Verbal fluency as a possible predictor for psychosis

BackgroundNeurocognitive abnormalities are prevalent in both first episode schizophrenia patients and in ultra high risk (UHR) patients.AimTo compare verbal fluency performance at baseline in UHR in patients that did and did not make the transition to psychosis.MethodBaseline verbal fluency performance in UHR-patients (n = 47) was compared to match first episode patients (n = 69) and normal controls (n = 42).ResultsVerbal fluency (semantic category) scores in UHR-patients did not differ significantly from the score in first episode schizophrenia patients. Both the UHR group (p < 0.003) and the patient group (p < 0.0001) performed significantly worse than controls. Compared to the non-transition group, the transition group performed worse on verbal fluency, semantic category (p < 0.006) at baseline.ConclusionsVerbal fluency (semantic category) is disturbed in UHR-patients that make the transition to psychosis and could contribute to an improved prediction of transition to psychosis in UHR-patients.     

A longitudinal study of neurocognitive function in individuals at-risk for psychosis

IntroductionClinically defined prodromal diagnostic criteria identify at-risk individuals with a 35–40% likelihood of developing a psychotic disorder within a year. The time course and predictive value of cognitive deficits in the development of psychosis has not been established.MethodsA comprehensive neurocognitive battery and clinical assessments were administered to 37 subjects meeting Criteria of Prodromal States (COPS) criteria for being at risk for psychosis, and two comparison groups: 59 first episode and 47 healthy subjects. Subjects were also evaluated at 6-month and 1-year follow-up periods. Primary analyses used a neurocognitive composite score derived from individual neurocognitive measures, including measures of vigilance, verbal memory, working memory, and processing speed.ResultsAt-risk subjects performed more poorly than healthy subjects (t = 2.93, P = 0.01), but better than first episode subjects (t = 4.72, p < 0.0001). At-risk subjects were particularly impaired on measures of vigilance and processing speed. Cognitive composite scores were significantly lower in at-risk subjects who progressed to psychosis (N = 11; z = − 1.2), while those at-risk subjects who did not progress to psychosis (N = 17) performed better (z = − 0.5), and not significantly different from controls. Poor CPT performance combined with better WAIS-R digit symbol performance predicted progression to psychosis. Severity of neurocognitive deficits was not related to duration of prodrome or to time to development of psychosis and neurocognitive function improved in all subjects except those who progressed to psychosis.ConclusionNeurocognitive impairment emerges early in the course of psychotic illness. Performance on tests of neurocognition may prove to be an early risk predictor for subsequent development of psychotic disorders.     

Characteristic brain hypoperfusion by 99mTc-ECD single photon emission computed tomography (SPECT) in patients with the first-episode schizophrenia

ObjectiveIn this study, we evaluated brain perfusion in patients with first-episode medicated schizophrenia using the new analytical method, statistical parametric mapping (SPM) applied to single photon emission computed tomography (SPECT).MethodWe performed SPECT with 99-Tc-ethyl cysteinate dimer (99mTc-ECD) of the brain and magnetic resonance imaging (MRI) in patients with schizophrenia (n = 30) and control subjects matched for age and gender (n = 37). A voxel-by-voxel group analysis was performed using SPM2 (Z > 3.0, P < 0.001, uncorrected for multiple comparisons).ResultIn comparison with control subjects, the volumes of the bilateral frontal areas were found to be decreased on MRI. Blood flow was found to be reduced in the bilateral temporal areas in the patients with schizophrenia on SPECT.ConclusionIn this study, patients with first-episode schizophrenia appeared to have significant bilateral temporal hypoperfusion, although temporal volumes were not significantly decreased in comparison with control subjects. Abnormality of temporal lobe blood flow in schizophrenia may show that functional changes occur earlier than structural changes, and may assist in the diagnosis of schizophrenia.     

