Mark A. Oldham

Bright light therapy for depression: A review of its effects on chronobiology and the autonomic nervous system

Bright light therapy (BLT) is considered among the first-line treatments for seasonal affective disorder (SAD), yet a growing body of literature supports its use in other neuropsychiatric conditions including non-seasonal depression. Despite evidence of its antidepressant efficacy, clinical use of BLT remains highly variable internationally. In this article, we explore the autonomic effects of BLT and suggest that such effects may play a role in its antidepressant and chronotherapeutic properties. After providing a brief introduction on the clinical application of BLT, we review the chronobiological effects of BLT on depression and on the autonomic nervous system in depressed and non-depressed individuals with an emphasis on non-seasonal depression. Such a theory of autonomic modulation via BLT could serve to integrate aspects of recent work centered on alleviating allostatic load, the polyvagal theory, the neurovisceral integration model and emerging evidence on the roles of glutamate and gamma-hydroxybutyric acid (GABA).

Circadian Rhythm Disruption in the Critically Ill: An Opportunity for Improving Outcomes.

Objectives:Circadian rhythms are severely disrupted among the critically ill. These circadian arrhythmias impair mentation, immunity, autonomic function, endocrine activity, hormonal signaling, and ultimately healing. In this review, we present a modern model of circadian disruption among the critically ill, discuss causes of these circadian arrhythmias, review observational and intervention studies of the effects of circadian-rhythm–restoring factors on medical outcomes, and identify needed key trials of circadian interventions in the critically ill. Data Sources:MEDLINE, EMBASE, PsychINFO, Google Scholar through December 2014. Study Selection:Articles relevant to circadian rhythms, melatonin, and light in the critically ill were selected. Data Extraction and Data Synthesis:Articles were synthesized for this review of circadian arrhythmia and the use of circadian-rhythm–restoring interventions among the critically ill. Conclusions:Circadian disruption often demonstrates serial degradation: initially, the amplitude attenuates along with delayed circadian phase. With increasing acuity of illness, circadian rhythmicity may be lost entirely. Causes of chronodisruption may be environmental or internal to the patient. In particular, inadequate daytime illumination and nocturnal light pollution disrupt healthy circadian periodicity. Internal causes of circadian arrhythmia include critical illness itself and subjective experience of distress and pain. Observational studies of windowed rooms and real-time ambient lighting have found that physiologic light-dark patterns may support recovery from critical illness. Studies of early morning bright light or evening melatonin agonists have found improved rates of delirium, enhanced sleep, and lower arrhythmia prevalence. The current evidence base emphasizes that lighting and melatoninergic interventions deserve to be tested in full-scale trials.

Pellagrous encephalopathy presenting as alcohol withdrawal delirium: a case series and literature review.

BackgroundAlcohol withdrawal delirium (AWD) is associated with significant morbidity and mortality. Pellagra (niacin deficiency) can be a cause of delirium during alcohol withdrawal that may often be overlooked.ObjectivesWe present a three-patient case series of pellagrous encephalopathy (delirium due to pellagra) presenting as AWD.MethodsWe provide a brief review of pellagra’s history, data on pellagra’s epidemiology, and discuss pellagra’s various manifestations, particularly as related to alcohol withdrawal. We conclude by providing a review of existing guidelines on the management of alcohol withdrawal, highlighting that they do not include pellagrous encephalopathy in the differential diagnosis for AWD.ResultsThough pellagra has been historically described as the triad of dementia, dermatitis, and diarrhea, it seldom presents with all three findings. The neurocognitive disturbance associated with pellagra is better characterized by delirium rather than dementia, and pellagra may present as an isolated delirium without any other aspects of the triad.DiscussionAlthough endemic pellagra is virtually eradicated in Western countries, it continues to present as pellagrous encephalopathy in patients with risk factors for malnutrition such as chronic alcohol intake, homelessness, or AIDS. It may often be mistaken for AWD. Whenever pellagra is suspected, treatment with oral nicotinamide (100 mg three times daily for 3–4 weeks) prior to laboratory confirmation is recommended as an inexpensive, safe, and potentially life-saving intervention.

Cognitive and functional status predictors of delirium and delirium severity after coronary artery bypass graft surgery: an interim analysis of the Neuropsychiatric Outcomes After Heart Surgery study.

