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SLEEPING PROBLEMS AND BIPOLAR
Walk the Road of Bipolar II-
Sleeping problems are a major symptom of being bipolar. Lack of sleep or too much sleep are symptoms of bipolar disorder. Scanning through the research abstracts leaves one shocked at how little research has been done. I suffer from bipolar II and am on medication. Before medication, I could subsist on little sleep and feel tired but keep on going and going and going...and accomplish a great deal. Now I am on medication and I swing. I found no articles on swinging from sleeping during the day to staying up all night. There were no articles about sleeping pills and if they helped to regulate sleeping habits. I am providing the articles that I found interesting and possibly helpful on sleep deprivation, even sleep deprivation as a form of therapy. The bias will be on articles related to bipolar disorder.
Many of us are given Seroquel, an atypical antipsychotic for mania but also for helping us get some uninterrupted sleep. For instance, I am on 100 m. of Seroquel and now can usually get four hours of uninterrupted sleep whereas before most of the time, I couldn't even get that.
  • : Bipolar Disord. 2005 Feb;7(1):98-101. : Dark therapy for mania: a pilot study.
    Barbini B, Benedetti F, Colombo C, Dotoli D, Bernasconi A, Cigala-Fulgosi M, Florita M, Smeraldi E.
    Department of Neuropsychiatric Sciences, Istituto Scientifico Universitario Ospedale San Raffaele, Milano, Italy.

    Barbini B, Benedetti F, Colombo C, Dotoli D, Bernasconi A, Cigala-Fulgosi M, Florita M, Smeraldi E. Dark therapy for mania: a pilot study. Bipolar Disord 2005: 7: 98-101. (c) Blackwell Munksgaard, 2005Background: Recent findings suggest that extended bed rest and darkness could stabilize mood swings in rapid cycling bipolar patients. Method: We exposed 16 bipolar inpatients affected by a manic episode to a regimen of 14 h of enforced darkness from 6 p.m. to 8 a.m. each night for three consecutive days [dark therapy (DT)]. Pattern of mood changes were recorded with the Young Mania Rating Scale (YMRS) and compared with a control group of 16 inpatients matched for age, sex, age at onset, number of previous illness episodes and duration of current episode, and were treated with therapy as usual (TAU). Results: Adding DT to TAU resulted in a significantly faster decrease of YMRS scores when patients were treated within 2 weeks from the onset of the current manic episode. When duration of current episode was longer, DT had no effect. Follow-up confirmed that good responders needed a lower dose of antimanic drugs and were discharged earlier from the hospital. Conclusions: Chronobiological interventions and control of environmental stimuli can be a useful add-on for the treatment of acute mania in a hospital setting.

  • Am J Psychiatry. 2005 Jan;162(1):50-7. : Sleep-related functioning in euthymic patients with bipolar disorder, patients with insomnia, and subjects without sleep problems.
    Harvey AG, Schmidt DA, Scarna A, Semler CN, Goodwin GM.
    Department of Psychology, University of California, Berkeley, 3210 Tolman Hall, No. 1650, Berkeley, CA 94720-1650.
    aharvey@berkeley.edu.

