Trajectory of neurological examination abnormalities in antipsychotic-naïve first-episode psychosis population: a 1 year follow-up study.

BACKGROUND: Neurological Examination Abnormalities (NES) are quantified by measuring subtle, partially localizable (cerebello-thalamo-prefrontal cortical circuit) and heritable neurological signs comprising sensory integration, motor coordination and complex motor sequencing that are associated with first-episode psychosis (FEP). A few studies have evaluated NES longitudinally and as a predictor for diagnostic and response classification, but these studies have been confounded, underpowered and divergent. We examined (1) baseline and longitudinal NES differences between diagnostic and year 1 response groups; (2) if NES predicts diagnostic and response groups and (3) relationships between clinical variables and NES measures in antipsychotic-naïve FEP. METHODS: NES and clinical measures were obtained for FEP-schizophrenia (FEP-SZ, n = 232), FEP non-schizophrenia (FEP-NSZ, n = 117) and healthy controls (HC, n = 204). Response groups with >25% improvement in average year 1 positive and negative symptomatology scores were classified as responsive (n = 97) and <25% improvement as non-responsive (n = 95). Analysis of covariance, NES trajectory analysis and logistic regression models assessed diagnostic and response group differences. Baseline and longitudinal NES relationships with clinical variables were performed with Spearman correlations. Data were adjusted for age, sex, race, socioeconomic status and handedness. RESULTS: Cognitive perceptual (COGPER) score was better than repetitive motor (REPMOT) at differentiating FEP-SZ from FEP-NSZ and distinguishing responders from non-responders. We identified significant group-specific associations between COGPER and worse GAF, positive and negative symptomatology and some of these findings persisted at 1-year assessment. CONCLUSION: NES are an easy to administer, bedside-elicited, endophenotypic measure and could be a cost-effective clinical tool in antipsychotic-naïve FEP.

Comparison of five actigraphy scoring methods with bipolar disorder.

The goal of this study was to compare 5 actigraphy scoring methods in a sample of 18 remitted patients with bipolar disorder. Actigraphy records were processed using five different scoring methods relying on the sleep diary; the event-marker; the software-provided automatic algorithm; the automatic algorithm supplemented by the event-marker; visual inspection (VI) only. The algorithm and the VI methods differed from the other methods for many actigraphy parameters of interest. Particularly, the algorithm method yielded longer sleep duration, and the VI method yielded shorter sleep latency compared to the other methods. The present findings provide guidance for the selection of signal processing method based on sleep parameters of interest, time-cue sources and availability, and related scoring time costs for the study.

Gray matter loss in young relatives at risk for schizophrenia: relation with prodromal psychopathology.

The maturation of neocortical regions mediating social cognition during adolescence and young adulthood in relatives of schizophrenia patients may be vulnerable to heritable alterations of neurodevelopment. Prodromal psychotic symptoms, commonly emerging during this period in relatives, have been hypothesized to result from alterations in brain regions mediating social cognition. We hypothesized these regions to show longitudinal alterations and these alterations to predict prodromal symptoms in adolescent and young adult relatives of schizophrenia patients. 27 Healthy controls and 23 relatives were assessed at baseline and one-year follow-up using scale of prodromal symptoms and gray matter volumes of hypothesized regions from T1-MRI images. Regional volumes showing deficits on ANCOVA and repeated-measures ANCOVAs (controlling intra cranial volume, age and gender) were correlated with prodromal symptoms. At baseline, bilateral amygdalae, bilateral pars triangulares, left lateral orbitofrontal, right frontal pole, angular and supramarginal gyrii were smaller in relatives compared to controls. Relatives declined but controls increased or remained stable on bilateral lateral orbitofrontal, left rostral anterior cingulate, left medial prefrontal, right inferior frontal gyrus and left temporal pole volumes at follow-up relative to baseline. Smaller volumes predicted greater severity of prodromal symptoms at both cross-sectional assessments. Longitudinally, smaller baseline volumes predicted greater prodromal symptoms at follow-up; greater longitudinal decreases in volumes predicted worsening (increase) of prodromal symptoms over time. These preliminary findings suggest that abnormal longitudinal gray matter loss may occur in regions mediating social cognition and may convey risk for prodromal symptoms during adolescence and early adulthood in individuals with a familial diathesis for schizophrenia.

Thalamic, Amygdalar, and hippocampal nuclei morphology and their trajectories in first episode psychosis: A preliminary longitudinal study✰.

