Pharmacotherapy of first-episode schizophrenia

BACKGROUND: A growing interest in first-episode schizophrenia reflects the belief that this line of investigation will lead to further developments regarding schizophrenia's aetiology, course and outcome. METHOD: Evidence from more recent clinical trials involving first-episode schizophrenia is integrated with neuroimaging data, specifically positron emission tomography, to provide direction regarding pharmacotherapy. RESULTS: Individuals with a first episode of schizophrenia appear particularly responsive to pharmacotherapy, as well as quite sensitive to side-effects. At the same time, current clinical and receptor-binding data support the efficacy of low-dose neuroleptic treatment. CONCLUSIONS: Early and effective treatment of schizophrenia has been associated with better long-term outcome. Low-dose neuroleptic therapy is an effective treatment strategy and the diminished risk of side-effects with this approach may further enhance compliance and outcome.     

Depression in people with first-episode schizophrenia

BACKGROUND: Depression has been described in people presenting with first-episode schizophrenia, a group at high relative risk of suicide. METHOD: This was a longitudinal cohort study of 113 people during an acute relapse and 13 having a first episode. Follow-up occurred at three months and at one year. This report compares level of depression in the first episode and in the relapsing group. Levels of depression were assessed using the Calgary Depression Scale for Schizophrenia (CDSS). RESULTS: The median CDSS score was statistically significantly higher in the first-episode group both during the acute phase and at three month follow-up. At one year the first-episode group continued to have higher levels of depression than the multiple episode group. CONCLUSIONS: For people with a first episode of schizophrenia, depression is a major problem during the initial acute phase and during the first year of illness. In light of the high risk of suicide in this population, recognition and treatment of depression requires greater attention.     

The dimensionality of schizophrenia concepts in first-episode psychosis

OBJECTIVE: To evaluate the efficacy of unreamed retrograde intramedullary (IM) nailing of fractures of the femoral shaft in a second series of patients using modifications suggested from our initial study. DESIGN: Prospective. SETTING: Level I trauma center. METHODS: Based on the findings of a previous study, we began a clinical series incorporating changes consisting of (a) inclusion of any patient with a femoral shaft fracture amenable to IM nailing (i.e., closed physes), (b) primary use of a split patellar tendon intercondylar distal femoral entry portal, and (c) the use of a full-length femoral implant having variable size availability and dynamization capability. Over a twelve-month period, thirty-four patients with thirty-five femoral shaft fractures were treated. The protocol called for planned dynamization in statically locked stable fractures and unstable fractures showing minimal healing at six to twelve weeks. Functional outcome was assessed by using the Knee Society clinical rating system. RESULTS: Incorporating the concepts of canal fill and early dynamization, there were only two nonunions (6 percent) in this series as compared with 14 percent in the previously reported series with an overall shorter time to union (12.6 versus 15 weeks). There were no infections or malunions. Postoperative complaints of knee pain were minimal (knee score average: 98 points) and knee function was excellent (knee score average: 97 points). CONCLUSIONS: Although not advocated as a replacement for other techniques, unreamed retrograde nailing is presented as a safe and beneficial fracture fixation method that should be added to the orthopaedic surgeon's treatment armamentarium. The operative technique is quick and simple, and blood loss is minimal. Early nail dynamization and early weight-bearing are important in minimizing the risk of nonunion.     

Neurocognition in first-episode schizophrenia: A meta-analytic review.

Compromised neurocognition is a core feature of schizophrenia. Following Heinrichs and Zakzanis’s (1998) seminal meta-analysis of middle-aged and predominantly chronic schizophrenia samples, the aim of this study is to provide a meta-analysis of neurocognitive findings from 47 studies of first-episode (FE) schizophrenia published through October 2007. The meta-analysis uses 43 separate samples of 2,204 FE patients with a mean age of 25.5 and 2,775 largely age- and gender-matched control participants. FE samples demonstrated medium-to-large impairments across 10 neurocognitive domains (mean effect sizes from ?0.64 to ?1.20). Findings indicate that impairments are reliably and broadly present by the FE, approach or match the degree of deficit shown in well-established illness, and are maximal in immediate verbal memory and processing speed. Larger IQ impairments in the FE compared to the premorbid period, but comparable to later phases of illness suggests deterioration between premorbid and FE phases followed by deficit stability at the group level. Considerable heterogeneity of effect sizes across studies, however, underscores variability in manifestations of the illness and a need for improved reporting of sample characteristics to support moderator variable analyses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Integrity of emotional and motivational states during the prodromal, first-episode, and chronic phases of schizophrenia.