    OBJECTIVE: The authors investigated sleep-related functioning in euthymic patients with bipolar disorder. METHOD: Euthymic patients with bipolar disorder (N=20), patients with insomnia (N=20), and subjects with good sleep (N=20) were compared on data from interviews and questionnaires and on findings from eight consecutive days and nights of sleep diary keeping (subjective sleep estimate) and actigraphy (objective sleep estimate). RESULTS: Seventy percent of the euthymic patients with bipolar disorder exhibited a clinically significant sleep disturbance. Compared with the other groups, the bipolar disorder group exhibited impaired sleep efficiency, higher levels of anxiety and fear about poor sleep, lower daytime activity levels, and a tendency to misperceive sleep. The bipolar disorder group held a level of dysfunctional beliefs about sleep that was comparable to that in the insomnia group and significantly higher than that in the good sleeper group. CONCLUSIONS: Insomnia is a significant problem among euthymic patients with bipolar disorder. Components of cognitive behavior therapy for insomnia, especially stimulus control and cognitive therapy, may be a helpful adjunct to treatment for patients with bipolar disorder.
  • Prog Neuropsychopharmacol Biol Psychiatry. 2004 Nov;28(7):1065-70.: Effects of clozapine on sleep in bipolar and schizoaffective disorders.
    Armitage R, Cole D, Suppes T, Ozcan ME.
    Department of Psychiatry, Sleep Study Unit, The University of Texas Southwestern Medical Center, 2201 Inwood Road, Dallas, TX 75235, USA.
    Roseanne.Armitage@med.umich.edu
    OBJECTIVE: Sleep disturbances are strongly associated with mood disorders, although the majority of data have been obtained in patients with major depressive disorder. Studies reporting results in bipolar disorder are few, and results have not been consistent. Clozapine is a prototype of atypical antipsychotics, which is effective in improving symptoms of manic episodes in patients with bipolar disorder, or schizoaffective disorder, bipolar type and has been shown to influence sleep in other psychiatric disorders. The present study evaluated the sleep effects of clozapine in bipolar and schizoaffective disorders. METHODS: Participants were 11 women and 4 men (range:28-53 years of age, mean 40.9+/-8.6 years), all with a history of mania by DSM-IV criteria for either bipolar I disorder or schizoaffective disorder, bipolar type. They participated in a sleep study at baseline and again after 6 months initiation of clozapine add-on therapy. RESULTS: Sleep latency was longer on clozapine and the number of awakenings were increased, whereas time in bed (TIB) and total sleep period (TSP) were increased (range: F=6.2-17.9; df=l,12; p<0.05). Although none of the individual sleep stage showed significant treatment changes, both Stage 2 and slow-wave sleep were increased and Stage 2 decreased on clozapine. Subjective sleep measures improved on clozapine with a small but significant improvement in how rested patients felt upon awakening (t=-2.1; df=26; p<0.05). CONCLUSION: Clozapine prolonged sleep latency, improved restedness, and increased total sleep time. Although lack of a control group limits interpretation of these results, they are in general agreement with studies in other psychiatric populations, and support the view that clozapine is primarily a NREM sleep enhancer. The improvement in restedness may be of positive clinical consequence
  • J Affect Disord. 2004 Oct;82 Suppl 1:S71-8.: A genome-wide scan of symptom dimensions in bipolar disorder pedigrees of adult probands.
    Faraone SV, Su J, Tsuang MT.
    Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.
    sfaraone@hms.harvard.edu

