Vocational rehabilitation improves cognition and negative symptoms in schizophrenia

Several studies in schizophrenia found a positive association between cognitive performance and work status, and it has been reported that good cognitive performance at the outset does predict the success of vocational interventions. However little has been done to investigate whether vocational interventions itself benefit cognitive performance. To test this hypothesis we performed a randomized, placebo-controlled trial to investigate in remitted schizophrenic patients the effect of a 6-months vocational rehabilitation program on cognitive performance. We recruited 112 remitted and clinically stable schizophrenic patients who aimed to enter a vocational rehabilitation program. From these, 57 immediately entered a 6-months vocational rehabilitation program, whereas the remaining 55 were allocated to a waiting-list; the latter formed our control group, which received during the 6 months out-clinic follow-up treatment. Before and after the 6-months period we assessed changes in cognitive performance through a neuropsychological test battery, as well as changes in the psychopathological status and in quality of life. We found that vocational rehabilitation significantly improved patients` performance in cognitive measures that assess executive functions (concept formation, shifting ability, flexibility, inhibitory control, and judgment and critics abilities). Moreover, after 6 months the vocational group improved significantly in the negative symptoms and in quality of life, as compared to controls. Together with results from the literature, our findings reinforce the notion that the inclusion of vocational interventions may enhance the effectiveness of therapeutic strategies for schizophrenia patients. (C) 2010 Elsevier B.V. All rights reserved.

Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment

The onset and early course of schizophrenia is associated with subtle loss of grey matter which may be responsible for the evolution and persistence of symptoms such as apathy, emotional blunting, and social withdrawal. Such 'negative' symptoms are unaffected by current antipsychotic therapies. There is evidence that the antibiotic minocycline has neuroprotective properties. We investigated whether the addition of minocycline to treatment as usual (TAU) for 1 year in early psychosis would reduce negative symptoms compared with placebo. In total, 144 participants within 5 years of first onset in Brazil and Pakistan were randomised to receive TAU plus placebo or minocycline. The primary outcome measures were the negative and positive syndrome ratings using the Positive and Negative Syndrome Scale. Some 94 patients completed the trial. The mean improvement in negative symptoms for the minocycline group was 9.2 and in the placebo group 4.7, an adjusted difference of 3.53 (s.e. 1.01) 95% CI: 1.55, 5.51; p < 0.001 in the intention-to-treat population. The effect was present in both countries. The addition of minocycline to TAU early in the course of schizophrenia predominantly improves negative symptoms. Whether this is mediated by neuroprotective, anti-inflammatory or others actions is under investigation.

Video-based quantification of body movement during social interaction indicates the severity of negative symptoms in patients with schizophrenia

In schizophrenia, nonverbal behavior, including body movement, is of theoretical and clinical importance. Although reduced nonverbal expressiveness is a major component of the negative symptoms encountered in schizophrenia, few studies have objectively assessed body movement during social interaction. In the present study, 378 brief, videotaped role-play scenes involving 27 stabilized outpatients diagnosed with paranoid-type schizophrenia were analyzed using Motion Energy Analysis (MEA). This method enables the objective measuring of body movement in conjunction with ordinary video recordings. Correlations between movement parameters (percentage of time in movement, movement speed) and symptom ratings from independent PANSS interviews were calculated. Movement parameters proved to be highly reliable. In keeping with predictions, reduced movement and movement speed correlated with negative symptoms. Accordingly, in patients who exhibited noticeable movement for less than 20% of the observation time, prominent negative symptoms were highly probable. As a control measure, the percentage of movement exhibited by the patients during role-play scenes was compared to that of their normal interactants. Patients with negative symptoms differed from normal interactants by showing significantly reduced head and body movement. Two specific positive symptoms were possibly related to movement parameters: suspiciousness tended to correlate with reduced head movement, and the expression of unusual thought content tended to relate to increased movement. Overall, a close and theoretically meaningful association between the objective movement parameters and the symptom profiles was found. MEA appears to be an objective, reliable and valid method for quantifying nonverbal behavior, an aspect which may furnish new insights into the processes related to reduced expressiveness in schizophrenia.

