Narcolepsy: differential diagnosis or etiology in some cases of bipolar disorder and schizophrenia?

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.     

Narcolepsy: pathophysiology and neuropsychological changes

Narcolepsy is now recognized as a distinctive disorder with specific pathophysiology and neurochemical abnormalities. Findings on the role of the neuropeptide hypocretin are opening new avenues of research and new strategies for therapy. Recently, neuropsychological and electrophysiological studies have provided evidence for reduced memory performance on standard memory tests in addition to subjective complaints of forgetfulness which may be related to changes in attentional processing. Further studies are, however, necessary to clarify the neuropsychological profile in narcolepsy. This review focuses on the recent advances in understanding narcolepsy.     

A model for narcolepsy.

A model for narcolepsy is developed on the basis of data obtained from brains collected at post mortem from three patients with narcolepsy. The concentration of dopamine, noradrenaline, and serotonin and their metabolites was measured in many brain regions. The number and affinity of the 3-H-spiperone and 3-H-prazocin binding sites was also measured in many of these regions to characterize the D-2 dopamine and alpha-1-noradrenergic receptors, respectively. Evidence for significantly increased serotonin levels and serotonin turnover was found in many brain regions. Noradrenaline turnover was increased in the frontal cortex. DOPAC/DA was significantly reduced in the striatum. The number of D-2 dopamine receptors, however, was markedly increased in this region. The number of alpha-1-noradrenergic receptors was significantly decreased in the frontal cortex and amygdala. Our neurochemical data demonstrating increased NA and 5-HT turnover suggest that locus coeruleus noradrenergic neurones and raphe serotonergic neurones are overactive in narcolepsy. Current evidence posits that increased activity in these neurones depresses the activity of cholinergic pedunculopontine (PP) REM sleep effector neurones. PP neurones project to and stimulate the dopaminergic substantia nigra compacta neurones. Decreased PP activity in narcolepsy, thus, could lead to pontine cholinergic supersensitivity and could also reduce the firing rates of dopaminergic neurones, as the low striatal ratio of DOPAC/DA suggests. An increase in the number of D-2 dopamine receptors in the striatum may result. The reason for the increased activity of the noradrenergic and serotonergic neurones remains to be determined, but immune inactivation of alpha-1-noradrenergic receptors may be the initiating event. Low alpha-1-noradrenergic receptor numbers may account for the chronic drowsiness of narcolepsy. The repeated entry into sleep, and into REM sleep in particular, may represent a homeostatic response to increase these receptor numbers and, thus, to increase alertness. Some therapeutic implications of this model are presented in the discussion.     

Blackout of my nights: Contentless,timeless and selfless report from the night in patients with central hypersomnias

At the extreme spectrum of consciousness during sleep, some patients with rare hypersomnias reported experiencing a specific night ‘blackout’ when sleeping, i.e., an absence of experiences or recall of them from sleep onset to offset. Thus, we explored through questionnaires the conscious experiences (dreaming experience, mind, self) during the night in 133 patients with idiopathic hypersomnia, 108 patients with narcolepsy, and 128 healthy controls. The night blackout was more frequent in idiopathic hypersomnia than in narcolepsy and control groups. Patients with idiopathic hypersomnia and frequent night amnesia had lower dream recall frequencies, and felt more often sleep as deep and mind as blank during the night. They had a higher proportion of slow wave sleep on their (retrospectively collected) sleep recordings than those without night blackout. This night blackout provides a new model for studying loss of consciousness during sleep, here as a contentless, selfless and timeless feeling upon awakening.     

Hypersomnia and the perception of sleep-wake states: some preliminary findings

35 hypersomniacs (20 with obstructive sleep apnea and 15 with narcolepsy) and 15 controls estimated sleep latency during systematic trials of attempting to remain awake during the day. The error in subjective assessment of sleep latency was more variable for both patient groups than for controls. In addition, narcoleptics could not provide a determination of sleep latency or differentiate sleep-wake states on nearly 23% of all trials. Ratings on a subjective sleepiness scale did not covary with objective sleep latency for any hypersomniac. The findings suggested that patients with either sleep apnea or narcolepsy had difficulty differentiating sleep and quiet wakefulness during the day.     