    Although twin and adoption show bipolar disorder (BP) has a strong genetic component, few chromosomal regions have been consistently implicated by molecular genetic studies. To address this issue, we sought to determine if quantitative dimensions of bipolar disorder symptoms would be useful for detecting genes that underlie the susceptibility to bipolar disorder. Subjects were 520 individuals diagnosed with bipolar I, bipolar II or schizoaffective disorder, bipolar type who had participated in the NIMH genetics initiative for bipolar disorder. We constructed symptom scores from 29 psychiatric symptoms recorded in the Diagnostic Interview for Genetic Studies (DIGS). Principal components factor analysis followed by a varimax rotation was used to extract symptom dimensions. Factor scores were calculated for all genotyped individuals in the sample, regardless of affection status. Heritable factors were used in a variance-components linkage analysis, which utilized the exact likelihoods of allele-sharing identical-by-descent for each pair of relatives within each pedigree. The principal components factor analysis resulted in five independent dimensions: depressed state, psychosis, sleep disturbances, psychomotor acceleration, and irritability. Two factors were significantly heritable: depression (h2=0.53, p<0.001) and irritable vs. euphoric mania (h2=0.35, p=0.03). These were subsequently used in a linkage analysis that resulted in LOD scores of <2.0, which are not statistically significant. The five constructs developed through factor analysis appear to be consistent with previous factor analyses. Notably, only the dimensions associated with the type of mood disturbance showed high heritability, which suggests that careful measurements of depression, euphoria and irritability may be particularly useful in clarifying the genetic etiology of bipolar disorder in future studies.
  • Am J Med Genet. 2003 Aug 15;121B(1):35-8. : Genetic dissection of psychopathological symptoms: Insomnia in mood disorders and CLOCK gene polymorphism.
    Serretti A, Benedetti F, Mandelli L, Lorenzi C, Pirovano A, Colombo C, Smeraldi E.
    Department of Psychiatry, Vita-Salute University, Fondazione Centro San Raffaele del Monte Tabor, Milan, Italy.
    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.
  • BMC Psychiatry. 2003 Jun 9;3(1):6. Epub 2003 Jun 09.: Seasonal changes, sleep length and circadian preference among twins with bipolar disorder.
    Hakkarainen R, Johansson C, Kieseppa T, Partonen T, Koskenvuo M, Kaprio J, Lonnqvist J.
    Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland.
    reeta.hakkarainen@ktl.fi

    BACKGROUND: We aimed at studying the seasonal changes in mood and behaviour, the distribution of hospital admissions by season, and the persistence of the circadian type in twins with bipolar disorder and their healthy co-twins. METHODS: All Finnish like-sex twins born from 1940 to 1969 were screened for a diagnosis of bipolar type I disorder. The diagnosis was assessed with a structured research interview, and the study subjects (n = 67) filled in the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Morningness-Eveningness Questionnaire (MEQ). For studying the persistence of the habitual sleep length and circadian type, we used data derived from the Finnish Twin Cohort Questionnaire (FTCQ). Bipolar twins were compared with their healthy co-twins. RESULTS: Bipolar twins had greater seasonal changes in sleep length (p = 0.01) and mood (p = 0.01), and higher global seasonality scores (p = 0.03) as compared with their co-twins with no mental disorder. Sunny days (p = 0.03) had a greater positive effect on wellbeing in the bipolar than healthy co-twins. CONCLUSIONS: Our results support the view that bipolar disorder is sensitive to the environmental influence in general and to the seasonal effect in specific. Exposure to natural light appears to have a substantial effect on wellbeing in twins with bipolar disorder.

  • Int J Neuropsychopharmacol. 2003 Jun;6(2):191-7. : Neuroendocrine profiles in mood disorders.
    Linkowski P.
    Sleep Laboratory, Department of Psychiatry, Hpital Erasme, Universit Libre de Bruxelles, Belgium.

    The study of neuroendocrine abnormalities in major mental illness, such as the unipolar and bipolar affective syndromes, has been the focus of interest in the past few years. The neuroendocrine window into the brain has been considered as a fruitful and promising approach to the study of mental disorders, as suggested by studies of some neuroendocrine challenge tests in depression that demonstrated their potential use as biological markers. The modern approach to hormonal dynamics focuses on the circadian and pulsatile profiles that truly represent physiological modulation and tests the hypothesis that an abnormality in circadian rhythms is present in affective illness. From the fundamental point of view, such studies performed using a frequent sampling interval over the 24-h cycle aim to clarify the control and significance of the temporal sleep and wake fluctuations of neuroendocrine system activities. Twenty-four-hour hypersecretion of cortisol, diurnal hypersecretion of growth hormone, and normal 24-h levels of prolactin have been reported in careful chronobiological studies of depressed patients, along with sleep recordings. In addition, a nocturnal quiescent period, and a subsequent increase towards the morning maximum, have been consistently found in a subset of depressed patients suffering from endogenous depression. After successful treatment with antidepressants, most of these abnormalities (with the exception of those found in the prolactin study) tend to correct. The normalization of the timing of hormonal secretion was accompanied by a correction of sleep abnormalities and in particular, a lengthening of the REM latencies. Normalization of cortisol secretion was associated with a decrease in the magnitude of episodic cortisol pulses whereas normalization of growth hormone secretion was due to a diminished number of secretory pulses. In conclusion, a disorder of circadian time-keeping seems to characterize acute episodes of major endogenous depression in some patients. This abnormality as well as the associated increases in adrenocorticotropic and somatotropic activities seem to be a state-, rather than trait-dependent phenomenon.