White matter pathway organization of the reward system is related to positive and negative symptoms in schizophrenia

The reward systemin schizophrenia has been linked to the emergence of delusions on the one hand and to negative symptoms such as affective flattening on the other hand. Previous Diffusion Tensor Imaging (DTI) studies reported white matter microstructure alterations of regions related to the reward system. The present study aimed at extending these findings by specifically investigating connection pathways of the reward system in schizophrenia. Therefore, 24 patients with schizophrenia and 22 healthy controls matched for age and gender underwent DTI-scans. Using a probabilistic fiber tracking approachwe bilaterally extracted pathways connecting the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), themedial and lateral orbitofrontal cortices (mOFC, lOFC), the dorsolateral prefrontal cortex (dlPFC) and the amygdala; as well as pathways connecting NAcc with mOFC, lOFC, dlPFC and amygdala resulting in a total of 18 connections. Probability indices forming part of a bundle of interest (PIBI) were compared between groups using independent t-tests. In 6 connection pathways PIBI-valueswere increased in schizophrenia. In 3 of these pathways the spatial extension of connection pathways was decreased. In schizophrenia patients, there was a negative correlation of PIBI-values and PANSS negative scores in the left VTA–amygdala and in the left NAcc–mOFC connection. A sum score of delusions and hallucinations correlated positively with PIBI-values of the left amygdala–NAcc connection. Structural organization of specific segments ofwhite matter pathways of the reward systemin schizophrenia may contribute to the emergence of delusions and negative symptoms in schizophrenia.

Video-based quantification of body movement indicates negative symptoms: a replication

Objective: In schizophrenia, abnormalities in nonverbal behaviors have always been considered as highly relevant. However, due to methodological limitations, nonverbal behavior was rarely quantified objectively. Recent methodological advances now allow a quantification of body movement from ordinary video recordings. We showed that patients’ objectively measured amount of movement in social role-play interactions was closely associated with their symptom profiles (Kupper, Ramseyer, Hoffmann, & Tschacher, Schizophrenia Research 2010). In the present study, a replication of these results in the context of semi-standardized PANSS (Positive and Negative Syndrome Scale) interviews was intended. Methods: 17 patients with schizophrenia were analyzed during the initial 15-min sequence of a videotaped PANSS interview using Motion Energy Analysis (MEA). The amount of patients’ movement was then correlated with their PANSS symptom scores. Results: Sizeable and significant correlations between negative symptoms and reduced movements (r = -.68, p<0.01) and reduced movement speed (r = -.80, p<0.001) were found. Moreover, cognitive symptoms were related to reduced movement speed (r = -.70, p<.01). Conclusion: Negative symptoms were reliably indicated by patients’ nonverbal behavior in psychopathology interviews. Hence, the main result of our earlier study, examining patients’ nonverbal behavior in role play tests, was replicated for the less structured interactions in psychopathological interviews. Results could encourage the use of MEA in a wide range of videotaped social interactions of patients with schizophrenia and other psychiatric disorders.

Social Cognition, Negative Symptoms and Psychosocial Functioning in Schizophrenia.

Although functional recovery could be advocated as an achievable treatment goal, many effective interventions for the treatment of psychotic symptoms, such as antipsychotic drugs, may not improve functioning. The last two decades of cognitive and clinical research on schizophrenia were a turning point for the firm acknowledgment of how relevant social cognitive deficits and negative symptoms could be in predicting psychosocial functioning. The relevance of social cognition dysfunction in schizophrenia patients’ daily living is now unabated. In fact, social cognition deficits could be the most significant predictor of functionality in patients with schizophrenia, non-redundantly with neurocognition. Emerging evidence suggests that negative symptoms appear to play an indirect role, mediating the relationship between neurocognition and social cognition with functional outcomes. Further explorations of this mediating role of negative symptoms have revealed that motivational deficits appear to be particularly important in explaining the relationship between both neurocognitive and social cognitive dysfunction and functional outcomes in schizophrenia. In this paper we will address the relative contribution of two key constructs—social cognitive deficits and negative symptoms, namely how intertwined they could be in daily life functioning of patients with schizophrenia.