The classical conditioning of sleep and wakefulness

Using a metronome beat as conditioned stimulus three cases are described in which this stimulus was presented in close temporal contiguity with experimentally-induced sleep or waking. Drugs or fatigue consequent upon sleep deprivation were used as unconditioned stimuli for sleep. One of the subjects was an anxiety neurotic, one had narcolepsy and the third was a student volunteer. No EEG indication of conditioned sleep was obtained but there was evidence of conditioned relaxation in the anxiety neurotic and conditioned arousal in the other two cases.     

What is the motor vehicle crash risk for drivers with a sleep disorder?

In many parts of the world, drivers with serious sleep disorders have restrictions on their licence – with the fitness-to-drive criteria varying across licensing jurisdictions. This study aimed to systematically review the literature that evaluated the available scientific evidence for the relationship between sleep disorders and two driving safety outcome measures: (i) motor vehicle crashes (MVC) and (ii) on-road driving test outcome. This review was registered with PROSPERO in July 2019 (see CRD42019144643). A systematic search of public health, psychology and transport databases was conducted on November 8th, 2019. The quality of evidence for each study was rated using the National Heart, Lung and Blood Institute Quality Assessment tools. Thirty-nine studies published between 1976 and 2015 met the inclusion criteria (n = 9 case-control; n = 24 cohort/cross-sectional; n = 6 before-after). Overall, the quality of evidence for 22 studies was rated as ‘good’, nine as ‘fair’ and eight as ‘poor’. Included studies addressed: sleep apnoea and sleep-related breathing disorders (n = 35); central disorders of hypersomnolence and narcolepsy (n = 5), and insomnia (n = 2), with some studies covering multiple sleep disorders. Of the thirty-five studies specifically investigating MVC risk associated with sleep apnoea, eighteen studies reported an increased risk (n = 11 ‘good’, n = 4 ‘fair’, n = 3 ‘poor’ quality), seven reported no difference in risk (n = 3 ‘good’, n = 4 ‘fair’ quality), and two provided inconclusive findings (n = 1 ‘good’, n = 1 ‘fair’ quality). Most studies suggested that increased sleep apnoea severity was associated with an increased MVC risk. Furthermore, untreated sleep apnoea was predominantly associated with increased risk, whilst decreased risk was associated with Continuous Positive Airway Pressure (CPAP) and uvulopalatopharyngoplasty (UPPP) treatments. Five studies (n = 3 ‘good’, n = 2 ‘fair’ quality) investigated MVC risk associated with disorders of hypersomnolence and narcolepsy, and all reported increased risk. Only two studies investigated MVC risk associated with insomnia, with inconsistent findings: one reporting increased MVC risk (‘good’) and one reporting no difference (‘fair’). Regarding impacts on on-road driving test outcome, our comprehensive search found no studies investigating the association between sleep disorders and this driving safety outcome measure. Notwithstanding the limitations of the included studies, the weight of evidence suggests a moderately elevated MVC risk for drivers with sleep disorders (sleep apnoea; hypersomnia and narcolepsy), with the majority reporting around two and a half times higher risk, and lower risk with treatment. This evidence is consistent with current fitness-to-drive guidelines, most of which specify licence restrictions conditional upon severity, treatment compliance and effective response to treatment. The generalisability of the findings is limited as many identified studies had methodological limitations, were conducted across a wide time period, in numerous licensing jurisdictions with different requirements, and across a diverse range of participant populations. A large-scale, population-based controlled study, in multiple licensing jurisdictions with equivalent licensing and fitness-to-drive requirements, is warranted to rigorously investigate MVC risk and sleep disorders, including evaluating the possible benefit of therapies.     

Epidemiologic study of sleep disorders in Kuwaiti adolescents.