BACKGROUND Cognitive and functional impairment increase risk for post-coronary artery bypass graft (CABG) surgery delirium (PCD), but how much impairment is necessary to increase PCD risk remains unclear. METHODS The Neuropsychiatric Outcomes After Heart Surgery (NOAHS) study is a prospective, observational cohort study of participants undergoing elective CABG surgery. Pre-operative cognitive and functional status based on Clinical Dementia Rating (CDR) scale and neuropsychological battery are assessed. We defined mild cognitive impairment (MCI) based on either (1) CDR global score 0.5 (CDR-MCI) or (2) performance 1.5 SD below population means on any cognitive domain on neurocognitive battery (MCI-NC). Delirium was assessed daily post-operative day 2 through discharge using the confusion assessment method (CAM) and delirium index (DI). We investigate whether MCI - either definition - predicts delirium or delirium severity. RESULTS So far we have assessed 102 participants (mean age 65.1 ± 9; male: 75%) for PCD. Twenty six participants (25%) have MCI-CDR; 38 (62% of those completing neurocognitive testing) met MCI-NC criteria. Fourteen participants (14%) developed PCD. After adjusting for age, sex, comorbidity, and education, MCI-CDR, MMSE, and Lawton IADL score predicted PCD on logistic regression (OR: 5.6, 0.6, and 1.5, respectively); MCI-NC did not (OR [95% CI]: 11.8 [0.9, 151.4]). Using similarly adjusted linear regression, MCI-CDR, MCI-NC, CDR sum of boxes, MMSE, and Lawton IADL score predicted delirium severity (adjusted R(2): 0.26, 0.13, 0.21, 0.18, and 0.32, respectively). CONCLUSIONS MCI predicts post-operative delirium and delirium severity, but MCI definition alters these relationships. Cognitive and functional impairment independently predict post-operative delirium and delirium severity.

Impact of Delirium After Hip Fracture Surgery on One-Year Mortality in Patients With or Without Dementia: A Case of Effect Modification

OBJECTIVES We evaluated whether delirium after hip fracture repair modifies the relationship between baseline dementia and one-year mortality after surgery. METHODS Patients age 65 years and older undergoing hip fracture repair surgery at John Hopkins Bayview Medical Center between 1999 and 2009 were eligible for this prospective cohort study. Baseline probable dementia was defined as either preoperatively diagnosed dementia per geriatrician or score less than 24 on the Mini-Mental State Examination. Delirium was assessed using the Confusion Assessment Method. Four cognitive groups were defined: 1) neither probable dementia nor delirium (NDD), 2) probable dementia only, 3) delirium only, or 4) delirium superimposed on dementia (DSD). Primary outcome of mortality was obtained through hospital records, obituaries, the National Death Index, and Social Security Death Index. RESULTS The current sample comprises 466 subjects (average age: 80.8 ± 7.0 years; 73.6% female). Of these, 77 (17%) were categorized as DSD, 68 (15%) probable dementia only, 73 (16%) delirium only, and 248 (53%) NDD. Cox regression revealed that DSD subjects had a significantly higher hazard of one-year mortality than NDD subjects (hazard ratio [HR]: 1.71, 95% CI: 1.06, 2.77) after adjusting for age, sex, medical comorbidity, and surgery duration. Trends toward greater mortality for probable-dementia and delirium only subjects were not significant (HR: 1.42 [95% CI: 0.80, 2.52] and 1.12 [95% CI: 0.64, 1.95], respectively). CONCLUSIONS Delirium after hip fracture repair surgery in patients with preoperative dementia modifies the risk of mortality over the first postoperative year. Patients with DSD have a nearly two-fold greater odds of one-year mortality than those without dementia or delirium.

The mind with a radio of its own: a case report and review of the literature on the treatment of musical hallucinations

Musical hallucinations (MH) have been labeled Oliver Sacks syndrome, and in the majority of cases, they occur in the context of a hearing loss. In these instances, they have been described as auditory Charles Bonnet syndrome because they are thought to represent a cortical release phenomenon. Patients with MH tend to have intact reality testing, and as such, the condition may also be described as musical hallucinosis. The temporal course of MH is variable, but given that they may improve or remit with time, education on their benign nature is often sufficient. MH also may improve when hearing loss is reversed. The use of ambient noise potentially ameliorates mild to moderate MH; however, where this is insufficient, somatic treatments may be considered. Case reports have documented successful use of low-dose antiepileptics, atypical antipsychotics and donepezil. We present a case of a 52-year-old man who received only partial relief from serial treatment with several psychotropic agents. He developed major depression with suicidal ideation in the context of persistent, intrusive MH that were refractory to several medication trials, and whereas a course of electroconvulsive therapy led to remission of depressive and suicidal symptoms, it provided only transient relief of his MH. In this article, we also provide a review of the literature on the neurobiology and treatment of MH.

Sedation in Critically Ill Patients

Sedation in the intensive care unit (ICU) is a topic that has been frequently researched, and debate still exists as to what are the best sedative agents for critically ill patients. There is increasing interest in sleep and circadian rhythm disturbances in the ICU and how they may impact on outcomes. In addition to patient-related and ICU environmental factors that likely impact sleep and circadian rhythm in the ICU, sedative and analgesic medications may also play a role.