  • J Affect Disord. 2003 May;74(3):209-17. : A systematic review of manic and depressive prodromes.
    Jackson A, Cavanagh J, Scott J.
    Department of Psychological Medicine, University of Glasgow, Gartnavel Royal Hospital, Glasgow, UK

    BACKGROUND: This paper explores whether individuals with a mood disorder can identify the nature and duration of depressive and manic prodromes. METHODS: Seventy-three publications of prodromal symptoms in bipolar and unipolar disorders were identified by computer searches of seven databases (including MEDLINE and PsycLIT) supplemented by hand searches of journals. Seventeen studies (total sample=1191 subjects) met criteria for inclusion in a systematic review. RESULTS: At least 80% of individuals with a mood disorder can identify one or more prodromal symptoms. There are limited data about unipolar disorders. In bipolar disorders, early symptoms of mania are identified more frequently than early symptoms of depression. The most robust early symptom of mania is sleep disturbance (median prevalence 77%). Early symptoms of depression are inconsistent. The mean length of manic prodromes (>20 days) was consistently reported to be longer than depressive prodromes (<19 days). However, depressive prodromes showed greater inter-individual variation (ranging from 2 to 365 days) in duration than manic prodromes (1-120 days). LIMITATIONS: Few prospective studies of bipolar, and particularly unipolar disorders have been reported. CONCLUSIONS: Early symptoms of relapse in affective disorders can be identified. Explanations of the apparent differences in the recognition and length of prodromes between mania and bipolar depression are explored. Further research on duration, sequence of symptom appearance and characteristics of prodromes is warranted to clarify the clinical usefulness of early symptom monitoring

  • CNS Spectr. 2003 Feb;8(2):120-6. : Narcolepsy: differential diagnosis or etiology in some cases of bipolar disorder and schizophrenia?
    Douglass AB.
    Department of Psychiatry, University of Ottawa, Ontario, Ontario, Canada.
    adouglas@rohcg.on.ca

    Does narcolepsy, a neurological disease, need to be considered when diagnosing major mental illness? Clinicians have reported cases of narcolepsy with prominent hypnagogic hallucinations that were mistakenly diagnosed as schizophrenia. In some bipolar disorder patients with narcolepsy, the HH resulted in their receiving a more severe diagnosis (ie, bipolar disorder with psychotic features or schizoaffective disorder). The role of narcolepsy in psychiatric patients has remained obscure and problematic, and it may be more prevalent than commonly believed. Classical narcolepsy patients display the clinical "tetrad"--cataplexy, hypnagogic hallucinations, daytime sleep attacks, and sleep paralysis. Over 85% also display the human leukocyte antigen marker DQB1*0602 (subset of DQ6). Since 1998, discoveries in neuroanatomy and neurophysiology have greatly advanced the understanding of narcolepsy, which involves a nearly total loss of the recently discovered orexin/hypocretin (hypocretin) neurons of the hypothalamus, likely by an autoimmune mechanism. Hypocretin neurons normally supply excitatory signals to brainstem nuclei producing norepinephrine, serotonin, histamine, and dopamine, with resultant suppression of sleep. They also project to basal forebrain areas and cortex. A literature review regarding the differential diagnosis of narcolepsy, affective disorder, and schizophrenia is presented. Furthermore, it is now possible to rule out classical narcolepsy in difficult psychiatric cases. Surprisingly, psychotic patients with narcolepsy will likely require stimulants to fully recover. Many conventional antipsychotic drugs would worsen their symptoms and make them appear to become a "chronic psychotic," while in fact they can now be properly diagnosed and treated.
  • J Clin Psychiatry. 2003;64 Suppl 6:18-22; discussion 28. : Response, remission, and recovery in bipolar disorders: what are the realistic treatment goals?
    Sachs GS, Rush AJ.
    Harvard Bipolar Research Program, Massachusetts General Hospital, Boston 02114, USA.
    sachsg@aol.com