A sample of 2,574 volunteer Kuwaiti boys (n = 1,309) and girls (n = 1,265) in secondary schools were recruited. Their ages ranged from 14 to 18 years. 13 items were used to assess prevalence of insomnia, hypersomnia, nightmares, sleepwalking, sleep terror, and narcolepsy. Participants were requested to respond according to the past month on a 5-point scale. The summation of responses in the last two options, i.e., "Much" and "Very much" was considered as the point prevalence rates. Girls had significantly higher mean ratings than boys on the following items: difficulty initiating sleep, fitful and disturbed sleep, waking up several times, nightmares, and sleep terror, while boys had significantly higher mean ratings on sleepwalking and "watching TV causes naps or sleep." The point prevalence on all the items for boys ranged from 4.6% to 35.2%, and that for girls ranged between 1.0% and 37.5%. One should keep in mind that the present sample was not a clinical one.     

Sleep paralysis and hallucinosis

Background: Sleep paralysis is one of the many conditions of which visual hallucinations can be a part but has received relatively little attention. It can be associated with other dramatic symptoms of a psychotic nature likely to cause diagnostic uncertainty. Methods and results: These points are illustrated by the case of a young man with a severe bipolar affective disorder who independently developed terrifying visual, auditory and somatic hallucinatory episodes at sleep onset, associated with a sense of evil influence and presence. The episodes were not obviously related to his psychiatric disorder. Past diagnoses included nightmares and night terrors. Review provided no convincing evidence of various other sleep disorders nor physical conditions in which hallucinatory experiences can occur. A diagnosis of predormital isolated sleep paralysis was made and appropriate treatment recommended. Conclusions: Sleep paralysis, common in the general population, can be associated with dramatic auxiliary symptoms suggestive of a psychotic state. Less common forms are either part of the narcolepsy syndrome or (rarely) they are familial in type. Interestingly, sleep paralysis (especially breathing difficulty) features prominently in the folklore of various countries.     

Personality traits in patients with narcolepsy

Narcolepsy is a lifelong disorder with the main symptoms of sleep attacks and cataplexy. In this study 49 narcoleptic patients were investigated with a battery of personality inventories, covering the following personality dimensions: anxiety-neuroticism, extraversion and socialization. The results were compared with three groups: normal subject, psychiatric inpatients with anxiety and outpatients with psychosomatic complaints. The main aim was to evaluate a clinical impression of a high degree of extraversion in narcoleptic patients, which according to Eysenck's model could be related to a disturbance in the arousal regulation. Narcoleptic patients had higher anxiety-neuroticism scores than normal individuals, particularly in terms of Somatic Anxiety. They had unexpectedly low scores in some socialization scales, and were contrary to our hypothesis slightly lower in the extraversion variables, than the comparison groups. The high scores in anxiety-neuroticism personality scales may depend on an anxiety-provoking effect of central stimulant drugs and/or a lability of the autonomic regulation associated with the disorder. Further, the strain caused by the narcoleptic symptoms may result in high scores in anxiety-neuroticism scales and low scores in socialization scales, via social-learning mechanisms. However, there may also be a coupling between the genetics of narcolepsy and biologically based personality traits.     

Methylphenidate enhances extinction of contextual fear

Methylphenidate (MPH, Ritalin) is a norepinephrine and dopamine transporter blocker that is widely used in humans for treatment of attention deficit disorder and narcolepsy. Although there is some evidence that targeted microinjections of MPH may enhance fear acquisition, little is known about the effect of MPH on fear extinction. Here, we show that MPH, administered before or immediately following extinction of contextual fear, will enhance extinction retention in C57BL/6 mice. Animals that received MPH (2.5-10 mg/kg) before an extinction session showed decreased freezing response during extinction, and the effect of the 10 mg/kg dose on freezing persisted to the next day. When MPH (2.5-40 mg/kg) was administered immediately following an extinction session, mice that received MPH showed dose-dependent decreases in freezing during subsequent tests. MPH administered immediately after a 3-min extinction session or 4 h following the first extinction session did not cause significant differences in freezing. Together, these findings demonstrate that MPH can enhance extinction of fear and that this effect is sensitive to dose, time of injection, and duration of the extinction session. Because MPH is widely used in clinical treatments, these experiments suggest that the drug could be used in combination with behavioral therapies for patients with fear disorders.     