Protéine C-réactive et agitation chez des patients atteints de schizophrénie : suivi d’une cohorte avec groupe témoin

BackgroundRecent studies first reported the relevant role of the immune system in the pathophysiology of schizophrenia and then the association between inflammation and agitation.ObjectivesIn this study, we aim to explore the relationship between CRP (C-reactive protein) levels and agitation in patients with schizophrenia.MethodsWe conducted a cohort study with a comparison group of 60 patients with a DSM5 diagnosis of schizophrenia who were followed by the Department of Psychiatry of the University Hospital of Marrakech in Morocco. Patients were divided into two groups according to the state of agitation evaluated by the PANSS Excitement scale. These two groups have been matched according to age and gender. A comparison of CRP level, clinical and laboratory characteristics between the two groups and a monitoring of CRP level in the agitated group after 3 weeks of treatment were performed.ResultsInpatients with agitation displayed a significantly high CRP (P < 0.0001), a high score of PANSS total (P < 0.0001), PANSS positive (P < 0.0001) and general PANSS (P < 0.0001). After treatment, there was a significant reduction in CRP (P < 0.0001) and PANSS excitement (P < 0.0001).ConclusionThese results confirm the role played by inflammation and immunity in agitation behavior in patients with schizophrenia and highlight the interest of the CRP assay at the time of admission of patients as a potential marker of agitation in hospitalized patients with schizophrenia.     

Decreased processing speed might account for working memory span deficit in schizophrenia,and might mediate the associations between working memory span and clinical symptoms

ObjectiveVerbal working memory span is decreased in patients with schizophrenia, and this might contribute to impairment in higher cognitive functions as well as to the formation of certain clinical symptoms. Processing speed has been identified as a crucial factor in cognitive efficiency in this population. We tested the hypothesis that decreased processing speed underlies the verbal working memory deficit in patients and mediates the associations between working memory span and clinical symptoms.MethodForty-nine schizophrenia inpatients recruited from units for chronic and acute patients, and forty-five healthy participants, were involved in the study. Verbal working memory span was assessed by means of the letter-number span. The Digit Copy test was used to assess motor speed, and the Digit Symbol Substitution Test to assess cognitive speed.ResultsThe working memory span was significantly impaired in patients (F(1,90) = 4.6, P < 0.05). However, the group difference was eliminated when either the motor or the cognitive speed measure was controlled (F(1,89) = 0.03, P = 0.86, and F(1,89) = 0.03, P = 0.88). In the patient group, working memory span was significantly correlated with negative symptoms (r = –0.52, P < 0.0001) and thought disorganisation (r = –0.34, P < 0.025) scores. Regression analyses showed that the association with negative symptoms was no longer significant when the motor speed measure was controlled (β = –0.12, P = 0.20), while the association with thought disorganisation was no longer significant when the cognitive speed measure was controlled (β = –0.10, P = 0.26).ConclusionsDecrement in motor and cognitive speed plays a significant role in both the verbal working memory impairment observed in patients and the associations between verbal working memory impairment and clinical symptoms.     

Double blind trial of adjunctive valacyclovir in individuals with schizophrenia who are seropositive for cytomegalovirus

ObjectiveTo investigate if adjunctive valacyclovir, an antiviral medication, reduces symptoms of persistent schizophrenia in individuals who are seropositive for cytomegalovirus (CMV).MethodN = 47 CMV seropositive schizophrenia outpatients were randomly assigned to receive valacyclovir 1 g twice daily (n = 24) or placebo (n = 23) for 16 weeks after a 2-week placebo run-in. Symptoms were assessed biweekly.ResultsThere was no significant difference in the change of positive, negative, general, or total PANSS symptoms between the valacyclovir vs. the placebo group.ConclusionsThe study did not demonstrate benefit of adjunctive valacyclovir for schizophrenia individuals with persistent symptoms who are CMV seropositive.     