Emotional and motivational dysfunction is fundamental to schizophrenia, and yet, the nature and scope of associated deficits are not well understood. This study assessed the integrity of emotional responding from the perspective of its underlying motivational systems during different phases of schizophrenia. Evaluative, somatic, and autonomic responses were measured during viewing of pictures categorized by emotional content, including threat, mutilation, contamination, illness, pollution, mild erotica, families, food, and nature. Participants were 13 patients at ultra high risk or prodromal for psychosis, 40 first-episode schizophrenia patients, 37 chronic schizophrenia patients, and 74 healthy comparison subjects. Irrespective of phase of illness, schizophrenia patients showed a robust and normal pattern of response across multiple systems, with differential engagement of the defensive and appetitive systems as a function of the motivational significance assigned to specific emotional contexts. Although the integrity of core motivational states also appeared to be intact in prodromal patients, a less consistent pattern of response was observed. As continuing efforts are made to identify emotional and motivational abnormalities in schizophrenia, identified deficits will likely be independent of a fundamental dysfunction in basic emotion and motivation response systems and involve integration with higher order processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

齐拉西酮对首发精神分裂症患者认知功能的影响

Cibee等研究显示,新型抗精神病药齐拉西酮对慢性精神分裂症患者的认知功能有影响,该研究以氯丙嗪为对照,进一步探讨齐拉西酮对首发精神分裂症患者认知功能的影响.     

Clinical correlates of anhedonia and perceptual aberration in first-episode patients with schizophrenia and affective disorder.

Examined the association between scales measuring physical anhedonia, social anhedonia, and perceptual aberration and premorbid functioning, clinical state, and current level of adjustment in 91 psychotic Ss. The patients were examined at the onset of their 1st psychotic episode and again 18 mo later. For patients with schizophrenia, anhedonia was significantly related to premorbid functioning. No association was found between the scales and clinical state or level of adjustment at intake or follow-up. In affective disorder patients, no correlation was found between premorbid functioning (a stable characteristic) and scale scores, but moderately large correlations emerged between the scales and clinical state and level of adjustment at both assessment times. These results suggest that schizophrenic and affective disorder patients endorse items on these scales for different reasons. The authors hypothesize that for patients with schizophrenia the scales assess enduring personality characteristics, whereas for the affective disordered patients they assess clinical condition at the time of testing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Autonomic conditioning in chronic schizophrenia.

Studied classical conditioning of autonomic responses of 28 chronic schizophrenic and 18 healthy Ss by means of a discrimination paradigm employing 3 tones differing in pitch as CSs, and 2 intensities of DC produced pain as UCSs. It was found that patients, as compared with the healthy control group, had normal resting physiological levels and UCRs, but significantly impaired CR amplitudes, reduced discrimination scores, and smaller orienting responses. Results suggest an impaired aptitude for emotional learning which might account for the severe impairment in social motivation and emotional maturity observed in these chronic schizophrenic patients. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

When doors of perception open: Visual contrast sensitivity in never-medicated, first-episode schizophrenia.

Schizophrenia is characterized by impaired visual contrast sensitivity and anomalous perceptual experiences. The aim of this study was to investigate these phenomena in unmedicated patients with first-episode schizophrenia. Visual contrast sensitivity was measured with pulsed-pedestal and steady-pedestal tests, which bias information processing toward the parvocellular and magnocellular pathways, respectively. Anomalous perceptual experiences were investigated with the Structured Interview for Assessing Perceptual Anomalies (SIAPA). Results revealed that patients with schizophrenia (n = 20) exhibited increased contrast sensitivity values on the magnocellular test relative to the control participants (n = 20). In the parvocellular condition, there was no significant difference between the two groups. The higher magnocellular contrast sensitivity values were associated with increased visual SIAPA scores, especially at the two lowest spatial frequencies (0.25 and 0.5 cycles/degree). These results indicate the heightened sensitivity of magnocellular pathways in unmedicated first-episode schizophrenia, which may contribute to anomalous perceptual experiences and sensory overloading. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spectral characteristics of sleep EEG in chronic insomnia

To determine whether the spectral characteristics of the sleep electroencephalogram (EEG) of insomniacs differ from that of healthy subjects, we compared in each of the first four non-rapid eye movement (NREM) and rapid eye movement (REM) episodes: (a) the time courses of absolute power, averaged over the subjects in each group, for the delta, theta, alpha, sigma and beta frequency bands; (b) the relationship between these time courses; and (c) the overnight trend of integrated power in each frequency band. The results show that NREM power, for all frequencies below the beta range, has slower rise rates and reaches lower levels in the insomniac group, whereas beta power is significantly increased. In REM, insomniacs show lower levels in the delta and theta bands, whereas power in the faster frequency bands is significantly increased. Thus, the pathophysiology of insomnia is characterized not only by the generally acknowledged slow wave deficiency, but also by an excessive hyperarousal of the central nervous system throughout the night, affecting both REM and NREM sleep. This hyperarousal is interpreted in terms of the neuronal group theory of sleep which provides a possible explanation for the discrepancies observed between subjective impressions and objective measures of sleep. Also, it is suggested that the progressive hyperpolarization of the thalamocortical neurons as sleep deepens is slower in the patient population and that this may explain the observed slow wave deficiency. The homeostatic control of slow wave activity, on the other hand, would appear to be intact in the patient population.     

