequent benzodiazepine therapy, the present study also points to a key-lock principle in the treatment of insomnia caused by anxiety disorders and neurophysiologically visualizes processes at the receptor level (e.g. benzodiazepine agonists versus inverse agonists). Copyright 2000 John Wiley & Sons, Ltd.

Full length article

The composition of the depressive syndrome was examined at both the acute and chronic phases of schizophrenic illness in 86 newly admitted patients. A subgroup with pronounced depression was defined, and a discriminant analysis was performed using symptoms from the Hamilton Rating Scale for Depression (HRSD) as discriminant variables. At the acute phase, the following nine symptoms from the HRSD were significant: depressed mood, guilt, suicide, retardation, three types of insomnia, and two somatic symptoms. At the chronic stable phase, only four symptoms were significant: depressed mood, suicide, general somatic symptoms, and loss of weight. Initial insomnia, middle insomnia, genital symptoms, and loss of insight were poorly correlated. The positive and negative symptoms and extrapyramidal side-effects were not discriminators at either phase. These findings suggest that only certain items from the HRSD may be crucial when assessing depression in schizophrenia.

Association of biogenic amine metabolites with symptomatology in delusional (psychotic) and nondelusional depressed patients

1. 1. The levels of the main norepinephrine, serotonin, and dopamine metabolite excretion in the urine, MHPG, 5HIAA and HVA respectively, were measured in 84 patients with major depressive disorder, 34 delusional (psychotic) and 50 nondelusional (DSM-III-R criteria). 2. 2. Associations with the 17 items of the HDRS were evaluated using the multiple regression analysis model. In the delusional group, MHPG excretion was positively related to the scores in the items of depressed mood (p = 0.04), middle insomnia (p = 0.008) and genital symptoms (p = 0.001). 5HIAA excretion was negatively associated with late insomnia (p = 0.02), work and interests (p = 0.001) and genital symptoms (p = 0.007). HVA was positively related to agitation (p = 0.043). In the nondelusional group the only association found was between agitation and HVA excretion (p = 0.03).

Total serum protein and serum protein fractions in depression: relationships to depressive symptoms and glucocorticoid activity

Recently, it has been reported that major depression is accompanied by changes in plasma protein concentrations indicative of an acute-phase protein (APP) response. The purpose of the present study was to examine total serum protein (TSP) and the electrophoretically separated major fractions of serum proteins (SP), i.e., albumin (Alb), α 1, α 2, β and γ globulin, in depression. Highly significant differences were found in TSP and the separated SP fractions between major depressed patients and normal controls and between melancholic and minor depressed patients. Major depressed subjects showed significantly lower TSP and Alb concentrations and a higher percentage of the α 1 globulin fraction than normal controls and minor depressed subjects. Major depressed subjects had significantly higher and lower percentages, respectively, of α 2 and γ globulin fractions than normal controls. In depressed subjects, there were significant negative correlations between TSP or Alb concentrations and severity of illness. Psychomotor retardation and anorexia were psychopathological correlates of lower TSP and Alb concentrations while middle insomnia and psychomotor retardation were related to changes in the α 1 and α 2 globulin fractions. Basal plasma cortisol values were significantly and positively related to serum α 2 globulin. The results support the view that major depression is accompanied by an APP response.

Insomnia in Generalized Anxiety Disorder: Polysomnographic, Psychometric and Clinical Investigations before, during and after Therapy with a Long- versus a Short-Half-Life Benzodiazepine (Quazepam versus Triazolam)

Within a double-blind, comparative study on the effects of the long-half-life benzodiazepine (BDZ), quazepam, and the short-half-life BDZ, triazolam, on clinical symptomatology, sleep and anxiety of 45 patients with insomnia based on a mild to moderate generalized anxiety disorder (GAD) (ICD-9 code: 307.42-1, 300,0; ASDC-APSS-Code: A.2.a), we compared, in a first step at baseline, drug-free polysomnographic and psychometric data of 22 patients recorded in the laboratory (L-group) and 21 patients recorded by the Oxford Medilog 9000 system at home (H-group) with those of normal controls. Sleep efficiency, total sleep time, wake within total sleep period (middle insomnia) and wake before buzzer (late insomnia) were significantly deteriorated in both patient groups as compared with controls, while sleep induction time only differed significantly in home recordings. Regarding sleep architecture, stage (S)2 was reduced, S3 and S4 increased in the H-group only, while no intergroup differences were seen in S1, SREM and REM latency. Subjective sleep quality was reduced in both patient groups, but not awakening quality. Psychometric tests in the morning demonstrated for the noopsyche, only a significantly deteriorated psychomotor activity in both patient groups. In the thymopsyche, evening well-being and mood in the morning were reduced in both the L- and H-group, affectivity and morning well-being only in the H-group. The psychopharmacological part of the study was completed by 40 patients (there were 4 drop-outs in the triazolam, 1 in the quazepam group). They were treated after 1 week placebo with either 15-30 mg (median 15 mg) quazepam or 0.25-0.5 mg (median 0.25 mg) triazolam for 4 weeks, and thereafter for 2 weeks with placebo. Anxiety (rated by HAMA and SAS) improved significantly with both drugs and remained improved throughout 2 weeks post-drug placebo, with quazepam being slightly superior to triazolam. Polysomnography demonstrated a shortened sleep onset only after quazepam. Sleep efficiency improved after acute administration of both drugs, but the improvement was maintained by quazepam only (tolerance development with triazolam). Rebound insomnia was observed only in the 1st post-triazolam placebo night (significant intergroup difference based on confirmatory testing). S2 increased, S3 + S4 decreased under and after quazepam, which represents a normalization in home-recorded GAD patients. S1 decreased with both drugs, SREM only under quazepam. Subjective sleep quality behaved very similarly to objective sleep efficiency. Awakening quality improved after acute therapy with both drugs, somatic complaints only with quazepam.(ABSTRACT TRUNCATED AT 400 WORDS)