    Bipolar disorder presents particular challenges with regard to assessing response to therapy. Criteria for determining remission and recovery have been suggested for mood disorders, but the clinical usefulness of these terms in bipolar disorder is elusive. Formal psychological rating scales may be impractical in a routine medical practice setting. As an alternative, clinicians might probe for information about particular "signal events," such as sleep disturbances, that may herald mood fluctuations. The ultimate goal of bipolar management should be complete and sustained remission, whenever possible, although most patients will not achieve this status for any significant length of time. Furthermore, overaggressive management might entail pushing medication doses to intolerable levels. Individual treatment goals should always take into account patient acceptance of side effect burden, allowing for trade-offs between treatment effect and quality of life. Noncompliance with therapy, notoriously common among patients suffering from bipolar disorder, can stem from drug side effects, treatment ineffectiveness, or even treatment success if the patient misses the manic symptoms. Despite effective treatment, relapse is common. Realistic treatment goals should strive for sustained symptom abatement while maximizing patient quality of life from visit to visit.

  • J Clin Psychiatry. 2003;64 Suppl 4:3-9. : Treatment of agitation in bipolar disorder across the life cycle.
    Alderfer BS, Allen MH.
    University of Colorado Hospital Department of Psychiatry, Denver, USA.

    Agitation is a common and difficult problem in psychiatric patients; patients with bipolar disorder constitute a substantial proportion of the agitated psychiatric population. Agitation is often seen in bipolar patients during acute manic states, when increased energy levels and reduced need for sleep lead patients to collide with the limits of others. Agitation also occurs during mixed and depressive states, which are characterized by fluctuating energy levels and periods of irritability. Although the prevalence of agitation is similar in men and women, its presentation often differs between the sexes. In addition, the presentations of bipolar disorder in children and in geriatric patients, and thus the manifestations of illness-related agitation, differ both from each other and from that of younger adults. Intensive treatment is required to manage agitated bipolar patients in a manner that rapidly decreases their suffering and maintains their safety and the safety of those around them. Considerations of speed and predictability tend to drive decisions in this setting more than concerns about tolerability. Oral or parenteral benzodiazepines, alone or in combination with an antipsychotic, are recommended as first-line treatment for the termination of behavioral emergencies in mania. Once behavioral control is restored, evidence suggests the combination of orally loaded divalproex sodium with an atypical antipsychotic is associated with more rapid improvement. Medication treatment of children and of geriatric patients must take into account developmental influences on the presentation of bipolar disorder in these different patient groups.

  • Eur Arch Psychiatry Clin Neurosci. 2002 Dec;252(6):288-93. : Can only reversed vegetative symptoms define atypical depression?
    Benazzi F.
    Outpatient Psychiatry Center, Ravenna and Forli, Italy.