The thalamus, amygdala, and hippocampus play important pathophysiologic roles in psychosis. Few studies have prospectively examined subcortical nuclei in relation to predicting clinical outcomes after a first-episode of psychosis (FEP). Here, we examined volumetric differences and trajectories among subcortical nuclei in FEP patients and their associations with illness severity. Clinical and brain volume measures were collected using a 1.5T MRI scanner and processed using FreeSurfer 6.0 from a prospective study of antipsychotic-naïve FEP patients of FEP-schizophrenia (FEP-SZ) (baseline, n = 38; follow-up, n = 17), FEP non-schizophrenia (FEP-NSZ) (baseline, n = 23; follow-up, n = 13), and healthy controls (HCs) (baseline, n = 47; follow-up, n = 29). Compared to FEP-NSZ and HCs, FEP-SZ had significantly smaller thalamic anterior nuclei volume at baseline. Longitudinally, FEP-SZ showed a positive rate of change in the amygdala compared to controls or FEP-NSZ, as well as in the basal, central and accessory basal nuclei compared to FEP-NSZ. Enlargement in the thalamic anterior nuclei predicted a worsening in overall psychosis symptoms. Baseline thalamic anterior nuclei alterations further specify key subcortical regions associated with FEP-SZ pathophysiology. Longitudinally, anterior nuclei volume enlargement may signal symptomatic worsening. The amygdala and thalamus structures may show diagnostic differences between schizophrenia and non-schizophrenia psychoses, while the thalamus changes may reflect disease or treatment related changes in clinical outcome.

Visual Cortical Alterations and their Association with Negative Symptoms in Antipsychotic-Naïve First Episode Psychosis.

Visual perceptual and processing deficits are common in schizophrenia and possibly point towards visual pathway alterations. However, no studies have examined visual cortical morphology in first-episode psychosis (FEP). In an antipsychotic-naïve FEP population, we investigated primary visual (V1), association area (V2), and motion perception (V5/MT) morphology compared to controls. We found reductions in the V1 and V2 areas, greater MT area and lower MT thickness in the FEP-schizophrenia group when compared to controls. Also, lower MT thickness was associated with worse negative symptoms. Our results shed light on this poorly studied area of visual cortex morphology in FEP.

Neurological abnormalities among offspring of persons with schizophrenia: relation to premorbid psychopathology.

BACKGROUND: Neurological Examination Abnormalities (NEA, often called "neurological soft signs") have been observed in early schizophrenia and may be heritable. We investigated the prevalence, and neurocognitive and psychopathological correlates of NEA among offspring of schizophrenia patients who are at increased genetic risk for this illness. METHODS: Neurological examinations were conducted on high risk (HR, n=74) and healthy comparison subjects (HS, n=86), using the Heinrichs-Buchanan scale. Cognitive-perceptual (CogPer) and repetitive motor (RepMot) subscores, and total NEA scores were computed. All HR and HS were assessed using K-SADS/SCID for diagnoses. Schizotypy was measured using the Magical Ideation and the Perceptual Aberration subscales (Chapman scale), attention using Continuous Performance Test (CPT-IP) and executive functions using the Wisconsin Card Sorting Test (WCST). RESULTS: CogPer (F(1,160)=7.14, p=0.008) but not RepMot NEA scores were higher in HR subjects compared to HS after controlling for age and sex. CogPer NEA scores were higher in HR subjects with axis I psychopathology compared to those without (F(2,170)-6.41, p=0.002). HR subjects had higher schizotypy scores (composite of the magical ideation and perceptual aberration scales) (F(1,141)=23.25, p=0.000004). Schizotypy scores were negatively correlated with sustained attention and executive functions. In addition, schizotypy was positively correlated with CogPer NEA scores. CONCLUSIONS: Young relatives at increased genetic risk for schizophrenia show more frequent NEA. CogPer but not RepMot NEA scores were elevated, consistent with our prior observation of CogPer NEA being relatively specific for schizophrenia. The observed relationships between NEA, cognitive impairments, schizotypy and axis I disorders suggest that NEA may characterize a subgroup of HR offspring at an elevated risk for psychopathology.

Clinical psychopathology in youth at familial high risk for psychosis.