Alcohol and Sedative-Hypnotic Withdrawal Catatonia: Two Case Reports, Systematic Literature Review, and Suggestion of a Potential Relationship With Alcohol Withdrawal Delirium

BACKGROUND Withdrawal from alcohol and sedative-hypnotics can be complicated by seizures, hallucinations, or delirium. Withdrawal catatonia is another, less commonly discussed complication that clinicians should appreciate. METHODS We present a case of alcohol withdrawal catatonia and a case of benzodiazepine withdrawal catatonia and offer a systematic review of previous cases of alcohol or sedative-hypnotic withdrawal catatonia. We outline clinical features that suggest a potential link between withdrawal catatonia and withdrawal delirium. RESULTS We identified 26 cases of withdrawal catatonia in the literature-all principally with catatonic stupor-with an average age of 56 years (range: 27-92) and balanced prevalence between sexes. Withdrawal catatonia tends to occur only after chronic use of alcohol or sedative-hypnotic agents with a typical onset of 3-7 days after discontinuation and duration of 3-10 days. Withdrawal catatonia is responsive to benzodiazepines or electroconvulsive therapy. Features that suggest a parallel between withdrawal catatonia and withdrawal delirium include time course, neurobiologic convergence, efficacy of benzodiazepines and electroconvulsive therapy, typical absence of abnormal electroencephalographic findings, and phenotypic classification suggested by a recent literature in sleep medicine. CONCLUSION Alcohol and sedative-hypnotic withdrawal may present with catatonia or catatonic features. The clinical and neurobiologic convergence between withdrawal catatonia and withdrawal delirium deserves further attention. In view of these similarities, we propose that withdrawal delirium may represent excited catatonia: these new viewpoints may serve as a substrate for a better understanding of the delirium-catatonia spectrum.

Comparison of impact of insomnia on depression and quality of life in restless legs syndrome/Willis-Ekbom disease and primary insomnia patients.

BACKGROUND Although insomnia is common among people with restless legs syndrome (RLS), its impact on the daily suffering of those with RLS remains unclear. This study aimed to compare the differential impact of clinical insomnia on depression and quality of life (QoL) among people with RLS, primary insomnia, and healthy controls. METHODS A total of 148 people with RLS, 115 with primary insomnia, and 117 healthy controls were enrolled into this cross-sectional study. Participants completed sleep, depression, and QoL questionnaires. Clinical insomnia was defined as Korean version of the Insomnia Severity Index (K-ISI) ≥ 15. Correlation coefficients between sleep measures and both depression and QoL were calculated. Multivariate regression was used to identify the clinical factors that were most closely associated with depression and QoL among people with RLS and primary insomnia. RESULTS Participants with RLS had insomnia and sleep quality at intermediate levels between the healthy controls and primary insomnia subjects, but those with clinical insomnia had equivalent depression and QoL scores regardless of RLS diagnosis. Insomnia severity correlated with depression and QoL in RLS and primary insomnia. Multivariate regression, however, revealed that RLS severity was the most overall predictive factor for depression and QoL among those with RLS. Insomnia severity was the strongest predictor in primary insomnia. CONCLUSION Insomnia was more closely associated with depression and QoL among people with primary insomnia than those with RLS, but clinical insomnia may have a significant impact in RLS as well. Future RLS studies should account for sleep quality in addition to RLS symptom severity when investigating mood and QoL.

Autoimmune Encephalopathy for Psychiatrists: When to Suspect Autoimmunity and What to Do Next

OBJECTIVE To provide a critical review of autoimmune encephalopathy-broadly defined as neuropsychiatric features directly related to an autoimmune process-relevant for psychiatric practice. METHODS We consulted rheumatology textbooks to define the scope of autoimmune conditions and identified recent reviews of rheumatic conditions, autoimmune vasculitis, and autoimmune encephalitis. We integrated these with primary reports to provide a clinically relevant overview of autoimmune encephalopathy. We focus on clinical features that should raise suspicion for autoimmunity. RESULTS Despite outlying conditions, 2 categories of autoimmune encephalopathy are described: (1) neuropsychiatric symptoms associated with rheumatic conditions and (2) antibody-associated autoimmune encephalitis. Rheumatic conditions principally include connective tissue disease and other vasculitides. These may present variously such as with unexplained delirium, cognitive decline, or depression. Autoimmune encephalitis may be diffuse or localized as in limbic, brainstem, or basal ganglia encephalitis. Unexplained delirium, psychosis, catatonia, strokes, and seizures are among common presenting symptoms. CONCLUSIONS Prompt identification and management of autoimmunity are critical for optimal outcomes. The fact that undiagnosed and, therefore, untreated autoimmunity leads to debilitation demands vigilance for these conditions. Close attention to the unusual nature and course of neuropsychiatric symptoms, associated neurological features, and review of systems as reviewed here should guide the skillful clinician.