Jean M. Miewald

Social Cognition Deficits Among Individuals at Familial High Risk for Schizophrenia

Social cognition in young relatives of schizophrenia probands (N=70) and healthy controls (N=63) was assessed using the Penn Emotion Recognition Test-40 to examine the presence of social cognitive deficits in individuals at risk for the disorder. Measures of neurocognitive function and prodromal psychopathology were collected to assess the cognitive and clinical correlates of social cognitive impairments in at-risk relatives. Results indicated that when compared with healthy controls, individuals at familial high risk for schizophrenia were significantly more likely to overattribute emotions to neutral faces, with such individuals frequently misinterpreting neutral faces as negative. In addition, at-risk individuals had significantly greater reaction times when completing emotion recognition tasks, regardless of valence. Impairments in neurocognition were largely independent of social cognitive performance, and emotion recognition impairments persisted after adjusting for deficits in neurocognitive function. Further, social cognitive impairments in the interpretation of neutral faces were significantly associated with greater positive and general prodromal psychopathology, whereas neurocognitive impairments were only associated with disorganization. These results suggest that impairments in social cognition may be unique endophenotypes for schizophrenia.

Weight gain in newly diagnosed first-episode psychosis patients and healthy comparisons: One-year analysis

BACKGROUND Various antipsychotics are associated with body weight gain. However, most study samples include high proportions of patients with chronic schizophrenia. We examined neuroleptic-induced weight gain in drug-naïve first-episode psychotic patients to limit confounding variables such as multiple past medication trials, history of partial adherence; or poor diet and a sedentary lifestyle, associated with chronic mental illness. METHODS Newly diagnosed first-episode psychosis patients treated with antipsychotic medication, a small group of patients not receiving antipsychotics, and healthy comparisons were followed for one year. Body weight differences and proportions of subjects with more than 7% weight gain were calculated. The effects of concomitant psychotropic medication on weight gain were explored. RESULTS Ninety-eight first-episode psychotics patient and 30 healthy controls were examined. Patients receiving neuroleptics gained significantly more weight than healthy controls (p=0.002). Olanzapine (91% gained >7%) increased body weight by 37.3+/-27.7 lb, followed by risperidone (51%; +16.6+/-22) and haloperidol (47%; +9+/-12), and perphenazine (10%; +3.4+/-6). Younger patients (r=-0.24, p=0.02) and patients with more negative symptoms at baseline (SANS global; r=0.22, p=0.04) gained more weight. A greater number of co-medications per patient, and co-prescription of antidepressants significantly and independently increased antipsychotic-associated weight gain. DISCUSSION The results confirm substantial and clinically significant weight gain introduced by antipsychotic treatment in drug-naïve first-episode psychotic patients, and identify several treatment-associated risk factors for weight gain. The magnitude of weight gain induced highlights potential health risks and points to the need for preventive measures such as behavioral weight control programs along with the initiation of pharmacotherapy.

Changes in forebrain function from waking to REM sleep in depression: preliminary analyses [of 18F]FDG PET studies

Based on recent functional brain imaging studies of healthy human REM sleep, we hypothesized that alterations in REM sleep in mood disorder patients reflect a functional dysregulation within limbic and paralimbic forebrain structures during that sleep state. Six unipolar depressed subjects and eight healthy subjects underwent separate [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET scans during waking and during their first REM period of sleep. Statistical parametric mapping contrasts were performed to detect changes in relative regional cerebral glucose metabolism (rCMRglu) from waking to REM sleep in each group as well as interactions in patterns of change between groups. Clinical and EEG sleep comparisons from an undisturbed night of sleep were also performed. In contrast to healthy control subjects, depressed patients did not show increases in rCMRglu in anterior paralimbic structures in REM sleep compared to waking. Depressed subjects showed greater increases from waking to REM sleep in rCMRglu in the tectal area and a series of left hemispheric areas including sensorimotor cortex, inferior temporal cortex, uncal gyrus-amygdala, and subicular complex than did the control subjects. These observations indicate that changes in limbic and paralimbic function from waking to REM sleep differ significantly from normal in depressed patients.