Sleep quality and cognitive impairments in remitted patients with schizophrenia in Nigeria

BackgroundDespite the ubiquity of sleep disturbance in schizophrenia, it has generally been overlooked as a potential contributor to cognitive impairments. The main aim of this study was to find out if impaired sleep quality contributes to cognitive impairments in patients with a diagnosis of schizophrenia who are in remission.MethodsThe study was conducted at the University College Hospital, Ibadan and State Hospital, Ibadan, Nigeria. The Pittsburgh Sleep Quality Index (PSQI) and Screen for Cognitive Impairment in Psychiatry (SCIP) were applied in this cross-sectional study, to all consecutive and consenting remitted outpatients with schizophrenia (N = 130). Other instruments such as Hamilton Depression Rating Scale (HDRS), the Positive and Negative Syndrome Scale (PANSS), sociodemographic and clinical measures were also applied.ResultsThere were 130 participants made up of 69 females (53.1%) and 61males(46.9%). The mean age of the participants was 38.5 ± 9.1 years. The prevalence of poor sleep quality in remitted patients with schizophrenia was 56.9%. Sleep quality was significantly negatively correlated with Verbal Learning Test-Immediate (VLT-I) (r(128) = -.18, P = .044) and Verbal Learning Test-Delayed (VLT-D) (r(128) = -.18, P = .037). The variables that independently predicted cognitive functioning were the VLT-I, odds ratio (OR) 0.66; 95% confidence interval ((CI) 0.49-0.88) and education (OR) 0.61;(CI) 0.40- 0.92).ConclusionPoor subjective sleep quality measured by the PSQI is linked to cognitive impairment in remitted patients with schizophrenia. We suggest that sleep quality in remitted patients with a diagnosis of schizophrenia should receive better attention by physicians.     

Neurocognitive improvements after best-practice intervention for chronic fatigue syndrome: Preliminary evidence of divergence between objective indices and subjective perceptions

BackgroundNeurocognitive difficulties are commonly reported by patients suffering from chronic fatigue syndrome (CFS). Moderate improvements from ‘best practice’ therapy are promising, but to date reported efficacy is based entirely on subjective measures. This is problematic, given the well-documented divergence between subjective perceptions and actual neurocognitive performance, including in this patient group.Material and MethodsSubjective and objective measures of neurocognitive performance were obtained from 25 patients with well-characterized CFS before and after the completion of a 12-week graded-activity program incorporating a cognitive training component. Additionally, self-reported symptoms, cardiac autonomic activity (a relevant biomarker of stress responsivity), and their relation to neurocognitive improvements were examined.ResultsSubstantive post-intervention improvements in subjective (p = 0.006) and objective (including faster responses speeds and greater accuracy, p's < 0.001) neurocognitive performance were documented. Participants also demonstrated reduced autonomic reactivity to the cognitive challenge at follow-up (p's ≤ 0.01). These improvements were accompanied by improvements in symptom ratings (p's ≤ 0.01). However, subjective ratings of neurocognitive difficulties, and CFS-related symptoms were not linked to objective performance improvements.ConclusionsThese initial data provide the first evidence of objective neurocognitive performance improvements accompanied by a significant reduction in responsiveness in stress-related neural pathways consequent to cognitive-behavioral/graded exercise therapy programs. These findings provide support for the effectiveness of such programs in remediating clinical status. These promising findings warrant further investigation, including replication in a larger sample utilizing more controlled study designs.     

TCF4 gene polymorphism and cognitive performance in patients with first episode psychosis

BackgroundSingle nucleotide polymorphisms in TCF4 gene have been consistently associated with schizophrenia in genome wide association studies, including the C allele of rs9960767. However, its exact role in modulating the schizophrenia phenotype is not known.AimsTo comprehensively investigate the relationship between rs9960767 risk allele (C) of TCF4 and cognitive performance in patients with first episode psychosis (FEP).Methods173 patients with FEP received a comprehensive neurocognitive evaluation and were genotyped for rs9960767. Carriers of the risk allele (CA/CC) were compared to non-carriers (AA) using Multivariate Analysis of Covariance MANCOVA. Ethnicity, negative symptoms and substance abuse were included as covariates.ResultsCarriers of the risk allele had a statistically significant lower performance in the cognitive domain of Reasoning/Problem-Solving compared to non-carriers (F_1,172 = 4.4, p = .038). There were no significant genotype effects on the other cognitive domains or general cognition. This effect on the Reasoning/Problem-Solving domain remained significant even when controlling for IQ (F_1,172 = 4.3, p = .039).Conclusionsrs9960767 (C) of TCF4 appears to be associated with neurocognitive deficits in the Reasoning/Problem-Solving cognitive domain, in patients with FEP. A confirmation of this finding in a larger sample and including other TCF4 polymorphisms will be needed to gain further validity of this result.     