    BACKGROUND: The definition of atypical depression (AD) has recently seen a rebirth of studies, as the evidence supporting the current DSM-IV atypical features criteria is weak. Study aim was to compare a definition of AD requiring only oversleeping and overeating (reversed vegetative symptoms) to the DSM-IV AD definition (always requiring mood reactivity, plus overeating/weight gain, oversleeping, leaden paralysis, and interpersonal sensitivity [at least 2]). METHODS: Consecutive 202 major depressive disorder (MDD) and 281 bipolar II outpatients were interviewed, during a major depressive episode (MDE), with the Structured Clinical Interview for DSM-IV. The DSM-IV criteria for AD were compared to a new AD definition based only on oversleeping and overeating, which was the one often used in community studies. Associations were tested by univariate logistic regression. RESULTS: The frequency of DSM-IV AD was 42.8 %, and that of the new AD definition was 38.7 %. DSM-IV AD, and the new AD definition, had almost all the same significant associations: bipolar II, female gender, lower age, lower age of onset, axis I comorbidity, depressive mixed state, MDE symptoms lasting more than 2 years, and bipolar family history. DSM-IV AD was present in 86 % of the new AD definition sample. The new definition of AD was significantly associated with all the other DSM-IV AD symptoms not included in it. The new AD definition was strongly associated with DSM-IV AD (odds ratio = 17.8), and had sensitivity = 77.7 %, specificity = 90.5 %, positive predictive value = 86.1 %, negative predictive value = 84.4 %, and ROC area curve = 0.85, for predicting DSM-IV AD. CONCLUSIONS: Results support a simpler definition of AD, requiring only oversleeping and overeating, and support the similar AD definition previously used in community studies. This definition is easier and quicker to assess by clinicians than the DSM-IV definition (mood reactivity and interpersonal sensitivity are more difficult to assess). Some pharmacological studies support this new AD definition (by showing better response to MAOI than to TCA, as shown in DSM-IV AD).

  • Prog Neuropsychopharmacol Biol Psychiatry. 2002 Oct;26(6):1041-5. : Co-occurrence of disturbed sleep and appetite loss differentiates between unipolar and bipolar depressive episodes.
    Papadimitriou GN, Dikeos DG, Daskalopoulou EG, Soldatos CR.
    Department of Psychiatry, Eginition Hospital, Athens University Medical School, 74 Vas. Sofias Avenue, 11528 Athens, Greece.
    egslelabath@hol.gr

    The aim of this study was to examine whether the co-occurrence of disturbed sleep and appetite loss, two commonly encountered somatic symptoms of depression, can differentiate the clinical expression of depressive episodes between bipolar (BP) and unipolar patients (UP). Forty BP and 40 UP outpatients were interviewed through the Schedules for the Clinical Assessment in Neuropsychiatry (SCAN) and the presence of sleep disturbance and appetite loss during their most severe depressive episode was determined. Other variables studied were patients' gender and age, clinical characteristics related to the course of the disease (age at onset, duration of illness, and number and frequency of depressive and manic episodes), severity of the worst major depressive episode, and presence or absence of certain associated symptoms during that episode (loss of energy, low interest, feelings of guilt and/or self-reproach, impaired concentration, suicidal ideation, and agitation or retardation). Appetite loss was found to be more frequently present in UP (78%) than BP patients (55%, P<.05). No significant difference in the occurrence of sleep disturbance was found between the two groups. Among BP patients, appetite loss was present in 73% of those with sleep disturbance vs. 33% of those without (P<.02), while no such difference in co-occurrence of sleep disturbance and appetite loss was noticed among UP patients (74% vs. 85%, respectively, n.s.); this finding did not seem to be related to differences in severity of depression among UP and BP patients. Furthermore, those BP patients with co-occurrence of the two somatic symptoms complained also of loss of energy and low interest more often than those without (P<.01 and P<.05, respectively). No similar differences were observed among UP patients. The results of the present study suggest that the pathophysiological mechanisms underlying depressive episodes may differ between BP and UP affective disorder, and that those BP patients with simultaneous occurrence of sleep disturbance and appetite loss can be considered to belong to a particular nosologic subgroup with potential therapeutic and prognostic implications.