Psychological Stress Is Associated With Heightened Physiological Arousal During NREM Sleep in Primary Insomnia

The objective of this study was to evaluate cross-sectional relationships among symptoms of psychological stress, sleep, and physiological arousal during non-rapid eye movement (NREM) sleep in a sample of 30 patients with chronic, primary insomnia (mean age, 30.2 years, 60% female). Study measures included indexes of subjective stress, visually scored sleep, and physiological arousal during NREM sleep: quantitative electroencephalogram (QEEG) and quantitative electrocardiogram (QEKG) measures. Psychological stress was more strongly related to indexes of physiological arousal during NREM sleep than to visually scored measures of sleep. Higher levels of perceived stress were associated with decreased EEG delta power (rho = −0.50, p < .01) and increased EEG beta power (rho = 0.38, p < .05). Increased frequency of stress-related avoidance behaviors was associated with decreased EKG high-frequency power (rho = −0.46, p < .05). Although QEEG measures were significantly correlated with sleep maintenance (QEEG delta power rho = 0.45, p < .01; QEEG beta power rho = −0.54, p < .01) and time spent in delta sleep (QEEG delta power rho = 0.65, p < .001; QEEG beta power rho = −0.65, p < .001), QEKG measures were unrelated to visually scored measures of sleep. Perceived stress and stress-related avoidance behaviors were associated with multiple indexes of physiological arousal during NREM sleep in patients with chronic, primary insomnia.

Insomnia and Objectively Measured Sleep Disturbances Predict Treatment Outcome in Depressed Patients Treated with Psychotherapy or Psychotherapy-Pharmacotherapy Combinations

OBJECTIVE Insomnia and objectively measured sleep disturbances predict poor treatment outcomes in patients with major depressive disorder (MDD). However, prior research has utilized individual clinical trials with relatively small sample sizes and has focused on insomnia symptoms or objective measures, but not both. The present study is a secondary analysis that examines the degree to which insomnia, objective sleep disturbances, or their combination predicts depression remission following pharmacotherapy and/or psychotherapy treatment. METHOD Participants were 711 depressed (DSM criteria) patients drawn from 6 clinical trials. Remission status, defined as a score of ≤ 7 on the Hamilton Depression Rating Scale (HDRS) over 2 consecutive months, served as the primary outcome. Insomnia was assessed via the 3 sleep items on the HDRS. Objectively measured short sleep duration (total sleep time ≤ 6 hours) and prolonged sleep latency (> 30 minutes) or wakefulness after sleep onset (> 30 minutes) were derived from in-laboratory polysomnographic sleep studies. Logistic regression predicted the odds of nonremission according to insomnia, each of the objective sleep disturbances, or their combination, after adjusting for age, sex, treatment modality, and baseline depressive symptoms. RESULTS Prolonged sleep latency alone (OR = 3.53; 95% CI, 1.28-9.73) or in combination with insomnia (OR = 2.11; 95% CI, 1.13-3.95) predicted increased risk of nonremission. In addition, insomnia and sleep duration individually and in combination were each associated with a significantly increased risk of nonremission (P values < .05). CONCLUSIONS Findings suggest that objectively measured prolonged sleep latency and short sleep duration independently or in conjunction with insomnia are risk factors for poor depression treatment outcome.

Slow-wave sleep and symptomatology in schizophrenia and related psychotic disorders

Deficits in slow-wave sleep (SWS), or delta sleep, are frequently seen in schizophrenia, but their relationship with schizophrenic symptomatology remains unclear. We examined the association between visually scored and automated measures of SWS and positive and negative symptoms in a series of unmedicated patients with schizophrenia and related psychotic disorders. Total and average automated delta wave counts were significantly inversely associated with negative symptoms overall, and the psychomotor poverty syndrome in particular. Total delta counts were also inversely related to the disorganization syndrome. No relation was seen between reality distortion or the Brief Psychiatric Rating Scale (BPRS) positive symptoms and SWS. These findings support the view that SWS deficits may be related to negative symptoms of schizophrenia and may perhaps be mediated by impaired functioning of frontothalamic neural circuits.