Psychomotor retardation, anorexia, weight loss, sleep disturbances, and loss of energy: Psychopathological correlates of hyperhaptoglobinemia during major depression

Recently, we have established that major depression is characterized by hyperhaptoglobinemia, which may be regarded as an index of an “acute” phase response in that illness. The present study investigates the psychopathological correlates of increased plasma concentrations of haptoglobin (Hp) in major depression. To this end, the authors studied the Hp levels in relation to depressive otems of the Structured Clinical Interview for DSM-III (SCID) and the Hamilton Rating Scale for Depression (HRSD) in 90 depressed subjects. There was a significant positive relationship between the SCID symptoms anorexia/weight loss, sleep, and psychomotor disorders and Hp plasma concentration. Hp plasma levels were significantly and positively correlated with overall severity of illness (HRSD). The HRSD symptom correlates of higher Hp levels were loss of interest, middle insomnia, and psychomotor retardation. Up to 31.4% of the variance in Hp plasma values could be explained by psychomotor disorders, anorexia, weight loss, middle insomnia, and less diurnal variation of mood. It is suggested that hyperhaptoglobinemia, as an index of an “acute” phase response in major depression, is related to the somatic dimension of depressive illness.

Sleep deprivation accelerates the response to nortriptyline

1. The authors examined the effect of total sleep deprivation (SD) in combination with nortriptyline in 20 patients with major depressive disorder (MDD). Patients underwent a 36-hour SD procedure followed by nortriptyline started on the evening after SD, with ratings for two weeks. 2. Eleven (55%) patients were responders; they showed a rapid and sustained remission after SD, whereas non-responders demonstrated the delayed results expected with nortriptyline. 3. High initial depression scores and absence of depersonalization were associated with response to SD, while being female and middle insomnia were associated with response to the combined regimen. 4. The combination of SD with antidepressants proves to be an effective and safe treatment modality.

Specificity of affective and autonomic symptoms of depression in Parkinson's disease.

Previous investigators have suggested that numerous symptoms used to diagnose depression, such as sleep or appetite disturbance, are non-specific in medically ill patients, and alternative diagnostic criteria should be developed. In the study this hypothesis was tested in Parkinson's disease (PD) by comparing patients with PD who reported a depressive mood with patients having PD but without a depressive mood. Depressed patients showed a significantly higher frequency of both autonomic and affective symptoms of depression. Depressed patients with PD reported a significantly higher frequency of worrying, brooding, loss of interest, hopelessness, suicidal tendencies, social withdrawal, self-depreciation, ideas of reference, anxiety symptoms, loss of appetite, initial and middle insomnia, and loss of libido when compared with non-depressed patients. No significant between-group differences, however, were observed in the frequency of anergia, motor retardation, and early morning awakening.

Prevalence of reported sleeplessness in northern Norway in relation to sex, age and season

As part of a comprehensive population health survey in the municipality of Tromsø, north of the Arctic Circle, men between 20 and 54 years and women between 20 and 49 years were presented a questionnaire containing questions about sleeplessness and its possible association with season. Of the 14,667 respondents, 41.7% of the women and 29.9% of the men said they were sometimes bothered by insomnia. Insomnia not associated with any special time of the year was reported by 16.9% of women and 16.2% of men; insomnia in the "dark period" (midwinter insomnia) was reported by 17.6% of women and 9.0% of men; insomnia in the midnight-sun period or in spring or autumn was much less common. Difficulty falling asleep was the most common type of insomnia, especially in winter and summer. Overall, the frequency of insomnia increased with increasing age, but with some notable differences with regard to type (initial insomnia showed little relation to age, whereas middle and late insomnia increased markedly with age) and seasonal type (insomnia in the midnight-sun period decreased with age, whereas the other seasonal types increased with age).

Depressive Illness and Placebo Response

Fifty-three depressed inpatients received placebo treatment as part of a multicenter double-blind placebo-controlled study of an investigational antidepressant, bupropion. Groups of placebo responders and nonresponders were identified based on percentage change on the Hamilton Depression Scale and validated against the Clinical Global Impression Scale. Although the diagnostic and demographic features of responders and nonresponders were generally similar, some differences emerged. Placebo nonresponders were more often associated with male gender, lack of college education, diagnosis of manic-depressive illness and greater lack of insight at baseline. Placebo responders largely consisted of females with a diagnosis of depressive neurosis. When the individual symptoms as measured by the Hamilton Depression Scale were examined, the nonresponders showed improvement only in psychological symptoms (i.e., lack of interest, guilt, and suicide). The responders showed consistent improvement in most symptoms except middle insomnia, loss of weight, and diurnal mood change. These results suggest that depressions of an endogenous nature are unlikely to respond to placebo and when they do respond, the vegetative symptoms are least likely to improve.

Depressive symptoms associated with dexamethasone resistance

Using split sample discriminant function analysis on a series of 63 consecutive depressed outpatients, the authors identified several items on the Hamilton Depression Rating Scale that were associated with dexamethasone resistance (late and middle insomnia, retardation, somatic and psychic anxiety, and obsessive-compulsive symptoms), and several items that were associated with dexamethasone suppression (genital symptoms, somatic-general symptoms, hypochondriasis, early insomnia, and depersonalizaton). The accuracy of the classification function was 100% for the index split sample, 84% for the overall sample, and 72% for the other split sample. The implications of these findings are discussed.