AIM: While the course of psychopathology has been explored from an index mental health diagnosis onwards, there are few detailed, prospective studies of the occurrence of clinical psychopathology in youth with familial risk for severe mental illnesses such as psychosis. We sought to describe the appearance of Axis I psychopathology in a unique sample of adolescents with a family history of schizophrenia (FHR). METHODS: One hundred and sixty two first- and second-degree relatives (mean age 15.7 ± 3.6; range 8-25) of probands with schizophrenia or schizoaffective disorder were assessed at baseline and annual intervals for up to 3 years, focusing on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) Axis I psychopathology. RESULTS: Fourteen individuals (8.6%) developed a psychotic disorder. One hundred and five subjects (65%) met criteria for an Axis I disorder over the course of the study, the most common of which was a depressive episode (40 subjects; 25%). Of the 148 individuals who did not develop psychosis, 91 (61%) had one or more Axis I disorders compared with 10/14 converters who had a comorbid Axis I disorder (71%). Ordered by increasing age of onset, diagnoses included cognitive and externalizing disorders, anxiety disorders, affective disorders, substance use disorders and psychotic disorders. CONCLUSIONS: In addition to an elevated risk of psychosis, young FHR relatives manifest a broad range of non-psychotic Axis I psychopathology in childhood and adolescence. This breadth of diagnoses has implications for the structure and function of mental health services for young people.

An integrated psychobiological predictive model of emergent psychopathology among young relatives at risk for schizophrenia.

OBJECTIVE: Studies of young relatives at elevated risk for schizophrenia have pointed to the importance of a variety of neurobiological, cognitive, and clinical risk factors for the disorder; yet few have employed integrated models to estimate the joint contribution of these factors to heightened schizophrenic risk. We tested the predictive power of an integrated psychobiological model of schizophrenia risk to subsequent psychopathology development among young relatives at risk for the disorder. METHODS: Young first (n=66) and second (n=20) degree relatives of schizophrenia probands were followed for an average of 3 (SD=1.13) years to examine their trajectories toward psychopathology development. Neurobiologic, cognitive, and clinical measures were employed in an integrated structural equation model to estimate their contribution to the prospective emergence of psychopathology. RESULTS: Results indicated that neurobiological, neurocognitive, and psychosis proneness factors at baseline were all uniquely predictive of subsequent psychopathology development, and that an integrated model of psychopathology development that took into account these factors provided an excellent fit to the observed data. Subsequent classification analyses of model accuracy using likelihood ratios adjusting for the base-rate of psychopathology development in this sample revealed that individuals identified by this model had a 71% chance of developing psychopathology in the future. CONCLUSIONS: An integrated model of biobehavioral risk factors may provide a powerful method for predicting psychopathology and schizophrenia risk in at-risk samples. If validated, this model may be useful for early detection and intervention programs. Future research will need to focus particularly on predicting schizophrenia development and refining models to further enhance sensitivity.

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.

Alterations in regional cerebral glucose metabolism across waking and non-rapid eye movement sleep in depression.

BACKGROUND: Depression is associated with sleep disturbances, including alterations in non-rapid eye movement (NREM) sleep. Non-rapid eye movement sleep is associated with decreases in frontal, parietal, and temporal cortex metabolic activity compared with wakefulness. OBJECTIVE: To show that depressed patients would have less of a decrease than controls in frontal metabolism between waking and NREM sleep and to show that during NREM sleep, they would have increased activity in structures that promote arousal. DESIGN: Subjects completed electroencephalographic sleep and regional cerebral glucose metabolism assessments during both waking and NREM sleep using [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography. SETTING: General clinical research center. PATIENTS: The study included 29 unmedicated patients who met the Structured Clinical Interview for DSM-IV criteria for current major depression and who had a score of 15 or greater on a 17-item Hamilton Rating Scale for Depression and 28 medically healthy subjects of comparable age and sex who were free of mental disorders. MAIN OUTCOME MEASURES: Electroencephalographic sleep and regional cerebral metabolism during waking and NREM sleep. RESULTS: Depressed patients showed smaller decreases than healthy subjects in relative metabolism in broad regions of the frontal, parietal, and temporal cortex from waking to NREM sleep. Depressed patients showed larger decreases than healthy subjects in relative metabolism in the left amygdala, anterior cingulate cortex, cerebellum, parahippocampal cortex, fusiform gyrus, and occipital cortex. However, in post hoc analyses, depressed patients showed hypermetabolism in these areas during both waking and NREM sleep. CONCLUSIONS: The smaller decrease in frontal metabolism from waking to NREM sleep in depressed patients is further evidence for a dynamic sleep-wake alteration in prefrontal cortex function in depression. Hypermetabolism in a ventral emotional neural system during waking in depressed patients persists into NREM sleep.