A reexamination of the relationship between growth hormone secretion and slow wave sleep using delta wave analysis

Sleep onset growth hormone secretion is a reliable and reproducible finding in young adults and children. Secretion typically occurs during the first non-REM period of sleep and, despite some evidence to the contrary, growth hormone secretion has frequently been associated with the first period of slow wave sleep. By measuring delta wave activity (0.5-2 Hz) instead of slow wave sleep and, accounting for the within subject variability, it has not been possible to demonstrate a consistent or statistically significant linear relationship between delta wave activity and sleep-related growth hormone secretion. This suggests the presence of more complex mediating factors and the possibility that sleep onset and growth hormone secretion are two separate processes which are independently stimulated by events associated with sleep onset.

Sleep and suicidality in psychotic patients

The purpose of the study was to determine whether polysomnographic rapid eye movement (REM) sleep parameters distinguish between psychotic patients with and without a history of suicidal behavior. We examined both hand‐scored and automated measures of rapid eye movement (REM) sleep in psychotic patients with and without a history of suicidal ideation or attempts. Patients with suicidal behavior had significantly increased REM activity and time both in the whole night data and in the first REM period. These findings suggest an association between REM sleep abnormalities and suicidal behavior, perhaps related to alteration in serotonergic function.

Sleep spindle deficits in antipsychotic-naïve early course schizophrenia and in non-psychotic first-degree relatives

Introduction: Chronic medicated patients with schizophrenia have marked reductions in sleep spindle activity and a correlated deficit in sleep-dependent memory consolidation. Using archival data, we investigated whether antipsychotic-naïve early course patients with schizophrenia and young non-psychotic first-degree relatives of patients with schizophrenia also show reduced sleep spindle activity and whether spindle activity correlates with cognitive function and symptoms. Method: Sleep spindles during Stage 2 sleep were compared in antipsychotic-naïve adults newly diagnosed with psychosis, young non-psychotic first-degree relatives of schizophrenia patients and two samples of healthy controls matched to the patients and relatives. The relations of spindle parameters with cognitive measures and symptom ratings were examined. Results: Early course schizophrenia patients showed significantly reduced spindle activity relative to healthy controls and to early course patients with other psychotic disorders. Relatives of schizophrenia patients also showed reduced spindle activity compared with controls. Reduced spindle activity correlated with measures of executive function in early course patients, positive symptoms in schizophrenia and IQ estimates across groups. Conclusions: Like chronic medicated schizophrenia patients, antipsychotic-naïve early course schizophrenia patients and young non-psychotic relatives of individuals with schizophrenia have reduced sleep spindle activity. These findings indicate that the spindle deficit is not an antipsychotic side-effect or a general feature of psychosis. Instead, the spindle deficit may predate the onset of schizophrenia, persist throughout its course and be an endophenotype that contributes to cognitive dysfunction.

Short-term stability of sleep and heart rate variability in good sleepers and patients with insomnia: for some measures, one night is enough.

STUDY OBJECTIVES Quantify the short-term stability of multiple indices of sleep and nocturnal physiology in good sleeper controls and primary insomnia patients. DESIGN Intra-class correlation coefficients (ICC) were used to quantify the short-term stability of study outcomes. SETTING Sleep laboratory. PARTICIPANTS Fifty-four adults with primary insomnia (PI) and 22 good sleeper controls (GSC). MEASUREMENTS Visually scored sleep outcomes included indices of sleep duration, continuity, and architecture. Quantitative EEG outcomes included power in the delta, theta, alpha, sigma, and beta bands during NREM sleep. Power spectral analysis was used to estimate high-frequency heart rate variability (HRV) and the ratio of low- to high-frequency HRV power during NREM and REM sleep. RESULTS With the exception of percent stage 3+4 sleep; visually scored sleep outcomes did not exhibit short-term stability across study nights. Most QEEG outcomes demonstrated short-term stability in both groups. Although power in the beta band was stable in the PI group (ICC = 0.75), it tended to be less stable in GSCs (ICC = 0.55). Both measures of cardiac autonomic tone exhibited short-term stability in GSCs and PIs during NREM and REM sleep. CONCLUSIONS Most QEEG bandwidths and HRV during sleep show high short-term stability in good sleepers and patients with insomnia alike. One night of data is, thus, sufficient to derive reliable estimates of these outcomes in studies focused on group differences or correlates of QEEG and/or HRV. In contrast, one night of data is unlikely to generate reliable estimates of PSG-assessed sleep duration, continuity or architecture, with the exception of slow wave sleep.