  • J Child Adolesc Psychopharmacol. 2002 Spring;12(1):11-25. : DSM-IV mania symptoms in a prepubertal and early adolescent bipolar disorder phenotype compared to attention-deficit hyperactive and normal controls.
    Geller B, Zimerman B, Williams M, Delbello MP, Bolhofner K, Craney JL, Frazier J, Beringer L, Nickelsburg MJ.
    Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA.
    gellerb@medicine.wustl.edu

    OBJECTIVE: To compare the prevalence of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) mania symptoms in a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP) to those with attention deficit hyperactivity disorder (ADHD) and normal community controls (CC). METHODS: To optimize generalizeability, subjects with PEA-BP and ADHD were consecutively ascertained from outpatient pediatric and psychiatric sites, and CC subjects were obtained from a random survey. All 268 subjects (93 with PEA-BP, 81 with ADHD, and 94 CC) received comprehensive, blind, baseline research assessments of mothers about their children and of children about themselves. PEA-BP was defined by DSM-IV mania with elation and/or grandiosity as one criterion to ensure that subjects had one of the two cardinal symptoms of mania and to avoid diagnosing mania only by criteria that overlapped with those for ADHD. RESULTS: Five symptoms (i.e., elation, grandiosity, flight of ideas/racing thoughts, decreased need for sleep, and hypersexuality) provided the best discrimination of PEA-BP subjects from ADHD and CC controls. These five symptoms are also mania-specific in DSM-IV (i.e., they do not overlap with DSM-IV symptoms for ADHD). Irritability, hyperactivity, accelerated speech, and distractibility were very frequent in both PEA-BP and ADHD groups and therefore were not useful for differential diagnosis. Concurrent elation and irritability occurred in 87.1% of subjects with PEA-BP. Data on suicidality, psychosis, mixed mania, and continuous rapid cycling were also provided. CONCLUSION: Unlike late teenage/adult onset bipolar disorder, even subjects with PEA-BP selected for DSM-IV mania with cardinal symptoms have high rates of comorbid DSM-IV ADHD. High rates of concurrent elation and irritability were similar to those in adult mania.

  • Psychiatry Res. 2001 Nov 30;104(3):239-46. : Dopaminergic augmentation of sleep deprivation effects in bipolar depression.
    Benedetti F, Campori E, Barbini B, Fulgosi MC, Colombo C
    . Istituto Scientifico Ospedale San Raffaele, Department of Neuropsychiatric Sciences, Universita Vita-Salute San Raffaele, Via Stamira d'Ancona 20, 20127 Milan, Italy.
    benedetti.francesco@hsr.it

    Total sleep deprivation (TSD) has been used in association with lithium salts and with serotonergic and noradrenergic antidepressants, leading to sustained improvements in patients affected by major depression. Current theories on the neurobiological mechanism of action of TSD propose a major role for enhanced dopamine activity. To test the clinical relevance of dopaminergic enhancement in TSD, we treated a homogeneous sample of 28 bipolar depressed patients with three cycles of TSD combined with placebo or with the dopaminergic antidepressant amineptine. Changes in mood over time were rated with self-administered visual analogue scales and with the Montgomery-Asberg Depression Rating Scale. Patients showed improved mean daily-mood scores after TSD, an effect that was highest at the first cycle and decreased with treatment repetition. Amineptine enhanced the effects of TSD on perceived mood during the first two TSD cycles, but patients in the placebo and amineptine groups showed comparable results at the end of the treatment. Despite its theoretical importance, the clinical usefulness of combining TSD with a dopaminergic agent must be questioned.