Decreased coherence in higher frequency ranges (beta and gamma) between central and frontal EEG in patients with schizophrenia: A preliminary report.

Schizophrenia is associated with a dysfunction of cognitive integration that may be due to abnormalities in inhibitory neural circuitry. A previous study found a failure of gamma band (25-45 Hz) synchronization in patients with schizophrenia compared to controls. Another recent study also stressed the importance of investigating high frequencies in the scalp-recorded sleep electroencephalogram (EEG). In this study, we compared coherence between first episode drug-naïve patients with schizophrenia (n=8) and age- and sex-matched normal controls (n=8) using two 32-s epochs of C4 and F4 EEG. The coherence was obtained using 4096 data points (128 Hz signal) using cross-spectral analysis with Blackman-Tukey window in beta (15.25-24.75 Hz) and gamma (25-44.75 Hz) frequency bands. We used wake, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep periods for the analyses. Our results show a significant decrease in coherence in both beta and gamma frequency bands in patients. Post-hoc 't' tests revealed a significantly lower coherence only during the wake stage in patients with schizophrenia in beta as well as gamma frequency bands. These results further support the importance of the analyses of high-frequency bands in the EEG and support previous findings of abnormal neural synchrony in patients with schizophrenia. These results have been discussed further in relation to wake and sleep stages.

Increased activation of anterior paralimbic and executive cortex from waking to rapid eye movement sleep in depression.

BACKGROUND: Depression is associated with sleep disturbances, including alterations in rapid eye movement (REM) sleep, that may relate to the neurobiology of the disorder. Given that REM sleep activates limbic and anterior paralimbic cortex and that depressed patients demonstrate increases in electroencephalographic sleep measures of REM, we hypothesized greater activation of these structures during waking to REM sleep in depressed patients. DESIGN: Subjects completed electroencephalographic sleep and regional cerebral glucose metabolism assessments during both waking and REM sleep using [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography. SETTING: Patients and healthy subjects recruited from the general community to participate in a research study of depression at an academic medical center. Patients Twenty-four unmedicated patients who met the Structured Clinical Interview for DSM-IV criteria for current major depression and who had a score of 15 or higher on a 17-item Hamilton Rating Scale for Depression; 14 medically healthy subjects of comparable age and sex who were free of mental disorders. MAIN OUTCOME MEASURES: Electroencephalographic sleep, semiquantitative and relative regional cerebral metabolism during waking and REM sleep. RESULTS: Depressed patients showed greater REM sleep percentages. While both healthy and depressed patients activated anterior paralimbic structures from waking to REM sleep, the spatial extent of this activation was greater in the depressed patients. Additionally, depressed patients showed greater activation in bilateral dorsolateral prefrontal, left premotor, primary sensorimotor, and left parietal cortices, as well as in the midbrain reticular formation. CONCLUSIONS: Increased anterior paralimbic activation from waking to REM sleep may be related to affective dysregulation in depressed patients. Increased activation of executive cortex may be related to a cognitive dysregulation. These results suggest that altered function of limbic/anterior paralimbic and prefrontal circuits in depression is accentuated during the REM sleep state. The characteristic sleep disturbances of depression may reflect this dysregulation.

Can age at sexual maturity act as a predictive biomarker for prodromal negative symptoms?

BACKGROUND: Puberty and reproductive hormones have been identified as having a potential role in schizophrenia. Earlier reports have suggested associations between later age at puberty and schizophrenia in males. Similarly, associations have been reported between testosterone levels and psychotic symptoms. In this report, we examined the association between age at puberty and prodromal symptoms of psychosis. METHODS: 58 child or adolescent family members of individuals with schizophrenia were interviewed using the Scale of Prodromal Symptoms and the Tanner Maturational Scale. Age at Tanner pubertal stage was determined and regression analyses were used to explore associations between prodromal symptoms and age at puberty. RESULTS: Among males, delayed age at puberty was associated with greater severity of prodromal symptoms; the association between negative prodromal symptoms and delayed age was significant (p=0.001). In females, the association was not statistically significant. CONCLUSIONS: Our results suggest that delayed age at puberty may be associated with negative prodromal symptoms of schizophrenia in males. Our findings suggest that delayed age at puberty could potentially be a predictive biomarker for psychopathology in males at risk for schizophrenia.