The Effects of Modafinil on Convergent and Divergent Thinking of Creativity: A Randomized Controlled Trial

Modafinil is a drug licensed for the treatment of narcolepsy and sleep apnea. Recently, modafinil has been reported to be used as a pharmacological cognitive enhancer by healthy individuals with no psychiatric disorders. This paper reports on a study that investigated the effects of modafinil on divergent and convergent thinking tasks of creativity. Sixty‐four healthy male (n = 31) and female (n = 33) volunteers participated in a randomized double‐blind placebo‐controlled parallel group design study. For the convergent thinking tasks, modafinil had no significant main effect on the Group Embedded Figures Task and the Remote Associates Task (RAT). However, a median split analysis showed that modafinil participants low in creativity personality trait had significantly higher RAT scores (Mean [M] = 6.85, SD = 3.39; 95% confidence interval [95% CI]: 5.53–8.2) than those high in creativity personality trait (M = 4.27, SD = 3.0; 95% CI: 2.4–6.0). For the divergent thinking tasks, relative to placebo (M = 1.195, SD = 0.28; 95% CI: 1.0–1.3), modafinil (M = 0.77, SD = 0.37; 95% CI: 0.63–0.92) significantly reduced the performance of flexibility scores and marginally reduced the elaboration scores as measured by the Abbreviated Torrance Test for Adults (ATTA). Overall, participants on modafinil (M = 6.3, SD = 2.6; 95% CI: 5.3–7.4) had significantly lower ATTA scores relative to participants on placebo (M = 9.5, SD = 2.3; 95% CI: 8.6–10.4). These results indicate that modafinil might reduce divergent thinking of creativity in healthy individuals. They suggest that, rather than being a more general cognitive enhancer, modafinil might have negative and subtle effects on creativity. However, the results are from a small‐scale trial, which tested a small number of participants. Therefore, the results need to be interpreted with caution. A replication with a large sample of participants is recommended.     

Using a self-evaluation system as a group contingency

The efficacy of a group-evaluation system was examined, with a reversal design, in two classes of students with disabilities. The results suggested that a group-evaluation system was effective in decreasing the inappropriate verbalizations of both groups. Student satisfaction data revealed that the students in both groups had positive reactions to the system. Factors contributing to the success of the intervention as well as suggestions for its implementation are discussed.     

Psychoanalysis of a patient who received a kidney transplant

A young man who had glomorulonephritis at age five was treated psychotherapeutically for an anxiety neurosis with phobic and obsessional features. He was referred for psychoanalysis at a time when he was approaching kidney failure, but was referred back for more psychotherapy with the possibility of future psychoanalysis. He underwent renal dialysis and then received a kidney transplant from a brother. The psychoneurosis became worse, and a psychoanalysis was begun about one year after the transplant operation. The clinical report illustrates the developmental effects of the childhood illness, as well as the patient's response to the adult treatment and the renal transplant. Nonanalytic observations by others on renal dialysis and transplant patients are reviewed and compared with the findings in this analysis. The psychoanalysis of a renal transplant patient is feasible if other indications for analysis are present. A previously unreported finding is the problem of changing a lifetime adaptation from illness to relative health. This involved the analysis of the narcissistic conflicts of the oedipal stage of development as well as the preoedipal maternal transference.     

The role of a parent's illness in the emotional experience of a child evidence from Klein's Narrative of a child analysis

Abstract

The analysis of Richard, described by Melanie Klein in Narrative of a Child Analysis, gives us some insight into the effect on a child of threats to the health of his parents. His mother was involved in a road accident when Richard was 2; his father collapsed during the time of the analysis when he was 10. This paper links these events with disturbances in Richard's relation to his father and to his mother, as well as with threats to his own integrity, as demonstrated in the analysis. Richard's reversal of roles with his father and mother is discussed, as are Klein's reaction to Richard's report of finding his father ‘ill and nearly fainting’ and Richard's response to her behaviour. The paper draws attention to the way in which a child's reaction to the ill health of one parent can affect relations with both parents, as well as disturbing his sense of himself.     