  • J Sleep Res. 2001 Sep;10(3):173-9. : A sleep diary and questionnaire study of naturally short sleepers.
    Monk TH, Buysse DJ, Welsh DK, Kennedy KS, Rose LR.
    Clinical Neuroscience Research Center, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
    monkth@msx.upmc.edu

    Whereas most people require more than 6 h of sleep to feel well rested, there appears to be a group of people who can function well on between 3 and 6 h of sleep. The aims of the present study were to compare 12 naturally short (3-6 h) sleepers (9 males 3 females, mean age 39.6 years, SD age 10.1 years) recruited by a media publicity campaign with age, gender and chronotype matched medium length (7-8.5 h) sleepers on various measures. Measurement instruments included diaries and questionnaires to assess sleep duration and timing, as well as questionnaire assessments of sleep pathology, morningness-eveningness, extroversion, neuroticism, pathological daytime sleepiness, subclinical hypomania, optimism, depressive symptoms, exercise, and work habits. Few measures showed reliable differences between naturally short sleepers and controls except the obvious ones related to sleep duration. There was, however, some evidence for subclinical hypomanic symptoms in naturally short sleepers.
  • J Psychiatry Neurosci. 2000 Nov;25(5):446-58. : Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders
    Boivin DB.
    Department of Psychiatry, Douglas Hospital, McGill University, Montreal, Que.
    boidia@douglas.mcgill.ca

    Recent evidence shows that the temporal alignment between the sleep-wake cycle and the circadian pacemaker affects self-assessment of mood in healthy subjects. Despite the differences in affective state between healthy subjects and patients with psychiatric disorders, these results have implications for analyzing diurnal variation of mood in unipolar and bipolar affective disorders and sleep disturbances in other major psychiatric conditions such as chronic schizophrenia. In a good proportion of patients with depression, mood often improves over the course of the day; an extension of waking often has an antidepressant effect. Sleep deprivation has been described as a treatment for depression for more than 30 years, and approximately 50% to 60% of patients with depression respond to this approach, especially those patients who report that their mood improves over the course of the day. The mechanisms by which sleep deprivation exerts its antidepressant effects are still controversial, but a reduction in rapid eye movement sleep (REM sleep), sleep pressure and slow-wave sleep (SWS), or a circadian phase disturbance, have been proposed. Although several studies support each of these hypotheses, none is sufficient to explain all observations reported to date. Unfortunately, the disturbed sleep-wake cycle or behavioural activities of depressed patients often explain several of the abnormalities reported in the diurnal rhythms of these patients. Thus, protocols that specifically manipulate the sleep-wake cycle to unmask the expression of the endogenous circadian pacemaker are greatly needed. In chronic schizophrenia, significant disturbances in sleep continuity, REM sleep, and SWS have been consistently reported. These disturbances are different from those observed in depression, especially with regard to REM sleep. Circadian phase abnormalities in schizophrenic patients have also been reported. Future research is expected to clarify the nature of these abnormalities

  • Prog Neuropsychopharmacol Biol Psychiatry. 2000 Feb;24(2):185-91.: Melatonin add-on in manic patients with treatment resistant insomnia.
    Bersani G, Garavini A.
    Department of Psychiatric Science and Psychological Medicine, University of Rome La Sapienza, Italy.
    bersani@axrma.uniroma.it

    1. A profound alteration of circadian rhythm of sleep is often a central feature in manic syndrome. Melatonin (MLT) is a main synchronizer of the sleep/wake cycle, playing a role of transduction to brain functioning of informations about periodical environmental changes, i.e. the duration of daylength. 2. In several sleep phase disorders, MLT exerts a therapeutic effect, by normalizing the sleep/wake cycle. 3. Eleven patients, 8 males and 3 females, aged 22-43, meeting DSM IV diagnostic criteria for Bipolar Disorder, Manic Type, were selected for the presence of insomnia not responding to usual hypnotic therapies (benzodiazepine). 4. All the patients were on antimanic treatment. MLT 3 mg per os was administrated at 22.30 h for 1 month, without changing the previous antimanic and hypnotic treatments. All patients showed a significantly longer duration of sleep following MLT add-on. The severity of mania showed a parallel significant decrease. 5. The results of this pilot clinical study suggest that MLT add-on can be useful in antimanic therapy to treat resistant circadian sleep alterations as well as consequently exert a global therapeutic action on the manic state.