Functional neuroimaging evidence for hyperarousal in insomnia.

OBJECTIVE: The authors investigated the neurobiological basis of poor sleep and daytime fatigue in insomnia. METHOD: [(18)F]Fluorodeoxyglucose positron emission tomography was used to assess regional cerebral glucose metabolism of seven patients with insomnia and 20 healthy subjects. RESULTS: Compared with healthy subjects, patients with insomnia showed greater global cerebral glucose metabolism during sleep and while awake, a smaller decline in relative metabolism from waking to sleep states in wake-promoting regions, and reduced relative metabolism in the prefrontal cortex while awake. CONCLUSIONS: Subjectively disturbed sleep in patients with insomnia is associated with greater brain metabolism. The inability to fall asleep may be related to a failure of arousal mechanisms to decline in activity from waking to sleep states. Further, daytime fatigue may reflect decreased activity in the prefrontal cortex resulting from inefficient sleep.

Measuring sleep habits without using a diary: the sleep timing questionnaire.

STUDY OBJECTIVES: To develop a single-administration instrument yielding equivalent measures of sleep to those obtained from a formal (2-week) sleep diary. DESIGN & SETTING: A single-administration Sleep riming Questionnaire (STQ) is described (and reproduced in the Appendix). Test-retest reliability was examined in 40 subjects who were given the STQ on two occasions separated by less than 1 year. Convergent validity was measured both by comparing STO-derived measures with objective measures derived from wrist actigraphy (n=23) and by comparing STQ-derived measures with other subjective measures derived from a detailed 2-week sleep diary in two nonoverlapping samples (n=101, 93). Correlations of STQ measures with age and momingness-eveningness (chronotype) were also examined. SUBJECTS: The analyses used sample sizes of 40, 23, 101, and 93 (both genders, overall age range 20y-89y). Most subjects were healthy volunteers; some Study 4 subjects were patients (enrolled in research protocols). RESULTS: Test-retest reliability for the STQ was demonstrated for estimates of bedtime (r = 0.705, p < 0.001) and waketime (r = 0.826, p < 0.001). Convergent validity using wrist actigraphy was demonstrated by correlations of 0.592 (p < 0.005) for bedtime, and of 0.769 (p < 0.001) for waketime. Diary studies indicated STQ bedtime and waketime data to be highly correlated (at about 0.8) with those obtained from a formal 2-week sleep diary. The STQ also provided data on estimated sleep latency and wake after sleep onset (WASO), which correlated reliably (at about 0.7) with average nightly ratings of these variables from a 2-week sleep diary. Mean estimated values of sleep latency and WASO from the two instruments were within 1 minute of each other. ST-derived bedtimes and waketimes correlated with both age and chronotype in the expected direction (older subjects earlier, morning types earlier). CONCLUSION: The STQ may be a reliable valid measure of sleep timing that could provide a time-efficient alternative to traditional sleep diaries.

Symptom reports in severe chronic insomnia.

STUDY OBJECTIVES: To describe patterns and severities of the daytime and nighttime symptoms of chronic insomnia patients. DESIGN: Exploratory chart review from clinicians' evaluation summaries, a self-report screening instrument, the Pittsburgh Sleep Quality Index, the Beck Depression Inventory, the Epworth Sleepiness Scale, and the Hopkins Symptom Checklist-90 (HSCL90). SETTING: A regional sleep disorders referral clinic. PATIENTS OR PARTICIPANTS: 94 patients with chronic insomnia (DSM-IV code 307.42), classified into the subgroups "Primary Insomnia," "Depression-Related," "Anxiety-Related," and "Other". INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Frequent symptoms occurred not only in nocturnal domains (e.g., sleep disturbances, environmental sensitivity), but also in daytime domains (e.g., cognitive difficulties, sleepiness). Compared to primary insomnia patients, those with depression-related insomnia endorsed more severe symptoms. All subgroups endorsed a generally similar symptom profile when single symptoms were considered in isolation. When considered conjointly, severe symptoms typical of depression and generalized social alienation had a high negative predictive value for primary insomnia. The number of severe symptoms on the HSCL90 was related to fewer sleep hours in the nonprimary insomnia subgroup but not in the primary insomnia subgroup. CONCLUSIONS: Patients with chronic insomnia report significant daytime as well as nighttime symptoms. Depression-related and primary insomnias were separable only by some highly characteristic symptoms of depression. Diagnostic subgroups of insomnia patients may vary in how their overall distress relates to diminished self-reported sleep. Nighttime and daytime symptoms need to be assessed together when measuring insomnia severity.

