PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders

OBJECTIVE: To determine whether there are abnormalities in the in vivo status of the serotonin type 2A (5-HT2A) receptor in late-life depression and Alzheimer's disease, the authors used positron emission tomography (PET) to assess patients with these two conditions and healthy subjects. METHOD: PET was performed by using [18F]altanserin to evaluate 5-HT2A receptor binding in 11 elderly patients with depression (four men, seven women; mean age = 65.0 years, SD = 5.5); nine Alzheimer's disease patients, including three with concurrent depression (two men, seven women; mean age = 69.7 years, SD = 5.0); and 10 age-matched healthy subjects (four men, six women; mean age = 69.8 years, SD = 5.0). Partial-volume correction of regional specific binding estimates was performed by using a method based on magnetic resonance imaging. RESULTS: No significant abnormalities in [18F]altanserin binding (binding potential) were observed in the patients with late-life depression, and no effect of depression on binding potential was present within the Alzheimer's disease group. However, the patients with Alzheimer's disease had significantly lower binding than the normal subjects in several brain regions, including the anterior cingulate, prefrontal cortex, and sensorimotor cortex. CONCLUSIONS: These results suggest that the 5-HT2A receptor is differentially affected in late-life depression and Alzheimer's disease, a finding that has implications for the etiological basis of mood and cognitive features of neuropsychiatric disorders of late life.     

Cardiac autonomic function during sleep in several neuropsychiatric disorders

Cardiac autonomic activity during sleep is only very slightly influenced by the emotional state of the patient and, unlike some of the traditional tests of autonomic function, may be studied in all patients. In an attempt to evaluate autonomic function in patients with different neuropsychiatric disorders, two different methods of quantifying the changes in sympathetic and parasympathetic cardiac control during sleep were used: (1) the ratios of consecutive R-wave (R-R) intervals before and after spontaneous body movements; (2) spectral analysis of R-R intervals. It was found that more than one third of patients with presenile Alzheimer’s disease had defective cardiac sympathetic control. Untreated parkinsonian patients showed predominantly defective parasympathetic, and to a lesser extent sympathetic, function during sleep. In these patients, as well as in patients with multiple sclerosis, autonomic evaluation during sleep led to earlier detection of impairment than the traditional tests during wakefulness. Narcoleptic patients and patients with panic disorder showed normal autonomic function during sleep, but had altered control levels during the wakeful period before sleep. The findings in these narcoleptic patients were probably related to the impairment of their sleep-wake cycle. The sympathetic overactivity found in patients with panic disorder was probably a result of cognitive activity, as the nocturnal data excluded an intrinsic defect in autonomic regulation.

     

Electroencephalographic sleep in mania

Electroencephalographic (EEG) sleep patterns were examined in nine unmedicated patients meeting DSM-III-R criteria for a current manic episode (four men and five women) for two to four consecutive nights. Compared with age- and sex-matched normal control subjects, manic patients exhibited significantly decreased total recording period, decreased time spent asleep, increased time awake in the last two hours of recording, shortened rapid eye movement (REM) latency, increased REM activity, and increased REM density. These results suggest that mania is associated with marked disturbances of sleep continuity and REM measures. Sleep continuity and REM sleep abnormalities of a similar nature and degree have been reported in major depression and psychotic depression. Thus, it is possible that various forms of affective disorders and psychotic disorders have pathophysiologic mechanisms in common.     

Periodic limb movements and other movement disorders in sleep: neuropsychiatric dimensions

Movement disorders such as Parkinson's disease and Tourette's syndrome, primarily manifest during wakefulness, intrude into sleep. There are some disorders, however, such as periodic limb movements in sleep, restless legs syndrome, paroxysmal nocturnal dystonia, bruxism, and somnambulism, which occur primarily during sleep. The diagnosis and management of these disorders pose a challenge to neuropsychiatric practice, not only because they may be difficult to distinguish from other neuropsychiatric disorders, but also because psychiatric disorders are often co-morbid with them. Study of these disorders is necessary for an understanding of the interaction of sleep and movement, and how disturbance in one may affect the other.     

Electroencephalographic sleep in depressive pseudodementia

Twenty-six patients with mixed symptoms of depression and cognitive impairment were studied with serial clinical ratings and sleep electroencephalograms during a one-night sleep-deprivation procedure. A subgroup of these patients with depressive pseudodementia (n = 8) had less severe symptoms of dementia at baseline and showed significant improvements in both Hamilton Depression Rating Scale scores and Profile of Mood States tension scores following sleep deprivation, while another subgroup of patients having primary degenerative dementia with depression (n = 18) showed no change or worsening in Hamilton depression and Profile of Mood States tension ratings. Baseline sleep measures demonstrated significantly higher rapid eye movement (REM) percent and phasic REM activity/intensity in pseudodemented compared with demented patients. While both groups had increases in sleep efficiency, sleep maintenance, and slow-wave sleep following sleep deprivation, recovery night 2 was characterized by greater first REM period duration in depressive pseudodementia than in dementia. These differences in REM sleep rebound (using an REM period 1 cutoff of greater than or equal to 25 minutes) permitted correct identification of 88.5% of patients. Implications of these data for current theories regarding sleep, aging, and psychopathology are discussed.     