Comparing how co-morbid depression affects individual domains of functioning and life satisfaction in schizophrenia

ObjectiveDepression in schizophrenia is often associated with reduced life satisfaction. Yet, it is not clear how depression influences different functioning domains. The relative impact across objective and subjective quality of life (QOL) has also not been clearly compared. This study sought to examine the differences in individual QOL indicators between schizophrenia patients with and without co-morbid depression. This was completed separately for objective and subjective QOL.Method57 patients with schizophrenia/schizoaffective disorder were classified into groups with (DP: N = 31, M = 45.81, SD = 10.29) and without depression (NDP: N = 26, M = 40.54, SD = 11.00) using MADRS scores. Objective and subjective QOL was assessed using Lehman's (1988) QOL Interview using five domains: daily activities and functioning, family relations, social relations, safety and health. z-scores were created for these domains (objective and subjective) based on responses from 44 healthy controls (M = 39.80, SD = 13.94).ResultsObjectively, DP patients had significantly reduced social interaction frequency compared to HCs. Subjectively, DP patients had significantly poorer scores than HCs on all five domains, and additionally reported poorer satisfaction with daily activities and health compared with the NDP group.ConclusionsPresence of depression in schizophrenia results in reduced self-reported life satisfaction across a broad spectrum of QOL domains. Objectively, depression resulted in decreased interactions with friends and peers, i.e. greater social isolation. The findings support the need to continue developing and implementing peer support groups in schizophrenia, a challenging task especially in the face of depression. More broadly, the assessment of depression in other illnesses is recommended.     

Interleukin 18 and cognitive impairment in first episode and drug naïve schizophrenia versus healthy controls

Alterations in the inflammatory and immune systems have been documented to occur from the earliest stages of schizophrenia, and have been associated with neurodevelopmental changes. Cognitive impairment is a core feature in the pathology of schizophrenia, and recent studies showed a significant increase in serum IL-18 in schizophrenia, and a putative role of IL-18 in neuroprogression and thus neurocognitive defects. The purpose of this study was to examine the association of IL-18 with cognitive deficits in schizophrenia. We recruited 77 first episode and drug naïve schizophrenic patients and 75 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-18 in both groups. Schizophrenic symptoms were assessed using the positive and negative syndrome scale (PANSS). We found that IL-18 levels were non-significantly higher in patients than controls (206.0 ± 92.9 pg/ml vs 193.2 ± 41.8 pg/ml, p = 0.28). Cognitive scores on the RBANS and nearly all of its five subscales (all p < 0.05) except for the Visuospatial/Constructional index (p > 0.05) were significantly lower in schizophrenic patients than normal controls. For the patients, IL-18 was positively associated with the Visuospatial/Constructional domain of cognitive deficits in schizophrenia. Our findings suggest that cognitive deficits occur during the acute stage of a schizophrenic episode, and IL-18 may be involved in Visuospatial/Constructional deficits of these patients.     

Association between altered physical activity and neurocognitive function among people with schizophrenia: A minimum 6-months' follow-up study