Parental perspectives on chronic schizophrenia

Parents of chronic schizophrenics are an understudied population. Few researchers have asked them about their wants, needs, and difficulties. The little work that has been done indicates that their suffering is great, their coping skills better than had been previously assumed, and the stresses they are experiencing almost unendurable. This paper looks at what parents are coping with: a child with a terribly debilitating disease about which little is known, a culture which heaps stigma and shame upon them, very difficult and often unworkable mental health and legal systems, and to top it all off, a large number of clinical (non-researchers) professionals who are ignorant about schizophrenia and often unsympathetic towards the parents. This paper then looks at what little data we have from parents about their needs, and offers suggestions about how parents and professionals might best work together, towards the benefit of all concerned.     

Electrodermal activity and clinical status in chronic schizophrenia.

Investigated the association between electrodermal nonresponsiveness and clinical state in schizophrenia. 63 patients with a Diagnostic and Statistical Manual of Mental Disorders-III (DSM-III) diagnosis of chronic schizophrenia served as Ss. Clinical status was assessed using multiple measures, including age of onset, symptom severity, illness duration, hospitalization history, global functioning, and occupational functioning. Electrodermal hypoactivity was found to be associated with poorer functioning and a more severe form of illness. In addition, hyporesponsive patients displayed more conceptual disorganization and alogia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Emotion recognition and social competence in chronic schizophrenia.

This study evaluated (a) whether chronic, medicated schizophrenia patients show deficits in emotion recognition compared to nonpatients, and (b) whether deficits in emotion recognition are related to poorer social competence. Two emotion recognition tests developed by S. L. Kerr and J. M. Neale (1993) and Benton's Test of Facial Recognition (A. Benton, M. VanAllen, K. Hamsher, & H. Levin, 1978) were given to patients with chronic schizophrenia and nonpatient controls. Patients' social skills, social adjustment, and symptomatology were assessed. Like Kerr and Neale's unmedicated patients, these patients performed worse than controls on both emotion recognition tests and the control test. For patients, facial perception was related to the chronicity of illness and social competence. Chronicity of illness may contribute to face perception deficits in schizophrenia, which may affect social competence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interferon-alpha as adjuvant treatment in chronic schizophrenia

The therapeutic use of interferon (IFN)-alpha administered as adjuvant medication in chronic schizophrenia was investigated. Natural leukocyte IFN-alpha was given to 9 long-term hospitalized chronic schizophrenic patients daily as subcutaneous injection of 3 million units 5 times a week. The trial followed a placebo-controlled double-blind crossover design. Each treatment period lasted for 8 weeks with a 2-week washout period in between. IFN-alpha did not prove to be beneficial for the total group of patients. Yet, 3 patients improved during the IFN-alpha drug period. The clinical improvement was seen as better social competence and less affective tension in the ward surroundings.     

Intellectual deficit in chronic schizophrenia and brain damage.

Studied scores on the WAIS and the Halstead Battery of Neuropsychological Measures (HB) of 100 chronic schizophrenic and 100 brain-damaged patients divided into equal groups of younger (ages 26-59) and older (ages 60 and over) Ss. A significant interaction of WAIS scores with diagnosis and of HB scores with diagnosis and age was found. Pattern analysis indicate that the younger Ss in both groups differed in WAIS Comprehension and Digit Span and HB Category. Older Ss differed in WAIS Comprehension, Digit Span, Picture Completion, Block Design, and HB Speech Discrimination. Results suggest differing intellectual deficit patterns in chronic schizophrenia and brain damage. (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

EEG coherence following acute and chronic clozapine in treatment-resistant schizophrenics.

Electroencephalographic (EEG) coherence is an index of brain regional coupling that has been found to be abnormal in people with schizophrenia but has not been systematically examined in response to neuroleptics. EEG coherence in slow (delta and theta) frequencies was assessed in 17 treatment-resistant people with schizophrenia at baseline, 2 hr after their first oral dose (25 mg) and after 6 weeks of clozapine treatment. Compared with EEG norms, participants exhibited significant interhemispheric and intrahemispheric coherence abnormalities prior to treatment. Both acute and chronic treatments altered coherence but differed with respect to their relationship to symptom reduction and their ability to normalize or augment pretreatment abnormalities. Findings are discussed in relation to "disconnection" theories of schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)