Electroencephalographic cerebral dysrhythmic abnormalities in the trinity of nonepileptic general population, neuropsychiatric, and neurobehavioral disorders

Subclinical electroencephalographic epileptiform discharges in neurobehavioral disorders are not uncommon. The clinical significance and behavioral, diagnostic, and therapeutic implications of this EEG cerebral dysrhythmia have not been fully examined. Currently the only connotation for distinctive epileptiform electroencephalographic patterns is epileptic seizures. Given the prevailing dogma of not treating EEGs, these potential aberrations are either disregarded as irrelevant or are misattributed to indicate epilepsy. This article reappraises the literature on paroxysmal EEG dysrhythmia in normative studies of the "healthy" nonepileptic general populations, neuropsychiatry, and in neurobehavioral disorders. These EEG aberrations may be reflective of underlying morpho-functional brain abnormalities that underpin various neurobehavioral disturbances.     

Sleep in neuropsychiatric disorders

Sleep disorders have been recognized for millennia as a common complication of medical and neurologic disease. Virtually all neuropsychiatric disorders carry with them the potential for disturbances of sleep. When such complications do exist, they are typically associated with decreased quality of life, increased morbidity, and, in some cases, increased mortality rates. The prevalence of major sleep disorders among neurologic patients is high, but the rate of detection and treatment is quite low. The major sleep-related problems in this population can be divided into six areas: insomnia, circadian rhythm (sleep-wake schedule) disorders, hypersomnia, sleep-related breathing disorders, motor disturbances in sleep, and parasomnias. In this brief review, general clinical principles, diagnostic assessment and management guidelines for each of these areas are considered and their specific manifestations in neuropsychiatric disorders identified.     

Electroencephalographic findings in urea-cycle disorders

Eleven electroencephalograms in 4 infants with urea-cycle disorders were reviewed. All infants had one or more abnormal EEGs. The abnormalities consisted mainly of multiareal spikes, spike-waves, or sharp-and-slow-wave activity. In addition, one patient, a term infant, exhibited exaggerated spindle-delta bursts. This infant, and also one other at a similar age, had monorhythmic paroxysmal theta activity. Clinically, all patients had seizures shortly preceding abnormal EEGs. EEG alterations were encountered over a wide range of elevated serum ammonia levels. Normal EEGs occurred in the face of slightly elevated levels. It is concluded that epileptiform EEG alterations may be a characteristic manifestation of urea-cycle disorders.     

Electroencephalographic sleep findings in depressed outpatients

We compared the electroencephalographic (EEG) sleep characteristics of 20 outpatients with those of 20 age-matched inpatients with major primary depressive disorders. Both groups showed similar patterns of sleep disturbance: reduced rapid eye movement (REM) sleep latencies, sleep efficiencies, and slow wave sleep. While the inpatients had greater REM activity in the first REM period than did the outpatients, both groups showed evidence of greater REM sleep time and REM activity during the first half of the night than do normals. The outpatients demonstrated a level of adaptation in that more REM sleep time and activity were present on night 2 than on night 1.     

Forgetting rates in neuropsychiatric disorders

OBJECTIVE—Previous studies have attributedaccelerated forgetting rates on recognition memory tasks to temporallobe pathology, but findings in some patient groups may have beenattributable to metabolic disruption. Findings in psychiatric disorderssuch as schizophrenia are conflicting. The purpose of the present study was to compare forgetting rates in patients with confusional states (post-elecroconvulsive therapy (post-ECT), delirium), with those obtained in schizophrenic patients (with putative temporal lobe pathology), non-ECT depressed patients, and healthy controls. Thefindings could also be compared with previous reports in patients withhead injury, focal structural lesions, and Alzheimer's dementia.
METHODS—Two studies employed a picture recognitiontask to examine forgetting rates, the first between delays of 1 minute,15 minutes, and 30 minutes, and the second between delays of 10 minutes, 2hours, and 24hours.
RESULTS—There were no significant differences inforgetting rates between 1 minute and 30 minutes, but the ECT groupshowed accelerated forgetting between 10 minutes and 2 hours comparedwith healthy controls, associated with a rapid decline in "hitrate". This was not attributable to differential changes in eitherdepression or severity of memory impairment. There were no differencesin forgetting rates across the other subject groups.
CONCLUSION—Post-ECT confusional state patients(similarly to "within post-traumatic amnesia" patients with headinjury) show accelerated forgetting on a recognition memory task and,in this, they contrast with patients who have focal structural lesionsor widespread cortical atrophy. Accelerated forgetting may reflect theeffect of disrupted cerebral metabolism on either "consolidation"or memory "binding" processes.