BackgroundThe long-term benefits of physical activity on neurocognitive function among patients with schizophrenia, specifically among inpatients, remain unclear. This preliminary study, with a minimum of 6-months' follow-up, examined alterations in physical activity and neurocognitive function in both inpatients and outpatients with schizophrenia.MethodsSymptoms and neurocognitive function were assessed at 2 intervals using the Positive and Negative Symptom Scale and Cognitrax, respectively. After each testing period, participants wore an accelerometer for 1 week to measure their levels and duration of physical activity. After the 6-months' follow-up (average duration, 235.9 ± 36.2 days), participants were divided into 2 groups based on either increased or decreased activity, as compared with baseline: increased-activity and decreased-activity groups.ResultsOf the 29 initially enrolled participants, 25 (mean age, 56.8 ± 11.8 years) completed the follow-up. Reaction times in the increased-activity group in daily activity (n = 10) improved as compared with the decreased-activity group (n = 15). Moreover, cognitive flexibility and executive function improved in the increased-activity group in steps (n = 7) compared with the decreased-activity group (n = 18). Finally, there was no association between the duration of moderate or vigorous exercise and neurocognitive function.ConclusionsTogether, our results suggest that increased daily activity and walking, but not high intensity activity, are associated with improved neurocognitive function in patients with schizophrenia.     

Effect of cannabidiol on schizophrenia based on randomized controlled trials: A meta-analysis

Studies and treatments of schizophrenia with cannabidiol (CBD) alone have been reported. However, there have been a variety of different results of the effects of CBD in schizophrenic patients based on the positive and negative syndrome scale (PANSS). Thus, the present meta-analysis aimed to determine the effects of CBD on schizophrenia. We searched internet databases and identified 774 potentially relevant studies, among which nine studies were ultimately included in our present meta-analysis. Our results showed that CBD treatments significantly decreased PANSS positive scores (95% CI, ?2.51, ?0.89, P = 0.27, I² = 18%) but had no effect on other PANSS scores. Interestingly, while the safety of CBD has continued to be further demonstrated over time despite the dosage of CBD being gradually increased, the dosage of delta-9-tetrahydrocannabinol (THC) has remained essentially unchanged. Following our present meta-analysis, we suggest possible mechanisms of CBD-based amelioration of schizophrenic symptoms, such as CBD-induced increases in fronto-striato-thalamic coupling.     

Diffusion tractography of the fornix in schizophrenia

BackgroundWhite matter fiber tracts, especially those interconnecting the frontal and temporal lobes, are likely implicated in pathophysiology of schizophrenia. Very few studies, however, have focused on the fornix, a compact bundle of white matter fibers, projecting from the hippocampus to the septum, anterior nucleus of the thalamus and the mamillary bodies. Diffusion Tensor Imaging (DTI), and a new post-processing method, fiber tractography, provides a unique opportunity to visualize and to quantify entire trajectories of fiber bundles, such as the fornix, in vivo. We applied these techniques to quantify fornix diffusion anisotropy in schizophrenia.MethodsDTI images were used to evaluate the left and the right fornix in 36 male patients diagnosed with chronic schizophrenia and 35 male healthy individuals, group matched on age, parental socioeconomic status, and handedness. Regions of interest were drawn manually, blind to group membership, to guide tractography, and fractional anisotropy (FA), a measure of fiber integrity, was calculated and averaged over the entire tract for each subject. The Doors and People test (DPT) was used to evaluate visual and verbal memory, combined recall and combined recognition.ResultsAnalysis of variance was performed and findings demonstrated a difference between patients with schizophrenia and controls for fornix FA (p = 0.006). Protected post-hoc independent sample t-tests demonstrated a bilateral FA decrease in schizophrenia, compared with control subjects (left side: p = 0.048; right side p = 0.006). Higher fornix FA was statistically significantly correlated with DPT and measures of combined visual memory (r = 0.554, p = 0.026), combined verbal memory (r = 0.647, p = 0.007), combined recall (r = 0.516, p = 0.041), and combined recognition (r = 0.710, p = 0.002) for the control group. No such statistically significant correlations were found in the patient group.ConclusionsOur findings show the utility of applying DTI and tractography to study white matter fiber tracts in vivo in schizophrenia. Specifically, we observed a bilateral disruption in fornix integrity in schizophrenia, thus broadening our understanding of the pathophysiology of this disease.     