Negative symptoms of schizophrenia and psychosocial treatment: thematic analysis of stakeholders’ perspectives

Objectives. Recent literature indicates variance in psychosocial treatment preferences for negative symptoms of schizophrenia. Attempts at defining therapeutic aims and outcomes for negative symptoms to date have not included major stakeholder groups. The aim of the present study was to address this gap through qualitative methods. Design. Thematic Analysis was applied to qualitative semi-structured interview data to gather the opinions of people who experience negative symptoms, carers, and healthcare professionals. Participants were recruited from two mental health sites (inpatient/community) to increase generalisability of results. Ten people participated in the research. Methods. Semi-structured interview scripts were designed utilising evidence from the review in Chapter 1 of effective psychosocial intervention components for specific negative symptoms. Interviews were audio recorded and transcribed verbatim. Thematic analysis was employed to analyse data. Results. A common theme across groups was the need for a personalised approach to intervention for negative symptoms. Other themes indicated different opinions in relation to treatment targets and the need for a sensitive and graded approach to all aspects of therapy. This approach needs to be supported across systemic levels of organisation with specific training needs for staff addressed. Conclusions. There is disparity in treatment preferences for negative symptoms across major stakeholders. The findings suggest an individualised approach to intervention of negative symptoms that is consistent with recovery. Implementation barriers and facilitators were identified and discussed. There remains a need to develop a better understanding of treatment preferences for patients.

Working memory in schizophrenia and mania: Correlation with symptoms during the acute and subacute phases

Objective: The aims of this study were to examine working memory in the acute-subacute phase of schizophrenia and mania and to examine correlations between working memory and specific symptom domains. Method: Visuospatial working memory and symptom profiles were assessed in three groups (schizophrenia group, n=19; mania, n=12; controls, n=19) on two occasions separated by 4 weeks. Results: Both patient groups had significant deficits on working memory compared to the well controls and the schizophrenia and mania groups were equally impaired. All groups showed equivalent improvement over time. In the patient groups, impaired working memory was significantly correlated with the presence of both negative symptoms and positive thought disorder. Conclusion: Impaired wet-king memory is found in both schizophrenia and mania during the acute-subacute phases. Further research is required in order to clarify the neurocognitive mechanisms linking impaired working memory with both negative symptoms and positive thought disorder.

Basic symptoms and the prediction of first-episode psychosis

Recent focus on early detection and intervention in psychosis has renewed interest in subtle psychopathology beyond positive and negative symptoms. Such self-experienced sub-clinical disturbances are described in detail by the basic symptom concept. This review will give an introduction into the concept of basic symptoms and describe the development of the current instruments for their assessment, the Schizophrenia Proneness Instrument, Adult (SPI-A) and Child and Youth version (SPI-CY), as well as of the two at-risk criteria: the at-risk criterion Cognitive-Perceptive Basic Symptoms (COPER) and the high-risk criterion Cognitive Disturbances (COGDIS). Further, an overview of prospective studies using both or either basic symptom criteria and transition rates related to these will be given, and the potential benefit of combining ultra-high risk criteria, particularly attenuated psychotic symptoms, and basic symptom criteria will be discussed. Finally, their prevalence in psychosis patients, i.e. the sensitivity, as well as in general population samples will be described. It is concluded that both COPER and COGDIS are able to identify subjects at a high risk of developing psychosis. Further, they appear to be sufficiently frequent prior to onset of the first psychotic episode as well as sufficiently rare in persons of general population to be considered as valuable for an early detection of psychosis.

Motor symptoms and schizophrenia

Classical schizophrenia literature reports motor symptoms as characteristic of the disorder. After the introduction of neuroleptic drugs, the existence of genuine motor disorders was challenged. Renewed interest arose as symptoms were found in never-medicated patients. Reports focused on abnormal involuntary movements, parkinsonism, neurological soft signs, catatonia, negative symptoms, or psychomotor slowing. Since these syndromes refer to different concepts, however, the definitions are not congruent and the symptoms overlap. The prevalence rates of motor symptoms in schizophrenia are surprisingly high, and recent studies indicate a possible pathobiology. In particular, the development and maturation of the human motor system appears to be closely linked to the emergence of motor symptoms observed in schizophrenia. Post-mortem and neuroimaging results demonstrated aberrant structure and function of premotor and motor cortices, basal ganglia, thalamus, and the connecting white matter tracts. Animal models have focused on aberrant neurotransmission and genetic contributions. Findings of localized abnormal oligodendrocyte function and myelination point to the special role of the white matter in schizophrenia, and recent studies specifically found an association between motor abnormalities and white matter structure in schizophrenia. This review of the literature supports the idea that motor symptoms are closely related to the neurodevelopmental disturbances of schizophrenia and a distinct syndromal dimension with its own pathophysiology.