     

Homocysteine and neuropsychiatric disorders

The author presents an overview of the current literature on homocysteine as a risk factor for neuropsychiatric disorders. The databases MEDLINE, Current Contents and EMBASE were searched (between 1966 and 2002) for English language publications with the key words 'Homocysteine' and 'Stroke'; 'Alzheimer Disease'; 'Cognitive Impairment'; 'Epilepsy'; 'Depression'; or 'Parkinson's disease'. Individual articles were hand searched for relevant cross-references. It is biologically plausible that high homocysteine levels may cause brain injury and neuropsychiatric disorders. Homocysteine is proatherogenic and prothrombotic, thereby increasing the risk of cerebrovascular disease, and may have a direct neurotoxic effect. Evidence for homocysteine as a risk factor for cerebral microvascular disease is conflicting but warrants further study. Cross-sectional and some longitudinal studies support increased prevalence of stroke and vascular dementia in hyperhomocysteinemic individuals. The evidence of increased neurodegeneration is accumulating. The relationship with depression is still tentative, as it is with epilepsy. Currently, treatment studies are necessary to place the evidence on a stronger footing, and maybe high-risk patients should be screened for hyperhomocysteinemia and this should be treated with folic acid. More research evidence is necessary before population screening can be recommended.     

Electroencephalographic sleep measures in prepubertal depression.

Two nights of electroencephalographic (EEG) sleep recording were performed in a group of prepubertal subjects with major depressive disorder (MDD) (n = 36, mean age = 10.4, SD = 1.5) and age-matched normal control children (n = 18, mean age = 10.1, SD = 1.6). All subjects were medically healthy and free of medications at the time of the study. There were no significant group differences for any major sleep variable after the initial adaptation night in this study. One subgroup of MDD subjects (n = 8) showed reduced REM latency on both recording nights, decreased stage 4 sleep, and increased REM time; this subgroup had significantly higher severity scores for depression but did not otherwise appear to be clinically distinct from the rest of the MDD subjects. Overall, the results indicate that the EEG sleep changes associated with depression in adults occurred less frequently in prepubertal MDD subjects.     

Deep brain stimulation in neuropsychiatric disorders

Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus, subthalamic nucleus, and internal globus pallidus has been put forth as an alternative to surgical ablation for the treatment of movement disorders. In this paper, the authors discuss the history and putative physiologic mechanisms underlying DBS of these target regions. The authors then review empirical findings pertaining to the effects of DBS on neurological symptoms, cognitive functioning, and psychiatric symptoms in Parkinson's disease and essential tremor, the disorders for which the procedure has been most extensively applied. Finally, emerging and potential novel areas of application of DBS for the treatment of neuropsychiatric disorders and symptoms are discussed.     

CSF beta-endorphins in childhood neuropsychiatric disorders

Thirty-one children with autistic disorder, 8 with the Rett syndrome (RS), 2 with childhood disintegrative disorder and 5 with infantile spasms were compared with healthy adult controls with respect to cerebrospinal fluid (CSF) beta-endorphin levels. The autistic disorder and RS groups showed significantly lower values than the other groups. There were no age trends within the various groups. Further study of CSF beta-endorphins in these disorders and blindly examined age matched controls is warranted.     

Electroencephalographic investigation of allergic disorders

Electroencephalograms were recorded and psychiatric examinations performed in a group of 275 random-selected patients, 121 male and 154 female, with various allergic diseases; the mean age was 34.3 years. The frequency of EEG abnormalities was in the patients, much and significantly (p < 0.01) higher (43.27%) than in the controls and in the Polish general population.Over 50% of the abnormal records concerned the temporal region and over 80% showed a sporadic character of the changes and their activation by hyperventilation. The patients were divided into three subgroups: (a) atopic allergies, (b) allergic contact dermatitis, and (c) classical allergic diseases involving non-immunological mechanisms. The three subgroups did not differ in the frequency of abnormal EEG records. Neurosis were found in 49 patients (17.81%), most frequently in cases of vasomotor rhinitis (34.37%) and least so in allergic contact dermatitis (8.82%).     

Neuroanatomic substrates of late-life mental disorders

Advances in magnetic resonance imaging (MRI) techniques have made it possible to quantify anatomic brain abnormalities in neuropsychiatric disorders. This review focuses on controlled, quantitative MRI studies in depression, degenerative disorders, and psychosis in the elderly. Although many of the anatomic abnormalities detected are observed across disorders, the patterns of regional involvement may be more selective and disorder specific. We integrate MRI findings with relevant clinical and neurobiologic observations in an attempt to develop a cohesive model of late-life psychiatric illness. Although the model primarily alludes to the pathophysiology of late-life depression, it may have broader biologic implications for other mental disorders in the elderly.