Implementation of a Culture-Specific Intervention for a Native American Community

Psychiatric services provided to Native Americans should be culturally relevant and integrated with the values and beliefs of the culture since Native Americans use Western health care as a last resort. Reduced utilization of services may be the result of cultural beliefs that sickness or illness comes from disharmony with oneself, one's community, and nature. Treatment entails resolving the disharmony and restoring a state of balance and integration. Western psychiatric services have not usually provided active psychiatric treatment, while simultaneously encouraging participation in native ceremonies and traditions of healing. For 3 years, the Wyoming State Hospital has offered Sweat Lodge ceremonies administered by the Wind River Reservation as part of a pattern of working together to improve the care of Native Americans admitted to the facility. Results indicate increased utilization of hospital services as well as increased patient and tribal satisfaction, improved health care outcomes, and reduced length of stay. This report argues that culturally specific and sensitive treatment interventions provide a concrete and specific benefit to the population which is targeted.     

Appraised changeability of a stressor as a modifier of the relationship between coping and depression: a test of the hypothesis of fit

The goodness of fit among the appraised changeability of a stressor, coping, and depression in people with psychiatric, physical health, work, and family problems was examined (N = 746). It was expected that problem-focused coping (as opposed to emotion-focused coping) would be used more and be more adaptive in situations appraised as changeable as compared with situations appraised as not changeable. Although few relationships existed between appraisal and coping, tests of fit between coping and depressed mood (maladaption) were much stronger. In people with nonpsychiatric conditions, problem-focused coping and depressed mood were negatively related when a stressor was appraised as changeable but were unrelated when a stressor was appraised as not changeable. Emotion-focused coping was positively related to depression when a stressor was appraised as changeable. No general relations were observed in the people with psychiatric conditions.     

Aphasia in a polyglot

A Greek-born aphasic who had been able to speak four languages (Romanian, Russian, Greek, German) was tested quantitatively for verbal expression (standard interview indexes) and verbal reception (fifth part of the Token Test). The form of aphasia (qualitative aspect) was found to be identical for all four languages. Quantitatively, his performance in the four languages was different, with the languages used most during the past 20 years (Romanian and Russian) being less impaired. Nevertheless, verbal reception was equally impaired quantitatively in all four languages. Treatment with semantic-syntagmatic methods performed in Romanian had a beneficial effect on speech in the other languages as well. The authors feel that the expressive disturbance noted in aphasia reflects involvement of deep as well as of surface structures of language, but the receptive disturbance reflects involvement of the deep structures only. This may account for quantitative discrepancies in expression without discrepancy in reception among the four languages, as well as the qualitatively identical features of the disturbance in verbal expression and reception.     

On becoming a psychoanalyst

One has the opportunity and responsibility to become an analyst in one's own terms in the course of the years of practice that follow the completion of formal analytic training. The authors discuss their understanding of some of the maturational experiences that have contributed to their becoming analysts in their own terms. They believe that the most important element in the process of their maturation as analysts has been the development of the capacity to make use of what is unique and idiosyncratic to each of them; each, when at his best, conducts himself as an analyst in a way that reflects his own analytic style; his own way of being with, and talking with, his patients; his own form of the practice of psychoanalysis. The types of maturational experiences that the authors examine include situations in which they have learned to listen to themselves speak with their patients and, in so doing, begin to develop a voice of their own; experiences of growth that have occurred in the context of presenting clinical material to a consultant; making self-analytic use of their experience with their patients; creating/discovering themselves as analysts in the experience of analytic writing (with particular attention paid to the maturational experience involved in writing the current paper); and responding to a need to keep changing, to be original in their thinking and behavior as analysts.     

The psychological implications of concealing a stigma: a cognitive-affective-behavioral model

Many assume that individuals with a hidden stigma escape the difficulties faced by individuals with a visible stigma. However, recent research has shown that individuals with a concealable stigma also face considerable stressors and psychological challenges. The ambiguity of social situations combined with the threat of potential discovery makes possessing a concealable stigma a difficult predicament for many individuals. The increasing amount of research on concealable stigmas necessitates a cohesive model for integrating relevant findings. This article offers a cognitive-affective-behavioral process model for understanding the psychological implications of concealing a stigma. It ends with discussion of potential points of intervention in the model as well as potential future routes for investigation of the model.