Cortisol awakening response in patients with psychosis: Systematic review and meta-analysis

The cortisol awakening response (CAR), defined as the increase in cortisol release in response to waking up, shows associations with social and environmental risk factors of schizophrenia and has been studied as a potential biomarker in schizophrenia. We report a systematic review and meta-analysis of 11 studies and 879 participants focusing on the CAR of patients with schizophrenia, first-episode psychosis, and at-risk mental states. Random-effects meta-analysis showed that CAR is attenuated in patients with psychosis compared to healthy controls (g = ⿿0.426, 95% CI ⿿0.585 to ⿿0.267, p < 0.001, 11 between-group comparisons, n = 879). Subgroup analysis showed flattened CAR in patients with schizophrenia (g = ⿿0.556, 95% CI ⿿1.069 to ⿿0.044, p < 0.05, 2 between-group comparisons, n = 114) and first-episode psychosis (g = ⿿0.544, 95% CI ⿿0.731 to ⿿0.358, p < 0.001, 6 between-group comparisons, n = 505), but not in individuals with at-risk mental states. These distinctive alterations of hypothalamic-pituitary-adrenal axis function may have important implications for CAR as a marker for transition risk. However, the lack of objective verification of sampling adherence in these studies may limit the interpretation of the results.     

Utility of the Montreal Cognitive Assessment (MoCA) and its subset in HIV-associated neurocognitive disorder (HAND) screening

ObjectivesThe Montreal Cognitive Assessment (MoCA) is a useful screening tool for mild cognitive impairment. We aimed to know whether the full MoCA and subsets of the full test are effective for detecting HIV-associated neurocognitive disorder (HAND).MethodsWe examined the socio-demographic, clinical, functional, and neuropsychological levels of 194 HIV-infected patients. We compared total scores and scores from each cognitive domain of MoCA between patients with and without HAND. We also examined the utility of subsets of the full test using a few selective domains. The diagnostic accuracies of MoCA and subset composition were evaluated.ResultsThe total scores of MoCA (P < 0.001) and scores from Trail Making Test-B (P = 0.020), attention domain (P = 0.005), and immediate (P = 0.003) and delayed recall (P = 0.002) differed between patients with and without HAND. A subset composed of Trail Making Test-B, rescored serial subtraction, and immediate/delayed recall showed a 69.2% accuracy.ConclusionsOur results suggest that the MoCA and its subsets alone are not sufficient in screening for HAND. Further studies will be needed to develop a simpler and easier screening tool for HAND based on this study.     

The relationship between insight and neurological dysfunction in first-episode psychosis

PurposeImpaired insight is commonly seen in psychosis and some studies have proposed that is a biologically based deficit. Support for this view comes from the excess of neurological soft signs (NSS) observed in patients with psychoses and their neural correlates which demonstrate a degree of overlap with the regions of interest implicated in neuroimaging studies of insight. The aim was to examine the relationship between NSS and insight in a sample of 241 first-episode psychosis patients.MethodTotal scores and subscale scores from three insight measures and two NSS scales were correlated in addition to factors representing overall insight and NSS which we created using principal component analysis.ResultsThere were only four significant associations when we controlled for symptoms. “Softer” Condensed Neurological Evaluation (CNE) signs were associated with our overall insight factor (r = 0.19, P = 0.02), with total Birchwood (r = ?0.24, P < 0.01), and the Birchwood subscales; recognition of mental illness (r = ?0.24, P < 0.01) and need for treatment (r = ?0.18, P = 0.02). Total Neurological Evaluation Scale (NES) and recognition of the achieved effects of medication were also weakly correlated (r = 0.14, P = 0.04).ConclusionThis study does not support a direct link between neurological dysfunction and insight in psychosis. Our understanding of insight as a concept remains in its infancy.     