Decreased nonlinear complexity and chaos during sleep in first episode schizophrenia: a preliminary report.

Schizophrenia is characterized by disturbed sleep architecture. It has been thought that sleep abnormalities may underlie information processing deficits associated with this disorder. Nonlinear analyses of sleep data can provide valuable information on sleep characteristics that may be relevant to the functions of sleep. This study examined the predictability and nonlinear complexity of sleep EEG time series in two EEG channels (C4 and F4) using measures of nonlinearity, such as symbolic dynamics and the largest Lyapunov exponent (LLE) in schizophrenia. A series of antipsychotic naive patients with first episode of schizophrenia or schizoaffective disorder and age-matched healthy controls were studied during awake period, stage 1/2, slow wave sleep (stage 3/4) and rapid eye movement (REM) sleep. Nonlinearity scores were significantly lower during awake stage in patients compared to controls suggesting that there may be a diminished interplay between various parameters for the genesis of waking EEG. Symbolic dynamics and LLE were significantly lower in patients during REM compared to healthy controls, suggesting decreased nonlinear complexity of the EEG time series and diminished chaos in schizophrenia. Decreased nonlinear complexity was also correlated with neurocognitive deficits as assessed by the Wisconsin card sorting test. Diminished complexity of EEG time series during awake and REM sleep in patients with schizophrenia may underlie the impaired ability to process information in psychotic disorders such as schizophrenia.

Prolonged untreated illness duration from prodromal onset predicts outcome in first episode psychoses.

Several, although not all, studies suggest that prolonged duration of untreated illness (DUI) predicts poor outcome in psychotic disorders such as schizophrenia. It is unclear whether this association can be explained by factors such as baseline deficits or poor premorbid adjustment. First episode psychotic patients were evaluated at 1 and 2 years following baseline evaluations. Predictive measures showing significant correlations with outcome were entered in multiple regression analyses with Strauss-Carpenter scale (SC) and Global Assessment of Functioning scale (GAF) outcome scores as dependent variables. Illness duration computed from the onset of the prodrome (DUI-pro), used both as a dichotomous and as a continuous measure, highly significantly predicted both GAF and SC scores at 2 years. On the other hand, baseline functioning significantly predicted the 1-year but not the 2-year outcome. When Premorbid Adjustment Scale (PAS) scores were additionally entered into the analyses in a smaller subset, the relation between DUI-pro and the 2-year outcome scores remained significant. Significant associations were also seen between outcome and baseline neuropsychological deficits involving attention and memory. Further research is needed to examine whether prolonged untreated illness is simply associated with poor outcome or plays a causal role in relation to outcome. The latter, if true, would strongly support therapeutic intervention efforts in the prodromal and early psychotic phases of schizophrenia.

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.

EEG power during waking and NREM sleep in primary insomnia.

OBJECTIVE: Pathophysiological models of insomnia invoke the concept of 24-hour hyperarousal, which could lead to symptoms and physiological findings during waking and sleep. We hypothesized that this arousal could be seen in the waking electroencephalogram (EEG) of individuals with primary insomnia (PI), and that waking EEG power would correlate with non-REM (NREM) EEG. METHODS: Subjects included 50 PI and 32 good sleeper controls (GSC). Five minutes of eyes closed waking EEG were collected at subjects' usual bedtimes, followed by polysomnography (PSG) at habitual sleep times. An automated algorithm and visual editing were used to remove artifacts from waking and sleep EEGs, followed by power spectral analysis to estimate power from 0.5-32 Hz. RESULTS: We did not find significant differences in waking or NREM EEG spectral power of PI and GSC. Significant correlations between waking and NREM sleep power were observed across all frequency bands in the PI group and in most frequency bands in the GSC group. CONCLUSIONS: The absence of significant differences between groups in waking or NREM EEG power suggests that our sample was not characterized by a high degree of cortical arousal. The consistent correlations between waking and NREM EEG power suggest that, in samples with elevated NREM EEG beta activity, waking EEG power may show a similar pattern.