Head movement synchrony in social interactions of patients with schizophrenia indicates symptoms, cognition and social functioning

Background: Disturbed interpersonal communication is a core problem in schizophrenia. Patients with schizophrenia often appear disconnected and "out of sync" when interacting with others. This may involve perception, cognition, motor behavior, and nonverbal expressiveness. Although well-known from clinical observation, mainstream research has neglected this area. Corresponding theoretical concepts, statistical methods, and assessment were missing. In recent research, however, it has been shown that objective, video-based measures of nonverbal behavior can be used to reliably quantify nonverbal behavior in schizophrenia. Newly developed algorithms allow for a calculation of movement synchrony. We found that the objective amount of movement of patients with schizophrenia during social interactions was closely related to the symptom profiles of these patients (Kupper et al., 2010). In addition and above the mere amount of movement, the degree of synchrony between patients and healthy interactants may be indicative of various problems in the domain of interpersonal communication and social cognition. Methods: Based on our earlier study, head movement synchrony was assessed objectively (using Motion Energy Analysis, MEA) in 378 brief, videotaped role-play scenes involving 27 stabilized outpatients diagnosed with paranoid-type schizophrenia. Results: Lower head movement synchrony was indicative of symptoms (negative symptoms, but also of conceptual disorganization and lack of insight), verbal memory, patients’ self-evaluation of competence, and social functioning. Many of these relationships remained significant even when corrected for the amount of movement of the patients. Conclusion: The results suggest that nonverbal synchrony may be an objective and sensitive indicator of the severity of symptoms, cognition and social functioning.

Dimensional approaches to schizophrenia: A comparison of the Bern Psychopathology scale and the five-factor model of the Positive and Negative Syndrome Scale

The aim was to examine to what extent the dimensions of the BPS map the five factors derived from the PANSS in order to explore the level of agreement of these alternative dimensional approaches in patients with schizophrenia. 149 inpatients with schizophrenia spectrum disorders were recruited. Psychopathological symptoms were assessed with the Bern Psychopathology Scale (BPS) and the Positive and Negative Syndrome Scale (PANSS). Linear regression analyses were conducted to explore the association between the factors and the items of the BPS. The robustness of patterns was evaluated. An understandable overlap of both approaches was found for positive and negative symptoms and excitement. The PANSS positive factor was associated with symptoms of the affect domain in terms of both inhibition and disinhibition, the PANSS negative factor with symptoms of all three domains of the BPS as an inhibition and the PANSS excitement factor with an inhibition of the affect domain and a disinhibition of the language and motor domains. The results show that here is only a partial overlap between the system-specific approach of the BPS and the five-factor PANSS model. A longitudinal assessment of psychopathological symptoms would therefore be of interest.

Neural activity during object perception in schizophrenia patients is associated with illness duration and affective symptoms

Background - Abnormalities in visual processes have been observed in schizophrenia patients and have been associated with alteration of the lateral occipital complex and visual cortex. However, the relationship of these abnormalities with clinical symptomatology is largely unknown. Methods - We investigated the brain activity associated with object perception in schizophrenia. Pictures of common objects were presented to 26 healthy participants (age = 36.9; 11 females) and 20 schizophrenia patients (age = 39.9; 8 females) in an fMRI study. Results - In the healthy sample the presentation of pictures yielded significant activation (pFWE (cluster) < 0.001) of the bilateral fusiform gyrus, bilateral lingual gyrus, and bilateral middle occipital gyrus. In patients, the bilateral fusiform gyrus and bilateral lingual gyrus were significantly activated (pFWE (cluster) < 0.001), but not so the middle occipital gyrus. However, significant bilateral activation of the middle occipital gyrus (pFWE (cluster) < 0.05) was revealed when illness duration was controlled for. Depression was significantly associated with increased activation, and anxiety with decreased activation, of the right middle occipital gyrus and several other brain areas in the patient group. No association with positive or negative symptoms was revealed. Conclusions - Illness duration accounts for the weak activation of the middle occipital gyrus in patients during picture presentation. Affective symptoms, but not positive or negative symptoms, influence the activation of the right middle occipital gyrus and other brain areas.

Further evidence for a deficit in switching attention in schizophrenia

In this study, sustained, selective, divided, and switching attention, and reloading of working memory were investigated in schizophrenia by using a newly developed Visual Attention Battery (VAB). Twenty-four outpatients with schizophrenia and 24 control participants were studied using the VAB. Performance on VAB components was correlated with performance of standard tests. Patients with schizophrenia were significantly impaired on VAB tasks that required switching of attention and reloading of working memory but had normal performance on tasks involving sustained attention or attention to multiple stimulus features. Switching attention and reloading of working memory were highly correlated with Trails (B - A) score for patients. The decline in performance on the switching-attention task in patients with schizophrenia met criteria for a differential deficit in switching attention. Future research should examine the neurophysiological basis of the switching deficit and its sensitivity and specificity to schizophrenia.

Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of schizophrenia and related disorders

Background: The Royal Australian and New Zealand College of Psychiatrists is co-ordinating the development of clinical practice guidelines (CPGs) in psychiatry, funded under the National Mental Health Strategy (Australia) and the New Zealand Health Funding Authority. This paper presents CPGs for schizophrenia and related disorders. Over the past decade schizophrenia has become more treatable than ever before. A new generation of drug therapies, a renaissance of psychological and psychosocial interventions and a first generation of reform within the specialist mental health system have combined to create an evidence-based climate of realistic optimism. Progressive neuroscientific advances hold out the strong possibility of more definitive biological treatments in the near future. However, this improved potential for better outcomes and quality of life for people with schizophrenia has not been translated into reality in Australia. The efficacy-effectiveness gap is wider for schizophrenia than any other serious medical disorder. Therapeutic nihilism, under-resourcing of services and a stalling of the service reform process, poor morale within specialist mental health services, a lack of broad-based recovery and life support programs, and a climate of tenacious stigma and consequent lack of concern for people with schizophrenia are the contributory causes for this failure to effectively treat. These guidelines therefore tackle only one element in the endeavour to reduce the impact of schizophrenia. They distil the current evidence-base and make recommendations based on the best available knowledge. Method: A comprehensive literature review (1990-2003) was conducted, including all Cochrane schizophrenia reviews and all relevant meta-analyses, and a number of recent international clinical practice guidelines were consulted. A series of drafts were refined by the expert committee and enhanced through a bi-national consultation process. Treatment recommendations: This guideline provides evidence-based recommendations for the management of schizophrenia by treatment type and by phase of illness. The essential features of the guidelines are: (i) Early detection and comprehensive treatment of first episode cases is a priority since the psychosocial and possibly the biological impact of illness can be minimized and outcome improved. An optimistic attitude on the part of health professionals is an essential ingredient from the outset and across all phases of illness. (ii) Comprehensive and sustained intervention should be assured during the initial 3-5 years following diagnosis since course of illness is strongly influenced by what occurs in this 'critical period'. Patients should not have to 'prove chronicity' before they gain consistent access and tenure to specialist mental health services. (iii) Antipsychotic medication is the cornerstone of treatment. These medicines have improved in quality and tolerability, yet should be used cautiously and in a more targeted manner than in the past. The treatment of choice for most patients is now the novel antipsychotic medications because of their superior tolerability and, in particular, the reduced risk of tardive dyskinesia. This is particularly so for the first episode patient where, due to superior tolerability, novel agents are the first, second and third line choice. These novel agents are nevertheless associated with potentially serious medium to long-term side-effects of their own for which patients must be carefully monitored. Conventional antipsychotic medications in low dosage may still have a role in a small proportion of patients, where there has been full remission and good tolerability; however, the indications are shrinking progressively. These principles are now accepted in most developed countries. (vi) Clozapine should be used early in the course, as soon as treatment resistance to at least two antipsychotics has been demonstrated. This usually means incomplete remission of positive symptomatology, but clozapine may also be considered where there are pervasive negative symptoms or significant or persistent suicidal risk is present. (v) Comprehensive psychosocial interventions should be routinely available to all patients and their families, and provided by appropriately trained mental health professionals with time to devote to the task. This includes family interventions, cognitive-behaviour therapy, vocational rehabilitation and other forms of therapy, especially for comorbid conditions, such as substance abuse, depression and anxiety. (vi) The social and cultural environment of people with schizophrenia is an essential arena for intervention. Adequate shelter, financial security, access to meaningful social roles and availability of social support are essential components of recovery and quality of life. (vii) Interventions should be carefully tailored to phase and stage of illness, and to gender and cultural background. (viii) Genuine involvement of consumers and relatives in service development and provision should be standard. (ix) Maintenance of good physical health and prevention and early treatment of serious medical illness has been seriously neglected in the management of schizophrenia, and results in premature death and widespread morbidity. Quality of medical care for people with schizophrenia should be equivalent to the general community standard. (x) General practitioners (GPs)s should always be closely involved in the care of people with schizophrenia. However, this should be truly shared care, and sole care by a GP with minimal or no special Optimal treatment of schizophrenia requires a multidisciplinary team approach with a consultant psychiatrist centrally involved.