Subtyping schizophrenia: A comparison of positive/negative and system-specific approaches

BackgroundSchizophrenia is a heterogeneous disorder. Over the years, different approaches have been proposed to approach this heterogeneity by categorizing symptom patterns. The study aimed to compare positive/negative and system-specific approaches to subtyping.MethodsWe used the Positive and Negative Syndrome Scale (PANSS) and Bern Psychopathology Scale (BPS), which consists of subscales for three domains (language, affect and motor behavior) that are hypothesized to be related to specific brain circuits, to assess cross-sectional psychopathological characteristics in a sample of 100 inpatients with schizophrenia spectrum disorders. We then categorized participants into positive/negative and system-specific subgroups to allow comparisons of the two approaches.ResultsThe analyses revealed correlations between the PANSS positive subscore and the BPS affective subscore (r = .446, p < .001) and between the PANSS negative subscore and the BPS motor behavior subscore (r = .227, p = .023). As regards the positive and negative subtype, more participants were classified as positive in the language-dominant subtype (30.3%) and affect-dominant subtype (30.3%), whereas more were classified as negative in the motor behavior-dominant subtype (44.4%). However, most patients met the criteria for the mixed subtype.ConclusionsThe results suggest that the positive/negative and system-specific approaches can be regarded as complementary. Future studies should examine both approaches in a longitudinal assessment of psychopathological symptoms and link them with qualitative-phenomenological approaches.     

Physical comorbidity,insight, quality of life and global functioning in first episode schizophrenia: A 24-month,longitudinal outcome study

This prospective study sought to determine the clinical impact of physical comorbidity on patients with first episode schizophrenia (FES) and we tested the hypothesis that patients with physical comorbidity were associated with poorer clinical and functional outcomes. The severity of psychopathology, insight, social/occupational functioning and quality of life were evaluated using Positive And Negative Syndrome Scale (PANSS), Scale to assess Unawareness of Mental Disorder, Global Assessment of Functioning Scale (GAF), and World Health Organisation Quality of Life-Bref Scale (WHOQOL-Bref) respectively at baseline and at 6, 12, 18 and 24 months. Out of 142 patients, physical comorbidity was present in 21.8% (n = 31) of the patients, and they were mainly related to the cardiovascular, respiratory and endocrine systems. Compared to baseline measurements, patients with physical comorbidity had greater awareness into the consequences of their psychiatric illness at 12 months, the need for treatment at 12 and 18 months, and better improvement of PANSS total and general psychopathology subscale scores at 24 months. FES patients with physical comorbidity also had less reduction in their WHOQOL-Bref scores in the physical health domain at 12 and 18 months and greater increase in the GAF scores at 18 and 24 months, indicating better subjective rating of quality of life and objective measure of their global functioning prospectively. Clinicians need to be aware of the substantial rates of physical comorbidity in FES patients which may not be necessarily associated with worse longitudinal outcomes and the findings should encourage even greater efforts at early identification and management of these physical conditions.     

Lamotrigine augmentation in patients with schizophrenia who show partial response to clozapine treatment

BackgroundSeveral placebo controlled studies investigating lamotrigine augmentation of clozapine in schizophrenia patients with partial response have shown varying results. The aim of this study was to further investigate the efficacy and safety of this augmentation strategy, and its effect on the glutamatergic system through utilizing mismatch negativity (MMN) component of auditory event related potentials.MethodsThe study was designed to evaluate the efficacy and safety of lamotrigine augmentation of clozapine in a 12-week, double-blind, placebo-controlled, prospective, randomized design. Thirty-four patients diagnosed according to DSM-IV schizophrenia criteria and with partial response to clozapine were included. Patients were randomized to 25 mg/day of lamotrigine or placebo, gradually increasing up to 200 mg/day on the 6th week. The change in psychopathology was assessed with Positive and Negative Syndrome (PANSS), Calgary Depression (CDS) and Clinical Global Impression-Severity (CGI-S) scales. A neuropsychological test battery was administered and MMN measurements were also obtained at baseline and endpoint. Safety evaluation included physical examination, UKU Side Effect Rating Scale (UKU) assessment and serum drug level measurements.ResultsNo significant differences were found between the two treatment groups in PANSS Positive and General Psychopathology, CDS, neurocognitive test and UKU scores, as well as MMN measurements. PANSS Total, Negative and CGI-S scores showed significant improvement compared to lamotrigine in the placebo group.ConclusionThis study did not show any benefit of augmentation of clozapine with lamotrigine in schizophrenia patients with partial response. The need for further investigation of other augmentation strategies of clozapine in partially responsive schizophrenia patients is evident.